Pharmacology MCQs - ANZCA

Question 1

GP01 [Mar96] A drug is given at a dose of 50 mg/kg to a 70 kg man. The plasma concentration after giving it is 10 mg/ml. The elimination half-life is 8 hours. Clearance would be: A. 1.3 l/h B. 3 l/hr C. 0.03 l/hr D. 125 l/hr

Answer 1

Vd = dose / concentraion = 3500 mg/10 mg/ml = 350 ml Clearance = 0.693 x Vd / t1/2 = 0.693 x 350 ml / 8 hrs = 30 ml / hr = 0.03 L / hr Therefore answer C is correct —Comment— OK, the maths is fine, but is it possible for a drug to have a VD of 350ml?? Is it possible for any drug to have a VD less than plasma volume?? Help please!

Question 2

GP02 [Mar96] A drug is given orally and 95% absorbed. Only 25% reaches the general circulation due to hepatic first pass metabolism. If hepatic blood flow is 1500 mls/min, the hepatic clearance is: A. 400 mls/min B. ? C. 1100 mls/min D. ? E. 1425 mls/min

Answer 2

Hepatic clearance = HER x HBF = ( (0.95 – 0.25) / 0.95 ) x 1,500 ml / min = 1,105 mls/min Extraction ratio= conc of inflow-conc outflow/conc of inflow

Question 3

GP03 [Jul97] Histamine release (no other details) GP03b [Feb12] Histamine when given IV causes: A. Bronchoconstriction B. ?

Answer 3

Bronchoconstriction through activation of H1 receptors - true. Histamine actives H1 receptors to constrict bronchial smooth muscles, whereas stimulation of H2 receptors relaxes bronchial smooth muscles. In normal patients the bronchoconstrictor action of histamine is negligible. Conversely, patients with obstructive lung disease, such as asthma or bronchitis, are more likely to develop increases in airway resistance in response to histamine. References Stoelting 4th ed p431.

Question 4

GP04 [Jul97] Rectal administration of drugs: A. Gives predictable blood levels B. From lower 1/3rd avoids first pass & upper 2/3rds doesn’t C. None undergoes first pass metabolism D. All of it undergoes first pass metabolism E. ?

Answer 4

Jul97 version: Best answer is B A false - “unpredicatable responses… follow rectal administration of drugs” (Stoelting 3rd Ed. p.9) B best answer - “Drugs administered into the proximal rectum are … transported via the portal venous system to the liver (first pass hepatic effect)… drugs absorbed from a low rectal administration site reach the systemic circulation without first passing through the liver.” (Stoelting 3rd Ed. p.9) C false - beware absolutes like all or none D false - beware absolutes. Also regarding pulmonary first pass below: I’m pretty sure they’re talking about hepatic first pass metabolism and not looking for esoteria like that. This question is basically about effect of rectal administration on first pass metabolism.

Question 5

GP04b Mar09 Rectal administration of drugs: A. Provides reliable absorption B. Administration in the lower third (below the dentate line) completely avoids hepatic first pass C. Is rapid due to the anastomoses between the superior and inferior haemorrhoid plexuses D. ? E. None of the above

Answer 5

his question is basically about effect of rectal administration on first pass metabolism. Katzung “Basic & Clinical Pharmacology” 7th ed (1998) on p42: The hepatic first-pass effect can be avoided to a great extent by use of sub-lingual tablets and transdermal preparations, and to a lesser extent by use of rectal suppositories. . Sub-lingual absorption provisdes direct access to systemic - not portal - veins. The trandermal route offers the same advantage. . Drugs absorbed from suppositories in the lower rectum enter vessels that drain into the inferior vena cava, thus bypassing the liver. . However, suppositories tend to move upwards in the rectum into a region where veins that lead to the liver, such as the superior hemorrhoidal vein, predominate. . In addition, there are extensive anastomoses between the superior and middle hemorrhoidal veins; thus, only about 50% of a rectal dose can be assumed to bypass the liver. Stoelting (2nd ed p7) also comments that a result of this unpredictable variability in percent of drug absorbed in the lower rectum versus the upper rectum that this explains “‘the unpredictable responses that follow rectal administration of drugs” Related Stuff The liver is NOT the the only organ invloved in a first pass effect. Drugs administered systemically have to pass through the lungs before reaching peripheral capillary beds, and the lung can take up (and even metabolise) some drugs. An example is fentanyl (& also pethidine) where the lungs act as a large inactive storage site. An estimated 75% of the initial fentanyl dose undergoes first-pass pulmonary uptake. Stoelting ( 2nd ed 1991 p85) references the following source: Roerig et al. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology. 1987 Oct;67(4):466-72 . “ . . . . The total uptake (mean +/- SE) during the first pass through the human lung for fentanyl and meperidine was 75.2 +/- 3.2% and 64.7 +/- 7.8% of the injected dose, respectively. The pulmonary uptake of morphine was very small, with 96.5 +/- 7.1% of the injected dose recovered in arterial blood after the first pass through the lung. . . . “ [1] Aug 15- C

Question 6

GP04c 15B Aug15 version with different options Regarding rectal administration of drugs A. Rectal indomethacin does not cause gastric symptoms B. Rectal administration is predictable and effective. C. Superior haemorrhoidal vein absorption results in hepatic first pass metabolism D. paracetamol cannot be given rectally

Answer 6

his question is basically about effect of rectal administration on first pass metabolism. Katzung “Basic & Clinical Pharmacology” 7th ed (1998) on p42: The hepatic first-pass effect can be avoided to a great extent by use of sub-lingual tablets and transdermal preparations, and to a lesser extent by use of rectal suppositories. . Sub-lingual absorption provisdes direct access to systemic - not portal - veins. The trandermal route offers the same advantage. . Drugs absorbed from suppositories in the lower rectum enter vessels that drain into the inferior vena cava, thus bypassing the liver. . However, suppositories tend to move upwards in the rectum into a region where veins that lead to the liver, such as the superior hemorrhoidal vein, predominate. . In addition, there are extensive anastomoses between the superior and middle hemorrhoidal veins; thus, only about 50% of a rectal dose can be assumed to bypass the liver. Stoelting (2nd ed p7) also comments that a result of this unpredictable variability in percent of drug absorbed in the lower rectum versus the upper rectum that this explains “‘the unpredictable responses that follow rectal administration of drugs” Related Stuff The liver is NOT the the only organ invloved in a first pass effect. Drugs administered systemically have to pass through the lungs before reaching peripheral capillary beds, and the lung can take up (and even metabolise) some drugs. An example is fentanyl (& also pethidine) where the lungs act as a large inactive storage site. An estimated 75% of the initial fentanyl dose undergoes first-pass pulmonary uptake. Stoelting ( 2nd ed 1991 p85) references the following source: Roerig et al. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology. 1987 Oct;67(4):466-72 . “ . . . . The total uptake (mean +/- SE) during the first pass through the human lung for fentanyl and meperidine was 75.2 +/- 3.2% and 64.7 +/- 7.8% of the injected dose, respectively. The pulmonary uptake of morphine was very small, with 96.5 +/- 7.1% of the injected dose recovered in arterial blood after the first pass through the lung. . . . “ [1] Aug 15- C

Question 7

GP05 [Mar99] [Jul00] [Apr01] [Jul04] [Feb07] LD50 is: A. Median lethal dose B. Determined in phase I clinical trial C. Determined from log-dose response curve D: Dose causing death in 50% of animals within ?1/?4 hours E. Half the mean lethal dose. F. Best expressed as ratio of lethal dose in 50% of animals to effective dose in 50%

Answer 7

Answer is A I agree A is most correct. But C appears to also be correct? Katzung (7th ed 1998 p29): “The quantal dose-effect curve is often characterised by stating the median effective dose (ED50), the dose at which 50% of individuals exhibit the specified quantal effect. (Note that the abbreviation ED50 has a different meaning in this context from its meaning in relation to graded dose-effect curves.) Similarly the dose required to produce a particular toxic effect in 50% of animals is called the median toxic dose (TD50). If the toxic effect is death of an animal, a median lethal dose (LD50) may be experimentally defined. “ Also: “Quantal dose-effect curves may also be used to generate information regarding the margin of safety to be expected from a particular drug used to produce a specified effect. One measure, which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect, is the therapeutic index. In animal studies, the therapeutic index is usually defined as the ratio of the TD50 to the ED50 for some therapeutrically relevant effect” A few important points to bear in mind: Some candidates start talking about LD50 as though this was something that could be determined for humans! If you are asked what method you would use to determine the LD50 of a new drug in humans be very wary. You should always very quickly remark that such is NEVER done in humans for obvious ethical reasons. The therapeutic index can be not very useful in some cases, for example if there is significant overlap between the effective and toxic curves. OECD countries in 2000 agreed to minimise the use of LD50 testing to minimise the number of animals killed. (The examiners are unlikely to know this - useful info for a viva) As regards the phase 1 clinical trials option: “Phase 1 includes the initial introduction of an investigational new drug into humans. These studies are closely monitored and may be conducted in patients, but are usually conducted in healthy volunteer subjects. . These studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. During Phase 1, sufficient information about the drug’s pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies. “ [1] SO: You NEVER determine a LD50 during phase 1 trials because these trials are done in HUMANS.

Question 8

GP06 - [Mar99] [Feb00] [Jul02] [Mar03] -Aug15 Which ONE of the following crosses the blood-brain barrier? A. GABA B. Propranolol C. Suxamethonium D. Edrophonium E. Dopamine

Answer 8

Answer is B Propranolol: Yes. From Stoelting 2nd ed p306: “Beta-blockers may cross the blood-brain barrier to produce side effects. For example, fatigue and lethargy are commonly associated with chronic propranolol therapy.” Suxamethonium-No: is charged (and rapidly metabolised). Does not cross BBB but can have indirect effects on brain function (eg apnoea->cerebral hypoxia). Edrophonium-No: It is a quaternary amine so is charged and cannot cross the blood-brain barrier. (In contrast, physostigmine is a tertiary amine anticholinesterase which can cross the BBB). Dopamine-No: From [1]: “Of importance for PD, dopamine, a neurotransmitter that is depleted in PD, does not’ pass the BBB but L-dopa does. In the brain L-dopa is converted to dopamine. This is important for treatment of PD symptoms with levadopa alone or in combination with carbidopa.” Carbidopa is a dopa decarboxylase inhibitor which inhibits the peripheral conversion of L-Dopa to dopamine (but not centrally as it does not cross the BBB). GABA -No. It is a non-essential amino acid and as such can be synthesised in the brain. It has difficulty crossing the BBB. References Bioavailability of Drugs to Brain and Blood brain barrier

Question 9

GP07 [Jul98] [Jul99] [Apr01] With regard to drug-receptor binding: A. A competitive antagonist has no intrinsic activity B. A partial agonist has less receptor affinity than a full agonist C. KD is maximal intrinsic efficacy

Answer 9

GP07 A - correct B - false C - false - “intrinsic affinity” is a confusing term for “efficacy”. KD relates to “affinity” / “potency” KD is the equilibrium dissociation constant, with units mmol/L. KA is the equilibrium affinity constant and is the reciprocal of KD, with units L/mmol. From Peck and Hill: The potency is determined by a drug’s KD; the lower the KD, the higher the potency. For many drugs, the ED50 (dose producing 50% of maximum response) corresponds to the KD. KD = [ligand] x [receptor] / [ligand-receptor complex] = k2/k1 = 1/KA Katzung 6e p16 says “…partial agonists competitively inhibit the responses produced by full agonists” - but doesn’t say “always” and I agree to be wary of questions with absolutes. A partial agonist at high concentrations may antagonise a full agonist, but at low concentrations they will exert an additive effect together.

Question 10

GP07b [Feb00] [Feb04] [Jul04] A partial agonist: A. Always antagonises a full agonist B: Can never be used to antagonise a full agonist C: Has a dose response curve similar to that of a full agonist in the presence of a non-competitive antagonist. D. ?

Answer 10

GP07b A - false - beware always B - false - beware never C - correct KD is the equilibrium dissociation constant, with units mmol/L. KA is the equilibrium affinity constant and is the reciprocal of KD, with units L/mmol. From Peck and Hill: The potency is determined by a drug’s KD; the lower the KD, the higher the potency. For many drugs, the ED50 (dose producing 50% of maximum response) corresponds to the KD. KD = [ligand] x [receptor] / [ligand-receptor complex] = k2/k1 = 1/KA Katzung 6e p16 says “…partial agonists competitively inhibit the responses produced by full agonists” - but doesn’t say “always” and I agree to be wary of questions with absolutes. A partial agonist at high concentrations may antagonise a full agonist, but at low concentrations they will exert an additive effect together.

Question 11

GP08 [Jul98] [Jul01] [Mar02] Placental transfer of drugs: A. Increases in late pregnancy B. Increases late because of decreased albumin C. Do not cross if MW > 600 daltons D. Lipid soluble drugs diffuse through placenta depending on concentration gradient E. Increased diffusion if greater plasma protein binding in fetus

Answer 11

A - no idea B - no idea C - no idea but may not be true (think facilitated transport for larger proteins) D - correct: From first principles (Fick’s law of diffusion, net flux across a semi permeable membrane is proportional to “D”, the diffusion coefficient, the surface area and the concentration gradient; and inversely proportional to the thickness. “D” itself is proportional to the solubility of the substance to the membrane and inversely proportional to the square root of the molecular weight of the substance.) Also Peck, Hill and Williams state that being “phospholipid in nature, the placental membrane is more readily crossed by lipid-soluble than polar molecules” (p.19) E incorrect - “plasma protein binding influences the rate and degree of diffusion of LAs across the placenta. Bupivacaine, which is highly protein bound (approx 95%) has an umbilical vein-maternal arterial concentration ratio of about 0.32 compared with a ratio of 0.73 for lignocaine (approx 70% protein bound) and a ratio of 0.85 for prilocaine (approx 55% protein bound)” (Stoelting 3rd ed. p.163) Whilst I hate to disagree, Peck and Williams p19 states “high protein binding in the foetus increases drug transfer across the placenta since foetal free drug levels are low.” hence I would say E is correct. M2C: I agree E is correct. C is also correct - I think it is Stoelting who says anything greater than around 500da crosses less easily. Whilst the objections to D being correct and the support of E are noted, the numbers quoted in Stoelting would appear to support that E is incorrect. i.e. at least in the case of bupivicaine vs lignocaine, only around 30% is transferred compared with around 75% for lignocaine which has the lower protein binding. Everyone however is free to make their own decision and we won’t really know who is right and who is wrong come exam time. Only the examiners (or the computer marking it) will know. :-) I think the quote from stoelting regarding option E is referring to maternal protein binding, while the question is referring to fetal protein binding. I agree that high protein binding in the mother will decrease diffusion across the placenta, but for 2 drugs with identical maternal protein binding, the one with higher fetal protein binding will have greater placental transfer (assuming pKa, lipid solubility the same for each) I agree - also, just saw in UptoDate that if drugs are unionised/lipid-soluble, they freely cross the placenta if MW 1000 g/mol) do not cross the placental membrane[11]” D and E likely true (as per above)

Question 12

GP09 [Jul98] [Jul99] Regarding pharmacokinetics: A. ? B. Half-life is inversely proportional to clearance C. ? D. Half-life is proportional to steady-state E. B & D

Answer 12

B definitely correct as clearance = 0.693 x Vd/ half life Discussion about D and E below just a thought, IR (infusion rate) = Cl * Css Cl = ke * Vd Ke = ln2 / T1/2 = 0.693 / T1/2 Hence, rearranging IR/Css = 0.693Vd / T1/2 Css = (IR * T1/2) / 0.693Vd so that steady state concentration is proportional to its half life at a given infusion rate. perhaps E ??? any thoughts?? D would be correct if the word “concentration” was put at the end of the option, to make it less ambiguous. In that case, E would be correct. I’m not entirely sure but i think the algebraic reasoning above may be incorrect…if you expand the terms IR & T1/2 out, everything cancels and you end up with Css=Css.

Question 13

GP10 [Jul99] [Jul04] An ether bond: A. Formed from condensation of 2 alcohols B. Hydroxyl group on middle bond C. ?

Answer 13

A - maybe right. If you combine two hydroxyls to form an ether, then you produce water (see the Wiki entry below), but is it the same as condensation? B - definitely WRONG Ether - “Any of a class of organic compounds in which two hydrocarbon groups are linked by an oxygen atom.” (“ether.” The American Heritage® Dictionary of the English Language, Fourth Edition. Houghton Mifflin Company, 2004. Answers.com 17 Feb. 2007.) From Wikipedia Ethers can be prepared in the laboratory in several different ways. One of the 3 ways is Dehydration of alcohols: R-OH + R-OH → R-O-R + H2O Is this the same as condensation? Yes! Condensation reactions also include formation of ester bonds from an alcohol and acid, and also forming peptide bonds from two amino acids. I think dehydration is the specific subset of condensation when water is produced. There are other condensation reactions that result in other, non-water, small molecules being formed…can’t think of any examples at present

Question 14

GP11 [Feb00] [Mar03] The NMDA receptor A. Ketamine is an agonist B. Requires glycine as a modulating protein to have its effect C. Mg+2 blocks the receptor D. Is not permeable to Calcium

Answer 14

C is the best answer Ketamine is an ANTAGONIST Glycine is an AMINO ACID (not a protein) - several persons submitting this question noted the “protein” wording) Mg+2 normally blocks the ion channel in the molecule When open, it is permeable to Na+, K+ and Ca+2 Regarding the NMDA Receptor: “The NMDA receptor gates a cation channel that is permeable to Na+, K+ and Ca+2 and is gated by Mg+2 in a voltage-dependent fashion. Agonists (glutamate, NMDA) and the coagonist glycine, required for full activation, bind to the extracellular domain” (from Hemmings & Hopkins “Foundations of Anesthesia” p250) Opening of the channel in the NMDA receptor requires ALL of the following: partial depolarisation of the cell membrane (to relieve the Mg+2 obstruction of the channel) binding of BOTH glutamate AND glycine (on extracellular side)

Question 15

GP12 [Feb00] [Jul02] Activated charcoal: A. Should be given with sorbitol B. Is not effective against theophylline C. Should be given with ipecac D. Should be given in a drug:charcoal ratio of 1:10 E. ?

Answer 15

Answer is D What is Activated charcoal? Chemically it is just pure carbon, but the way it is produced gives it a HUGE surface area. A tennis court has a SA of about 260m2 so just one gram has an average of more than TWICE that. Ref [1]. “Activated charcoal is used in water filters, medicines that selectively remove toxins, and chemical purification processes. Activated charcoal is carbon that has been treated with oxygen. The treatment results in a highly porous charcoal. These tiny holes give the charcoal a surface area of 300-2,000 m2/g, allowing liquids or gases to pass through the charcoal and interact with the exposed carbon.” (from [2]) Activated charcoal is a fine, black, odorless, and tasteless powder. It is made from wood or other materials that have been exposed to very high temperatures in an airless environment. It is then treated, or activated, to increase its ability to adsorb by reheating with oxidizing gas or other chemicals to break it into a very fine powder. Activated charcoal is pure carbon specially processed to make it highly adsorbent of particles and gases in the body’s digestive system. . Activated charcoal has often been used since ancient times to cure a variety of ailments including poisoning. Its healing effects have been well documented since as early as 1550 B.C. by the Egyptians. However, charcoal was almost forgotten until 15 years ago when it was rediscovered as a wonderful oral agent to treat most overdoses and toxins. (from [3]) ??15 years The sorbitol option Some activated charcoal products contain sorbitol. Sorbitol is a sweetener. It also works as a laxative, for the elimination of the poison from the body. Products that contain sorbitol should be given only under the direct supervision of a doctor because severe diarrhea and vomiting may result. - from Medline plus Regarding Sorbitol, In AMH (July 2008) there are two types of Activated Charcoal mentioned that are thus Available in Australia: “oral liquid, 50 g, in 46% sucrose, 250 mL, Carbosorb X (PL) oral liquid, 50 g, in 40% sorbitol, 250 mL, Carbosorb XS (PL)” But in “practice points” it mentions: “Sorbitol provides no additional benefit to charcoal in most poisonings and may result in diarrhoea and volume depletion.” Regarding 1st dose: “1 g/kg to a maximum of 50–100 g for each dose of activated charcoal.” So you can use it with sorbitol, but it is just one option. The theophylline option Consider this abstract: Effect of the surface area of activated charcoal on theophylline clearance GD Park et al. Journal of Clinical Pharmacology, 1984; 24:289-292 . The effect of the surface area of activated charcoal on theophylline clearance was studied. Eight fasting, healthy men received intravenous infusions of either aminophylline (6 mg/kg, N = 3) or theophylline (5 mg/kg, N = 5) over 1 hour followed by either 5 Gm standard activated charcoal every 2 hours, 20 Gm every 2 hours, or 5 Gm PX-21 activated charcoal (with 3.6 times the surface area) every 2 hours. …..(some content deleted) … . We conclude that the clearance of theophylline is related to the surface area of activated charcoal administered and that PX-21 may be a more potent activated charcoal product for enhancing theophylline removal. and this from a page about treatment of theophylline overdose: Gastrointestinal decontamination . To block absorption, administer oral activated charcoal (1 mg/kg, not to exceed 20 g) every 2 hours until the serum theophylline level has fallen to less than 20-25 mcg/mL. . For vomiting, administer metoclopramide, droperidol, or ondansetron. Avoid ipecac because it does not reduce absorption. Avoid phenothiazine antiemetics (eg, prochlorperazine, perphenazine) because they lower the seizure threshold from [4]. The ipecac option What’s the sense of giving something (charcoal) only to give another drug (ipecac) to vomit it up? However, the two can be used together IF ipecac is given first, then activated charcoal after a period of time: Activated charcoal is available without prescription. However, in case of accidental poisoning or drug overdose an emergency poison control center, hospital emergency room, or doctor’s office should be called for advice. In case that both syrup of ipecac and charcoal are recommended for treatment of the poison, ipecac should be given first. Charcoal should not be given for at least 30 minutes after ipecac or until vomiting from ipecac stops. Activated charcoal is often mixed with a liquid before being swallowed or put into the tube leading to the stomach.” (from [5]. The drug:charcoal ratio option For those (?rare) occasions when the dose of ingested drug/toxin is known, there is a recommendation on a drug:charcoal ratio: Give 10 times as much charcoal BY WEIGHT as drug ingested. Initial dose, 1 g per kg of body weight or 25 to 100 g orally or via gastric tube (as a slurry in water) or if the quantity of toxin ingested is known, 10 times the amount of ingested toxin by weight is given. Repeat-dose, 0.25 to 0.5 g per kg of body weight (15 to 30 g) every 2 to 4 hours is given orally or by gastric tube. Following administration of activated charcoal, it is recommended that a cathartic be administered to enhance removal of the drug-charcoal complex since failure to excrete the drug-charcoal complex promptly may result in enhanced toxicity. When multiple doses of activated charcoal are required, administration of a small dose of cathartic with every second or third charcoal dose is recommended. Do not use cathartic with every activated charcoal dose. Warning 1. It should be used with caution in patients with absence of bowel sounds. 2. It may cause swelling of abdomen or pain and black stools. 3. The effectiveness of oral acetylcysteine and other oral medications may be decreased when used concurrently with activated charcoal. 4. Chocolate syrup or ice cream or sherbet should not be used as vehicles for the administration of activated charcoal since they will decrease the adsorptive capacity of the activated charcoal. from p29 [6] When NOT to use activated charcoal Just in case this is an option in future versions of this question. Activated charcoal is used in the emergency treatment of certain kinds of poisoning. It helps prevent the poison from being absorbed from the stomach into the body. Sometimes, several doses of activated charcoal are needed to treat severe poisoning. Ordinarily, this medicine is not effective and should NOT be used in poisoning if - Corrosive agents such as alkalis (lye) and strong acids, - Alcohols or - Miscellaneous: boric acid, iron, lithium, - Petroleum products (e.g., cleaning fluid, coal oil, fuel oil, gasoline, kerosene, paint thinner), have been swallowed, since it will not prevent these poisons from being absorbed into the body. from [7] Mnemonic: Avoid if CAMP BAIL - where the BAIL coverrs the miscellaneous ones My notes: a. Teik Ok ICU book p.948 says don’t give with sorbitol. Found an A&E book which stated there was no evidence that it does any good. b. G&G 11e p1748 says “serial doses enhance elimination of theophylline” and other sources list theophylline as one of the few intoxications where a.c. is definitely recommended. c. no advantage over charcoal alone and charcoal can adsorb the emetic agent and reduce it’s effect - think this was also from G&G d. this is definitely true as above G&G: 11e p.1748

Question 16

GP13 [Apr01] [Jul04] Therapeutic index: A. Easy to determine in humans B. ? C. D. E. Derived from LD50/ED50

Answer 16

From Yentis: Therapeutic index is defined experimentally as the ratio of median lethal dose to median effective dose -therefore answer is E THERAPEUTIC INDEX “The ratio of the drug dose which produces an undesired effect to the dose which causes the desired effects is a therapeutic index and indicates the selectivity of the drug and consequently its usability. It should be noted that a single drug can have many therapeutic indices, one for each of its undesirable effects relative to a desired drug action, and one for each of its desired effects if the drug has more than one action. “ An alternative more general definition: “Therapeutic index can be evaluated as the relative position of the dose-efficacy and the dose-side effect curves.” The “position” of each curve is determined from its 50% response position, and the “relative” aspect is determined by taking the ratio of the 2 curve positions - with the undesired effect in the numerator and the desired effect in the denominator. The point of getting this ratio is that it provides some information about the “margin of safety” with use of the druug.

Question 17

GP14 [Apr01] [Jul04] (A Basic drug with a pKa of 8.7) A. ? B. ? C. Will be predominantly ionised at plasma pH

Answer 17

A basic drug will be predominantly ionised at a pH below its pKa For a drug with a pKa of 8.7 undegoing the reaction: B + H+ BH+: At pH = pKa we can calculate the following: pH = pKa + log([B]/[BH+]) (Henderson-Hasselbalch equation) If pH = pKa then this simplifies to pKa = pKa + log([B]/[BH+]) log([B]/[BH+]) = 0 Thus, taking anti-logs (easy as log 1 = 0): ([B]/[BH+]) = 1 so [B] = [BH+] -> 50% ionised & 50% unionised By doing similar calculations using the Henderson-Hasselbalch equation, the ratio B/BH+ can be determined at any pH value. For example: For pH = pKa + 1 -> 10% ionised & 90% unionised (approx) For pH = pKa -> 50% ionised & 50% unionised For pH = pKa - 1 -> 90% ionised & 10% unionised For pH = pKa - 2 -> 99% ionised & 1% unionised “Bases ionised Below, Acids ionised Above”

Question 18

GP15 [Apr01] [Jul02] [Mar03] Oxygen toxicity A. Causes convulsions at less than 100 kPa B. Causes lipid peroxidation at less than 100 kPa C. ? D. ? E. ?

Answer 18

A is incorrect. CNS toxicity occurs at > 200 kPa B. correct In general, “hazards” associated with oxygen use include hypoventilation, i.e. in pts with CPOD who are chronic CO2 retainers Absorption Atelectasis ( alveolar collapse)- high oxygen concentrations can cause atelectasis in areas of low ventilation relative to perfusion. VC can be decreased by 500-800ml as a consequence Retinopathy of prematurity ( previously called retrolental fibroplasia) - FIO2 > 0.50 to neonates can encourage “disorganized vascular proliferation and fibrosis”.. which can make the retina opaque, .” as well as retinal detachment” Bronchopulmonary dypasia - in neonates Fire hazard Pulmonary toxicity In the acute situation, use of 100% O2 ( PaO2 > 600mm Hg,) is not associated with toxicity. Dose time toxicity curves state that 100% O2 administered longer than 12 hours are associated with toxic effects, namely tracheobroncial irritation ( manifested as coughing, retrosternal burning, chest tightness, “substernal distress”). The pathophysiology of oxygen toxicity may arise from several mechanisms, such as: inactivation of enzymes, release of inflammatory mediators, action of dioxygen moecule as a free radical, formation of a superoxide free radicals, formation of hydrogen peroxide. Ultimately oxygen derived free radicals act on DNA, lipids ( disrupts alveolar capillary membrane), and sulphydryl contatining proteins. With regards to hyperbaric O2 therapy, the degree of toxicity is related to the pressures used as well as duration of usage. At > 2 atmospheres ( > 200 KPA) the risk of CNS toxicity emerges, i.e. convulsions, muscular twitches, behavior changes. From my reading, B appears to be true, assuming they are referring to “100 kPa” as alveolar PO2. “ Chronic O2 administration of 100% O2 at 1atm results in PO2 of 713 mm Hg/ 95 kPa, which can lead to lipid peroxidation”. References Faunce - ANZ Intensive care & Primary exam, 9th ed. p 60, Lange- Clinical Anaesthesiology 4th ed p. 1028-9

Question 19

GP16 [Jul01] With regard to log/dose response curves: A. The response is fairly linear over the 20-80% range. B. The Dose is fairly linear over the 20-80% range C. The ED50 and slope are characteristic for each drug D. ? E. ?

Answer 19

Best answer is probably A From Aitkenhead 4th p. 21: “Conventionally, log-dose is plotted against effect, resulting in a sigmoid curve which is approximately linear between 20 and 80% of maximum effect” Could they all be right? C sounds right, as does B (although this does not mention response) or is it not B because it is not really linear if you have to use a logarithmic scale to get that shape graph? I think A is most correct. B seems incorrect - the dose is not linear on a logarithmic scale C could be true also Stoelting page 17 4th Ed cover it faily well with regard to C and seems to indicate this is correct. Slope influenced by number of receptors drug must ocupy to have effect, and ED50 measure of potency which shouldn’t change for each drug. I haven’t found anything regarding the 20-80% thing though

Question 20

GP18 [Jul01] With regards to diffusion through a membrane: A. Directly proportional to thickness B. Inversely proportional to thickness C. Inversely proportional to Surface area D. Inversely proportional to concentration difference E. ?

Answer 20

Fick’s Law of Diffusion: A - False B - True C - False D - False Law is: . v_gas ~ A.D.(p1-p2) / T where D ~ solubility / sqrt (MW) See: West, p.26

Question 21

GP19 [Mar02] [Mar03] [Mar08] Which of the following has it’s action related to a ligand gated ion channel? A. Metoclopramide B. Phenylephrine C. Morphine D. Vecuronium E. Salbutamol

Answer 21

Answer D. Vecuronium Lengthy notes Sorry about my lengthy notes here (mainly to convince myself I know it, but also, this is core stuff that didn’t leap out when I first read about these drugs). First part is unreferenced and my interpretation of the action of drugs at the Nicotinc Ach receptor. The second part on opioids is a cut and past from wiki on opioid receptors. Good luck. NMJ nACh Receptor The Nicotinic Ach receptor is a ligand gated ion channel (2 alphas beta gamma and delta or epsilon). To activate the channel two Acetylcholine molecules bind to each of the alpha subunits and open the channel, then dissociate and are quickly metabolised by acetylcholinestarase in the NMJ. Because the enzyme is in the NMJ there is a gradient rapidly for Ach to dissociate from the receptor back into the NMJ. Suxamethonium binds both alphas and activates the channel –> action potential spread –> fasciculation. Sux is not metabolised in the NMJ as the Plasmacholinesterase is in the – yep you guessed – plasma. So there is no rapid gradient to dissociate from the receptor until some sux begins to diffuse out of the NMJ into the plasma then the bound sux can dissociate. So receptors are held open for much longer by sux than Ach. Non-depolarizers all have a molecular structure which includes an-Ach like portion. This binds to a single alpha subunit and the bulky molecule blocks the receptor. As it only binds a single alpha subunit the channel is not opened and no depolarisation occurs. Opioid receptors Opioid receptors: G protein linked with opioids as ligands (but no channel). The endogenous opioids are dynorphins, enkephalins and endorphins. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). There are three major subtypes of opioid receptors: [1] delta opioid receptor (δ) OP1 δ1, δ2 kappa opioid receptor (κ) OP2 κ1, κ2, κ3 mu opioid receptor (μ) OP3 μ1, μ2 (Sigma receptors (σ) were once considered to be opioid receptors, but are not usually currently classified as such.) The receptors were named using the first letter of the first ligand that was found to bind to them. Morphine was the first chemical shown to bind to mu receptors. The first letter of the drug morphine is `m’. But in biochemistry there is a tendency to use Greek letters so they converted the ‘m’ to μ. Similarly a drug known as ketocyclazocine was first shown to attach itself to kappa receptors.[2] The opioid receptor types are ~70% identical with differences located at N and C termini. The μ receptor (the μ represents morphine) is perhaps the most important. It is thought that the G protein binds to the third intracellular loop of the opioid receptors. Both in mice and humans the genes for the various receptor subtypes are located on different chromosomes. Separate subtypes have been identified in human tissue. Research has so far failed to identify the genetic evidence of the subtypes, and it is thought that they arise from post-translational modification of cloned receptor types.[3] An additional opioid receptor has been identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or ORL 1 receptor. From Stoelting 4th Ed: pg 89. “All 3 receptor classes couple to G proteins and subsequently inhibit adenylyl cyclase, decrease the conductance at voltage gated calcium channels, or open inward flowing potassium channels.” Suggests that opioid act via ligand gated ion channel and hence C correct. I think you have looked into it a bit too deeply. potassium channels are most likely activated in a similar way to those related to M2 muscarinic receptors in the AV node. ie Beta and delta (rather than usual Alpha subunit) of G protein activated ion channel (ie Still ligand activating G protein which THEN activates ion channel). Prob the same for Calcium channel but not sure. Would have to go for D Vec is a competitive antagonist for ligand gated ion channel. ::Agreed. A G-protein-coupled-receptor is a metabotropic receptor and IS NOT an ionotropic receptor (ligand-gated ion channel). References 1. Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006).75 years of opioid research: the exciting but vain quest for the Holy Grail. Brit. J. Pharmacol.147, S153–S162 2. [1] 3. Fries, DS (2002). Opioid Analgesics. In Williams DA, Lemke TL. Foye’s Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.

Question 22

GP20 [Jul02] Zero order kinetics means: A. ? B. ? C. Drug is eliminated at a constant rate regardless of dose. D. Elimination half time will vary according to dose. E. ?

Answer 22

Most correct answer is C, but would be better if worded “drug is eliminated at a constant rate regardless of plasma concentration” Zero-order kinetics (also referred to as saturation kinetics): the rate of elimination of a drug from the plasma is constant irrespective of the plasma concentration this differs from the exponential patterns of elimination seen in first-order kinetics A good example of this is ethanol, which is cleared from plasma at approx 4mmol/L/hour regardless of plasma concentration. The underlying reason for this constant rate of elimination is that the rate of oxidation by the enzyme alcohol dehydrogenase reaches a maximum at low ethanol concentrations (due to limited cofactor availability). Consequences of zero-order kinetics: duration of action is strongly dependent on drug dose the relationship between steady-state plasma concentration and dose is unpredictable D is also correct I think; elimination half-life is constant for first order processes, but varies with dose (and is thus a half-time) for zero order processes. in relation to D it is explained n wikipedia [1] t1/2 = initial conc/(2k) where k = r which is the constant rate of elimination. So increasing the dose or initial concentration will proprtionally increase the T1/2. D also seems correct.

Question 23

GP21 [Feb04] All exist as racemic mixtures except: A. Thiopentone B. Lignocaine C. Bupivacaine D. Isoflurane E. Enflurane

Answer 23

Answer is B. Lignocaine is achiral and therefore does not have enantiomeric forms. A racemic mixture contains equal amounts of two enantiomers (non-superimposable mirror image molecules) of a chiral molecule; polarized light can be pass through a solution of these without being rotated. (Things get more complicated when the molecule has more than one chiral centre.) NB I think sodium thiopentone exists as a mixture of tautomers, which by definition have different connections between the same atoms, and therefore can’t be enantiomers and can’t give rise to a racemic mixture. (Stoelting p.127 implies, and Hemmings/Hopkins p.299 clearly states that thiopental is a racemic mixture - given both are texts I’d be happy to accept that thiopental is a racemic mixture and the answer is “B”). Furthermore, the tautomerism confers asymmetry to the barbituric ring thus making the C2 carbon chiral. NO - the C2 carbon has a double bond in the enol AND keto form. No carbon with a double bond can be chiral (ever, anywhere). If you meant the C5 carbon, it is not chiral either. Why? Because keto-enol (or in the case of thiopentone, thial-thioketone) tautomerism is a rapidly reversible process, in the supposedly asymetric form (thial) the double bond can point toward C4 or C6, those electrons are delocalised between C4 and C6 thus removing any asymmetry. The C5 carbon is never chiral in thiopentone. It only has 1 chiral centre which is the carbon attached to C5 in the longer of the 2 chains on C5. PS I’d disagree with that definition of a racemic mixture being only composed of enantiomers. Mivacurium is a unequal racemic mixture of diastereoisomers (geometric).

Question 24

GP22 [Feb04] Clearance of a drug with a high hepatic extraction will be: A. Decreased in shock ??? B. Increased in high output states ??? C. ? D. ? E. ?

Answer 24

The clearance of drugs with a high hepatic extraction ratio are highly dependent on the flow through the liver. For example, a drug with a hepatic extraction ratio of 1.0 will have twice the clearance when the hepatic blood flow is doubled. Conversely a drug with a low hepatic extraction ratio will have its clearance minimally affected by doubling the hepatic blood flow. Therefore: A - correct as shock will decrease hepatic blood flow and hence clearance B - correct as increased cardiac output will increase hepatic blood flow and hence clearance Both are true I think. The clearance of drugs with a low extraction ratio (ER) is minimally affected in absolute terms by changes in blood flow (a 50 % increase or decrease of very little is still very little), whereas it will have a much larger (in absolute terms) impact for drugs with a high ER. Clearance = ER x blood flow. I think A is more correct because high output does not always correlate to higher hepatic blood flow whereas in shock, hepatic blood flow will definitely decrease.

Question 25

GP23 [Feb04] The chemoreceptor trigger zone: A. Contains 5HT3 and D2 receptors B. Not involved in inner ear mediated nausea C. ? D. ? E. ?

Answer 25

Both A and ?B are correct. From Ganong (21st ed) p235-236: The Vomiting Centre exists in the reticular formation in the medulla. Afferents to this include: Viceral afferent pathways from the Upper GI Mucosa relayed via Sympathetic and Vagal Nerves Vestibular Nuclei afferents located in the inner ear that respond to motion, causing motion sickness Other afferents from the diencephalon and limbic systems - the response to nauseating smells and sickening sights The Chemoreceptor Trigger Zone (CTZ) whose cells are located in the area postrema (on the lateral wall of the 4th ventricle). This area is known as one of the circumventricular organs and is outside the Blood Brain Barrier. Lesions of the CTZ do not abolish the response to GI irritation or the motion sickness response. The Area Postrema has 5-HT3 and D2 receptors. This is why 5-HT3 antagonists and D2 antagonists are effective anti-emetics. Regarding part B - Kam p174 states that "impulses arising from endolymph movements in the utricle and saccule of the vestibular apparatus are relayed via the vestibular nucleus and VIIIth nerve to the CTZ". KB's books also states "The pathway is partly via the CTZ and partly directed to the vomiting centre. Drugs which block the CTZ do not completely prevent or treat motion sickness. Anticholinergic drugs such as hyoscine are more effective." Therefore B is probably wrong. A : true B : false CTZ has all the receptors for 5-HT3, muscarinic, histamine-1, dopamine-2 and opioid receptors; it also receives input from vestibular labyrinth

Question 26

GP24 [Feb04] [Jul04] Glutamate A. Dissociates slowly from the NMDA receptor B. Does not act at AMPA and kainate receptors C. Inhibitory neurotransmitter in CNS D. ?

Answer 26

A - correct (see below) B - incorrect (has actions at NMDA, kainate and AMPA receptors according to Ganong Ed.22 2005 Table 4-2) C - incorrect; glutamate is an excitatory neurotransmitter Ref: Glutamate unbinding reveals new insights into NMDA receptor activation Alasdair J. Gibb The Journal of Physiology Volume 574 Issue 2 Page 329 - July 2006 doi:10.1113/jphysiol.2006.114017 Volume 574 Issue 2

Question 27

GP25 [Feb04] Regarding pharmacokinetics in pregnancy: A. Paracetamol uptake increased B. Increased sensitivity and faster onset with thiopentone C. Hepatic clearance decreased by decreased protein binding D. ? E. ?

Answer 27

B is correct (See Gin et al in ref section) Some notes unreferenced as they are from memory only: A. False - Delayed gastric emptying = delayed absorption B. True - Increased cardiac output increases speed of onset C. False - Decreased PPB = Increased free drug available for hepatic extraction B is correct, but I don't think it is due to the increased cardiac output. The increased cardiac output will result in a lower thiopentone concentration in blood leaving the heart (essentially indicator dilution), and as cerebral blood flow remains constant, an increased CO will result in the same flow to the brain, but this flow will be a smaller percentage of total cardiac output. Therefore, the pregnant brain will receive the same volume per unit time of blood but with a lower thiopentone concentration which would normally causes an apparent resistance to a stated dose, so other factors must cause the observed response of increased sensitivity (eg decreased PPB or the effects of progesterone) "The dose of thiopentonal needed to produce anaesthesia in early pregnancy (7-13weeks gestation) is decreased about 18% compared with that for nonpregnant females." Stoelting. 4th ed. p132. "The half-emptying time and the final gastric emptying time did not differ in the first and third trimesters and postpartum, but gastrointestinal transit time was significantly longer in the third trimester of pregnancy than postpartum" - Journal of Gastroenterology August 2001 http://www.ncbi.nlm.nih.gov/pubmed/11519832 B true : My reason would be that during pregnancy there is a reduction in plasma albumin and hence, unbound STP is more readily available for its effect site. I too feel an increase in cardiac output will cause a delay in speed of onset of the drug. For example, a patient with low cardiac output state require lower dose during induction

Question 28

GP26 [Jul04] Which is an antagonist at the NMDA receptor? A. Dexamethasone B. Dextropropoxyphene C. Dexmedetomidine D. Dextromethorphan E. Dexmethamphetamine

Answer 28

Answer is D - "Although dextromethorphan is known to function as an NMDA-receptor antagonist, the dextromethorphan-binding sites are not limited to the known distribution of NMDA receptors (Elliott et al., 1994)." from Goodman and Gilman Dextromethorphan, marketed primarily as an antitussive, is an antagonist of the glutamatergic NMDA receptor (Ref:Wikipedia ) A - synthetic glucocorticold steriod B - Dextropropoxyphene napsylate is a centrally acting, synthetic opioid analgesic structurally related to methadone (MIMS) C - full alpha 2 agonist E - Sympathomimetic

Question 29

GP27 [Jul04] Comparing dexamethasone and hydrocortisone: A. Both are endogenous hormones B. Dexamethasone has 8x potency of hydrocortisone C. Both have mineralocorticoid activity D. Dexamethasone is the only water-soluble compound

Answer 29

From Peck, Hill and Williams: A - Incorrect as dexamethasone is synthetic B - incorrect as dexamethasone has 25 times the potency (use 4mg qid vs 100mg qid) C - ?incorrect as ?dexamethosone has very little if no mineralocorticoid activity D - ? correct - beware absolutes (dex is the ONLY...) but below seems convincing. Glucocorticoids are steroid hormones and thus will be naturally less water soluble and more lipophilic hydrocortisone (ie cortisol) is the main endogenous glucocorticoid in humans, dexamethasone is synthetic dexaethasone has 25 times the anti-inflammatory potency of hydrocortisone glucocorticoids have weak mineralcorticoid activity hydrocortisone is made up in water for injection Therefore, it would seem that C is the correct answer From MIMS: Dexamethasone is synthetic, hydrocortisone is endogenous Dexamethasone is 25x as potent as hydrocortisone. Dexamethasone and betamethasone have almost no mineralocorticoid activity Dexamethasone is water soluble (about 3000 x as H2O soluble as hydrocortisone, which is listed as practically insoluble in H2O [1]). 'Solu-Cortef' is the sodium succinate ester, which adds to its water solubility, and explains why it appears to be H2O soluble in a clinical setting. Hydrocortisone can't be that water soluble - there's a preparation available with cyclodextrins Comparison of potency Glucocorticoid activity Mineraldocorticoid activity Dose Equivalent Hydrocortisone 1 1 100mg Prednisolone 4 0.8 25mg Methyl Pred 5 0.5 20mg Dex 25 0 4mg Fludrocortisone 10 125 N/A Just so happens the usual doses make sense!

Question 30

GP28 A drug has hepatic extraction ratio of 0.7 and is 30% abosorbed, what is the bioavailability A. 0.3 B. 0.7 C. 0.21 D. 0.09 E. 0.03

Answer 30

0.3 x (1- 0.7) = 0.09

Question 31

GP29 Which of the following drugs cannot cross the BBB? A. Ondansetron B. Scopolamine C. Metoclopramide D. Droperidol E. Domperidone

Answer 31

E

Question 32

GP30 Mar09 [Mar10] With regard to LD50: A. Is the mean lethal dose in animals B. Something about probit’s relation to standard deviation C. Animals are given increasing doses of a drug until they die D. ? E. Something about log concentration being plotted against something using probits to linearize the data for humans

Answer 32

NOTE: Similar MCQs: GP05 LD50: GP13 Therapeutic index: Comments GP 30 ( mar 09) very difficult question we know A wrong C sounds tempting. B, D ,E god knows. quick google search in wikipedia about dose response relationship brought out the following Statistical analysis of dose-response curves may be performed by regression methods such as the probit model or logit model, or other methods such as the Spearman-Karber method. Empirical models based on nonlinear regression are usually preferred over the use of some transformation of the data that linearizes the dose-response relationship. Dose-response curves can be fit to the Hill equation (biochemistry) to determine cooperativity. Problems exist regarding non-linear relationships between dose and response, thresholds reached and 'all-or-nothing' responses. These inconsistencies can challenge the validity of judging causality solely by the strength or presence of a dose-response relationship. A threshold model or linear no-threshold model may be more appropriate, depending on the circumstances. Endocrine disruptors have also been cited with producing one effect at high dose and a different effect at low doses.' follow up on the matter proved too time consuming and confusing so just gave up! March10 D quantal dose response curve sound right as we re looking at population % effect to drug (ED50or LD50 in this case) as opposed to graded dose response curves which look at an individual response eg muscle relaxants and 95% reduction in twitch height (EC50). [goodman] D is correct - Quantal dose-response curves Wrong answers: A - ??What?? Wrong by exclusion! B - is the 'median' lethal dose! C - no, quantal E - no, you group the animals and give each group a fixed dose. JB2012 Re probit crap: "Method A: Using your hand drawn graph, either created by eye or by calculating the regression by hand, find the probit of 5 in the y-axis, then move down to the x-axis and find the log of the concentration associated with it. Then take the inverse of the log and voila! You have the LC50." [http://userwww.sfsu.edu/efc/classes/biol710/probit/ProbitAnalysis.pdf] So A is wrong as Probit = 5 is the LC50 (?or LD50) TW

Question 33

GP30 (Mar10 version) Which is true for LD50? A. a probit score of 5 means it is 5 SD away from the median B. mean lethal dose C. calculated from graded dose-response curves D. calculated from quantal dose-response curves E. you keep giving a bunch of animals a drug until the animals die

Answer 33

NOTE: Similar MCQs: GP05 LD50: GP13 Therapeutic index: Comments GP 30 ( mar 09) very difficult question we know A wrong C sounds tempting. B, D ,E god knows. quick google search in wikipedia about dose response relationship brought out the following Statistical analysis of dose-response curves may be performed by regression methods such as the probit model or logit model, or other methods such as the Spearman-Karber method. Empirical models based on nonlinear regression are usually preferred over the use of some transformation of the data that linearizes the dose-response relationship. Dose-response curves can be fit to the Hill equation (biochemistry) to determine cooperativity. Problems exist regarding non-linear relationships between dose and response, thresholds reached and 'all-or-nothing' responses. These inconsistencies can challenge the validity of judging causality solely by the strength or presence of a dose-response relationship. A threshold model or linear no-threshold model may be more appropriate, depending on the circumstances. Endocrine disruptors have also been cited with producing one effect at high dose and a different effect at low doses.' follow up on the matter proved too time consuming and confusing so just gave up! March10 D quantal dose response curve sound right as we re looking at population % effect to drug (ED50or LD50 in this case) as opposed to graded dose response curves which look at an individual response eg muscle relaxants and 95% reduction in twitch height (EC50). [goodman] D is correct - Quantal dose-response curves Wrong answers: A - ??What?? Wrong by exclusion! B - is the 'median' lethal dose! C - no, quantal E - no, you group the animals and give each group a fixed dose. JB2012 Re probit crap: "Method A: Using your hand drawn graph, either created by eye or by calculating the regression by hand, find the probit of 5 in the y-axis, then move down to the x-axis and find the log of the concentration associated with it. Then take the inverse of the log and voila! You have the LC50." [http://userwww.sfsu.edu/efc/classes/biol710/probit/ProbitAnalysis.pdf] So A is wrong as Probit = 5 is the LC50 (?or LD50) TW

Question 34

GP31 [Mar10] Which is not a ligand gated channel?. A. Alpha-2 Receptor B. 5HT3 Receptor C. Nicotinic cholinergic receptor D. GABA receptor E. NMDA receptor

Answer 34

A. Alpha-2 Receptor - receptors linked to G protiens A is correct B. 5HT3 Receptor - is ligand gated C. Nicotinic cholinergic receptor - is ligand gated D. GABA receptor - ligand gated E. NMDA receptor - is ligand gated Comment: odd question "Which is not a ligand gated channel?" - then lists a bunch of receptors Aren't all receptors ligand gated ? - given that is the definition of a receptor ? wording remembered incorrectly ? possibly which of the following receptors is directly linked to a ion channel (ie ionotropic) which would make A correct (still) bah Ion channels: gated / ungated Gated: ligand / voltage / 2nd messenger / mechano Receptors: ionotropic, metabotropic, nuclear Ionotropic receptors are directly linked to ion channels Metabotropic receptors act via second messengers G-proteins (assoc with GPCR) mainly affect second messangers (metabotropic) but can also directly affect ion channels eg Kir (ionotropic) Adrenoreceptors are metabotropic 5-HT3 receptors are ionotropic (all the others are metabotropic) Nicotinic receptors are ionotropic (unlike muscarinic which are metabotropic) GABAa receptor is ionotropic (but GABAb is metabotropic) NMDA receptor is ionotropic (but also voltage sensitive)

Question 35

GP32 G proteins: A. Always have 3 subunits B. Alpha subunit has intrinsic GTPase activity C. One G protein only attached to one G protein coupled receptor D. Spans membrane 7 times

Answer 35

A Always and Never! B Sounds about right to me (Yentis) C only! Who knows. D Its Gprotein coupled receptor does. A - Not true, there are large and small G proteins (see below) B - True; it's intrinsic but allosterically activated (see below) C - True, although this is inferred from GPCR diagrams (see below) D - The G protein receptor does, not the G protein itself From Wikipedia (http://en.wikipedia.org/wiki/G\_protein) "G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, sometimes referred to as the "large" G proteins that are activated by G protein-coupled receptors and made up of alpha (α), beta (β), and gamma (γ) subunits. There are also "small" G proteins (20-25kDa) that belong to the Ras superfamily of small GTPases. These proteins are homologous to the alpha (α) subunit found in heterotrimers, and are in fact monomeric." "The Gα subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity" Also from Wikipedia (http://en.wikipedia.org/wiki/G\_protein-coupled\_receptor) "Upon receptor activation, the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit." "GPCRs are integral membrane proteins that possess seven membrane-spanning domains" "When the receptor is inactive, the GEF domain may be bound to an also inactive α-subunit of a heterotrimeric G-protein." This wording and all diagrams on the page suggest one G-protein beinds to each GPCR. - Comment: Peck and Hill, p27: "The G-protein system produces signal amplification... A single activated GCPR can stimulate multiple G-proteins and each G-protein can activate several intermediate messengers." As a result I would answer B.

Question 36

GP33 [Aug11] When is the safest time to give a drug to a lactating mother? A. 3 - 4 hours before breastfeeding B. Immediately before breastfeeding C. Immediately after breastfeeding D. 30 - 60 minutes after breastfeeding E. Either A or D

Answer 36

Answer E - lifted straight from the book: "If the nursing mother must take medications and the drug is a relatively safe one, she should optimally take it 30-60 minutes after nursing and 3-4 hours before the next feeding." -from Katzung 11th ed, Ch59 Why do you have to take it 30-60 minutes after nursing? If the purpose is to minimize the concentration of the drug in breast milk, the only thing that matters is the duration elapsed prior to the next feeding. The 30-60 minutes bit doesn't make much sense. --Yy 19:10, 10 May 2014 (CDT)

Question 37

GP34 [Aug11] Which of the following drugs has low first pass metabolism A. Lignocaine B. Morphine C. Metoclopramide D. Midazolam E. Aspirin

Answer 37

A. Lignocaine: has high lung uptake, but is this truly "first pass metabolism" (as the lung is more like storage, less actual metabolism). However, if given orally it would probably have a high hepatic first pass metabolism. B-E: Bioavailability values of the others (from Smith, "Drug in Anaesthesia and Intensive Care" 4Ed) Morphine: 44% Metoclopramide: 32-95% Midazolam: 44% Aspirin: 70% No good answer, but aspirin seems best. Thoughts anyone? JB2012 From Wikipedia (http://en.wikipedia.org/wiki/First\_pass\_effect) Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine (lignocaine). Lignocaine, morphine and midazolam are all mentioned there. Metoclopramide bioavailability varies from 30-100% (Bateman, 1983, Clinical pharmacokinetics of metoclopramide). Aspirin bioavailability 80-100% according to reference.medscape.com. Thus I'd say the answer is A. Aspirin. Comment: Stoelting 4E p282 states aspirin is rapidly hydrolysed in the liver - but it doesn't give a bioavailability figure. The same text also states that metoclopramide undergoes "extensive" first pass metabolism. Combined with the Wiki reference above, I'd probably agree that aspirin is the best answer to a bad question.

Question 38

GP35 [Aug11] All are secreted by the proximal tubule in the kidney except: A. Diazepam B. Morphine C. Probenicid D. Penicillin E. Frusemide

Answer 38

A - Diazepam is not. B - Morphine is C - Probenicid is D - Penicillin - main mechanism of clearance E - Frusemide - is part of it's mechanism of action Useful table at [1]] http://en.wikipedia.org/wiki/Table\_of\_medication\_secernated\_in\_kidney I don't know about others, but I had a hard time finding the specific site of excretion in the recommended texts!

Question 39

GP36 [Aug11] Elimination coefficient Units (Repeat) A. ? B. mcg/ml C. mg/ml D. ? E. ?

Answer 39

Presumably these questions specified whether the drug in question underwent First or Zero Order kinetics assuming that it was for First Order Kinetics, the answer will always be time-1

Question 40

GP36b [Feb12] [Jul12] The units of rate constant k are? A. mg/min B. mcg/kg/min C. min D. min-1 ( true - see below) E. ml-1

Answer 40

Presumably these questions specified whether the drug in question underwent First or Zero Order kinetics assuming that it was for First Order Kinetics, the answer will always be time-1

Question 41

GP37 [Aug11] Which drug reversibly inhibits platelet aggregation?\* Repeat\* A. clopidogrel B. warfarin C. [[heparin] D. diclofenac E. aspirin

Answer 41

Answer: diclofenac Aspirin covalently, ie. irreversibly binds to cox-1 Diclofenac reversibly binds to cox-1 clopidogrel binds irreversibly to platelet ADP receptors, thus inhibiting ADP activation of the GPIIb/IIIa complex Heparin does not affect platelet function- is involved in clotting cascade Warfarin does not affect platelet function - is involved in clotting cascade

Question 42

Which of the following causes reversible inhibition of platelet function? A. aspirin B. heparin C. warfarin D. diclofenac E. clopidogrel

Answer 42

Answer: diclofenac Aspirin covalently, ie. irreversibly binds to cox-1 Diclofenac reversibly binds to cox-1 clopidogrel binds irreversibly to platelet ADP receptors, thus inhibiting ADP activation of the GPIIb/IIIa complex Heparin does not affect platelet function- is involved in clotting cascade Warfarin does not affect platelet function - is involved in clotting cascade

Question 43

Which one causes reversible impairment of platelet function? A. Aspirin B. diclofenac C. clopidogrel D. heparin E. warfarin

Answer 43

Answer: diclofenac Aspirin covalently, ie. irreversibly binds to cox-1 Diclofenac reversibly binds to cox-1 clopidogrel binds irreversibly to platelet ADP receptors, thus inhibiting ADP activation of the GPIIb/IIIa complex Heparin does not affect platelet function- is involved in clotting cascade Warfarin does not affect platelet function - is involved in clotting cascade

Question 44

Which one is not a second messenger? A. c-AMP B. c-GMP C. Ca2+ D. G Proteins E. Nitric oxide

Answer 44

A - True B - True C - True D - True - G-Proteins are coupled to receptors and they activate second messengers E - True

Question 45

Feb 2012 options: A. c-AMP B. c-GMP C. Guanine cyclase D. G Proteins E. Nitric oxide (Edit: I thought option C may have been Ca++, not guanine cyclase)

Answer 45

A - True B - True C - True D - True - G-Proteins are coupled to receptors and they activate second messengers E - True

Question 46

G proteins A. binds 4 sites B. has 2 alpha subunits C. D. E.

Answer 46

A - not sure B - False - heteroTRImeric - 3 different subunits - alpha, beta and gamma

Question 47

If a drug has a Vd of 0.6L/kg, it is reasonable to assume: A. It distributes throughout TBW, and is not lipid soluble. B. Something about Vd equals body water volume ...

Answer 47

A - false - seems counterintuitive to be able to distribute throughout TBW whilst being lipid insoluble. PH&W divides VD into 3 groups: drugs that are confined to the plasma - highly protein bound or too large to cross the vascular endothelium; those with limited distribution e.g. NDMRs which are polar, poorly lipid soluble and bulky, hence limited to tissues with fenestrated capillaries (i.e. muscle) - they cannot cross cell membranes and work extracellularly those with extensive distribution - highly lipid soluble, small MW and weak plasma protein binding, and others which are sequestered by tissues B - true total body water for a 70kg man is 42litres or 42/70 = 0.6L/kg Brandis p1: "What is the total body water in an adult male?" - "42 litres in the 70 kg man. This is 60% of total body weight (le 600 mls H2O/kg body wt.) "

Question 48

[[GP41] Feb11 Which drug is optimally given as a racemic mixture? A. morphine B. bupivacaine C. noradrenaline D. methadone E. dexmedetomidine

Answer 48

Comments re the Feb11 version: Dexmedetomidine is not racemic. Methadone is and there is some vague google discussion about an enantiomer being better than the other. What does optimally mean because bupivacaine (racemic) is more potent but more toxic. Evers and Maze make no discussion on the chirality fo norepinephrine (they also have an entry for noradrenaline in the index!). At a guess, the only answer where racemic applies with a real discussion would therefore be B. If only they had put tramadol there. Comment - answer D - methadone L isomer is an opioid receptor agonist, d isomer blocks the NMDA receptor, therefore optimal effect from methadone is the racemic mixture The question should read "Which drug is most effective given as a racemic mixture". It is asking which racemic mixture is most effective, not if its better than an enantiomer. Racemic morphine, noradrenaline, and methadone are not as efficacious as their active enantiomer (the "inactive" enantiomer has weaker actions). Dexmetetomidine is not racemic. Therefore, this leaves bupivacaine. Racemic bupivacaine is equally as efficacious as levobupivacaine but racemic bupivacaine has more toxicity. Answer is B. Re the [Aug11] version: A. Noradrenaline -\>false - d-norad (and d-adren) are half as active as the levo forms (levo isoprenaline is 1000x more active than dextro (Stoelting 4th ed page 294) B. Morphine -\> False morphine has 5 chiral centres and only one stereoisomer has significant activity. C. Methadone -\> TRUE - d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity, L- isomer has mu agonist activity D. Bupivacaine -\> false levobupivacaine has a similar potency and efficacy to bupivacaine, but with a better CVS toxicity profile E. Dexmedetomidine -\> false DEXmedetomidine - it could hardly be dextrorotatory in a racemic mixture.

Question 49

GP41 [Aug11] Drug given optimally as racemic mixture: A. Noradrenaline B. Morphine C. Methadone D. Bupivacaine E. Dexmedetomidine

Answer 49

Comments re the Feb11 version: Dexmedetomidine is not racemic. Methadone is and there is some vague google discussion about an enantiomer being better than the other. What does optimally mean because bupivacaine (racemic) is more potent but more toxic. Evers and Maze make no discussion on the chirality fo norepinephrine (they also have an entry for noradrenaline in the index!). At a guess, the only answer where racemic applies with a real discussion would therefore be B. If only they had put tramadol there. Comment - answer D - methadone L isomer is an opioid receptor agonist, d isomer blocks the NMDA receptor, therefore optimal effect from methadone is the racemic mixture The question should read "Which drug is most effective given as a racemic mixture". It is asking which racemic mixture is most effective, not if its better than an enantiomer. Racemic morphine, noradrenaline, and methadone are not as efficacious as their active enantiomer (the "inactive" enantiomer has weaker actions). Dexmetetomidine is not racemic. Therefore, this leaves bupivacaine. Racemic bupivacaine is equally as efficacious as levobupivacaine but racemic bupivacaine has more toxicity. Answer is B. Re the [Aug11] version: A. Noradrenaline -\>false - d-norad (and d-adren) are half as active as the levo forms (levo isoprenaline is 1000x more active than dextro (Stoelting 4th ed page 294) B. Morphine -\> False morphine has 5 chiral centres and only one stereoisomer has significant activity. C. Methadone -\> TRUE - d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity, L- isomer has mu agonist activity D. Bupivacaine -\> false levobupivacaine has a similar potency and efficacy to bupivacaine, but with a better CVS toxicity profile E. Dexmedetomidine -\> false DEXmedetomidine - it could hardly be dextrorotatory in a racemic mixture.

Question 50

GP42 [Feb12] When calculating loading dose which of the following factors is not taken in to account? A. T1/2 Keo B. Vd C. Target concentration D. ?? Maybe previous doses given? E. ? maybe clearance

Answer 50

Re Feb12 version: A. T1/2 Keo -\> TRUE - is the effect site equilibration time, and does not affect the required plasma concentration to be acheived B. Vd -\> false - this is definitely needed C. Target concentration -\> false - this is definitely needed D. ?? Maybe previous doses given? -\> not sure E. ? maybe clearance ? -\> don't think so Bioavailability is relevant for oral administration ?15A version also present on 14B paper? For 14B/15A version, context sensitive half life (option E) likely is the best answer. I have no idea what Leo is.

Question 51

15A version When calculating a loading dose prior to infusion of a drug, what factors are NOT considered: A. Vd B. Leo C. Toxicity and side effects D. Plasma concentration E. Context sensitive half time

Answer 51

Re Feb12 version: A. T1/2 Keo -\> TRUE - is the effect site equilibration time, and does not affect the required plasma concentration to be acheived B. Vd -\> false - this is definitely needed C. Target concentration -\> false - this is definitely needed D. ?? Maybe previous doses given? -\> not sure E. ? maybe clearance ? -\> don't think so Bioavailability is relevant for oral administration ?15A version also present on 14B paper? For 14B/15A version, context sensitive half life (option E) likely is the best answer. I have no idea what Leo is.

Question 52

GP43 [Feb12] The liver oxidation reactions generally: A. Increase hydophobicity B. Decrease lipophylicity C. Decrease polarity D. Make more water-soluble

Answer 52

A. Increase hydophobicity -\> false B. Decrease lipophylicity -\> TRUE, as a consequence of increasing polarity and water solubility C. Decrease polarity -\> false D. Make more water-soluble -\> true

Question 53

GP44 [Feb12] Drugs cause Hypersensitivity reaction: A. Type 1 hypersensitivity is IgG mediated B. Type 3 - something about happen...eh? C. T cell involved in all types of hypersensitivity D. ? E. ?

Answer 53

A False -\> IgE B ? C - False -\> in type IV only Hypersensitivity Type I -\> Immediate hypersensitivity - IgE Mediated - occurs within minutes of exposure to an antigen - cross linking of membrane bound IgE on blood basophils or mast cells causes degranulation - release of histamine, leukotrienes, and eosinophil chemotactic factor, inducing anaphylaxis, asthma, hay fever or urticaria in affected individuals. Type II -\> Cytotoxic hypersensitivity -aka: Antibody-mediated hypersensitivity - IgG or IgM + antigen -\> complex -Transfusion reactions - if not matched preformed Ab in recipient serum bind to donor RBC cell membrane antigens -\> activate complement cascade -\> Membrane Attack Complex -\> cell lysis. -Mechanism of ABO and Rhesus incompatibility. Rhesus disease preventable by admininstration of anti D Ab to Rh D-ve mother 24-48hours post partum with a Rh D+ve baby. Type III -\> Immune complex hypersensitivity - due to presence of elevated levels of antigen-antibody complexes that deposit on basement membranse of tissues and vessels. -\> complement activation -\> chemotaxis and anaphylatoxic - \>increased vascular permeability and neutrophil recruitment. -\> skin rashes, glomerulonephritis and arthritis. - 3-4 days post exposure to antigen Type IV -\> Cell-mediated (or delayed) hypersensitivity - AKA: T cell mediated hypersensitivity - 2-3 days post exposure - T helper1 cells -\> local inflammation recruited under influence of

Question 54

GP45 [Feb12] Dopamine receptors: A. 3 subtypes (receptors, not antagonists) B. GPCRs C. effect on cAMP or something (yeah, or some intracellular second messenger) D. something about D2 receptors

Answer 54

A - false - 5 types B - True - all are GPCR (some Gs(D1 and D5) and some Gi (D2, D3, D4) C - True - they either Stimulate (Gs) or Inhibit (Gi) cAMP D - Dopamine Receptors 5 types D1 like receptor family - Gs protein ↑cAMP – D1, D5 D2 like receptor family - Gi protein ↓cAMP – D2, D3, D4 CNS: There are 3 main dopaminergic pathways containing D1-5 Nigrostriatal – motor control. Mesolimbic/mesocortical – behavioural effects Tuberohypophyseal – endocrine control (prolactin) The medulla contains D2 at the chemoreceptor trigger receptor zone – causes nausea & vomiting Action Agent Selectivity Usage Agonist Bromocriptine Carbergoline Non selective D2 Selective Rx of Parkinson’s & prolactinomas. Antagonist Prochlorperazine Droperidol Metoclopramide All D2 selective Antiemetics Periphery: D1 receptors are postsynaptic on renal, mesenteric, splenic & coronary vascular smooth muscle causing vasodilation. Renal effects are strongest ↑blood flow. Also located in the proximal tubule → natriuresis through inhibition of Na+/K+ATPase pump. D2 receptors are presynaptic and inhibit noradrenaline and perhaps acetylcholine release. Action Agent Selectivity Usage Agonist Dopamine Fenoldopam Non selective D1 Selective Inotrope Antihyopertensive Antagonist Domperidone D1 selective (prokinetic effects may be due to ↑ Acetylcholine in the gut.) Antiemetic

Question 55

GP46 [Feb12] Bromocriptine? A. Is a dopamine agonist B. ...?COMT C. ?

Answer 55

Bromocriptine? A. Is a dopamine agonist -\> TRUE B. ...?COMT -\> not a COMT inhibitor Agonist at dopamine receptors: http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=GP46

Question 56

GP47 [Aug11] [Feb12] (NB: This Q also recorded as FE08) Hartmanns solution: A. calcium 2mmol/l B. lactate 5mmol/l C. isotonic with plasma D.

Answer 56

A - true B - False - 29mmol/litre C - False - very slightly hypotonic Plasma tonicity is 290mOsmol/litre (clearly a simplistic answer with no account for haematocrit etc.)\* hartmanns contains 278mmol/litre According to wikipedia Hartmann's contains: 131 mEq of sodium ion = 131 mmol/L 111 mEq of chloride ion = 111 mmol/L 29 mEq of lactate = 29 mmol/L 5 mEq of potassium ion = 5 mmol/L 4 mEq of calcium ion = 2 mmol/L 131+111+29+5+2= 278mmol/litre

Question 57

GP43 Aug15 All of the below act via increasing cAMP except A. Digoxin B. Glucagon C. Adrenaline D. ? E. ?

Answer 57

?

Question 58

IN01 [Mar96] Which compound(s) is/are broken down in soda-lime? A. Nitrous oxide B. Halothane C. Sevoflurane D. Desflurane E. All of the above

Answer 58

Comments A - False B - True C - True D - False E - False The above answers were obtained from Table 2-1 p.37 of Stoelting 3rd Ed. Of the six gases listed (N2O, halothane, enflurane, isoflurane, desflurane, sevoflurane), only halothane and sevoflurane were NOT stable in soda lime at 40 degrees. See Stoelting: Carbon monoxide results from the degradation of CF2 containing moieties of volatiles (Des\> En\> Iso)... Sodalime (and baralyme) degrades all halogenated anaesthetics (due to the interaction of the anaesthetic with the small amounts of NaOH or KOH in the absorbant), although desflurane appears to be more stable at below 80 degrees celcius than the others. Sevoflurane degrades the most. Increased temperatures lead to greater degradation, whilst increased water concentration in the absorbent decreases degradation. The temperature in the absorbant with low flow closed circuit anaesthesia is about 40-60 degrees. The main consequences of degradation are: loss of anaesthetic agent (clinically not significant if the absorbent is kept moist), and toxicity. exploding sodalime canisters (if it gets hot enough!) Toxicity from the production of compound A from Sevoflurane, and from the degradation product of halothane as well. Compound A has been shown to cause proteinuria and enzymuria in humans (dose-related exposure) but has only been shown to be nephrotoxic in rats. Dry absorbants can degrade desflurane, isoflurane and enflurane producing carbon monoxide, although rarely in clinically significant amounts. Doesn't Des/En/Isoflurane react with CO2 absorbent producing carbon monoxide? Or is this not considered as a "breakdown" process? References & related material 'The Pharmacology of Inhaled Anaesthetics', Eger et al.

Question 59

IN02 [Mar96] Regarding nitrous oxide at 70%: A. Synthetised from ? & N2 at 273C B. Decreases muscle blood flow by 30% C. Decreases cerebral autoregulation 24% D. ?

Answer 59

INO2 A - incorrect. "Manufactured by heating ammonium nitrate to 240 degrees celsius and removing impurities... by passage through scrubbers and waters" (Yentis et. al., Anaesthesia and Intensive Care A-Z, 2004, p.371) B - probably incorrect - "Nitrous oxide does not change SVR" (Stoelting 3rd ed p46) C - ?correct. "increases cerebral blood flow and ICP slightly" (Yentis 2004, p.371, and Stoelting), which indicates a decrease in autoregulation, but is it by 24%?! Correction: Nitrous oxide does NOT relax skeletal muscles (page 72 Stoelting)

Question 60

IN02b [Jul97] Nitrous oxide (N2O): A. ?Increases/decreases CBF B. Is an effective oxidant C. Is made by heating nitrogen and oxygen in an iron retort D. Decreases pulmonary artery pressure in neonates

Answer 60

IN02b A - correct if says INCREASES CBF, see answer for C IN02 B - Note the yellow warning sticker on the cylinder [1] C - Incorrect, see answer A for IN02 D - Incorrect. NITRIC oxide is used to treat pulmonary hypertension, not nitrous oxide

Question 61

IN02c [Feb08] Nitrous oxide at 70% A. 99% equilibration at 3 minutes B. About 10L uptake within first 3 minutes C. Reduces muscle blood flow by 30% D. Decreases cerebral autoregulation by 70% E. ?

Answer 61

IN02c Nitrous oxide at 70% A. 99% equilibration at 3 minutes - incorrect; takes longer than this - Stoelting p27 ' Inhalation of a constant PI of nitrous oxide... for 10 minutes results in a PA that is \>80% of the PI).' Figure 1.18 indicates around 90% equilibtration at 3 mintues, 98% at 10 minutes. B. About 10L uptake within first 3 minutes - Incorrect Stoelting p27 'up to 10 liters during the first 10 to 15 minutes'. C. Reduces muscle blood flow by 30%. - I think this is the only likely answer. Recall that it has a muscle relaxant effect, reducing metabolic requirements thus vasoconstricting via metabolic autoregulation. D. Decreases cerebral autoregulation by 70% - Incorrect. Recall that this is 0.69 MAC - CBF will be minimally altered.

Question 62

IN03 [Mar96] [Jul96] [Jul97] [Jul98] [Jul99] The following drugs are (potent) triggers for malignant hyperthermia EXCEPT: A. Decamethonium B. Suxamethonium C. Isoflurane D. Halothane E. Calcium F. Sevoflurane G. Tubocurarine H. Nitrous oxide (Different options on different papers)

Answer 62

The drugs which are triggers for MH are: All potent inhalational agents All depolarizing muscle relaxants (ie succinylcholine, decamethonium) Safe Drugs: All other anesthetic drugs including N2O, thiopentone, benzodiazepines, droperidol, ketamine, etomidate, propofol, narcotics, non-depolarizing muscle relaxants, anticholinergics, anticholinesterases, local anesthetics Avoid verapamil, diltiazem potential hyperkalemia if Dantrolene given (Ref: UCLA MH site From the MHAUS site: Use local or regional anesthesia but general anesthesia with non-triggering agents is acceptable. Safe drugs include: barbiturates, benzodiazepines, opioids, nondepolarizing neuromuscular blockers and their reversal drugs, and nitrous oxide. For this MCQ,the options which are NOT triggers are: Calcium Tubocurarine Nitrous oxide - considered safe but a weak trigger, increased risk 1.3 times (Stoelting 3rd ed p65) The depolarisers are the most potent triggers, increasing the risk of triggering an episode by a factor of about four (from 1/250,000 adult anaesthetics, to 1/60,000). References Oh's Intensive Care Manual, 5th, ISBN:0750651849, p768 UCLA Malignant hyperthermia The ABCs of MH (at MHAUS)

Question 63

IN04 [Mar96] [Mar03] IPPV with Isoflurane at 1 MAC results in: A. Depresses cardiovascular reflexes more than halothane B. Causes decreased conduction velocity C. Maintains cerebral autoregulation D. Equal respiratory depression to enflurane E. Reduction in cardiac output by 25% F. Increased vasodilatation

Answer 63

A - False - Isoflurane reduces SVR with a baroceptor mediated increase in heart rate. Halothane reduces contractility as well as abolishing baroceptor mediated tachycardia. Decreased cardiac conductivity with halothane causes bradycardia and catecholamine sensitivity. (Peck 2nd ed 110-119) B - False - No effect on conduction at 1 MAC, however may decrease at \>1.5MAC (see reference below) C - True: "autoregulation of CBF in response to changes in systemic blood pressure is retained during administration of 1 MAC isoflurane but not halothane"; Fig 2-7 (Stoelting 3rd ed, p.41) D - False - Enflurane is the worst regards respiratory profile. Most reduced tidal volume and highest pCO2. E - False: "Halothane, but not isoflurane... produce dose dependent decreases in cardiac output when administered to healthy human volunteers" (Stoelting 3rd ed, p.45) F - True: "Isoflurane... decrease(s) systemic vascular resistance... reflect(ing) substantial (up to fourfold) increases in skeletal muscle flow"; Fig 2-15 (Stoelting 3rd ed, p. 46) Volatiles I have loved: Halothane: Worst on heart contractility, heart rate low and catecholamine sensitising and incr. CBF. Preserves SVR and resp. Hepatitis (two forms) Isoflurane: Remember coronary steal, cardiac pre-conditioning (ATP dependant K channels), no change CBF up to 1 MAC. Pungent. Enflurane: Worst respiratory depression, epileptiform EEG. Sevo: Only memorable stuff is physical...largest MW, BP, lowest SVP. remember Cpd A. Des: Pungent - breath hold and secretions, sympathetic stim if rapid increase in Fi. High MAC. Lowest B:G coeffic. Carbomonoxide poisoning (also iso and enfl). All this from Peck Hill and Williams 2nd 110-119. Ozaki S, Nakaya H, Gotoh Y, Azuma M, Kemmotsu O, Kanno M. Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. This study was undertaken to determine whether isoflurane, a volatile anesthetic that is reported to possess a wide margin of cardiovascular safety, exerts electrophysiological effects on cardiac tissue. By use of standard microelectrode techniques, effects of isoflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity were examined in guinea pig papillary muscles. Isoflurane decreased action potential amplitude and action potential duration in a concentration-dependent fashion. Isoflurane at 1.5 and 2.0 MAC decreased conduction velocity with as little influence on the maximum rate of rise of action potential upstroke as that exerted by halothane and enflurane. However, the effect of isoflurane in slowing intraventricular conduction was less than that of halothane and enflurane when compared at equi-MAC concentrations. Thus, isoflurane may be a safer anesthetic for the patients with intraventricular conduction abnormalities.

Question 64

IN05 [Mar96] [Mar98] The effect of increased cardiac output on Pa versus time for volatile agents is: A. No effect B. Decrease slope C. Decrease then increase slope D. Increase then decrease slope

Answer 64

B- decreases slope, as Pa equilibrates with PA. PA will be reduced (Decreased FA/FI curve) due to transport away from lungs by increased C.O.

Question 65

IN06 [Mar96] [Jul97] [Apr01] Nitrous oxide: A. Supports combustion B. Is flammable C. Causes muscle rigidity D. In tissues is slower to reabsorb than oxygen E. Has a partition coefficient of 0.76 F. All of the above G. Is formed by heating oxygen & nitrogen H. Induces methionine synthetase I. Oxidises the cobalt in vitamin B12

Answer 65

06 A true - "Although... nonflammable, it will support combustion" (Stoelting 3rd ed. p.37) B false - see above C uncertain - "it causes minimal skeletal muscle relaxation" (Stoelting 3rd ed. p.37) D uncertain E false - partition co-efficient 0.46: Table 2-1 (Stoelting 3rd ed. p.37) F false G false - "The gas is prepared commercially by the thermal decomposition of ammonium nitrate" ("nitrous oxide." The Columbia Electronic Encyclopedia, Sixth Edition. Columbia University Press., 2003. Answers.com 16 Feb. 2007. http://www.answers.com/topic/nitrous-oxide) H false - see below I true - see below For option (C) - True: "N2O does not relax skeletal muscles, and in doses \>1 MAC (hyperbaric)it may produce skeletal muscle rigidity" - p65 Stoelting for D - would it not be reabosrbed from tissues quicker due to being not very soluble in tissues? Therefore having a higher partial pressure in the tissues, and therefore maintaining a higher partial pressure gradient for reabsorption... (Have a look at Resorption of a Pneumothorax in Brandis for the principles I was thinking about)

Question 66

IN06b [Mar98] [Jul98] Nitrous oxide: A. Has MW of 42 B. Critical temperature 32 C C. Formed by using iron as a catalyst D. Does not support combustion E. ?? has saturated vapour pressure of 24]] kPa F. Produced using ammonium sulphate in an iron retort G. Boiling point 32C H. ??. . . ammonium nitrate . . . copper vessel ?? (Multiple options as this represents 2 separate N2O questions on Mar98 paper)

Answer 66

06B A false - MW 44 B false - see below C uncertain D false - see above E false - it is a gas at 20 degrees, therefore no SVP F False - formed from ammonium NITRATE not sulphate G False - see below H uncertain E - In Peck, Hill, Williams it states the SVP as 5200kPa (p.111), so, wrong anyway, but it is listed as a SVP E -\> it is a vapour until the critical temperature is exceeded, then it becomes a gas. Vapour can be compressed into liquid whereas a gas cannot. The critical temperature of nitrous is 36.4 degrees celcius. The vapour pressure is the pressure seen in the nitrous cylinders in theatre and is usually 'fixed' at 5200kPa until the tank is near empty (ie. when there is no liquid nitrous left inside, then it begins to drop linearly until the tank is empty). [lewildbeast] Regarding vitamin B12 & N2O: The cobalt ion on B12 is oxidised by nitrous oxide so that it cannot act as the cofactor for methionine synthase. This reduces the synthesis of methionine, thymidine, THF, and DNA. N2O is also thought to directly inhibit Methionine synthetase which catalyses the synthesis of tetrahydrofolate, a substrate for thymidine in DNA synthesis. The MW of N2O is 44, and its critical temperature is 36.5. Its boiling point is -88 degrees. It does support combustion but is not flammable. (Peck and Williams, "Pharm for Anaesthesia and Intensive Care") There is a good article called "The risks and benefits of nitrous oxide" referring to this in Anaesthesia and Intensive Care by Paul Myles et al, in 2004. Flammable is a substance which under normal conditions has the ability to catch fire with a minimal ignition source (such as a spark). An example of this might be a substance such as propane. - Combustible materials would be any material that will burn. In this category we could also place propane and the like but it would also include materials that need more vigorous conditions to burn and are not likely to catch fire with a simple spark. An example of a combustible material of this sort would be wood or paper. In my opinion therefore, all flammable materials are combustible, but all combustible materials are not necessarily flammable.

Question 67

IN07 [Mar97] [Mar03] Desflurane: A. Takes 5 minutes to reach equilibrium B. Is fastest to approach equilibrium of any inhaled anaesthetic agent C. Is a fluorinated diethyl ether D. ?

Answer 67

IN07 [c] Desflurane A. False - equilibrium approx \>20-30 minutes (??source) B. Perhaps true - "Solubility characteristics and potency permit rapid achievement of an alveolar partial pressure necessary of anaesthesia" (Stoelting 3rd Ed. p. 38) Also note that blood:gas coefficient is 0.42 (the lowest ratio in table 2-1 c.f. nitrous oxide 0.46) and therefore is should theoretically have fastest equilibrium. C. False - desflurane is a fluorinated methyl ethyl ether, not a diethyl ether (Stoelting 3rd ed. p.38) D. ? Nitrous is faster to achieve equilibrium than Des because the oil:gas partition coefficient of N2O is so much lower (1.4) cf Des (18.7) Nitrous however is not really considered a volatile anaesthetic (just as you wouldn't consider Xenon a volalite anaesthetic) so b is still correct. I disagree that B is correct: the question refers to inhaled anaesthetic, which N2O indisputably is... Note regards option B: Nitrous has a few features that allow more rapid equilibrium. PA = Pa = PB at equilibrium. Factors helping keep PA high are needed therefore. Yes the lower oil:gas partition is important in preventing the fat stores soaking up the N2O. Remember also that N2O has the unique feature of concentrating effect whereby large amounts of nitrous diffuse from alveoli into blood, thus concentrating the remaining gases in the lung. This also creates a gradient of pressure for more nitrous to move into the lung. These two factors allow nitrous to have the fastest onset to equilibrium despite not having the lowest blood:gas coefficient. Now if the question says volatiles forget xenon and N2O, but if it says agent/inhaled anaesthetic etc then include them for sure. --\> agree time vs FA/FI graph peck and hill page 116 - N2O is at the top for a reason: very low solubility / blood:gas PC (0.46) and concentration effect - yes des has a slightly lower solubility / blood:gas PC (0.42) but lacks the concentration effect

Question 68

IN08 [Mar97] [Jul97] Regarding sevoflurane: A. The vapour pressure is less than enflurane B. The vapour pressure is greater than isoflurane C. Cardiovascular side effects are similar to isoflurane D. Molecular weight less then isoflurane E. Boiling point greater than enflurane

Answer 68

Tip (this is easier than memorising the table below): Sevo has the HIGHEST MW and BP; It has the LOWEST SVP; It has a relatively high MAC (only DES and N2O are greater); It has a relatively low blood:gas coefficient (only DES and N2O are lower IN08 A true B false C unsure - has effects similar to isoflurane AND halothane D false E true Note: Option C is false - Isoflurane has the potential for coronary steal and halothane is the most potent for both conduction disturbances and reduced contractility. Halothane leaves the SVR alone compared with other volatiles....it's effects are on the heart. http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN08

Question 69

IN08b [Jul97] [Feb00] Sevoflurane: A. Is a methylethyl ether B. Is odourless C. Is stable in soda lime at 37 degrees D. Has a boiling point higher than enflurane E. Has a molecular weight lower than desflurane

Answer 69

Tip (this is easier than memorising the table below): Sevo has the HIGHEST MW and BP; It has the LOWEST SVP; It has a relatively high MAC (only DES and N2O are greater); It has a relatively low blood:gas coefficient (only DES and N2O are lower) IN08b A false - it's a fluorinated methyl isopropyl ether B uncertain C false - produces compound A D true E false B- uncertain?? Are you kidding..have a sniff next time. It's described as sweet smelling to hint to us we can use it for gas induction. Reply: it is so NOT sweet, I don't like the smell, neither do most of the kiddies that got gassed, even with the strawberry mask guys, it has a smell. And you are not supposed to like it much. http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN08

Question 70

IN08c [Jul98] [Jul99] Sevoflurane: A. Molecular weight greater then enflurane B. MAC less than enflurane C. Contains Cl & F D. SVP sevo \> enflurane

Answer 70

Tip (this is easier than memorising the table below): Sevo has the HIGHEST MW and BP; It has the LOWEST SVP; It has a relatively high MAC (only DES and N2O are greater); It has a relatively low blood:gas coefficient (only DES and N2O are lower) IN08c A true B false C false D false See table http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN08

Question 71

IN09 [Mar97] [Jul98] [Jul00] Uptake of N2O when breathing 70%: A. More than one litre absorbed in the first minute B. Equilibrium (?90%) is achieved in 3mins C. Absorb 10 litres ?at time of ?90% equilibration / ?in first 3 mins D. At steady state, uptake is 200mls/min E. Produces surgical anaesthesia

Answer 71

The Severinghaus formula for N2O uptake is VN2O=1000.t-0.5 Where VN2O is ml/min at time t (in minutes) A) Uptake is 1L in the first minute. B) Equilibrium (90%) is achieved at 3 minutes (see graph in Stoelting) C) Do the maths (okay, I've done it) uptake in first three mins is 2285ml. D) In the 90th minute, 105ml is taken up. I guess steady state is after this??? E) MAC of N2O is 104-106% not 70% "Due to its relative insolubility, the alveolar concentration of N2O approaches the inspired concentration fairly rapidly; 90% equilibration occurring within 15 minutes and 100% equilibration within 5 hours." - Sasada & Smith I agree that the graph(s) in Stoelting suggest that FA/FI approaches 0.9 within 3 mins, however, combining 2 sources may mean that C is the correct answer as stated above, Sasada says that 90% equilibration is achieved within 15 mins Stoelting (p.27, 4th ed) says that at inhaled concentration of 60-70%, about 10L of nitrous is taken up within the first 10-15 mins Therefore, C could be correct combining these 2 sources Stupid question: at steady state, isn't net uptake of N2O zero? It's not metabolised, therefore when PI=PA there will be no uptake or excretion. Therefore D is wrong.

Question 72

IN10 [Mar97] [Jul98] [Mar99] [Jul01] [Jul04] N2O causes the second gas effect because: A. It is relatively insoluble B. Reaches equilibrium faster than the more soluble second gas C. Larger volume D. Its high concentration

Answer 72

Most correct answer D (or C could be argued to be true... see below). The second gas effect refers to the situation where volatile agents used alongside N2O achieve an accelerated rise in alveolar partial pressure (and hence reduced induction time) compared to what they would achieve if used as a single agent. A. N2O is relatively insoluble when compared with other potent inhaled anaesthetics with a blood:gas partition coefficient of 0.47. It should be noted however that desflurane has an even lower blood:gas coefficient of 0.42 and hence is more insoluble. Desflurane does not cause the second gas effect and so it is not the low solubility that is responsible for the second gas effect. A low blood gas coefficient is important solely in determining a rapid achievement of an alveolar and brain partial pressure of the drug. B. The lower the blood:gas partition coefficient then the faster a gas will reach equilibrium as already stated in (A) above. This does not contribute to the second gas effect. C. The large volume uptake of N2O is an important contributing factor in creation of the 2nd gas effect (see (D) below). The reason that large volumes of N2O are absorbed from the alveoli is due to the high concentration of nitrous oxide that is inspired and the initial steep concentration gradient that is generated, during or soon after induction. Due to this sequence of events, option D appears to be technically "more correct" as the high inhaled concentration precedes the uptake of large volumes of N2O from the alveoli. D. The relatively low potency of N2O ensures that effective administration requires concentrations of 40-70%. The high concentrations that are administered result in the uptake of a large volume of gas (in the initial phases). This initial large uptake (as much as 1-2L/min) has 2 effects: The gases remaining in the alveoli are concentrated (including the remaining N2O) Negative pressure is created which draws bronchial and tracheal gas into the alveolar space to replace it. It is these 2 effects which together accelerate the rate of rise in alveolar partial pressure of the 2nd gas. Nitrous oxide is distinguished by the fact that it is the only inhaled anaesthetic to be administered in such high concentrations hence D appears to be the correct answer. - I also read that it is due to the fact that nitrous is 20 x more soluble than nitrogen and oxygen, so the rapid/large uptake of N2O (into the pulmonary capillaries) is far greater than the nitrogen diffusing out of the pulmonary capillaries into the alveoli (thereby decreasing the volume of the alveoli and concentrating other gases that are still present) - Comment: Stoelting (p. 25): "The second gas effect reflects the ability of high-volume uptake of one gas (first gas) to accelerate the rate of increase of the PA of a concurrently administered 'companion' gas (second gas). For example, the inital high-volume uptake of nitrous oxide accelerates the uptake of companion (second) gases such as oxygen and volatile anaesthetics. This increased uptake of the second gas reflects increased tracheal inflow of all the inhaled gases... due to the high-volume uptake of the first gas." This would suggest C to be the correct answer but I'd be keen to hear other people's opinions.

Question 73

IN11 [Jul97] Desflurane: A. Is non-irritant to the airways B. Is more/less potent than sevoflurane C. Has a higher molecular weight than ?isoflurane/?enflurane D. Is a chlorinated methyl ethyl ether

Answer 73

Des is quite irritant to airways. Des is less potent (MAC 6.35, range 5.75-10.65%) than sevoflurane (MAC 2.0, range 1.71-2.05%). Des has a lower molecular weight (168) than any other volatile used in anaesthetics (though the ambos use methoxyflurane MW 164). Des is a FLUORINATED methyl ethyl ether.

Question 74

IN12 [Jul97] [Apr01] Effects of volatile agents include: A. Halothane increases hepatic artery and portal blood flow B. Isoflurane causes hypotension by reducing cardiac output C. ? D. ?

Answer 74

Halothane acts as a vasoconstrictor on hepatic circulation. Decrease in MAP due to isoflurane results from a decrease in systemic vascular resistance \* so A and B are both false References Stoelting & Hillier 4th ed page 51 & 65

Question 75

IN12b [Feb04] Volatiles A. Halothane causes less cerebral vasodilation than enflurane B. Isoflurance causes less cerebral vasodilation than halothane

Answer 75

The vasodilating effect of halothane is greater than isoflurane, sevoflurane or desflurane. Additional info: Sevoflurane has dose-dependant cerebral vasodilatory effect but is less than that of iso and desflurane. Isoflurane is best at maintaining CBF relative to cerebral metabolic oxygen requirements. Autoregulation of CBF is maintained in response to changes in MAP during the use of 1MAC Isoflurane but not in the case of halothane,hence greater brain swelling seen in animals anaesthetised with this drug. "Halothane increases CBF more than any other volatile agent" - Peck + Williams 2nd Ed p111 \* so A is false, B is true References Miller 6th ed page 829 Stoelting 4th ed page 49

Question 76

IN13 [Jul97] [Jul98] [Jul99] [Apr01] Problems with MAC: A. Large interspecies variability B. Affected by temperature and other factors C. Affected by obesity D. ?

Answer 76

?

Question 77

IN13b [Mar96] [Jul98] [Feb00] [Jul01] MAC: A. Is decreased in the elderly B. Is unchanged throughout pregnancy C. Increases in hypothermia D. ?Decreased/?increased with hyper/hypo-kalaemia E. ? Alt version (Jul 01) All the factors decrease MAC except: A. Pregnancy B. Hyperthermia C. Hypothermia D. Hypoxia E. ?

Answer 77

MAC is affected by temperature (decreased by hypothermia (4-5% for each degree C), increased by hyperthermia, is decreased in the elderly by about 6-7% per decade over 40, and is decreased by acidosis and hypoxia. Therefore: 13 B is correct. 13b, A is correct. Alt version B is correct. 13c: MAC-Bar is the minimum alveolar concentration of volatile at one atmosphere that ablates the sympathetic (adrenergic) response to a standardised noxious stimulus (skin incision). Whilst there is considerable variability between agents for MAC-BAR, it is universally reduced by opioids. A (13c) - MAC is 0.29 in 70% N2O (Sasada & Smith) 13c A) False - from birth, MAC increases to a peak at the age of 6 months, then declines gradually until the adult value is reached (Aitkenhead + Smith) B) False - pregnancy decreases MAC (Peck + Williams) C) False - see above D) False - MAC of halothane in 70%N2O is 0.29% July 01 Version: A) True B) False - 50% of patients C) ????? - see above for definition D) False - increased CO2 causes sympathetic stimulation -\> increases MAC (Aitkenhead + Smith 5th ed p14) According to Stoelting (4th Ed, p.34), hypoxia only affects MAC when paO2 95mmhg) References Eger et al. "Age, minimum alverolar anaesthetic concentration and minimum alverolar anaesthetic concentration-awake". Anesthesia and Analgesia2001;93:947-53 MAC article in BJA In relation to age q13c A Miller 6th Edn writes.... In humans, MACs of volatile agents are maximal in infants at approximately 6 months of age. MAC values gradually decrease with increasing age, and the MAC in the octogenarian is approximately one half that in the infant. The increase in potency (i.e., decrease in MAC) with increasing age is seen for all inhaled anesthetics, and the change averages approximately 6% per decade of age.[15] on "The Worldwide Anaesthetist" website, it says that hypercarbia does lower the MAC - anyone else got a reference for this? (for the last question)

Question 78

IN13c [Mar99] [Apr01] [Jul01] MAC: A. Highest between ages 2 to 5 yrs B. Increases with pregnancy C. MAC BAR is concentration at which 95% do not move D. Is 0.2% halothane in 70% N2O E. ?

Answer 78

MAC is affected by temperature (decreased by hypothermia (4-5% for each degree C), increased by hyperthermia, is decreased in the elderly by about 6-7% per decade over 40, and is decreased by acidosis and hypoxia. Therefore: 13 B is correct. 13b, A is correct. Alt version B is correct. 13c: MAC-Bar is the minimum alveolar concentration of volatile at one atmosphere that ablates the sympathetic (adrenergic) response to a standardised noxious stimulus (skin incision). Whilst there is considerable variability between agents for MAC-BAR, it is universally reduced by opioids. A (13c) - MAC is 0.29 in 70% N2O (Sasada & Smith) 13c A) False - from birth, MAC increases to a peak at the age of 6 months, then declines gradually until the adult value is reached (Aitkenhead + Smith) B) False - pregnancy decreases MAC (Peck + Williams) C) False - see above D) False - MAC of halothane in 70%N2O is 0.29% July 01 Version: A) True B) False - 50% of patients C) ????? - see above for definition D) False - increased CO2 causes sympathetic stimulation -\> increases MAC (Aitkenhead + Smith 5th ed p14) According to Stoelting (4th Ed, p.34), hypoxia only affects MAC when paO2 95mmhg) References Eger et al. "Age, minimum alverolar anaesthetic concentration and minimum alverolar anaesthetic concentration-awake". Anesthesia and Analgesia2001;93:947-53 MAC article in BJA In relation to age q13c A Miller 6th Edn writes.... In humans, MACs of volatile agents are maximal in infants at approximately 6 months of age. MAC values gradually decrease with increasing age, and the MAC in the octogenarian is approximately one half that in the infant. The increase in potency (i.e., decrease in MAC) with increasing age is seen for all inhaled anesthetics, and the change averages approximately 6% per decade of age.[15] on "The Worldwide Anaesthetist" website, it says that hypercarbia does lower the MAC - anyone else got a reference for this? (for the last question)

Question 79

Jul 01 version: With regards to MAC: A. The MAC of Halothane with 70%N2O is 0.29 B. Concentration at which 95% of patients don’t move after a surgical stimulus C. MAC-BAR ?? D. Decreased by increased CO2 E. ?

Answer 79

MAC is affected by temperature (decreased by hypothermia (4-5% for each degree C), increased by hyperthermia, is decreased in the elderly by about 6-7% per decade over 40, and is decreased by acidosis and hypoxia. Therefore: 13 B is correct. 13b, A is correct. Alt version B is correct. 13c: MAC-Bar is the minimum alveolar concentration of volatile at one atmosphere that ablates the sympathetic (adrenergic) response to a standardised noxious stimulus (skin incision). Whilst there is considerable variability between agents for MAC-BAR, it is universally reduced by opioids. A (13c) - MAC is 0.29 in 70% N2O (Sasada & Smith) 13c A) False - from birth, MAC increases to a peak at the age of 6 months, then declines gradually until the adult value is reached (Aitkenhead + Smith) B) False - pregnancy decreases MAC (Peck + Williams) C) False - see above D) False - MAC of halothane in 70%N2O is 0.29% July 01 Version: A) True B) False - 50% of patients C) ????? - see above for definition D) False - increased CO2 causes sympathetic stimulation -\> increases MAC (Aitkenhead + Smith 5th ed p14) According to Stoelting (4th Ed, p.34), hypoxia only affects MAC when paO2 95mmhg) References Eger et al. "Age, minimum alverolar anaesthetic concentration and minimum alverolar anaesthetic concentration-awake". Anesthesia and Analgesia2001;93:947-53 MAC article in BJA In relation to age q13c A Miller 6th Edn writes.... In humans, MACs of volatile agents are maximal in infants at approximately 6 months of age. MAC values gradually decrease with increasing age, and the MAC in the octogenarian is approximately one half that in the infant. The increase in potency (i.e., decrease in MAC) with increasing age is seen for all inhaled anesthetics, and the change averages approximately 6% per decade of age.[15] on "The Worldwide Anaesthetist" website, it says that hypercarbia does lower the MAC - anyone else got a reference for this? (for the last question)

Question 80

IN14 [Mar98] [Mar99] Systemic vascular resistance is LEAST changed with: A. Isoflurane B. Sevoflurane C. Desflurane D. Enflurane E. Halothane

Answer 80

Halothane minimally changes SVR but decreases MAP by decreasing contractility and cardiac output. References Stoelting & Hillier 4th ed page 53 Comments Halothane decreases SVR by 15-18% leading to a decrease in systolic and diastolic blood pressure. It has little effect on coronary vascular resistance.

Question 81

IN15 [Mar98] [Jul98] [Mar99] MAC awake during emergence when patient will respond to command: A. 0.1 B. 0.2 C. 0.3 D. 0.5 E. ?0.7 ?0.8

Answer 81

MAC awake is typically one third of MAC. For halothane it is more than 50% and for nitrous oxide is more than 60% Some MAC awake concentrations Halothane 0.4% Iso 0.5% Sevo 0.6% Des 2.5% N2O 68% -- Ref: Eger et al. 0.3 is the quoted value. But when did you last see a patient wake up from Sevo with 0.3 MAC onboard? Let alone following command? When have you ever used a purely sevoflurane anaesthetic? Try withholding your other drugs, and see when they respond to commands... References Eger, et al, The Pharmacology of Inhaled Anesthetics, 3rd ed, page 27

Question 82

IN16 [Jul98] [Jul99] Isoflurane & enflurane are: A. Structural isomers B. Enantiomers C. Diastereomers D. Optical isomers E. Configurational isomers

Answer 82

A is correct A configurational stereoisomer is a stereoisomer of a reference molecule that has the opposite configuration at a stereocenter (e.g., R- vs S- or E- vs Z-). This means that configurational isomers can be interconverted only by breaking covalent bonds to the stereocenter, for example, by inverting the configurations of some or all of the stereocenters in a compound.

Question 83

IN17 [Mar96] [Jul96] Sevoflurane: A. Is broken down in the body to Compound A which has been shown to be toxic to rats B. Has a blood:gas partition coefficient of 2.3 C. Is a irritant causing coughing on induction D. Has a boiling point of 24]] degrees centigrade E. Has Cl & F atoms in its structure F. None of the above (Note: Compound A is a breakdown product produced in the CO2 absorber; it is not produced by biotransformation)

Answer 83

Broken down to compound A in CO2 absorber Blood:gas partition coefficient 0.65 Produces bronchodilation and causes the least amount of airway irritation Boiling point is 58.5 Contains 7 F and no Cl atoms (anaesthesiauk.com)[1] Note that Stoelting is incorrect in its diagram of sevoflurane; Desflurane has 6 "F" by the way. References Stoelting & Hillier 4th ed pages 43 & 45

Question 84

IN18 [Mar99] [Feb00] With isoflurane anaesthesia, MAC awake is: A. 0.1% vol B. 0.3% vol C. 0.5% vol D. 0.5% vol E. 1% vol

Answer 84

"Mean MAC-awake obtained with slow alveolar washout was similar for isoflurane (0.25 (SD 0.03) MAC), and enflurane (0.27 (0.04) MAC) and significantly greater than values obtained by fast alveolar washout (isoflurane: 0.19 (0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isoflurane and enflurane was significantly less than that of halothane, which was 0.59 (0.10) MAC as evaluated by the slow and 0.50 (0.05) MAC as evaluated by the fast alveolar washout method." Gaumann, Mustaki, Tassonyi, MAC-awake of isoflurane, enflurane and halothane evaluated by slow and fast alveolar washout in Br J Anaesth. 1992 Jan;68(1):81-4 Answer C is correct - 0.25x1.15%~=0.3% (Note: not sure if this is a good study or not, but it seems to give some concrete numbers) MAC awake of isoflurane is 0.49% therefore C and D are closest to right Perhaps one of the options were remembered wrong - or are the examiners really trying to make life difficult? Hmm..MAC awake of isoflurane is 0.38 of MAC. 0.38\*1.15 is close to 0.4%(0.437%) perhaps that was what option C was. How did u derive 0.49%? Stoelting 4e says 0.4 Faunce says 0.4 Eger says 0.49 one third MAC would be 0.33x1.15=0.379 Maybe option c or d was actually 0.4?? Otherwise I'd probably go for 0.5 (err on the side of keeping the pt asleep :) ) Note: From a practical stance, MAC awake is the point where we can predict the patient can maintain their own airway at the end of an operation...so aim for the lower number. We don't watch the number at the start and go....0.1...0.2...0.3...0.49..he's MAC asleep now, lets start the case!! Obviously with a hat full of morphine this becomes an academic number rather than a practical one. Nitrous has the best MAC awake..0.6-0.7 MAC, so if you use nitrous you can turn the volatile off as they stitch and then at the last moment turn off the nitrous and they are often responsive when the ET nitrous is still quite high. !!MAC awake is the point when the patient responds to verbal command!! References Eger page 27

Question 85

IN19 [Mar99] [Jul04] Isoflurane: A. Is a halogenated methyl ethyl ether B. Higher boiling point than sevoflurane C. No odour D. Enantiomer of enflurane

Answer 85

Halogenated methyl ethyl ether - True Boiling point is 48.5, Sevoflurane boiling point is 58.5 Pungent, ethereal odour Structural isomer of enflurane, not an enantiomer only halothane requires thymol as a preservative References Stoelting & Hillier 4th ed page 43-44

Question 86

[IN19]b [Aug 11] Isoflurane: A. is a halogenated methyl ethyl ether B. an enantiomer of enflurane C. has a boiling point higher than sevoflurane D. requires thymol as a preservative E. ?

Answer 86

Halogenated methyl ethyl ether - True Boiling point is 48.5, Sevoflurane boiling point is 58.5 Pungent, ethereal odour Structural isomer of enflurane, not an enantiomer only halothane requires thymol as a preservative References Stoelting & Hillier 4th ed page 43-44

Question 87

IN20 [Mar99] MAC of halothane with 70% N2O is: A. 0.25% B. 0.5% C. 0.75% D. 1.0%

Answer 87

Sasada and Smith says 0.29% Oxford handbook says 0.27% I think you can derive it: (1-70/104)\*0.75=0.24 In other words MAC is additive, and with the MAC of nitrous being 105 (or 104, the 70% being roughly 2/3), the MAC of halothane is 0.75% and thus 1/3 of this is 0.25

Question 88

IN21 [Mar99] All reduce MAC except: A. Aminopyridine B. hypothermia C. pregnancy D. hypoxia

Answer 88

MAC is decreased by hypothermia, pregnancy, hypoxia A is correct. Aminopyridines are presumably excitatory as can evoke glutamate and GABA release in presence of calcium. Aminopyridine is a voltage-gated, fast potassium channel blocker capable of improving axonal conduction by facilitating the propagation of action potentials in demyelinated nerve fibers. See: http://jpet.aspetjournals.org/cgi/content/full/316/1/216?ck=nck

Question 89

IN22 [Jul98] Nitrous oxide is NOT relatively contra-indicated with: A. Pneumothorax B. Ear surgery C. Postoperative nausea & vomiting D. Renal failure

Answer 89

N2O has low blood solubility (0.46) so it tends to fill up body cavities. Pleural space, middle ear and bowel will be expanded by N2O. Therefore it should be avoided in patients with pneumothorax, middle ear or bowel surgery. N2O has side effect of post-operative nausea and vomiting. N2O is not metabolized by our body and is eliminated through exhalation. So it be can administered to patients with renal failure.

Question 90

IN23 [Jul99] [Jul02] [Mar03] [Jul04] Which of the following does NOT affect the speed of induction with a volatile agent? A. FRC B. Obesity C. pCO2 D. Cardiac output E. Body mass F. MAC

Answer 90

A incorrect. FRC affects the rate of induction, e.g. in adults is 1.5:1; in neonates is 5:1 & onset is more rapid B is correct. (Although obesity can decrease FRC) C incorrect. PCO2 will affect ventilation (i.e. high PCO2 increases respiratory rate, increasing uptake & vice versa) D incorrect. Cardiac output will affect the speed of induction, especially of a highly fat soluble agent E basically same as B. F is incorrect. MAC is potency of inhaled anaesthetic, so much like other drugs (ie, muscle relaxants), the lower the potency, the higher the inspired concentration required (and faster the uptake), and therefore the higher the concentration gradient. This is really only clinically significant for Nitrous oxide (causing the "concentration effect").

Question 91

IN23 alt Regarding the time constant for volatile anaesthetic uptake in the lungs A. Affected by agent concentration B. Affected by obesity C. Not affected by FRC D. Affected by restrictive lung disease

Answer 91

Alternate version Time constant isn't affected by agent concentration, is affected by FRC, and therefore is affected by obesity, and I'm not sure about restrictive lung disease. Any thoughts? For the first question if it is a choice for one correct answer, E (body mass) should be correct as body mass per se does not affect uptake. Option E is not the same as B as a high body mass does not entail obesity. Obesity will decrease FRC and is therefore an indirect contributor to speed of induction. However, since the previous versions of the question seem to not include body mass as an option, B, obesity probably is the best out of this lot. pCO2 may not increase respiratory rate depending on the status of respiratory reflexes in various pathological conditions, and in very high pCO2 may decrease respiratory rate. Further, it may increase cardiac output which has a different effect on speed of induction. However, which ever way it goes, it will always have some sort of effect on the speed of induction, albeit of variable significance.

Question 92

IN24 [Feb00] 22g of Nitrous oxide at STP occupies a volume of: A. 3.6 litres B. 11.2 litres C. 22 litres (? or 22.4 litres) D. 44.1 litres

Answer 92

MW of N2O = 44 Daltons so one mole of N2O weighs 44g (and 22 g = 1/2 mol). 1 mol of gas at STP occupies 22.4 litres So, 0.5 mole (22g) of N2O at STP occupies 11.2 litres. Q: Is the MW of N2O 44 Daltons A: Yes, MW of N2O = 14+14+16 = 44 Da. The Dalton is an alternative name of the atomic mass unit (or molecular weight).(See ref below)

Question 93

IN25 [Jul00] [Mar03] [Jul04] Wash in (? washout) of volatile anaesthetics is reduced in neonates because: A. Reduced FRC B. Increased cardiac index C. Decreased plasma protein levels? D. (Something about blood:gas partition coefficients being different in neonate)

Answer 93

Wash in (? washout) of volatile anaesthetics is reduced in neonates because: A. Reduced FRC B. Increased cardiac index - ?true - I presume neonates have a very high CI due to their high metabolism and relatively hyperdynamic state; this would reduce the time to equilibrium (in the wash in phase) C. Decreased plasma protein levels? - no idea D. (Something about blood:gas partition coefficients being different in neonate) - no idea The washout of inhalational anaesthetics A. Increases with elimination by the liver - true, drugs eliminated by the liver will be eliminated faster B. Related considerably with the duration of anaesthesia - don't think so C. Increases in the neonates compared to an adult - no idea D. ? This question is probably poorly remembered. I couldn't make sense of the comments below

Question 94

The washout of inhalational anaesthetics A. Increases with elimination by the liver B. Related considerably with the duration of anaesthesia C. Increases in the neonates compared to an adult D. ?

Answer 94

Wash in (? washout) of volatile anaesthetics is reduced in neonates because: A. Reduced FRC B. Increased cardiac index - ?true - I presume neonates have a very high CI due to their high metabolism and relatively hyperdynamic state; this would reduce the time to equilibrium (in the wash in phase) C. Decreased plasma protein levels? - no idea D. (Something about blood:gas partition coefficients being different in neonate) - no idea The washout of inhalational anaesthetics A. Increases with elimination by the liver - true, drugs eliminated by the liver will be eliminated faster B. Related considerably with the duration of anaesthesia - don't think so C. Increases in the neonates compared to an adult - no idea D. ? This question is probably poorly remembered. I couldn't make sense of the comments below

Question 95

IN26 [Jul01] With regard to compound A: A. Increased production in Baralyme compared to sodalime B. More likely in children C. Sevoflurane metabolites cause hepatotoxicity D. Sevoflurane is METABOLISED to Compound A in the liver E. ?

Answer 95

Sevoflurane degrades in alkali (eg sodalime, baralyme) esp if desiccated to produce compound A. This substance causes nephrotoxicity in rats and has caused concern that similar toxicity may occur in humans. However the risk is extremely low. Nonetheless, the FDA has mandated a minimum FGF of 2 lpm when using sevoflurane. Compound A is neither produced in the liver, nor does it cause hepatotoxicity. Compound A is produced at a greater rate in Baralyme than sodalime. - Miller 6th ed page 251 "Compound A is hepatotoxic in animals, but the concentration present in the anaesthesia breathing circuit are far below the toxic levels in animals. Nevertheless, small increases in the plasma alanine aminotransferase have been obseerved in volunteers receiving sevoflurane for prolonged periods of time during which the compound A concentrations averaged 41ppm." Stoelting 4th Ed Page 68.

Question 96

IN27 [Jul01] Concerning the effects of various volatile agents on cerebral blood flow under conditions of 1 MAC and normocarbia: A. Halothane produces greater increase than enflurane B. Isoflurane produces greater increase than enflurane C. Any change produced depends upon cerebral metabolic rate D. Change in CBF is due to change in cardiac output E.

Answer 96

A is correct Isoflurane causes a greater increase in CBF at a MAC equivalent. Not correct, based on refs. But according to Eintrei et al.: Isoflurane does NOT increase CBF at 1 - 1.5 MAC So I think the more obvious answer A is more correct. Peck and Williams 2nd ed: The increase in CBF and ICP (for enflurane) lies between those observed with Halothane and Isoflurane." pg 113 Halothane increases CBF more than any other volatile" pg 111 Hence A is most likley the correct answer. Peck, Hill & Williams also says that: Isoflurane produces the best balance between increased CBF and decreased CMRO2 (cerebral autoregulation preserved up until 1 MAC). I think A is correct Miller ed 7 fig 13.8 (mislabelled) and text: Halothane increases CBF 191% where as enflurane increases 45% and isoflurane 19% (similar but marginally greater than sevo)! Stoelting p48: Halothan \> Enflurane \> ?N2O \> Isoflurane ~ Desflurane \> Sevoflurane References Stoelting & Hillier 4th Ed page 48-49 Miller Peck, Hill & Williams Eintrei C, Leszniewski W, Carlsson C. Local application of 133 xenon for measurement of regional cerebral blood flow (r CBF) during halothane, enflurane and isoflurane anesthesia in humans. Anesthesiology l985 ; 63: 391-4

Question 97

IN28 [Jul01] Which of the following drugs is not associated with EEG epileptiform activity A. Propofol B. Enflurane C. ? D. ? E. ?

Answer 97

Enflurane and sevoflurane , but not desflurane or isoflurane can predispose the brain to convulsive activity.(Eger pg 147)

Question 98

IN29 [Jul04] Which does not increase risk of increased carboxyhaemoglobin in blood during anaesthesia? A. Dry absorbent B. Baralyme C. Low flows D. Desflurane E. Halothane

Answer 98

Carbon monoxide is produced when volatile anaesthetics containing CHF2 are degraded by strong bases. Factors influencing production of carbon monoxide: Dryness of CO2 absorbent - hydration prevents CO formation High CO2 absorbent temperatures - occurs with low flows and increased metabolic CO2 production Type of CO2 absorbent Halothane and sevoflurane do not possess a vinyl group and therefore do not produce carbon monoxide when exposed to CO2 absorbents References Stoelting and Hillier 4th ed page 79

Question 99

IN30 [Jul04] The concentration effect for N2O is due to A. Increased conc of N2O B. Faster eqilibrium of N2O than the second soluble second gas C. ? D. ?

Answer 99

A: increased conc. Because N2O is given in such large conc, it increases its own uptake. Concentration effect can be thought of as N2O performing the 2nd gas effect on itself. The concentration effect results from 2 factors, the concentrating effect and an augmentation of inspired ventilation. So administration of higher concentrations of N2O initally results in the uptake of substantial volumes of gas this large uptake concentrates the gases remaining in the alveoli. It also creates a negative pressure that can increase the volume of gas inspired. For nitrous this is the concentration effect and for other gases it is the 2nd gas effect.(Eger pg64)

Question 100

Anaesthetic preconditioning... A. Sevoflurane and propofol are equally effective B. At least 1.0 MAC Isoflurane necessary C. something about Adenosine receptors D. thought to be due to closure of KATP channels E. Opioids do not produce preconditioning

Answer 100

Yeah not a nice question. Not sure how well remembered. Save this for the part 2! A Umm no I dont think so or otherwise all those CABG's would be run on TIVA. B It is dose dependent so no. C Perhaps. It involves stimulation adenosine receptors. D It is through opening/activation of K-ATPase channels. (A more obvious answer if the question is incorrectly remebered) E Opioids amplifies the preconditioning via volatiles through stabilization in the open state of the mitochondrial K-ATP channel (the main end-effector in anaesthetic preconditioning)

Question 101

IN31 IN33 Which volatile anaesthetic is metabolised least? \*repeat\* A. Desflurane B. Isoflurane C. Halothane D. Sevoflurane E. Enflurane

Answer 101

A. Desflurane - 0.02% - True B. Isoflurane - 0.2% C. Halothane - 15-20% D. Sevoflurane - 5% E. Enflurane - 3%

Question 102

IN33 Volatile metabolism A. Iso 0.2% by CYP2E1 B. Isoflurane 0.2% metabolised in the kidneys C. Other wrong options for Iso/other agents

Answer 102

A - True B- False - hepatic metabolism

Question 103

IN33b [July 2012] Metabolites of isoflurane: A. 2% to hexafluroisopropyl B. 0.2% C. 0.2% via renal ?conjugation D. 0.5% ... E. 2% fluoride

Answer 103

A - False - 0.2% metabolised B - possibly true C - false - hepatic not renal D - false - not 0.5% E - false - not 2% 0.2% of Isoflurane is hepatically metabolised to trifluroacetic acid by cytochrome p-450 ref -stoelting handbook 2nd Ed page75

Question 104

IN34 The therapeutic index of modern volatiles is in the order of: A. 10

Answer 104

A. 10

Question 105

IN35 Which of the following regarding nitrous oxide and Xenon is true? A. Xenon limited by cost B. Xenon is less lipid soluble than nitrous C. Nitrous and Xenon have MAC of \> 100% and

Answer 105

A - True. Xeonon is expensive to extract from atmosphere and although is completely reusable (nil metabolism) most is lost to the atmosphere. B - True. C - True. D - False. Nitrous is unable to produce surgical anaesthesia as the sole agent. E - True. Both are readily extractable. Note: I agree - the stem probably asks for that which is FALSE. - However, the question asks about "both"... so A might be true, but is only about xenon Xenon is less soluble in blood, but I couldn't find a source regarding lipid solubility C definetely true Nitrous may not induce surgical anaesthesia with a MAC \> 100% (therefore wil not produce surgical anaesthesia in over 50% of patients even at 100% - which would make them hypoxic of course) I suppose air is readily available, and probably ammonium nitrate, I'm just playing the devil's advocate added 6 Feb 2009: Oil:gas partition coefficients: N2O=1.4, Xe=1.9 [Peck, Hill & Williams 3rd ed p125] =\> more Xe in oil than gas (cf N2O) =\> Answer B is FALSE

Question 106

Desflurane is better in obesity because (a.k.a. "Of the following, what feature of desflurane makes it most suitable for bariatric anaesthesia?) A. mac 6.6% - false the potency of the agent isn't relevant B. blood:gas coefficient 0.42 - true C. saturated vapour pressure 669 (600mmHg?) - false D. oil:water coefficient 346 - false - The oil:water partition coefficient (aka the fat:blood coefficient.) of Desflurane is 27.2 (steolting 4th ed page 27 table 1.7) E. ?

Answer 106

"The pharmacokinetics of the elimination of inhaled anaesthetics depends of the length of administration and the blood:gas solubility of the inhaled anaesthetic" (stoelting 4th ed page 32) Desflurane is better in obesity because it is less soluble in blood and therefore washes out faster (as indicated by it's low bood gas partition coefficient of 0.42) The lack of accumulation of Desflurane in the increased fat stores is described by its low oil:water (fat:blood) partition coefficient and this is the other component in its rapid washout at the end of surgery. WRT this question though, the number quoted for the coefficient is quite wrong. a oil:water coefficient of 346 would describe a very fat soluble agent - likely to lead to a slower wake up. The dominant factor is the washout from blood to gas... if this is fast enough, it doesn't matter how much is redistributing back into the blood as it is rapidly washed out of the alveolus.

Question 107

Mechanism of IMOBILITY with volatiles / ? specific volatile?: A Stimulation of GABAa receptors - False B C E Stimulation of Glycine receptors - True

Answer 107

read stoelting 4th ed page 35-36

Question 109

IN38 Toxicity of methoxyflurane when used for analgesia is due to A - Fluoride induced nephrotoxicity

Answer 109

Yep - 70% of dose is metabolised to inorganic fluoride, which is nephrotoxic. This toxicity has been extrapolated to other fluorinated volatiles (including sevoflurane) despite a lack of data to support it. stoelting 4th ed page 70

Question 110

Metabolites of sevoflurane: A - Fluoride ions and hexafluroisopropyl B - Compound A and TFA C - hexafluroisopropyl (HFIP) and trifluroacetic acid D - Other compounds and combos. E - TFA and fluoride ions

Answer 110

A True B False: compound A is not a metabolite C False not a TFA D: meh E False not TFA Table: http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN39

Question 111

Mechanism of action of nitrous oxide: A - Stimulation of GABA receptors B - Inhibition of GABA receptors C - Stimulation of NMDA receptors D - Inhibition of NMDA receptors E - Stimulation of Glycine receptors

Answer 111

A - false minimal effect at GABAA, although analgesia may be 2o to opiodergic & GABAergic interneurones in the peri-aqueductal grey matter. B - false see above C - false see below D - true - non competitive inhibition (sassada and smith 4th ed page 250) E - false

Question 112

With regards to isoflurane, sevoflurane and desflurane: A - Desflurane and Sevoflurane both have chloride ion in structure? A2 (My memory of it was des and iso. Anyone else?) B - Isoflurane is not broken down in CO2 absorbants C - They can all cause an increase in cerebral blood flow and ICP

Answer 112

A - false - des contains Carbon, Hydrogen, Oxygen and Fluorine only A2 - false - see above B - false - produces CO (as do desflurane (worst) and enflurane) - CHF2 moeity is the causative group. Sevo may also form CO if the exothermic reaction with dry soda lime occurs C - true, dose dependent until MAP / CO falls significantly - uncouples CMRO2 and CBF.

Question 113

EN01 [Mar96] [Jul97] Chlorpropamide: A. Inhibits ADH secretion B. Has a short duration of action (? Half-life

Answer 113

Chlorpropamide: A. Inhibits ADH secretion - false "Carbamazepine and chlorpropamide also enhance the antidiuretic effects of vasopressin by unknown mechanisms. In rare instances, chlorpropamide can induce water intoxication." From Goodman and Gilman Ch 29 B. Has a short duration of action (? Half-life C. Increases glucose entry into cells - true Chlorpropamide is a sulfonylurea. "The major action of sulfonylureas is to increase insulin release from the pancreas" (Katzung Ch 41) and thus increase glucose entry into cells. D. Is prolonged in renal failure - true "All the sulfonylureas are metabolized by the liver, and the metabolites are excreted in the urine. Metabolism of chlorpropamide is incomplete, and about 20% of the drug is excreted unchanged. Thus, sulfonylureas should be administered with caution to patients with either renal or hepatic insufficiency." (Goodman and Gilman Ch 60) E. ? Chlorpropamide is a sulphonylurea with duration of action 27-72 hours. It is renally excreted so action will be prolonged in renal failure: D is best answer. It acts by increasing insulin release so C is also correct. Peck, Hill and Williams 2nd ed p352. "Chlopropamide - its long t1/2 and partial reliance on renal elimination results in a greater chance of hypoglycaemia, especially in the elderly. It may also cause facial flushing and vomiting following alcohol and rarely may enhance ADH secretion resulting in hyponatraemia. Photosensitivity may also occur.....In the presence of renal failure its t1/2 is prolonged(p351)"

Question 114

EN02 [Jul97] [Jul01] Sulphonylureas: A. High incidence of lactic acidosis B. Good in patients with depleted insulin stores C. Metformin & phenformin are examples D. Increased glucose utilisation in the peripheries E. Are related to sulphonamides

Answer 114

A High incidence of lactic acidosis: false - "Biguanides were largely abandoned because of the risk of severe lactic acidosis" as opposed to sulfonylureas (Stoelting 3rd ed. p.433) B Good in patients with depleted insulin stores: false - they work by increasing release of insulin from pancreatic islet cells and therefore have no role in type 1 diabetes (insulin deplete) C Metformin & phenformin are examples: False - metformin is a biguanide D Increased glucose utilisation in the peripheries probably false - they don't increase utilisation, they simply increase insulin to increase glucose UPTAKE but not usage E Are related to sulphonamides True - they are "derivatives of sulfonamides" (Stoelting 3rd ed. p.430)

Question 115

Jul 01 version: With regards to sulphonylureas: A. Work effectively if insulin stores depleted B. Cause a lactic acidosis C. Tolbutamide, (..something else..), phenformin are examples D. Highly protein bound E. ?

Answer 115

Jul 01 version: With regards to sulphonylureas: A Work effectively if insulin stores depleted false - see above B Cause a lactic acidosis false - see above C Tolbutamide, (..something else..), phenformin are examples false - phenformin is a biguanide D Highly protein bound true - "these drugs are weakly acidic and circulate bound to protein (90-98%), principly to albumin" (Stoelting 3rd ed. p.431) Answer for Jul 01 version: D Sulphonylureas work by increasing release of insulin from B-cells of islets of Langerhans. Therefore if someone is depleted of stores, they cannot be of use by this mechanism. However they also do increase insulin sensitivity in the periphery and hence are not considered of "no" use. Biguanides can be associated with lactic acidosis, not sulphonylureas. Sulphonylureas are generally highly protein bound. (eg: glibenclamide has 97% plasma protein binding)

Question 116

EN03 [Jul01] Glipizide is: A. A biguanide B. Half life 4-6hrs C. Causes metabolic acidosis /lactic acidosis D. Not contraindicated in hepatic failure E. Highly bound to albumin F. Is ineffective in patients with low insulin stores

Answer 116

Glipizide is a sulphonylurea with half life 4-7hours (Stoelting). It is highly bound to albumin 90-99% and metabolised in the liver.Thus B and E are true. Comment A. A biguanide - FALSE: sulphonylurea B. Half life 4-6hrs - true: see table in Stoelting 3rd ed p431 but duration of action is longer C. Causes metabolic acidosis /lactic acidosis - FALSE: biguanides do this D. Not contraindicated in hepatic failure - FALSE: liver metabolism is extensive for sulphonylureas E. Highly bound to albumin - TRUE F. Is ineffective in patients with low insulin stores - TRUE

Question 117

EN04 Repaglinide A. Inhibits potassium ATPase channels in beta cells B. Acts on gene receptors to do loads of things C. Decreases glucose absorption from the gut D. Acts on sulphonylurea receptors in extrapancreatic sites

Answer 117

"repaglinide and the phenylalanine derivative, nateglinide differ in structure and timing of action form sulfonylurea drugs. Although these drugs may exert effects on β cells similar to sulfonylureas drugs, they have a more prompt peak effect (about 1 hour) and a shorter duration of action (about 4 hours). β cell stimulants lower HbA1C about 1%" '(Stoelting 4th ed. p.484) As actions are similar to sulphonyureas: A. - True - this causes an influx of calcium and stimulation of exocytosis of insulin storage granules B. - False - see above C. - False - see above D: - likely false - not clear - "the closure of potassium channels in extrapancreatic tissue... (which are of unknown but probably minimal significance." (Katzung 11th ed. p. 738)

Question 118

EN05 - [Feb 2012] - [[15A|Feb 15] In severe post-partum haemorrhage (or: Administration of oxytocics for uterine atony post C-section...) A. 10IU oxytocin will cause ?hypotension B. Ergometrine causes ischaemia (myocardial) via coronary steal C. Something about adrenaline D. PGE2 will cause vasoconstriction and severe hypertension E. PGF2α may cause bronchconstriction

Answer 118

n severe post-partum haemorrhage (Feb15 = Administration of oxytocics for uterine atony post C-section...) A. 10IU oxytocin will cause ?hypotension - True - decreased SVR B. Ergometrine causes ischaemia (myocardial) via coronary steal D. PGE2 will cause vasoconstriction and severe hypertension - false causes tachycardia and increased cardiac output - Stoelting does not mention hypertension. E. PGF2α may cause bronchconstriction - True Uses for Oxytocin: - :Induction and augmentation of labour at term :Counteraction of uterine atony and therefore haemorrhage Preparation: :synthetic proteins identical to the endogenously produced hormone from the posterior pituitary (minus other contaminating proteins) :potency described in units Absorption :well absorbed, completely metabolised by GIT chymotrypsin - 0% bioavailabilty Metabolism :rapid hydrolysis in the liver and kidneys by oxytocinase. Side Effects: :direct relaxation of vascular smooth muscles - decreased SVR and therefore MAP + Flushing and reflex tachycardia and increased cardiac output. (hypotension is especially marked in hypovolaemic patients) :slight vasopressin like activity when given in high doses - may predispose to water intoxication (risk minimised if oxytocin given in an electrolyte rather than glucose solution. Ergometrine Uses :treatment of post partum/post abortion uterine atony and prevention of haemorrhage secondary to atony :treatment of migraine (likely secondary to cerebral vasoconstriction - caffeine increases oral absorption of ergotamine by a factor of two,) Preparation :product of grain fungus :common ancestor (ergonine) with LSD (lysergic acid diethyl amide.) Side Effects :intense vasoconstriction - caution (in fact essentially contraindication) in precelampsia :nausea and vomiting - likely reflecting direct CNS effect Prostaglandins in obstetrics Actions :Act on G-Protein coupled receptors :produce cervical ripening :increase uterine contractility Uses :induction of labour :termination of pregnancy and treatment of PPH secondary to uterine atony Classes :PGE2 - Dinoprostone given PV :PGE2α (Dinoprost / carboprost - given amniotic or intramyometrial injection - tendency to cause N&V + diarrhoea) :PGE1 analogues (Gemeprost or Misoprostol given PO PV or PR) - other actions included decreasing gastric acid secretion, increased gastric mucosal good flow and mucosal barrier formation. Side Effects :Uterine pain / rupture / foetal distress :Nausea and vomiting :Diarrhoea - stimulation of GI smooth muscle :Bronchoconstriction - PGE2α :Large doses can decrease SVR and MAP - N.B. beware PGF2α embolism causing cardiovascular collapse after amniotic injetgion :Genital oedema and anaphylaxis

Question 119

EN05b [Aug 2011] Oxytocin 10 units given IV A. ? B. metabolised in liver C. Causes hypotension by direct effect on heart D. ? E. ?vasodilation

Answer 119

Oxytocin 10 units given IV B. metabolised in liver - True - rapid hydrolysis in the liver and kidneys by oxytocinase. C. Causes hypotension by direct effect on heart - false - decreased SVR E. ?vasodilation - True Uses for Oxytocin: - :Induction and augmentation of labour at term :Counteraction of uterine atony and therefore haemorrhage Preparation: :synthetic proteins identical to the endogenously produced hormone from the posterior pituitary (minus other contaminating proteins) :potency described in units Absorption :well absorbed, completely metabolised by GIT chymotrypsin - 0% bioavailabilty Metabolism :rapid hydrolysis in the liver and kidneys by oxytocinase. Side Effects: :direct relaxation of vascular smooth muscles - decreased SVR and therefore MAP + Flushing and reflex tachycardia and increased cardiac output. (hypotension is especially marked in hypovolaemic patients) :slight vasopressin like activity when given in high doses - may predispose to water intoxication (risk minimised if oxytocin given in an electrolyte rather than glucose solution.

Question 120

EN06 Feb15 Metformin: A. Causes hypoglycaemia B. Excreted unchanged C. Lactic acidosis incidence 50 per 1000 patient years (this was the wording - good luck!) D. Decreases hepatic gluconeogenesis E. ?

Answer 120

B & D are correct - Sasada & Smith From [1]: Hypoglycaemia is rare when used alone. 90% excreted unchanged in urine "In a Cochrane review, the estimated upper limit for the incidence of lactic acidosis in metformin users was 4.3 cases per 100 000 patient-years compared with 5.4 cases per 100 000 patient-years in those assigned to other treatment groups." Metformin decreases hyperglycemia primarily by suppressing glucose production by the liver (hepatic gluconeogenesis) -Wikipedia

Question 121

EN07 Feb15 Dexamethasone: A. short acting B. naturally occurring C. no mineralocorticoid activity D. glucocorticoid E. ?

Answer 121

C Yentis on dexamethasone and Ganong on adrenal cortex

Question 122

MD01 [Mar96] [Jul97] [Mar03] Oxytocin: A. Synthetised in posterior pituitary B. Poorly absorbed orally C. Metabolised by oxytocinase in the liver D. Bolus dose will increase central venous pressure E. Bolus dose will increase systemic vascular resistance F. Metabolised by the liver and kidney (see also EM15)

Answer 122

MD01 Oxytocin: A. Synthetised in posterior pituitary - INCORRECT; synthesised in the hypothalamus and released from the posterior pituitary B. Poorly absorbed orally - CORRECT; oxytocin, as a polypeptide is rapidly metabolised in the digestive tract by peptidases to amino acids and small peptides C. Metabolised by oxytocinase in the liver - INCORRECT; "The human oxytocinase/insulin-regulated aminopeptidase (OTase/IRAP) is a 1024 amino acid type II integral membrane protein that is expressed mainly in fat, muscle and placenta tissues" [1] D. Bolus dose will increase central venous pressure - INCORRECT; "High doses of oxytocin produce a direct relaxant effect on vascular smooth muscles" (Stoelting 3rd ed. p.424) E. Bolus dose will increase systemic vascular resistance - INCORRECT; "manifests as a decrease in systolic and diastolic blood pressure" (Stoelting p.424); also "hypotension, tachycardia and ECG changes have been observed following intravenous administration of concentrated solutions. Rapid intravenous injection of as little as 2 IU can cause acute hypotension accompanied by flushing and reflex tachycardia. Bradycardia and arrhythmias have been reported. Hypertension may occur rarely." (MIMS[2]) F. Metabolised by the liver and kidney - ?INCORRECT; see answer for C. Sasada+Smith says 'rapidly removed from the plasma by hydrolysis in the liver and kidney (by the action of oxytocinase)' which would make C and F correct

Question 123

MD01b [Mar99] [Jul99] Oxytocin: A. Has diuretic effect B. Partially depolarises uterine muscle / ?effect on membrane threshold C. Causes emesis D. Increases threshold of receptors for depolarisation E. Hypertension

Answer 123

MD01b [Mar99] [Jul99] Oxytocin: A. Has diuretic effect - INCORRECT; it has an ADH-like effect (only different by two peptides from ADH/vasopressin) B. Partially depolarises uterine muscle / ?effect on membrane threshold - MAY BE CORRECT (depending how the answer is worded); "Oxytocin exerts a contracting effect on the pregnant uterus by lowering the threshold for depolarisation of the uterine smooth muscle" (Stoelting 3rd ed. p.712) C. Causes emesis - CORRECT of any drug; MIMS[3] states "nausea and vomiting have been reported" D. Increases threshold of receptors for depolarisation - INCORRECT; see answer B E. Hypertension - INCORRECT; see previous question comment: - oxytocin can cause hypertension (especially in conjunction with another vasoconstrictor), and there has been reported maternal deaths from SAH in the context of severe hypertensive episodes (FDA product info), so it depends on how the question is worded - bolus dose tends to cause hypotension as in the first question

Question 124

MD01c [Feb00] Oxytocin: A. Ringed octapeptide B. Effects on uterus antagonized by beta agonists C. ADH like effect D. ?

Answer 124

MD01c [Feb00] Oxytocin: A. Ringed octapeptide - INCORRECT; it is a nonapeptide; the biologically active form is also known as oxytocin disulphide is an octapeptide wikipedia B. Effects on uterus antagonized by beta agonists - correct; salbutamol is a tocolytic, while oxytocin is used to increase contractions C. ADH like effect - correct; "oxytocin has... the antidiuretic activity of ADH" (Stoelting p. 712)

Question 125

MD02 [Mar96] [Mar97] [Jul97] [Jul98] [Jul99] [Feb00] Cisapride: A. Will increase gastric motility in the presence of atropine B. Can be used to treat opioid induced gastric stasis C. Decreases/increases lower oesophageal sphincter tone (?due to atropine) D. Decreases gastric pH E. Increases gastric volume F. Blocks histamine receptors G. Agonist at D2 receptors

Answer 125

From Goodman & Gillman (9th ed): A. False - Cisapride acts via release of Ach from the myenteric plexus in the GIT. Its actions are blocked by atropine. B. True - "Opioid-induced gastric stasis... is reversed by cisapride" (Stoelting 3rd ed. p.450) C. "Increases lower oesophageal sphincter tone" (Stoelting p.450) D. False. Neither cisapride nor metoclopramide reduce gastric acid secretion and therefore affect gastric pH but both are prokinetics and reduce gastric volume. Both have some 5-HT4 action but only metoclopramide acts on enteric D2 receptors. E. False - "cisapride has no effect on ... gastric fluid volume" (Stoelting p.450) F. False G. False - "cisapride lacks dopamine agonist effects" (Stoelting p.450) Cisapride is a prokinetic agent with actions throughout the gastrointestinal tract. It acts as an agonist at muscarinic (M2) and some serotonergic (5HT4) receptors, and as an antagonist at other serotonergic (5HT3) receptors. Cisapride increases smooth muscle tone, strength and possibly the co-ordination of contractions. This results in improved transit of gastrointestinal contents. Cisapride has therefore been widely used in disorders due, or believed to be due, to disordered gastrointestinal motility. It can cause cardiac arrhythmias especially at higher doises or when used in combination with drugs which inhibit its metabolism. The cardiac toxicity of cisapride is attributed to its inhibition of potassium channels in the myocardium. This concentration-dependent effect leads to prolongation of the QT interval which increases the risk of torsade de pointes and sudden death. Toxicity is seen in all age groups, and is enhanced by higher doses, individual susceptibility due to disease or genetic factors, co-administration of drugs inhibiting the metabolism of cisapride via cytochrome P450 3A4 (e.g. macrolides, azole antifungals, grapefruit juice)2, or other drugs which prolong the QT interval (e.g. quinidine, sotalol).

Question 126

MD03 [Mar96] [Jul97] [Jul98] Regarding the plasma half-life of heparin: 7A. Clearance affected by warfarin B. Depends on site of injection C. Less for low MW heparins D. Depends on dose given

Answer 126

MD03 [Mar96] [Jul97] [Jul98] Regarding the plasma half-life of heparin: A. Clearance affected by warfarin - INCORRECT B. Depends on site of injection - INCORRECT: site will affect absorption but not half-life C. Less for low MW heparins - INCORRECT: LMW heparin has a "longer elimination half-time" (Stoelting 3rd ed. p.459) D. Depends on dose given - CORRECT: "For example, the elimination half-time after a heparin dose of 100U/kg IV was 56 minutes and increased to 152 minutes after a dose of 400U/kg IV" (Stoelting 3rd ed. p.453)

Question 127

MD03b [Jul97] Heparin: A. Has a half life dependent on dose B. Inactivates factors XII, XI, X, IX C. ? D. ? (see also [[MD49)

Answer 127

MD03b [Jul97] Heparin: A. Has a half life dependent on dose - CORRECT: see answer D of above B. Inactivates factors XII, XI, X, IX - INCORRECT: has its effect by binding antithrombin C. ? D. ? Answer is D (MD03) and A (MD03b) Heparin exhibits complex pharmacokinetics and is cleared by two mechanisms. The rapid, saturable phase of elimination is thought to be due to receptor-mediated internalisation of heparin by endothelial cells and macrophages A slower, nonsaturable renal mechanism also clears heparin from the plasma Hence clearance and half-life pharmacokinetic properties will be related to dose Biological t 1/2 of heparin increases from 30min following IV bolus dose of 25 units/kg to 150min following a bolus dose of 400 units/kg In addition to enhancing activity of antithrombin III, 'at low concentrations factor Xa is inhibited, while factors IXa, XIa and XIIa are progressively inhibited' and 'platelet aggregation becomes inhibited at high concentrations' (Peck+Hill) - I suspect that option B is bit of a trick as it is only the active forms of these factors (with the 'a' after them) that are inhibited, so it looks at first glance like it would be true, but is actually false. References Unfractionated Heparin, Low Molecular Weight Heparins, and Pentasaccharide: Basic Mechanisms of Actions, Pharmacology and Clinical Use ( Feb 2005:Hematology/Oncology Clinics of North America 19(1)

Question 128

MD04 [Mar96] [Jul99] [Apr01] Paracetamol: A. Has an active metabolite B. Interferes with renal blood flow C. Does NOT cause gastric irritation D. Causes methaemoglobinaemia E. Maximum adult dose 4g

Answer 128

Paracetamol metabolism 80% is metabolised by hepatic micorsomal enzymes and converted to sulfate and glucuronide 5% is excreted unchanged remainder is metabolised to active metabolite called N-acetyl-p-benzoquinone. Comment: inactive metabolite per Stoelting. Paracetamol is a weak COX-1 and COX-2 inhibitor in peripheral tissues and hence possesses no significant anti-inflamatory effects. Adverse effects: mild increase in hepatic enzymes, dizziness, excitement, disorientation. Hemolytic anaemia and methemoglobinemia reported rarely. Overdoses: Ingestions of 12-15g (normal adult daily dose 4g) associated with severe hepatotoxicity with centrilobular necrosis and sometimes acute renal tubular acidosis. Based on above info: answers to the questions: March 96: A. Has an active metabolite: FALSE - paracetamol "is converted... in the liver to inactive metabolites" (Stoelting p.253) B. Interferes with renal blood flow: FALSE C. Does NOT cause gastric irritation: TRUE - paracetamol "does not cause gastic irritation" (Stoelting p.253) D. Causes methaemoglobinaemia: False - phenacetin, a drug which is metabolised to paracetamol can cause methaemoglobinaemia in patients with a G6P deficiency (Stoelting p.254) E. Maximum adult dose 4g: TRUE - Daily adult dose is 4g. COMMENT: but this version of the question didn't say "per day" - check the wording on the exam day!!

Question 129

Apr 2001 version: Paracetamol: A. Frequently causes dyspepsia (?gastric irritation) B. Acid-base abnormalities common with overdose C. Maximum dose 4 grams in adult D. ? E. ?

Answer 129

April 01: A. Frequently causes dyspepsia (?gastric irritation): False - GI irritation not common. B. Acid-base abnormalities common with overdose: True: Hepatoxicity major feature of paracetamol overdose, but acid-base abnormalites and renal failure are NOT uncommon C. Maximum dose 4 grams in adult: True: Daily adult dose 4g. COMMENT: but this version of the question didn't say "per day" - check the wording on the exam day!! Damn these examiners. I reluctantly agree that the wording of E and C above "Maximum dose 4g in adults" is dodgy and confusing. Obviously the maximum daily dose is 4g but the maximum dose is different for single doses in adults depending on the route (20mg/kg per rectum [1] or 1000mg for IV or oral dosing). Clinically we often give 2000mg PR suppositories, do we not?

Question 130

MD04b [Jul98] [Mar99] [Feb00] [Jul04] Paracetamol: A. Is a powerful anti-inflammatory agent B. Should never be given in a dose \> 20 mg/kg to children C. Increased risk of hepatic necrosis in chronic alcoholics D. Sulphate conjugation is major metabolic pathway E. pKa 3.5 F. ?Glutathione conjugation

Answer 130

MD04b [Jul98] [Mar99] [Feb00] [Jul04] A. Is a powerful anti-inflammatory agent - FALSE B. Should never be given in a dose \> 20 mg/kg to children - TRUE BUT dosage is 15mg/kg in children --\> I disagree: FALSE, see below C. Increased risk of hepatic necrosis in chronic alcoholics - TRUE: tend to be deficient in glutathione so more prone to damage by NAPQI (see below) D. Sulphate conjugation is major metabolic pathway - PARTLY TRUE: glucuronide and sulphate congugation the major pathway (90-95%); the rest is dealt with by glutathione E. pKa 3.5 - no, paracetamol pKa is 9.5 F. ?Glutathione conjugation - no idea (FALSE, see below) Comment: Metabolism of paracetamol is mainly to the glucuronide conjugate, and less to the sulphate. Glutathione conjugation via sulphydryl group is the means by which the toxic intermediate is rendered harmless. BTW if we're going to be punctilious about it (and apparently we are) I think the compound in question is called N-acetyl-p-benzoquinoneimine by its mother (see Peck Hill and Williams 2nd edition p142) According to a Google search, pK of paracetamol is 9.5

Question 131

[Feb 2000] [Jul01] Paracetamol: A. Has analgesic, antipyretic and anti-inflammatory effects B. Is metabolised to BENZOQUINONIMINE which is inactivated by conjugation to glutathione C. Dose should not exceed 4000mg/day in an adult (Alt: Minimum toxic dose 8-12G/day in an adult) D. Gastric irritation is common

Answer 131

Feb 00: A. Has analgesic, antipyretic and anti-inflammatory effects: False. "anti-inflammatory effects... are weak" (Stoelting p.253) B. Is metabolised to BENZOQUINONIMINE which is inactivated by conjugation to glutathione: False. Metabolised to N-acetyl-P-benzoquinoneimine. C. Dose should not exceed 4000mg/day in an adult: True: Daily adult dose 4g. D. Gastric irritation is common: False. Gastric irritation not common.

Question 132

July 2004 Paracetamol: A. Has analgesic, antipyretic and anti-inflammatory effects B. Is metabolised to N-methyl-p-benzoisopuinonimine conjugated to glutathione C. Toxic dose is 10 times the normal ?daily dose? D. pKa 3.5 E. ?

Answer 132

July 04: A. Has analgesic, antipyretic and anti-inflammatory effects: False - does not have anti-inflammatory effect. B. Is metabolised to N-methyl-p-benzoisopuinonimine conjugated to glutathione: Wrong. Metabolised to N-acetyl-P-benzoquinoneimine. C. Toxic dose is 10 times the normal ?daily dose?: False. Toxic dose is only 2-3 times the daily adult dose. D. pKa 3.5: False. pKa of paracetamol is 9.5

Question 133

MD05 [Mar96] Aspirin: A. At low doses inhibits prostacyclin B. Reversibly inhibits lipoxygenase C. Irreversibly inhibits cycloxygenase D. Can cause asthmatic reactions

Answer 133

A. At low doses inhibits prostacyclin – No, it doesn’t inhibit prostacyclin – it inhibits its synthesis B. Untrue- Lipoxygenase pathway remains intact (page 283 Pharm&Physiol in Anesthetic Practice, Stoelting&Hillier 4th Edition). C. True- Aspirin irreversibly acetylates cyclooxygenase. D. Can cause asthmatic reactions - Yes. Aspirin induced asthma occurs in 8-20% of all asthmatic adults. The incidence is higher with accompanying sinus symptoms/nasal polyps. Though the lipoxygenase pathway is intact, blockage of cyclooxygenase causes a derangement of arachidonic acid metabolism with increased production of leukotrienes causing bronchospasm and possible hypotension. see above reference (in answer for B) Comment: Arachidonic acid is either metabolised into prostaglandins/prostacyclin via the COX pathway, or into leukotrienes via the lipo-oxygenase pathway (LOX). When the COX pathway is inhibited by NSAIDs, more arachidonic acid remains to enter the LOX pathway. This results in a relative excess of leukotrienes, which cause smooth muscle contraction in the bronchioles, and thus bronchospasm can occur as a result of NSAID use. I wonder whether the examiners chose C or D as correct one. Neither seems particularly "more" correct.

Question 134

MD06 [Mar97] [Jul97] [Jul99] [Feb00] Serotonin (5-HT) is most common in: A. Platelets B. Enterochromaffin cells C. Cerebral cortex (?neurones) D. Pineal gland E. GIT F. Mast cells

Answer 134

From Goodman&Gillman (9th ed): "Enterochromaffin cells in the mucosa appear to be the location of the synthesis and most of the storage of 5-HT in the body" Wiki says 90% body stores.

Question 135

MD07 [Mar97] [Jul97] [Jul98] [Mar99] [Feb00] Mannitol: A. Metabolised in the liver B. Half-life is proportional to GFR C. Increases Na+ D. Excretion is dependent on GFR E. Urine will be hyperosmolar compared to plasma F. Absorbed orally G. Isotonic H. Clearance dependent on GFR (see also [[CD17)

Answer 135

A. Metabolised in the liver - UNSURE B. Half-life is proportional to GFR - FALSE (recall t1/2 inversely proportional to clearance) C. Increases Na+ - UNSURE ("Osmotic diuretics increase the urinary excretion of nearly all electrolytes, including Na+, K+, Ca2+, Mg2+, Cl–, HCO3–, and phosphate" and "Extraction of water also causes hyponatremia" BUT "On the other hand, loss of water in excess of electrolytes can cause hypernatremia and dehydration" - all from Goodman and Gillman electronic edition) D. Excretion is dependent on GFR - likely correct (80% renal excretion, 20% biliary and metabolism according to table 28-3 in Goodman and Gillman) E. Urine will be hyperosmolar compared to plasma - likely false (urine is normally looks quite dilute after administration of mannitol; anecdotal evidence with n= F. Absorbed orally - FALSE ("mannitol and urea must be administered intravenously" - Goodman and Gilman electronic ed) G. Isotonic - likely FALSE (it draws water out of cells therefore hypertonic) H. Clearance dependent on GFR - likely correct (as per answer D)

Question 136

MD07b [Feb04] Mannitol: A. is a sugar and is not metabolised B. does not increase delivery of sodium to distal tubule C. ? D. ? E. ?

Answer 136

Stoelting p490 - not absorbed from the GIT - It is not metabolised and does not enter cells, its only means of clearance from the plasma is by glomerular filtration - Mannitol is filtered and not reabsorbed so increases osmolarity of renal tubular fluid and prevents reabsorption of water. Sodium is diluted in this retained water and so less is reabsorbed. Therefore there is an osmotic diuretic effect eith urinary excretion of water, sodium, chloride, and bicarb. Urinary pH is not altered. - Urine will be isotonic to plasma I think. Comment I disagree with urine being isotonic. The urine still meets with a progressively increasing gradient in the collecting ducts. Increased urine output does not mean change in urine osmolality per se. The increased renal tubular flow would have a wash out effect on the renal medullary gradient causing a decreased gradient. However, in the normal individual, urine should be hyperosmolar, unless of course there is minimal ADH acting on CD. In short, urine can still either be hypo/iso/hyper-osmolar Addit - only other thought is does isotonic refer to its original consitution, in which case it is definitely hyperosmolar.

Question 137

MD08 [Mar97] [Jul97] [Mar99] [Mar03] [Jul04] Gastric drugs: Which is true? A. Sucralfate is a mixture of sulphated sucrose and bismuth that sits in the ulcer B. Gastrin & acetylcholine directly & indirectly inhibit H+ secretion C. Misoprostil decreases gastric acid and causes marked constipation D. Pirenzipine is less effective than H2 blockers E. Omeprazole reversibly inhibits proton pump

Answer 137

From Goodman & Gillman 9th Edition: A. False - sulphated sucrose and Al(OH)3 B. False - enhance H+ secretion C. False - although decreases gastric acid, causes diarrhoea D. True E. False - irreversibly inhibits: "The activated form then binds covalently with sulfhydryl groups of cysteines in the H+,K+-ATPase, irreversibly inactivating the pump molecule. Acid secretion resumes only after new pump molecules are synthesized and inserted into the luminal membrane, providing a prolonged (up to 24- to 48-hour) suppression of acid secretion, despite the much shorter plasma half-lives (0.5 to 2 hours) of the parent compounds" - from Goodman and Gillman Ch36 Note. Pirenzipine is an M1 Muscarinic Antagonist References Peck states that PPi's REVERSIBLY block K/H ATPase pump in the parietal cells PECK IS WRONG aditional,i agree with the prior statement,mims also agrees on reversible. Both Evers and Maze (p766) and G&G state irreversible inhibition of the proton pump. And unlike Peck, they're both recommended texts...

Question 138

MD09 [Mar97] [Feb00] A decrease in renal function might be expected with: A. Gentamicin B. Cis-platin C. Busulphan D. Methotrexate E. All of the above

Answer 138

A decrease in renal function might be expected with: A. Gentamicin - TRUE ("Nephrotoxicity is usually reversible and mild. It occurs in 5–25% of patients receiving gentamicin for longer than 3–5 days." - Lange Pharmacology online edition Ch 45) B. Cis-platin - TRUE ("Cisplatin-induced nephrotoxicity has been largely abrogated by adequate pretreatment hydration and diuresis." - Goodman and Gillman Ch 51) C. Busulphan - UNSURE but likely FALSE (No mention in Goodman and Gillman Ch 51: "The major toxic effects of busulfan are related to its myelosuppressive properties, and prolonged thrombocytopenia may be a hazard. Occasional patients experience nausea, vomiting, and diarrhea. Long-term use leads to impotence, sterility, amenorrhea, and fetal malformation. Rarely, patients develop asthenia and hypotension, a syndrome resembling Addison's disease, but without abnormalities of corticosteroid production. High-dose busulfan causes veno-occlusive disease of the liver in up to 10% of patients, as well as seizures, hemorrhagic cystitis, permanent alopecia, and cataracts. The coincidence of veno-occlusive disease and hepatotoxicity is increased by its coadministration with drugs that inhibit CYPs, including imidazoles and metronidazole, possibly through inhibition of the clearance of busulfan and/or its toxic metabolites") MIMS: Busulphan (renal & urinary disorders) Common: creatinine elevated, dysuria, oliguria. Common: blood urea nitrogen (BUN) increased, haematuria, moderate renal insufficiency. D. Methotrexate - TRUE ("Additional toxicities of methotrexate include alopecia, dermatitis, interstitial pneumonitis, nephrotoxicity, defective oogenesis or spermatogenesis, abortion, and teratogenesis." E. All of the above - UNSURE: this question is likely to have been remembered incorrectly. IF another drug other than busulphan were the answer to C, the likely most correct answer will be E.

Question 139

MD10 [Mar97] [Jul02] Thrombocytopaenia is a side-effect of which ONE of the following: A. Busulphan B. Cis-platin C. Methotrexate D. All of the above E. ?

Answer 139

Thrombocytopaenia is a side-effect of which ONE of the following: A. Busulphan - TRUE ("The major toxic effects of busulfan are related to its myelosuppressive properties, and prolonged thrombocytopenia may be a hazard" Goodman and Gilman Ch 51) B. Cis-platin - TRUE ("Cisplatin causes mild-to-moderate myelosuppression, with transient leukopenia and thrombocytopenia." C. Methotrexate - TRUE ("The primary toxic effects of methotrexate and other folate antagonists used in cancer chemotherapy are exerted against rapidly dividing cells of the bone marrow and GI epithelium. Mucositis, myelosuppression, and thrombocytopenia reach their maximum in 5 to 10 days after drug administration, and except in instances of altered drug excretion, reverse rapidly thereafter" Goodman and Gilman Ch 51) D. All of the above - TRUE - very likely if all are cytotoxics then they will cause thrombocytopaenia as these drugs will affect high turnover cells. E. ?

Question 140

MD11 [Jul97] [Jul98] [Jul99] Theophylline levels increased with: A. Smoking B. Phenytoin C. Cimetidine D. ?

Answer 140

Elimination half-time of theophylline is decreased in smokers (Stoelting 3rd ed p285), so levels will decrease. Clearance of theophylline is increased nearly twofold during administration of phenytoin (p676 Goodman & Gillman 9th ed) Cimetidine inhibits cytochrome p450 and can increase levels of drugs that are substrates for this, such as theophylline (p1011 Goodman & Gilman 10th ed). Answer is C.

Question 141

MD13 [Jul97] [Feb00] When a beta agonist binds to protein G: A. There is a fall in cAMP B. The signal is amplified 108 times

Answer 141

Several sources indicate that the wording on the paper in July 97 was as above but this was an error by the examiner. A beta-agonist does not bind directly to the G protein but binds to a G-protein coupled receptor. When used again on the Mar 2000 paper, the question had been corrected to read: “When a ligand binds to a receptor linked to a G-protein: “) (see also EM18 in Physiol MCQs) When a beta agonist binds to protein G: A. There is a fall in cAMP - FALSE: beta agonists normally increase cAMP (Ganong table 1-6) B. The signal is amplified 108 times - UNSURE but probably TRUE: G-protein coupled receptors generally amplify the signal

Question 142

MD14 [Jul97] [Apr01] Dantrolene: A. Is a benzyl-isoquinoline derivative B. Undergoes oxidative and reductive metabolism C. Inhibits sodium channel activation D. Causes a marked reduction in contractility E. Not effective as prophylaxis because of poor oral bioavailability F. Acts via ryanodine receptor

Answer 142

MD14 A false - it is a "hydantoin derivative"[1]. Dantrolene looks nothing like a benzylisoquinoline alkaloid (compare the structures Fig 3-2 p.78 and 33-8 p.529 StoeltPP3rd) FYI: "The principle benzylisoquinoline alkaloids present in opium, which lack opioid activity, are papaverine and noscapine" (StoeltPP3rd p.77) "Neuromuscular-blocking drugs are either benzylisoquinolinium compounds or aminosteroid compounds" StoeltPP3rd p.182 They would appear to be the "curiums" such as atracurium, mivacurium, etc. B no idea - "Dantrolene is metabolised in the liver, principally to 5-hydroxydantrolene" StoeltPP3rd p.529 C false - Acts by "decreasing the amount of calcium released from the sarcoplasmic reticulum" StoeltPP3rd p.529 D false - "Therapeutic doses have little or no effect on cardiac and smooth muscles" StoeltPP3rd p.529 E false - "Prophylaxis ... may be with oral administration" "Pharmacology and Physiology in Anesthetic Practice", R. K. Stoelting and S. C. Hillier, 3rd ed, Lippincott-Raven, 1999. p.530) F true - "Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic reticulum, an essential step in muscle contraction"[2] and dantrolene is a "clinically used antagonist"[3]

Question 143

Alt version: Dantrolene: A. Benzylisoquinolonium B. Undergoes hepatic and renal metabolism C. Profound myocardial depression D. Poor oral bioavailability

Answer 143

Alt version A false - see above B ?false - see above and "Less than 1% of dantrolene appears unchanged in urine" StoeltPP3rd p.529 C false - see above D ?false - may have poor oral bioavailability BUT it is still used orally to prevent malignant hyperthermia. Best answer: D Intravenous administration of dantrolene 2.4 mg/kg results in plasma concentrations of 4.2 μg/mL, which blocks up to 75% of skeletal muscle contraction. Dantrolene inhibits release of calcium from intracellular storage in the sarcoplasmic reticulum of skeletal muscle. It acts at the interface between the T-tubular system and sarcoplasmic reticulum. The exact mode of dantrolene's action is not completely understood, though recent studies have identified the ryanodine receptor as a dantrolene-binding site. Answer F is unlikely to be correct, since it is still not clear whether a direct or indirect inhibition of the ryanodine receptor is ultimately responsible for dantrolene's action in decreasing intracellular calcium concentration. Calcium reuptake is not affected. Dantrolene is a phenyl hydantoin derivative. Hence answer A incorrect. Dantrolene metabolism is via hydroxylation, reduction and acetylation in the liver. Hence answer B incorrect. Dantrolene inhibits calcium ion release. So answer C incorrect. Oral bioavailability is relatively high, with about 70% of an oral dose absorbed, but this does vary widely. Hence E incorrect. The answer to C depends on the wording of the option: referring to cardiac or skeletal. It makes sense less Ca2+ = less contractility and if I remember correctly flaccidity on waking is a side effect on dantrolene. Comment: I hate these oxidation/reduction/hydroxylation options. From Goodman & Gilman 12e Table 6-2: Oxidative reactions include N- and O-dealkylation, hydroxylation, N- and S-oxidation and deamination. This means that Dantrolene, which has a hydroxylated metabolite, undergoes oxidative and reductive metabolism and that B is correct in the 1st version of the question. References Krause et al. (2004). Dantrolene – A review of its pharmacology, therapeutic use and new developments. Anaesthesia. Volume 59 Page 364, April. Halsall and Hopkins. (2003). Malignant hyperthermia. British Journal of Anaesthesia. Volume 3 (1), Page 5. Sasada and Smith. Drugs in anaesthesia and intensive care. 3rd edition, Oxford University Press, 2003. Page 86.

Question 144

MD15 [Jul97] Omeprazole: A. Irreversibly inhibits the parietal cell B. Acts at apical membrane of parietal cell C. Acts at the basolateral membrane of the parietal cell

Answer 144

A- Omeprazole does bind irreversibly. The long lasting binding is only overcome by the synthesis of new pump molecules. The CELL is not inhibited however - only the pump. B- Yes, this is the luminal side where the proton pump (H/K ATPase) is located which is the final common pathway of H secretion C- Basolateral membrane is where ACh, Histamine, Gastrin signal H+ secretion (pre proton pump) and NOT where omeprazole has effect. ..As per mims the action is reversible. References & related material Rang,Ritter & Dale / "Drugs in Anaesthesia & Intensive Care" -Sasada & Smith J Physiol Pharmacol. 2001 Dec;52(4 Pt 1):639-56. "Pharmacological regulation of gastric acid secretion in the apical membrane of parietal cells; a new target for antisecretory drugs." Okabe S, Shimosako K, Amagase K.

Question 145

MD16 [Mar98] Diclofenac: A. Plasma protein binding is ....% B. Percent absorption . . % C. Mechanism of action via increase in endorphins D. ?

Answer 145

From Goodman & Gillman (9th ed): Plasma protein binding 99%, Significant first pass metabolism only 50% available systemically Comment: disagree with this. The dose PO would be different if it underwent first pass metabolism and it isn't. It is not a discussion point in Rang, Katzung, Stoelting, BNF or Mims. Another comment: All well and good to reference books that don't answer the question, but Smith (Drugs in Anaesthesia and Intensive Care) does answer it: bioavailability 60%. Also, it's in Goodman & Gilman which is a prescribed text, so this clears it up: "There is a substantial first-pass effect, such that only 50% of diclofenac is available systemically." Acts via inhibition of cyclooxygenase decreasing prostaglandin production

Question 146

MD17 [Mar98] [Apr01] [Jul04] Regarding phenytoin A. Acts via blockade of Na channels and via effect on K channels B. Weak base with pKa 8.3 C. Has active metabolites D. ? E. ?

Answer 146

A: No Phenytoin acts on Na+ channels blocking the inward membrane current and preferentially acting on repetitively firing cells. It does NOT act on K+ Channels B: No Its pKa is 8.3 but is a weak ACID C: No it does NOT have active metabolites. Phenytoin has membrane stabilising activity and slows inwad Na and Ca influx during depolarization in excitable tissue; it also delays outward potassium efflux. Therefore A correct. Sassada and smith pg 308 References & related material "Formation of active metabolites of anticonvulsant drugs. A review of their pharmacokinetic and therapeutic significance." Eadie. Clin Pharmacokinet 1991 Jul;21 (1):27-41 "Drugs in Anaesthesia & Intensive Care" - Sasada & Smith Pharmacology - Rang, Ritter & Dale Interesting article that suggests phenytoin blocks K+ channels [1]

Question 147

MD18 [Mar98] [Mar99] [Feb00] [Apr01] [Jul02] [Mar03] Which ONE of the following decrease gastric pH? A. Omeprazole B. Famotidine C. Calcium salts D. Misoprostil E. PGE2

Answer 147

Which ONE of the following decrease gastric pH? A. Omeprazole - false (increases pH) B. Famotidine - false (increases pH) C. Calcium salts - potentially true (see Goodman and Gilman fig 36-1: Ca dependent pathway stimulating H/K/ATPase) D. Misoprostil - false (increases pH) E. PGE2 - false (increases pH)

Question 148

July 2000, 2002 and 2003 version : Which ONE of the following decreases gastric acid secretion?: A. ? B. Misoprostil C. Cisapride D. Na citrate E. Metoclopramide

Answer 148

July 2000, 2002 and 2003 version : Which ONE of the following decreases gastric acid secretion?: A. ? B. Misoprostil - TRUE C. Cisapride - FALSE D. Na citrate - FALSE E. Metoclopramide - FALSE

Question 149

Apr 2001 version: Decrease gastric pH: A. Calcium salts B. H2 antagonists (?ranitidine) C. Omeprazole D. Pirenzipine E. PGE2

Answer 149

Decrease gastric pH: A. Calcium salts - TRUE see above B. H2 antagonists (?ranitidine) - false C. Omeprazole - false D. Pirenzipine - false E. PGE2 - False Miller ('25) found that the gastric pH was lowered from. 3.85 to 3.23. ..... parathormone, or the injection of Ca salts, depresses gastric acid secretion

Question 150

MD19 [Jul98] [Mar99] [Feb00] [Jul01] [Jul04] NSAIDs: A. Exhibit no selectivity for COX 1 & 2 B. Exert renal effects other than effect on afferent arterioles C. Cause renal toxicity separate to inhibition of prostaglandins D. Aspirin & ketorolac irreversibly bind COX1 & 2 E. Directly cause gastrointestinal ulceration Alt version: NSAIDs: A. All inhibit COX 1 B. Aspirin and ketoralac inhibit COX irreversibly C. They can cause renal toxicity by mechanisms other than alterations in renal blood flow by PG mediators.

Answer 150

toelting p 281 4Ed A false - COX 2 Selective NSAIDs do exhibit selectivity (inhibiting COX2 not COX1). B maybe - Prostaglandins participate in autoregulation of renal blood flow and GFR and also influence the tubular transport of ions and water. So for B - NSAIDs exert effects by inhibiting production of PGs which have more than just afferent art. effects. So B is indirectly true. C true - Nonselective NSAIDs interfere with production of vasodilating prostaglandins and may result in decreases in GFR and Na+ retention manifesting as systemic hypertension and oedema. "When renal toxicity does manifest it is likely due to NSAID induced inhibition of PG synthesis leading to renal medullary ischemia." (StoeltPP3rd p.249) However can also get Tubulointerstitial nephritis caused by NSAIDs (analgesic nephropathy) --\> chronic nephritis and renal papillary necrosis. Phenacetin originally assoc. I am not sure of the exact mechanism of this though. Phenylbutazone causes significant Na+ retention due to reversible direct effect on renal tubules. D false - Aspirin inhibits irreversibly, Ketorolac does not. E false - GIT irritation is indirect via PG inhibition via inhibition of COX1. References ("Pharmacology and Physiology in Anesthetic Practice", R. K. Stoelting and S. C. Hillier, 3rd ed, Lippincott-Raven, 1999. p.249)

Question 151

MD20 [Jul98] [Mar99] Irreversible cardiomyopathy can be due to: (OR: Which of the following causes dose-dependent cardiac toxicity?) A. Vincristine B. Bleomycin C. Danorubicin D. Asparaginase E. Cyclophosphamide F. All of the above

Answer 151

Best answer is C - Danorubicin as per Tables 55-2, 55-4 and 55-6 in "Basic & Clinical Pharmacology", B. G. Katzung, 9th ed., McGraw-Hill, 2003. pp. 905, 912 and 918 Irreversible cardiomyopathy can be due to: (OR: Which of the following causes dose-dependent cardiac toxicity?) A. Vincristine - FALSE: "clinical toxicity is mainly neurological" Goodman and Gilman ch 51 B. Bleomycin - FALSE: significant cutaneous toxicity, most serious adverse reaction is pulmonary toxicity Goodman and Gilman Ch 51 C. Danorubicin - TRUE: "Cardiac toxicity is a peculiar adverse effect observed" Goodman and Gilman D. Asparaginase - FALSE: "Its most serious toxicities result from its antigenicity as a foreign protein" Goodman and Gilman Ch 51 E. Cyclophosphamide - FALSE: mainly nausea and vomiting, ulceration, skin pigmentation, pulmonary fibrosis according to Goodman and Gilman F. All of the above - FALSE From Goodman & Gillman 9th Ed Daunorubicin - cardiomyopathy (-\>congestive failure) is a unique characteristic of the anthracycline antibiotics (daunorubicin, doxorubicin & Idarubicin) (See Doxorubicin toxicity) Vincristine - ischemic cardiac toxicity has been reported Bleomycin - pulmonary toxicity the issue, although coronary artery disease has been reported Asparaginase / Cyclophosphamide - no mention of cardiac toxicity 5FU and its prodrugs are associated with coronary vasospasm.

Question 152

MD21 [Jul98] [Jul99] [Mar02] Streptokinase: A. Acts on circulating plasmin (F) B. When administered IV causes increased blood pressure? (T) C. Is significantly more efficacious in preventing mortality if given within 1 hour of onset of chest pain, compared with being given within 3-6 hours? (T) D. Is significantly more effective in preventing death from MI when used in combination with aspirin? (T) E. Is not useful in treatment of lower limb DVT? (F)

Answer 152

A false - Streptokinase acts on plasminogen, the precursor to produce plasmin. B false - Intravenous administration has been shown to reduce blood pressure and total peripheral resistance. C true - The reduction in mortality when using streptokinase is time dependent. The GISSI study demonstrated a 47% reduction in mortality if streptokinase was given within one hour of the onset of chest pain, 23% reduction if treated within three hours, and 17% reduction if treated between three and six hours from onset of symptoms. These differences are statistically significant. D true (I think most correct)- The ISIS-2 study showed that reduction in the odds of death in patients treated within four hours was 53% for the combination of Streptokinase and aspirin, and 35% for Streptokinase alone. In addition, the reduction was still significant when treatment was started 5-24 hours after symptom onset: 33% for the combined therapy and 17% for Streptokinase alone. E false - A comprehensive review of the English literature evaluating streptokinase (SK) in the treatment of deep venous thrombosis (DVT) of the lower extremity reveals complete lysis of thrombi in as many as 70% of patients studied. The degree of lysis is affected by duration of symptoms before treatment, degree of occlusion, thrombus location, and development of a plasma proteolytic state. SK-treated patients have not been found to have a greater incidence of major hemorrhagic complications when compared with heparin-treated patients. SK is clearly beneficial in the treatment of DVT if patients are properly selected and carefully managed. Proper patient selection and a recommended treatment protocol are described (Am J Med. 1990 Apr;88(4):389-95). Note: In the original question, EACA was mentioned, ? antagnoist to streptokinase. (Epsiolon- )Aminocaproic acid is a competitive inhibitor of activation of plasminogen, thereby reducing conversion of plasminogen to plasmin. Aminocaproic acid also directly inhibits plasmin activity, but higher doses are required than are needed to reduce plasmin formation. Therefore, EACA does competitively antagonise streptokinase. (Additionally: Aminocaproic acid is used to treat severe hemorrhaging caused by thrombolytic agents such as alteplase (tissue-type plasminogen activator), streptokinase, or urokinase, however, the efficacy of this therapy in humans remains unproven).

Question 153

MD22 [Mar99] [Apr01] [Mar03] Gastric lavage: A. Not useful if more than one hour has elapsed B. In children, use normal saline instead of water C. Contraindicated if poison corrosive D. Is performed in the right lateral position E. Should not be performed in the unconscious

Answer 153

A. False - may be useful for as long as 24hrs after ingestion B. True - increase risk of water intoxication if use water C. True (and probably most correct) - as is emesis D. False - should be performed in left lateral position E. False - can be performed in the unconscious as long as airway is secured

Question 154

MD23 [Mar99] [Apr01] Long term prednisolone 20mg/day will result in: A. Increased lymphocyte count B. Increased capillary permeability C. Metabolic alkalosis D. ??glucose E. ?

Answer 154

A true - "tend to increase the... number of circulating leukocytes" (Stoelting 3rd ed p.422); but also false in the acute setting as they will decrease circulating lymphocytes (p.422 also) B no idea C most correct - "hypokalaemic metabolic alkalosis reflects mineralocorticoid effects of corticosteroids on distal renal tubules" (Stoelting p.421) D will mess with glucose as they "inhibit the use of glucose in peripheral tissues" (Stoelting p.421) i disagree with A as per mims "Haematological. Corticosteroids will increase the total white blood cell count, with an increase in neutrophils and a decrease in monocytes, lymphocytes and eosinophils". in practice - tend to see a neutrophilia with lymphopenia, therefore A = incorrect

Question 155

MD24 [Mar99] NSAIDs cause gastric side-effects by: A. Direct effects on mucosa B. Indirect effects C. ?

Answer 155

B is true. Inhibit PG production Indirect actions due to decreased PG's Decreased mucosal blood flow Decreased protective mucus / bicarbonate layer increased gastric acid production

Question 156

MD25 [Mar99] Phenylbutazone: A. Interferes with heparin metabolism B. Increases warfarin plasma concentration C. Decreases warfarin plasma concentration D. Reduces the elimination of warfarin

Answer 156

Stoelting 287 Phenylbutazone displaces drugs including warfarin, oral hypoglycaemics and sulfonamides. Increased bleeding occurs with coadministration of warfarin or aspirin. Warfarin predominantly bound to albumin (99% PB - Sasada & Smith p396) so in the first question B seems correct, with the second A, C. Stoelting 4th ed p513 also says that phenylbutazone inhibits metabolic clearance of warfarin leading to increased plasma levels & potentiates its anticoagulant effect.So B is also true for July 2000 version. Phenylbutazone is used as a non-steroidal anti-inflammatory drug (NSAID) for the treatment of chronic pain, including the symptoms of arthritis. Its use is limited by such severe side effects as suppression of white blood cell production and aplastic anemia.

Question 157

July 2000 version: Phenylbutazone's effect on the coagulation system are due to: A. Binding to albumin, displacing warfarin B. Inhibiting warfarin metabolism C. ? some interaction with aspirin D. ? effect on platelets

Answer 157

Stoelting 287 Phenylbutazone displaces drugs including warfarin, oral hypoglycaemics and sulfonamides. Increased bleeding occurs with coadministration of warfarin or aspirin. Warfarin predominantly bound to albumin (99% PB - Sasada & Smith p396) so in the first question B seems correct, with the second A, C. Stoelting 4th ed p513 also says that phenylbutazone inhibits metabolic clearance of warfarin leading to increased plasma levels & potentiates its anticoagulant effect.So B is also true for July 2000 version. Phenylbutazone is used as a non-steroidal anti-inflammatory drug (NSAID) for the treatment of chronic pain, including the symptoms of arthritis. Its use is limited by such severe side effects as suppression of white blood cell production and aplastic anemia.

Question 158

MD26 [Jul98] [Jul99] With respect to prednisone: A. Prednisone is converted to active prednisolone in the gut B. Prednisone 5mg is equivalent to 100mg cortisol C. Betamethasone has equivalent mineralocorticoid activity D. Methylprednisolone ? Alternative version of options A & E: A. Prednisone is converted to prednisolone after absorption from the gut. E. Betamethasone has adrenocorticoid and mineralocorticoid activity

Answer 158

Most correct answer A in both choices: Prednisone is "rapidly converted to prednisolone after its absorption from the GIT" (Stoelting p.416) Prednisone is converted to active drug prednisolone in the liver. B - 5mg prednisone = 20mg Hydrocortisone/ Cortisol C - Betamethasone has no mineralocorticoid activity. Comment: the above doesn't make sense: absorption in the gut, biotransformation in the liver: doesn't that make the option of "biotransformation in the gut" wrong?

Question 159

MD27 [Jul98] [Jul99] [Jul00] Aspirin: A. Greatest absorption is from the stomach B. Peak plasma level is achieved in 30]] minutes C. Has cross-reactivity with all NSAIDs D. Half-life 4 hours

Answer 159

A. False: most absorption is from the small intestine, less from the stomach B. True: Peak serum concentrations (of salicylate, aspirin's rapid first pass metabolite) occur within 0.25 to 2 hours (Anesthetic Pharmacology, Evers&Maze, 2004, p939) C. True - "cross-react(ivity) to all inhibitors of prostaglandin synthesis." (Stoelting p.253) D. False - The plasma half life of aspirin is 15 minutes, however the plasma half life of salicylate that of 2-12 hours (dose dependent). (Anesthetic Pharmacology, Evers&Maze, 2004, p939). ie brief pharmacokinetic half-life, but long pharmacodynamic half-life. I don't think B is true as it is asking about aspirin not salicylic acid. The plasma half life of aspirin is 15-20 min so peak concentrations of aspirin must be much less than that. Also both Goodman & Gilman and Kazung says peak salicylic acid plasma concentration occurs in 1-2 hrs.

Question 160

July 2000 version: Aspirin: A. Plasma half-life 4 hrs B. Peak plasma concentration within 10mins of oral administration C. Requires conversion to salicylic acid for activity D. ? is more ?? than salicylic acid E. Better absorption if food in stomach F. Cross reactive sensitivity with all NSAIDs

Answer 160

see above for A, B, F C. False: Aspirin has more pharmacologic activity than salicylate E. False. The reasoning for dosage with meals for aspirin and other NSAIDS is to reduce the incidence of GI effects

Question 161

MD28 [Jul98] [Mar03] Organophosphates: A. Phosphorylate the esteratic site B. Phosphorylate the anionic site C. ? D. ? (See also MB11, MB27)

Answer 161

Organophosphates phosphorylate the esteratic site of acetylcholinesterase (p183 2nd ed Peck & Williams).

Question 162

MD29 [Mar99] [Feb00] Warfarin affects: A. Factor XIII B. Protein S (? or Protein C) C. ?

Answer 162

Warfarin acts by inhibiting the enzymes Vitamin K Epoxide Reductase and Vitamin K Reductase. This prevents the formation of the reduced form of Vitamin K (hydroquinone) which acts as a cofactor in the gamma-carboxylation of glutamic acid residues in Clotting Factors II, VII, IX and X as well as anticoagulant Proteins C and S. Gamma carboxylation is necesary for the biological activity of these factors as it confers Ca++ binding properties that are essential for their catalytic action. Inhibition by Warfarin is competitive, reflecting the structural similarity between Warfarin and Vitamin K. Answer: B - Protein S or C. References Pharmacology - Rang and Dale 5th ed. Basic and Clinical Pharmacology - Katzung.

Question 163

MD30 [Jul99] [Feb00] Bleomycin A. Related to nitrogen mustard B. Can cause agranulocytosis (or: frequently causes myelosuppression) C. Causes pulmonary toxicity in 90% of patients D. Is an alkylating agent E. Causes pulmonary oxygen toxicity due to production of superoxide radicals

Answer 163

Bleomycin is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus. Bleomycin probably induces lung toxicity through the induction of oxygen radicals, with recruitment of leukocytes and fibroblasts augmenting the early inflammatory and later fibrotic reactions (Ref: Clin Chest Med 11: 21-30, 1990) it causes pulmonary toxicity in about 4% of patients (Stoelting) Bleomycin and vincristine differ from the other chemotheraputic agents in that they do not cause myelosuppression (pharm at a Glance) It is not an alkylating agent nor related to nitrogen mustard correct answer: E

Question 164

MD31 [Jul99] Which drug causes the most anaphylaxis? A. Suxamethonium B. High potency non-depolarisers C. ? D. ?

Answer 164

Faunce 290 Sux has the greatest incidence of histamine release (no numbers) others are atracurium, mivacurium and alcuronium in descending order. A. Better be careful reading this question in future - as the frogs have shown Roc accounts for more anaphylaxis than sux. Then again it's "low" potency

Question 165

MD32 [Jul99] [Jul04] Syrup of Ipecac A. Is not effective in phenothiazine overdose B. Has peripheral irritant and direct CTZ action C. The syrup is more potent than the fluid D. ?

Answer 165

Per Goodman&Gillman 9th Ed A. false - may be effective even when antiemetic drugs such as phenothiazines have been ingested B. True - local irritant on GI tract + effect on CTZ C. False - fluid 14x more potent

Question 166

MD33 [Feb00] Regarding antiemetics which drug has anti-5HT3, anti-H1 and anti-D2 actions: A. Ondansetron B. Scopalamine C. Domperidone D. Droperidol E. Prochlorperazine F. Chlorpromazne Also remembered as: Which of the following anti-emetics have D2, ACh, 5 HT-3 antagonist effects? Which drug is a D2 antagonist, H1 antagonist and 5HT3 receptor antagonist?

Answer 166

F. Chlorpromazine - Antagonist at D2, muscarinic, alpha1&2, H1, 5HT receptors as per Peck,Hiil&Williams 2nd ed

Question 167

MD34 [Jul99] [Feb00] With regard to nitric oxide: A. It is anaesthetic at high concentration B. May improve V:Q mismatch C. Is a liquid in the cylinder, gas at room temperature D. ?

Answer 167

May improve V:Q mismatch A. NITROUS oxide is an anaesthetic gas of low potency and low blood solubility. It has a MAC of 104 (at 37 degrees, 760mmHg for 30-55years old). [Pharm and Phys in Anesth. Practice, Stoelting, 3rd] B. NITRIC oxide is an endogenously produced vasodilator and acts as a chemical messenger in many systems - cardiovascular tone, platelet regulation, CNS signaling, GIT smooth muscle relaxation, immune regulation, and possible as an effector for volatile anaesthetic agents. It diffuses into target cells and activates guanylate cyclase to increase cGMP. Half-time is less than 5 seconds and it is avidly bound and deactivated by haemaglobin. In the pulmonary system, it may contribute to bronchodilation and to selective dilatation of blood vessels supplying ventilated segments. [Pharm and Phys in Anesth. Practice, Stoelting, 3rd] C. NITROUS oxide is stored in cylinders as a liquid under pressure at room temperature. The vapour form is inequilibrium with the liquid phase, and a 4.7L E cylinder contains about 85% liquid N2O, which can supply around 1500L of gas. [Evers and Maze, Anesth. Pharm.] if the Q was totally about nitrous oxide so the best answer would be c. Reference Peck Hill & Williams 2nd Ed

Question 168

MD35 [Feb00] [Jul01] [Jul06] Ethanol A. About 35% excreted via the lungs B. Concentration falls at a fixed rate with respect to time C. Only 60% is metabolised, the remainder being excreted in expired air D. Is excreted at a rate independent of the plasma concentration E. Constant elimination independent of plasma concentration F. Elimination is independent of the rate of absorption from the GIT

Answer 168

90-98% metabolised, mainly by liver zero order kinetics - constant amount per unit time Therefore E per Goodman&Gillman 11thed B, D and F would apply for 0 order kinetics too. From Rang & Dale, 3rd ed., p 658, it says that 'because the rate of hepatic metabolism of ethanol shows the property of saturation at quite low ethanol concentrations, the fraction of ethanol removed is greatest when the concentration is low, and decreases as the concentration increases. Thus, if ethanol absorption is rapid and portal vein concentrations high, most of the ethanol escapes into the systemic circulation, whereas with slow absorption, more is removed by first-pass metabolism.' Kazung says ethanol exhibits capacity limited elimnination (also phenytoin)so that clearance will vary depending on the concentration of drug that is achieved. Also called saturable-, dose- or concentration-dependent, nonlinear, and Michaelis-Menton elimination. When concentration is high relative to Km (the drug concentration at which the rate of elimination is 50% of Vmax), it becomes "pseudo-zero order" so that elimnination rate becomes almost independent of concentration.

Question 169

MD36 [Feb00] Which drugs cause convulsant activity? A. Cocaine B. Lithium C. Norpethidine D. Enflurane E. All of the above

Answer 169

All of the above - Goodman & Gillman 11th ed

Question 170

MD37[Feb00] Metoclopramide A. Increases gastric emptying faster with an oral dose than an IV dose B. Causes diarrhoea in children C. Is a dopamine agonist D. ?

Answer 170

Gastric emptying is a known effect of metoclopramide, and I couldn't find a specific study looking at oral v IV, however, the 'onset of action' of oral is 30-60min, compared with 1-3 min for IV, suggesting that (A) is false. Diarrhoea is a known side-effect in children Metoclopramide is a dopamine receptor antagonist

Question 171

MD38[Feb00] [Jul00] Physostigmine A. Causes (? excitatory activity / ?alerting response) on the EEG B. Doesn’t cross the blood brain barrier C. Doesn’t cause sedation D. Only has its effects at nicotinic receptors E. Causes amnesia F. Causes excitatory activity on the EEG G: Is/isn’t a quaternary ammonium that does/doesn’t cross BBB

Answer 171

A and F correct - "In low concentrations, the lipid soluble cholinesterase inhibitors cause diffuse activation on the EEG and a subjective alerting response" (Katzung 9th ed. p.103) Its a tertiary amine, crosses BBB, may precipitate seizures so not used now (previously was used in TCA overdose) References Goodman & Gillman 11th Ed Katzung 9th ed. p103

Question 172

MD39[Jul00] Drugs filtered and secreted in the PCT include: A. Penicillin B. Probenecid C. Chlorothiazide D. ?

Answer 172

MD39 A ?Correct - "Penicillin is reapidly excreted by the kidneys into the urine... about 10% of renal excretion is by glomerular filtration and 90% by tubular secretion" (Katzung 9th ed p.738 and almost identical in Stoelting p468) B ?correct - "In the kidneys it is filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule. Probenecid's exact mechanism of action in the kidneys' nephrons is unknown."[1] C ?dunno - Chlorothiazide is a thiazide diuretic

Question 173

Also remembered as: Which basic drug is secreted by the kidney for excretion? A. Procainamide B. Probenecid C. Penicillin D. Acetazolamide

Answer 173

Alternative A - Procainamide is hepatically metabolised by CYP2D6 (?source) B - see above C - see above D ?dunno - carbonic anhydrase inhibitor acting at the proximal tubule Penicillin is an acidic drug and Probenecid competes for it at the PCT for excretion to increase plasma levels. So I think the answer is acetazolamide if the question has been remembered correctly. Agree. Probenecid, penicillins, chlorothiazide (not a loop - it's a thiazide) all acids. So for alt. version must be A or D, procaine is a base so by elimination must be D?? Couldn't find anywhere whether acetazolamide is an acid or base (any chemists out there??). Thiazides can inhibit tubular secretion of urate and precipitate gout, so presumably they compete with the transporter for secretion?? Procainamide is an analogue of Procaine so it could very well be a weak base. Also, Procainamide is excreted by the kidneys and metabolised by the liver. 'In humans, 40% to 60% of procainamide is excreted unchanged by the kidneys' (Stoelting, 4th ed., 0 376). So we're still left with A and D with the alt. version... just can't find anything about acetazolamide though... Regarding acetazolamide: "The pH of a suspension 1g Acetazolamide in 50 ml water is 4.0 to 6.0 (McEvoy, 1995)." [[2]] And procainamide "A 10% solution in water has a pH of 5 to 6.5"[[3]] Procainamide is a weak base (it is derived from the LA procaine). http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list\_uids=8564238&dopt=Abstract Elimination occurs via both glomerular filtration & active tubular secretion (Mims) Probenecid & penicillin are both acids that undergo glomerular filtration & active tubular secretion (Mims, Stoelting) Acetazolamide is a weak acid with pKa 7.2 (Mims), not sure about its elimination. The best answer should be procainamide.

Question 174

MD40 [Jul00] Which of the following is bacteriostatic only? A. Penicillin B. Gentamicin C. Vancomycin D. Trimethoprim E. ?Cefoxitin /?cefuroxime

Answer 174

Beta-lactams, gentamicin & vancomycin are mostly bacteriocidal; sulpha drugs & trimethoprim are mostly bacteriostatic. Trimethoprim - Goodman&Gillman 11th ed

Question 175

MD41[Jul00] With respect to serotonergic receptor action, which ONE of the following is true? A. Sumiatriptan is a 5HT1 antagonist B. Ondansetron is a 5HT3 agonist C. ?Serotonin is a 5HT3 agonist D. Metoclopramide is a 5HT4 agonist E. ?

Answer 175

With respect to serotonergic receptor action, which ONE of the following is true? A. Sumiatriptan is a 5HT1 antagonist - false B. Ondansetron is a 5HT3 agonist - false C. ?Serotonin is a 5HT3 agonist - true D. Metoclopramide is a 5HT4 agonist - true E. ? Sumatriptan - 5HT1 agonist Ondansetron - 5HT3 antagonist Metoclopramide - 5HT3 antagonist (Rang & Dale 7E table 15.1 p197: Metoclopramide is a 5HT4 AGONIST) Serotonin - 5HT agonist References Goodman & Gillman 11th ed Table 16-3 in Katzung 9th ed. p.270

Question 176

MD41b Which is not a serotonin receptor antagonist A. sumatriptan B. ondansetron C. ketanserin D. cyproheptadine E. clozapine

Answer 176

MD41b Which is not a serotonin receptor antagonist A. sumatriptan -true 5HT1 Agonist B. ondansetron - false 5HT3 Antagonist C. ketanserin - false 5-HT2 anatagonist & affinity for α1 & H1 D. cyproheptadine - false 5-HT2 antagonist amongst others (AChM1-5, D3& H1,5-HT1, α1, α2, 5HT6, 5HT7, D1, D2 & 5HT3) E. clozapine - false 5HT2 antagonist Sumatriptan - 5HT1 agonist Ondansetron - 5HT3 antagonist Metoclopramide - 5HT3 antagonist (Rang & Dale 7E table 15.1 p197: Metoclopramide is a 5HT4 AGONIST) Serotonin - 5HT agonist References Goodman & Gillman 11th ed Table 16-3 in Katzung 9th ed. p.270

Question 177

MD42[Jul00] Acetazolamide: A. ? secreted by the renal tubules B. ? diuresis C. ? develop tachyphylaxis

Answer 177

Carbonic anhydrase inhibitor. weak diuretic rapid development of tolerance (tachyphylaxis) References Goodman & Gillman 11th ed

Question 178

MD43[Jul00] Best antiemetic for motion sickness: A. Metoclopramide B. Ondansetron C. ? D. ? E. Hyoscine

Answer 178

None of the above - First generation antihistamines best Katzung 9th ed Hyoscine would be best out of the three Comment: Scopolamine is renowned as the best anti sea sickness med, via transdermal patches limited in some by hallucinogenic potential.

Question 179

MD44 [Jul00] Complications of salbutamol used in asthma treatment include the following EXCEPT: A. Tachycardia B. Decreased V/Q mismatch C. Tremors D. Pulmonary oedema E. Hyperkalaemia

Answer 179

Tachycardia, tremors - yes Decreased V/Q mismatch - no (may increase V/Q mismatch due to reversal of hypoxic pulmonary vasoconstriction) - I suspect this would have said 'increased v/q mismatch' (how could decreased v/q mismatch be considered a complication?) making E the odd one out Pulmonary oedema - ?? yes with terbutaline Hyperkalaemia - no (causes hypokalaemia) Goodman&Gillman 11th ed, PeckHillWilliams 2nd ed

Question 180

MD45[Apr01] (Antibiotic sensitivities against certain bacteria) A. Penicillin and …? B. Amoxycillin and …staph +? C. Flucloxacillin and G +ve? D. ?cephalosporin and …?

Answer 180

Penicillins 1. Narrow spectrum penicillins are mainly active against gram +ve organisms, but are inavtivated by beta-lactamases. Include: Benzylpenicillin, procaine penicillin (IMI preparation and provides blood evels for 24hrs), benzathine penicillin (IMI and provides low levels of benzylpen for 4 weeks), phenoxymethylpenicillin (penV, po formulation) 2. Narrow spectrum penicillins with antistaphylococcal activity - stable to beta lactamases produced by Staphylococci. Includes diclox, fluclox and methicillin. 3. Moderate spectrum penicillins also called the aminopenicillins, incl. amoxycillin and ampicillin - have greater activity than benzylpenicillin against some gram negative organisms e.g. E Coli, H infl. But they are destroyed by beta lactamase producing strains. Drugs of choice for enterococcal infections. 4. Broad spectrum penicillins (beta-lactamase inhibitor combinations). Beta lactamase inhibitors Incl clavulanate, sulbactam, and tazobactam inhibit the enzymes produced by staph aureus, bacteroides fragilis, e. coli, klebsiella, neisseria gonorrhoea and h.infl.. They extend the spectre of activity of amoxycillin and, ticarcillin and piperacillin when in combination. 5. Broad spectrum penicillins with antipseudomonal activity. Ticarcillin and piperacillin are the only pen with activity against pseudomonas aeruginosa Cephalosporins: A. Moderate spectrum . Cephalexin, cephalothin and cephazolin. Active against strep and staph incl beta lactamase prod staph. Inactive against enterococci or listeria . Gram -ve activity against ecoli, and kleb sp. Inactive against many gram -ve aerobes. B. moderate spectrum with anti haemophilus activity - cefuroxime and cefaclor C. Moderate spectrum with anti anaerobic activity cefoxitin treats bacteroides fragilis. D. Broad spectrum cefoxitime and ceftriaxone covers the majority of commnity acquired g -ve rods. E. Broad spectrum cephalosporins and antipseudomonal activity - ceftazidime and cefepime covers majority of enteric gram -ve rod organisms, incl pseud aeruginosa Reference: therapeutic guideline antibiotic, version 13.

Question 181

MD46[Apr01] Aspirin overdose: A. Causes metabolic & respiratory acidosis B. Causes metabolic & respiratory alkalosis C. Causes metabolic alkalosis & respiratory acidosis D. Causes metabolic acidosis & respiratory alkalosis

Answer 181

Classically aspirin (being an acid) causes a metabolic acidosis with an increased anion gap, but its direct stimulatory effects on the respiratory centre causes an respiratory alkalosis. Later on it could cause a respiratory acidosis. \_\_\_\_\_\_\_\_\_\_\_\_\_\_ Aspirin's ability to cause a significant metabolic acidosis is more likely due to its uncoupling of oxidative phosphorylation and tendency towards anaerobic metabolism with subsequent buildup of lactic acid, as well as reduced renal elimination of strong acids. See Stoelting 4th ed p284 under CNS stimulation

Question 182

MD47[Apr01] Atropine overdose in neonates A. Causes hyperpyrexia B. ??

Answer 182

certainly does - Katzung 9th ed Adverse effects of Atropine: Hyperthermia (due to loss of sweating) in paediatric population Central cholinergic syndrome in the elderly Tachycardia, tachyarrhythmias blurred vision, loss of balance, dilated pupils Initial bradycardia at low doses (?weak partial agonist effect)

Question 183

Which drug does NOT have antiemetic properties? \*repeat\* A. propofol B. ondansetron C. dexamethasone D. etomidate E. midazolam

Answer 183

A F B F C F D T E F

Question 184

MD49 [Apr01] [Jul01] [Jul02] [Jul04] Low molecular weight heparin A.Has better bioavailability B. Molecular weight 1/10 that of normal heparin C. More protein bound than heparin D. ? E. ?

Answer 184

A. True. (Pharm&Physiol in Anesethetic Practice, Stoelting&Hillier, p511) B. Unclear: Unfractionated heparin is a mixture of low and high molecular weight fractions ranging 3000-30,000 daltons. LMWH ranges from 2000-10,000 daltons. (Anesthetic Pharmacology, Evers&Maze, p 931) LMWH are derived from standard UFH by chemical depolymerisation to fragments approx 1/3 the size of heparin. [Stoelting 4e p511] C. False. LMWH is less protein bound than unfractionated heparin, thus pharmacokinetics are more consistent, making response more predictable.

Question 185

MD50[Apr01] [Jul01] [Mar03] [Jul04] Desmopressin A Increases factor X B Increases factor V C Causes sustained severe hypertension D Can be used to improve haemostasis in haemophilia E Increases factor VIII activity F. ?v2B receptors?

Answer 185

Desmopressin is used to reduce urine production in central diabetes insipidus patients and to promote the release of von Willebrand factor and factor VIII in patients with coagulation disorders such as type I von Willebrand disease, mild hemophilia A, and thrombocytopenia. Desmopressin is not effective in the treatment of hemophilia B or severe hemophilia A. m2c: Stoelting 4e p.627 : "Greatly increases factor VIII activity in patients with mild to moderate haemophilia and von Willebrand's disease." same page also says can get hypotension, although earlier chapter mentions increased BP "can occur". Go figure. I guess the point is there is no major effect on BP because of reduced pressor effect compared with AVP. See BL09 - author of comment there states effect is via V1a, whereas Stoelting definitely says it is a V2 effect on the endothelial cells. :)

Question 186

MD51 [Jul01] An intravenous infusion of 8.4% sodium bicarbonate to a healthy adult may cause: A. Hypotonicity B. Intracellular Acidosis C. Ionized Hypercalcaemia D. ?Respiratory Alkalosis E. Rebound Metabolic Acidosis

Answer 186

Brandis p38 - almost word for word (is that allowed?) A incorrect 8.4% NaHCO3 is a one molar solution because the molecular weight of NaHCO3 is 84 = 84g/L = 8.4g/100mls. But each molecule of NaHCO3 dissociates into 2 particles in solution so the osmolality is double the molality. ie 2 osmoles/kg = 2000mOsm/kg = about 7 times the plasma osmolality. 100mls of the solution would then have 200 mOsm. The ECF HCO3 will cause decrease in H+ concentration. I think this then causes H+ to move out of the cells and K+ to move in. If this is true, B would also be incorrect. Don't know about C,D,E can some smart person help me? Rebound alkalosis is a complication so E would be incorrect. Also read somewhere that hypocalcaemia is a complication (but could be a trick q - ionised or total?) The dissociation of HCO3 would form CO2, which then diffuses into cell to cause intracellular acidosis (from P Kam's lecture notes). This intracellular acidosis has been mentioned before. Keeping in mind that the "neutral pH" intracellularly is thought to be anywhere from 6.8-7.0 where [H+]=[OH-]. See off-the-record discussions at queensland part one course. Lots of sources mention a paradoxical intracellular acidosis occuring following bicarbonate administration due to CO2 production, and this seems to be one of the arguments against its use. It also causes hypocalcaemia. See Current Opinion in Critical Care. 14(4):379-383, August 2008.

Question 187

MD51b [Feb04] Bicarbonate A. Complications include intracellular acidosis B. 100ml of 8.4% NaCO3 has 200 milliosmoles C. ?

Answer 187

Brandis p38 - almost word for word (is that allowed?) A incorrect 8.4% NaHCO3 is a one molar solution because the molecular weight of NaHCO3 is 84 = 84g/L = 8.4g/100mls. But each molecule of NaHCO3 dissociates into 2 particles in solution so the osmolality is double the molality. ie 2 osmoles/kg = 2000mOsm/kg = about 7 times the plasma osmolality. 100mls of the solution would then have 200 mOsm. The ECF HCO3 will cause decrease in H+ concentration. I think this then causes H+ to move out of the cells and K+ to move in. If this is true, B would also be incorrect. Don't know about C,D,E can some smart person help me? Rebound alkalosis is a complication so E would be incorrect. Also read somewhere that hypocalcaemia is a complication (but could be a trick q - ionised or total?) The dissociation of HCO3 would form CO2, which then diffuses into cell to cause intracellular acidosis (from P Kam's lecture notes). This intracellular acidosis has been mentioned before. Keeping in mind that the "neutral pH" intracellularly is thought to be anywhere from 6.8-7.0 where [H+]=[OH-]. See off-the-record discussions at queensland part one course. Lots of sources mention a paradoxical intracellular acidosis occuring following bicarbonate administration due to CO2 production, and this seems to be one of the arguments against its use. It also causes hypocalcaemia. See Current Opinion in Critical Care. 14(4):379-383, August 2008.

Question 188

Aug15 108. Side effect 8.4% NaHCO3 administration A. Intracellular acidosis B. Rebound metabolic acidosis C. ... Other options were easy to rule out

Answer 188

Aug15 Version A. As above B. Oral sodium bicarbonate can cause 'acid rebound' but this refers to gastric pH; not blood pH (Stoelting, 5th ed p699)

Question 189

MD52 [Jul01] [Jul04] Cyclo-oxygenase-1 (COX-1) isoenzyme: A. Is increased by inflamation B. Is ?predominant mode of action of indomethacin C. Is increased by lipopolysaccaride D. Is NOT involved in gastric mucosal protection E. Is increased by cytokines

Answer 189

A FALSE is constitutively expressed i.e always there. B TRUE probably. Saasada says not, but Katzung says predominant COX 1. - PHW also says that Indomethacin (and aspirin) have much higher affinity for COX 1 than COX 2 C FALSE These increase COX 2. D FALSE One of primary roles. "Housekeeping" also platelet and renal prostaglandin synthesis. E FALSE COX 2 increased by cytokines

Question 190

MD53 [Jul01] Caffeine A. Is a CNS depressant B. Causes cerebral vasoconstriction C. Reduces the acidity of gastric fluid secretion (or: Not a gastric irritant) D. Reduces plasma glucose level E. Is a potent diuretic. F. Has been shown to be dependence producing G. Does not show an improvement in psychomotor function

Answer 190

A False - CNS stimulant B. True - Stoelting 593 4th Edition c. False - Stoelting 593, 4th - may cause secretion of acidic gastric fluid D. Stoelting again - caffeine may increase plasma glucose concentrations E. Is a diuretic F. Surely true G. Yentis 83 - traditionally thought to improve performance and mood, whilst reducing fatigue Which is the best? ?B

Question 191

MD54 [Jul02] Which of the following drug interactions is mediated by serotonin? A. ? B. ? C. ? D: Pethidine & Tranylcypromine E. ?

Answer 191

Tranylcypromine is a non-selective irreversible MAOI. Peck p277 states that tranylcypromine is potentially the most dangerous as it possess stimulant activity. Pethidine reduces 5-HT uptake from nerve endings, causing excessive central 5-HT activity (Yentis p345).

Question 192

MD55 [Feb04] Metabolism of which drug is decreased in pseudocholinesterase deficiency: A. Mivacurium B. Cocaine C. Procaine D. Remifentanil E. Esmolol

Answer 192

Presumably the question meant in pseudocholinesterase deficiency. This would make the answer A - Mivacurium Regarding cocaine and procaine Metabolised by plasma esterases NOT cholinesterases (S&S say the predominant type = benzoylecgonine) Metabolised by plasma esterases, probably pseudocholinesterase (G&G) Metabolised by pseudocholinesterases (Miller's) The last two are the set texts so I guess A, B, C are correct?? Maybe this is why the question hasn't been asked for a while

Question 193

MD56 [Jul04] What drugs affecting ganglia ? A. Hexamethonium, B. ?carbachol C. ? D. ? E. ?

Answer 193

Hexamethonium is an autonomic ganglion blocker. Carbachol is a cholinergic agonist (choline ester) - stimulates parasympathetics (muscarinic more than nicotinic). Stoelting 4e p263 : "Carbachol retains a high level of nicotinic activity, particularly on autonomic ganglia, which may reflect drug-induced release of endogenous acetylcholine from the terminals of cholinergic fibers."

Question 194

MD57[Jul04] Which of these agents does NOT reduce uterine contractions? A. Nifedipine B. Glycerol trinitrate C. Indomethacin D. Isoprenaline E. Phenytoin

Answer 194

By lack of reference - Phenytoin By elimination I think... the others all do. A,B and D definitely do. Indomethacin inhibits prostaglandin synthesis & has been used as a tocolytic but "concerns remain about effect on foetal circulation". Phenytoin blocks Na+ and Ca++ influx into excitable tissues and acts as a membrane stabiliser. Hard to pick between C and E. Indomethacin is used as a tocolytic in preterm labour, so probably E "Phenytoin is free of tocolytic activity..." (Shah and Kelly)

Question 195

MD58 [Jul04] Which of the following is the MOST COMMON side effect of oxytocin? A. Hypotension B. ADH effect C. Supraventricular tachycardia D. Histamine release

Answer 195

A - True - due to direct relaxant effect on smooth muscle -- decrease in systolic and diastolic BP and appearance of flushing B - not that common "slight AVP" effect in high doses according to Stoelting 474 C - not common D - not mentioned in Stoelting, Sasada and Smith, Yentis states 393 can cause rash, nausea and allergic reactions A the best That's why we should give small boluses each time to avoid hypotension during ERPC Agreed. As per UK Confidential Enquiry into Maternal Deaths (Report titled "Why Mothers Die - 1997 - 1999"): It seems not to be widely appreciated that Syntocinon® (Alliance) can cause profound, fatal hypotension, especially in the presence of cardiovascular compromise. Administration should follow the guidance in the British National Formulary, Martindale and other standard formularies. When given as an intravenous bolus the drug should be given slowly in a dose of not more than 5 iu. [[1]]

Question 196

MD59 [Jul04] Cause of hypotension during iv Vancomycin administration A. ? B. ? C. ?

Answer 196

Possibilities - "red man syndrome" with histamine release, anaphylactoid reactions with associated hypotension, erythema and bronchospasm, normal plasma tryptase levels. Stoelting p536 states that "assertions that anaesthesia accentuates vancomycin induced hypotension are not supported in the scientific data".

Question 197

Which of the following is a non particulate antacid A. Aluminium hydroxide B. Sodium citrate C. Magnesium hydroxide D. Cimetidine E. ?

Answer 197

Sodium citrate is a non-particulate antacid. Compared with particulate antacids, non-particulate antacids: Are less likely to cause a foreign body reaction if aspirated. Mix with gastric fluid more completely.

Question 198

MD61 Mechanism of action of ondansetron? A - blocks ligand gated ion channel - True, blocks non selective cation channel - only 5HT3 subtype are ion channels, others are GPCR B peripheral blockade 5HT3 - false - central and peripheral action - CTZ and vagal afferents / myenteric plexus C blockade 5HT4 - false - low affinity D increases amount of serotonin in CTZ - false I think, but only rough lack of confirmatory information (I'm pretty sure A said cation channel)

Answer 198

?

Question 199

MD62 Which of the following is true regarding action on platelets? A. Non-selective COX inhibitors act irreversibly - false B. Clopidogrel acts reversibly C. ? D. Abciximab acts reversibly E. ?

Answer 199

A. Non-selective COX inhibitors act irreversibly - false B. Clopidogrel acts reversibly - false, it acts irreversibly, hence the need to await both the clearance of clopidogrel and the turnover of new platelets before certain high risk surgical interventions. C. ? D. Abciximab acts reversibly - true - platlet glycoproein IIb/IIIa inhibitor - monoclonal antibody - difficult answer. Whilst the plasma half life is short at ten minutes, with a t1/2B of about 30 minutes, effects on platelet function can be seen for up to 48 hours after the infusion has been terminated, and low levels of glycoprotein IIb/IIIa receptor blockade are present for up to 15 days after the infusion is terminated." - wikipedia. This to me implies that the action is reversible as platelets take longer than that to be replaced with new ones, therefore previously inhibited platelets must have their inhibition of function reversed E. ? References I cannt understand why A false.Aspirin binding is nonselecive & irreversible.any help?

Question 200

MD63 Regarding warfarin? A. Affects platelet function B. Increases the action of vitamin K epoxide reductase C. ?More effective when given as an intravenous dose D. Doesn't cross the placenta E. Peak effect 36-72 hours following dose

Answer 200

A Affects platelet function - false B Increases the action of vitamin K epoxide reductase - false - it inhibits it preventing formation of Vit K and therefore factors II, VII, XI & X\> C ?More effective when given as an intravenous dose - false ' oral bioavailability of 100% (Sassada and Smith 4th ed) D Doesn't cross the placenta. - false - it is teratogenic so must cross the placenta. "Extensive protein binding prevents diffusion into erythrocytes, cerebrospinal fluid and breast milk. Warfarin however does cross the placenta and produces exaggeratedeffects in the fetus, who has limited avility to synthesize clotting factors." (steolting 4th ed page 513) E Peak effect 36-72 hours following dose - true (see stoelting 4th ed page 512 table 27.1)

Question 201

Phenytoin A. Half life is 12 hours B. Used as an antiarrythmic drug C. Toxixity produces megaloblastic anaemia due to vitamin B12 defeciency D.

Answer 201

A - true - t1/2B is 9 - 22 hours. above the therapeutic range the kinetics change to zero order and therefore the elimination half life extends rapidly B - true, but there are better agents so this is a rare use currently C - false - it is folate dependent

Question 202

MD64 MD66 Cox 2 inhibitors cause: A decrease incidence of GI ulcers B decrease expression of COX-2

Answer 202

A - true, when compared to non-selective NSAIDS B - dont think so, they just inhibit the function of it

Question 203

Mechanism of action of metoclopramide A ? B.

Answer 203

Peripheral and central D2 antagonism. potentially prokinesis mediated via 5HT4 antagonism.

Question 204

Glucagon: A. acts through beta receptors B. increases gut motility (?or decreases) C. increases sympathetic activity D. decreases/increases K+ E. increases catecholamine release

Answer 204

Glucagon: A acts through beta receptors - false - beta receptor activation can trigger glucagon release, and glucagon can increase cAMP in the myocardium, bypassing Beta receptors, hence it's use in Beta-blocker overdose. (see Stoelting 4th ed page 331) B increases gut motility (?or decreases) - decreases motility and often evokes nausea and vomiting. C increases sympathetic activity - I thought it was increases adrenaline release? - increases cAMP and therefore contractility D decreases/increases K+ - increases (impairs K+ entry into cells (think opposite of insulin.) E - increases catecholamine release - true "Glucagon stimulates release of catecholamines and could evoke systemic hypertension in patients with unrecognised phaeochromocytoma. (Stoelting 4th ed page 319)

Question 205

MD68 The MOST common side effect of doxorubicin is: A - pulmonary toxicity B - renal failure C - hepatic failure D - coagulopathy E - cardiomyopathy

Answer 205

A F B F C F D F E T Doxorubicin - side effects other than nausea and vomiting - myelosupression, cardiomyopathy and mucusitis. (stoelting 4th ed page 555) The problem here is to know what was asked. If it was "most common side effect" then its a bit trivial. Thus "Acute nausea and vomiting occurs frequently and may be severe. This may be alleviated by antiemetic therapy. Mucositis (stomatitis and esophagitis) may occur within 5 to 10 days of beginning therapy, and most patients recover from this adverse effect". But doxorubicin has severe dose-related side effects of myelosuppression and myocardial toxicity (See doxorubicin toxicity for details from FDA.) If the question was actually about the most common serious side effect then the answer is different.

Question 206

Phenytoin toxicity with an initial large loading dose what might be one of the first signs you see? A. nystagmus B. decreased seizure control C. tremor D. sedation

Answer 206

Phenytoin toxicity with an initial large loading dose what might be one of the first signs you see? A - nystagmus - true - several sources list this first, but with no specific reference to plasma concentrations B - decreased seizure control - high concentration of phenytoin have been reported to be associated with seixures - seems unlikely to be common from a single large dose if there are only case reports about it C - tremor D - sedation According to Stoelting 4th page 577: "Side effects of phenytoin include CNS toxicity that manifests clinically as nystagmus, ataxia, diplopia, vertigo (cerebellar-vestibular dysfunction) and is likely when plasma phenytoin concentration is \>20μg/mL' According to Sasada and Smith 4th Ed: "The Concentration dependent side effects include, nausea and vomiting, drowsiness, behavioural disturbances, tremor, ataxia, nystagmus, paradoxical seizures, peripheral neuropathy and cerebellar damage."

Question 207

FFP: A. Something about FFP being treated for viruses B. Something about matching of FFP C. Contains all clotting factors D. Contains a signifcant amount of sodium E. Maybe an option about the temperature stored???

Answer 207

A - false not treated but all donated blood products are screened B - true it is type matched, after all, it contains all the antibodies to Red Cell Surface Antigens that could cause a transfusion reaction, but it is not crossmatched to individual C - All? well probably yes, as it is basically the entire cohort of blood products minus the platelets and red cells. D - refer to the following abstract data from Ewalenko P et all, Crit Care Med 1986 Feb;14(2): 145-6 535 mg/dl glucose, 172 mEq/L sodium, 73 mEq/L chloride, 3.5 mEq/L potassium, 15 mEq/L 5.5 g/dl protein with 60% albumin. therefore '"FFP is a hyperosmolal, hyperglycemic, hypernatremic, and hypochloremic solution which may be a less effective volume expander than other albumin-containing solutions, due to its lower albumin content."

Question 208

MD71 Aspirin is A. Less efficacious than clopidogrel B. As potent as abciximab C. Something with ibuprofen D. ? E. ?

Answer 208

A - true B - false seems unlikely - abciximab has a major bleeding incidence of 10-21% post angioplasty and that clearly is higher than for aspirin C -

Question 209

MD72 Vancomycin: A. Is less sensitive than penicillin for methicillin sensitive Staphylococci B. ? C. Something like "equal sensitivity for both gram positive and negative bacteria" D. Can be used orally in outpatient E. Half life of ?12 hours and not removed by haemodialysis

Answer 209

A - true "vancomycin is not as effective as an antistaphylococcal penicillin for treatment of serious infections such as endocarditis caused by methicillin-susceptible strains." (Katzung 11th ed page 787) B ? C - false - with the exception of flavobacterium it is active only agains gram-positivies particularly staph - katzung 11th ed page 786 D - false - only used orally for GIT infections - e.g. pseudomembranous colitis etc... not conditions amenable to outpatient care ("no" oral bioavailability.) E - false - dr wiki lists a t½β of 4- 11 hours in normal adults and 6-11 days in anephric patients. Also:"roughly 50% of vancomycin is removed during a standard haemodialysis run when using a modern high flux membrane) [1]

Question 210

MD73 A patient for surgery is allergic to azithromycin. What else would you avoid? A. Clindamycin B. tobromycin C. clarithromycin D. .?..-mycin E. ..?..mycin

Answer 210

Presumably other macrolide antibiotics -\> see list

Question 211

MD74 11A Most common side effect of 1g IV vancomycin? A. hypotension and histamine release B. ...something about hepatitis C. ...something about renal failure D. hypertension E. ?

Answer 211

?

Question 212

MD75 Aug15 These drugs are safe in porphyria except: A. propofol B. atropine C. suxamethonium D. droperidol E. diazepam

Answer 212

?

Question 213

MD76 Feb15 Ondansetron - most common side effect: A. headache B. constipation C. sedation D. hypotension E. extra pyramidal side effects

Answer 213

"most common" ?? Both headache and constipation are side effects of ondansetron. Unsure which is "most common". According to reference below, more common SEs are: Confusion dizziness fast heartbeat fever headache shortness of breath weakness According to wikipedia: "Ondansetron is a well-tolerated drug with few side effects. Constipation, dizziness, and headache are the most commonly reported side effects associated with its use."

Question 214

MD77 Aug14 Pre treatment with dantrolene causes: A. ? B. Ileus C. Muscle weakness D. Contraction E. ?

Answer 214

Based on its mechanism of action, muscle weakness (option C) seems to be the best answer.

Question 215

SP01 [Mar96] [Jul98] [Jul99] [Feb06] Tests that use ranking of data: A. Can be applied to any distribution B. Include the chi square test C. Have greater power than non-ranking (?parametric tests) tests D. Are preferred when normal distribution cannot be confirmed E. ?

Answer 215

A. true. nonparametric tests commonly use ranking of data. B. false C. less power than nonranking tests D. ??. nonparametric tests, which commonly use ranking of data, are preferred when normal distribution cannot be confirmed. Spearman, Kendall, and Wilcoxon tests use ranking of data. Chi square test uses categorical data. I am confused by the term "ranking of data". From the above answers I assume that non-parametric tests (i.e. those that are NOT normally distributed) use this method. Some notes about parametric vs non-parametric: parametic tests have more power than non-parametric tests non-parametric tests can be used on normally distributed data, but they are more effective compared with parametric tests when used on non-normally distributed data and hence are preferred when normal distribution cannot be confirmed

Question 216

SP02 [Mar96] [Feb00] [Jul02] [Mar03] [Feb06] Standard error of the mean: A. Is proportional to sample size (n) B. Is greater for sample than SD of population C. Measures variance within a sample D. Measures dispersion around population mean E. The difference between the sample mean and the population mean.

Answer 216

Standard error of the mean: A. Is proportional to sample size (n) - WRONG: its inversely proportional to the square root of n B. Is greater for sample than SD of population - WRONG: SEM=SD/SQRT(n) so SEM must be smaller than sample SD. (Exception: If n=1 then SEM=SD) C. Measures variance within a sample - WRONG: It measures variance within the "sampling distribution" (the distribution of all sample means of a given sample size) and NOT the "sample distribution" (the distribution of actual sample values). Remember that variance is just the SD squared. D. Measures dispersion around population mean -~CORRECT (but only "sort of"): The SEM measures dispersion of the collection of sample means around the mean of the sampling distribution (which is equal to the population mean). So because these means are equal it does measure dispersion of sample means around a mean that is equal to the population mean so is correct in this convoluted way. HOWEVER, one assumes the "real" question had its option worded much better than this so that there was at least one of the options (& possibly this one) that was clearly correct. (Strictly speaking, this option as worded here is wrong) E. The difference between the sample mean and the population mean - WRONG: it cannot do this

Question 217

SP03 [Mar96] [Jul98] [Mar02] [Jul02] The use of the chi-square test is inaccurate: A. With a 2x2 contingency table B. When expected value of any cell

Answer 217

Answer - B (Expected value in any cell "The approximation to the chi-square distribution breaks down if expected frequencies are too low. It will normally be acceptable so long as no more than 10% of the events have expected frequencies below 5"[[1]] "As mentioned before, chi square is a nonparametric test. It does not require the sample data to be more or less normally distributed (as parametric tests like t-tests do), although it relies on the assumption that the variable is normally distributed in the population from which the sample is drawn. But chi square, while forgiving, does have some requirements: The sample must be randomly drawn from the population. Data must be reported in raw frequencies (not percentages); Measured variables must be independent; Values/categories on independent and dependent variables must be mutually exclusive and exhaustive; Observed frequencies cannot be too small. ...the smaller the expected frequencies, the less valid are the results of the chi-square test. We'll discuss expected frequencies in greater detail later, but for now remember that expected frequencies are derived from observed frequencies. Therefore, if you have cells in your bivariate table which show very low raw observed frequencies (5 or below), your expected frequencies may also be too low for chi square to be appropriately used. In addition, because some of the mathematical formulas used in chi square use division, no cell in your table can have an observed raw frequency of 0."[[2]]

Question 218

SP04 [Jul97] The mean in a very large sample: A. Numerically greater than the standard deviation B. Is always equal to the mode C. Is more than the median D. Represents a normal distribution E. Gets larger as the sample size increases

Answer 218

This question seems to be a reference to the Central Limit Theorem, which states that in a large sample, the distribution [correction: OF THE MEAN] will resemble a normal distribution- even if the distribution in the population the sample is taken from is not a normal distribution. A. ?! this seems wrong: Mean = Sum(x...)/n SD = SQRT[(mean-x)sqrd]/n-1 Thereby there is a tendancy for SD to be greater as it uses (n-1) as a denominator. B. will tend to be similar to the mode, but they won't necessarily be equal C. the mean and the median should tend to be similar D. seems to be what this question is getting at E. ?! this also seems wrong Addendum: CLT is misunderstood above - one good way of thinking of it is to recgonised that: "The distribution of an average tends to be Normal, even when the distribution from which the average is computed is decidedly non-Normal.". An example is a uniform population distribution from which many samples are taken and the mean of each sample calculated. The distribution of the MEAN of these samples becomes a normal distribution as N increases. This is illustrated nicely at: http://www.statisticalengineering.com/central\_limit\_theorem.htm

Question 219

SP05 [Mar98] [Jul02] [Mar03] The standard normal distribution: A. Standard deviation is one B. Mean, median & mode are the same C. Mean is one D. Mode is one

Answer 219

"The standard normal distribution is the normal distribution with a mean of zero and a variance of one" (Wikipedia)[[1]] A - Correct as above B - correct as mean, median and mode the same with a standard distribution C - Incorrect; mean is zero in a standard normal distribution D - Incorrect; mode is zero Mean, median and mode are equal in a normal distribution. References how can the mean and mode be ZERO ! --\> if a data set includes negative numbers and is a normal distribution around 0, mean = mode = 0 A STANDARD normal distribution has mean zero and standard deviation 1. (95% of observations will fall between -2 and 2) Any normal distribution data can be converted to this by subtracting the mean and dividing by the standard deviation to give the new dataset which now follow the standard normal distribution.

Question 220

SP06 [Mar98] [Jul00] In a study for depth of epidural catheter insertion, the mean is 4.4 and the standard deviation is 0.3, which ONE of the following is true? A. If a normal distribution, 68% of values wold lie between 4.1 and 4.7cm B. None was greater than 5.5 cm (or ?6.8cm) C. The least distance was...?? D. 99% of the sample lies within 1.96 SD of the mean E: 500 patients had catheters at some length.

Answer 220

A. True. +/- 1 SD 68%, +/- 2 SD 95.4%, +/- 3 SD 99.7% B. Unknown from the data. C. Least distance is unknown from the data given. D. Assuming a normal distribution, 1.96 SD from the mean would include around 95% of the sample, not 99%. E. This is meaningless.

Question 221

SP07 [Mar98] Simple linear regression: {graph of straight line crossing y axis at +3} A. y = 3 + 6x B. y = 3 + 0.6x C. ? D. None of the above

Answer 221

Need to see the graph to determine the gradient of the line. However, with the given information both A and B are true. For x=0, y=3; for both. In addition, the gradient of the straight line will be the "rise over run" For a simple linear function... y = mx + c Gradient (m) = (y2-y1)/(x2-x1)

Question 222

SP08 [Jul98] [Mar99] [Jul01] Which one of the following statements regarding the standard deviation is true? A. Mean +/- one SD includes 50% of values B. Mean +/- one SD includes 66.7% of values C. Mean +/- two SDs include 99% D. Mean +/- three SDs include 99.73% E. Mean +/- 1.96 SD includes 99.73%

Answer 222

Definition of standard deviation is: SD = sqrt (variance) = sqrt [Sum(x - xbar)^2 / (n-1)] For a normally distributed population: mean +/- 1 SD includes 68% of values, mean +/- 2 SD includes 95.4% of values, mean +/- 3 SD includes 99.7% of values so: A. false B. false C. false D. true E. false Also: mean +/- 1.96 SD includes 95% of values NB. This assumes a normal distribution.

Question 223

SP09 [Jul98] Ordinal data: A. Assumes a normal distribution B. ? C. ?

Answer 223

A is incorrect- ordinal data does not assume a normal distribution Ordinal data are categorical data where there is a logical ordering to the categories. A good example is the Likert scale that you see on many surveys: 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly agree. While computation of a median is easily justified for ordinal data, some statisticians have reservations about computing a mean for ordinal data. Nominal Data: classification data, e.g. m/f no ordering, e.g. it makes no sense to state that M \> F arbitrary labels, e.g., m/f, 0/1, etc Ordinal Data ordered but differences between values are not important e.g., political parties on left to right spectrum given labels 0, 1, 2. or e.g., Likert scales, rank on a scale of 1..5 your degree of satisfaction. or e.g., restaurant ratings Interval Data ordered, constant scale, but no natural zero differences make sense, but ratios do not (e.g., 30°-20°=20°-10°, but 20°/10° is not twice as hot! e.g., temperature (C,F), dates Ratio Data ordered, constant scale, natural zero e.g., height, weight, age, length

Question 224

SP10 [Feb00] Paired t-test A. Assumes the normal distribution B. Is a nonparametic test

Answer 224

A - Assumes a normal distribution; is a parametric test. B - Yes and No. The t-distribution is broader and flatter than the normal distribution (for small samples). It approaches the normal distribution with an increasing sample size. However, an assumption of the t-test is that the underlying population has a normal distribution. Yes and No? The t-test assumes a normal distributions, so it is a parametric test, so B is false.

Question 225

SP11 [iq] [Jul06] In a clinical trial, a patient either vomits or not. What type of data is this? A. Ordinal B. Nominal C. Ratio D. Interval

Answer 225

B. nominal comments\*\*\* This sounds ridiculous. While the labels "vomited and "didn't vomit" are nominal, the study surely counted how many people vomited and how many didn't vomit. This data, say, 54 vomited and 13 didn't, is clearly discrete ratio data (where 0 vomit means nobody vomited). The "vomit" and "didn't vomit" are simply labels, not actual data. Surely the word data refers to the numbers here. Disagree: The type of data is nominal. Its frequency (which you mention) is a measure of the data irrespective of the type of the data. Refer to male female example below. types of data Nominal Data: classification data, e.g. m/f no ordering, e.g. it makes no sense to state that M \> F arbitrary labels, e.g., m/f, 0/1, etc Ordinal Data ordered but differences between values are not important e.g., political parties on left to right spectrum given labels 0, 1, 2. or e.g., Likert scales, rank on a scale of 1..5 your degree of satisfaction. or e.g., restaurant ratings Interval Data ordered, constant scale, but no natural zero differences make sense, but ratios do not (e.g., 30°-20°=20°-10°, but 20°/10° is not twice as hot! e.g., temperature (C,F), dates Ratio Data ordered, constant scale, natural zero e.g., height, weight, age, length

Question 226

SP12 [Feb00] [Jul00] [Apr01] Odds ratio: A. Is prevalence vs. incidence B. Gives an indication of ?? in exposed vs non-exposed patients ??C. Formula is Number of positive outcomes/ Number of negative outcomes ??C. Formula is Number of positive outcomes/ Number of possible positive outcomes D. Gives the prediction of a disease outcome knowing the risk factors E. Gives prediction of risk factors with a known disease outcome

Answer 226

A. is incorrect B. the question may be 'gives an indication of risk in exposed vs non-exposed patients' which would be correct C. the odds of an event are calculated by 'positive' outcomes/'negative' outcomes. the odds ratio is calculated by dividing the odds in the exposed group by the odds in the control group D. i'm unsure what this answer is getting at E. and unsure about this one too Odds The odds of an event are calculated by dividing the number of events by the number of nonevents. For example, on average 51 boys are born in every 100 births, so the odds of any randomly chosen delivery being that of a boy is: number of boys 51 / number of girls 49, or about 1.04 If the odds of an event are greater than one the event is more likely to happen than not (the odds of an event that is certain to happen are infinite); if the odds are less than one the chances are that the event won't happen (the odds of an impossible event are zero). Odds ratios An odds ratio is calculated by dividing the odds in the treated or exposed group by the odds in the control group. Relative risks Few people have a natural ability to interpret event rates which are reported in terms of odds ratios (which may be why bookmakers always use them). Understanding risks, and relative risks, seems to be something easier to grasp. The risk (or probability) of having a boy is simply 51/100, or 0.51. If for some reason we were told that the risk had doubled (relative risk = 2) or halved (relative risk = 0.5) we feel we have a clear perception as to what this would mean: the event would be twice as likely, or half as likely to occur. Risks and odds In many situations in medicine we can get a long way in interpreting odds ratios by pretending that they are relative risks. When events are rare, risks and odds are very similar. For example, in the ISIS-4 study 2,231 of 29,022 patients in the control group died within 35 days: a risk of 0.077 [2,231/29,022] or an odds of 0.083 [2,231/(29,022 - 2,231)]. This is an absolute difference of 6 in 1000, or a relative error of about 7%.This close approximation holds when we talk about odds ratios and relative risks, providing the events are rare.

Question 227

SP13 [Jul00] With respect to 95% confidence intervals: A. Equals mean +/- 1.96 SE B. Will contain the population mean 95% of the time C. Tells variability of sample D. Tells 5% chance of finding sample result E. Assumes a normal distribution

Answer 227

A. This is true when the sample size is large, but not when the sample size is small B. True C. False- this is standard deviation D. False E. False Confidence Intervals Confidence intervals are calculated from the standard error of the mean, which is calculated from the standard deviation and sample size. The confidence interval is a range, with a 95% probability that the population value lies somewhere within this range. The confidence interval can be calculated for a number of different things, including mean, risk ratio, median, and regression analyses. Confidence intervals allow estimation of population parameters from sample statistics. The CI gives an estimate not only of the parameter itself, but also of precision. The wider the CI, the less precise the value derived from the sample. P-values are of use in a drug trial because they indicate the probability of the null hypothesis being correct. They are an indication of the statistical significance of the result- they do not, in comparison to confidence intervals, give any clinical information. They do not give an indication of the magnitude of any observed differences and therefore no indication of the clinical significance of the result. Confidence intervals are often preferred when presenting results because they also provide information about statistical significance, and also the accuracy of the sample estimates, and also the magnitude of effect. References Myles and Gin, Statistical Methods for Anaesthesia and Intensive Care

Question 228

SP14 [Jul01] [Jul04] Students t-test A. Used to compare 2 groups B. Used if groups have different variance C. For small size samples D. ? E. ?

Answer 228

A. True - Analysis of more than two groups shoud be done with ANOVA (or using the t-test and a Boferroni correction - but this is not recommended). B. False - one of the assumptions is that the samples have the same variance C. True - This is a strength of this test. Commonly used for sample n Ref. Myles & Gin

Question 229

SP15 [Jul01] [Jul04] All of the following tests EXCEPT one, can be used to compare two dissimilar groups: A. Chi square B. Mann whitney U test C. Wilcoxon signed ranks sum test D. Spearman rank order E. Kruskall Wallis test (Alt version: Tests applied to small groups include all EXCEPT: )

Answer 229

A - Incorrect B - Incorrect C - incorrect D - correct because while the others look for a difference (albeit sometimes by trying to prove the null hypothesis - that they are the same - is incorrect), the Spearman rank order looks for a strength of correlation E - incorrect The chi-square test "Studies often collect data on categorical variables that can be summarized as a series of counts. These counts are commonly arranged in a tabular format known as a contingency table. For example, a study designed to determine whether or not there is an association between cigarette smoking and asthma might collect data that could be assembled into a 2−2 table. In this case, the two columns could be defined by whether the subject smoked or not, while the rows could represent whether or not the subject experienced symptoms of asthma. The cells of the table would contain the number of observations or patients as defined by these two variables. "The chi-square test statistic can be used to evaluate whether there is an association between the rows and columns in a contingency table. More specifically, this statistic can be used to determine whether there is any difference between the study groups in the proportions of the risk factor of interest. Returning to our example, the chi-square statistic could be used to test whether the proportion of individuals who smoke differs by asthmatic status." ("chi-square test." Encyclopedia of Public Health. The Gale Group, Inc, 2002. Answers.com 15 Jun. 2007. http://www.answers.com/topic/chi-square-test) Mann Whitney Test "A procedure used in nonparametric statistics to determine whether the means of two populations are equal" ("Mann-Whitney test." McGraw-Hill Dictionary of Scientific and Technical Terms. McGraw-Hill Companies, Inc., 2003. Answers.com 15 Jun. 2007. http://www.answers.com/topic/mann-whitney-test-statistics) "In statistics, the Mann-Whitney U test (also called the Mann-Whitney-Wilcoxon (MWW), Wilcoxon rank-sum test, or Wilcoxon-Mann-Whitney test) is a non-parametric test for assessing whether two samples of observations come from the same distribution. The null hypothesis is that the two samples are drawn from a single population, and therefore that their probability distributions are equal. It requires the two samples to be independent, and the observations to be ordinal or continuous measurements, i.e. one can at least say, of any two observations, which is the greater. More generally, the Wilcoxon-Mann-Whitney two-sample test may be thought of as testing the null hypothesis that the probability of an observation from one population exceeding an observation from the second population is equal to 0.5. Another alternative interpretation is that the test assesses whether the Hodges-Lehmann estimate of the difference in central tendency between the two populations is zero. The Hodges-Lehmann estimate for this two-sample problem is the median of all possible differences between an observation in the first sample and an observation in the second sample. It is commonly thought that the MWW test tests for differences in medians but this is not strictly true. "It is one of the best-known non-parametric significance tests. It was proposed initially by Wilcoxon (1945), for equal sample sizes, and extended to arbitrary sample sizes and in other ways by Mann and Whitney (1947). MWW is virtually identical to performing an ordinary parametric two-sample t test on the data after ranking over the combined samples." ("Mann-Whitney U." Wikipedia. Wikipedia, 2007. Answers.com 15 Jun. 2007. http://www.answers.com/topic/mann-whitney-u) Wilcoxon signed rank test "The Wilcoxon signed-rank test is a non-parametric alternative to the paired Student's t-test for the case of two related samples or repeated measurements on a single sample. The test is named for Frank Wilcoxon (1892–1965) who proposed this, and the rank-sum test for two independent samples (Wilcoxon, 1945). "Like the t-test, the Wilcoxon test involves comparisons of differences between measurements, so it requires that the data are measured at an interval level of measurement. However it does not require assumptions about the form of the distribution of the measurements. It should therefore be used whenever the distributional assumptions that underlie the t-test cannot be satisfied." ("Wilcoxon signed-rank test." Wikipedia. Wikipedia, 2007. Answers.com 15 Jun. 2007. http://www.answers.com/topic/wilcoxon-signed-rank-test) Spearman rank correlation Spearman rank correlation is a statistical method "used as a measure of correlation in nonparametric statistics when the data are in ordinal form" ("Spearman's rank correlation coefficient." McGraw-Hill Dictionary of Scientific and Technical Terms. McGraw-Hill Companies, Inc., 2003. Answers.com 15 Jun. 2007. http://www.answers.com/topic/spearman-s-rank-correlation-coefficient) and thus is used to find an association rather than a difference Kruskal Wallis "In statistics, the Kruskal-Wallis one-way analysis of variance by ranks (named after William Kruskal and W. Allen Wallis) is a non-parametric method for testing equality of population medians among groups. Intuitively, it is identical to a one-way analysis of variance with the data replaced by their ranks. It is an extension of the Mann-Whitney U test to 3 or more groups. "Since it is a non-parametric method, the Kruskall Wallis test does not assume a normal population, unlike the analogous one-way analysis of variance. Population variabilities among groups do not have to be equal. To get around this limitation of the Kruskal-Wallis test, some statisticians suggest using a robust test for equal locations among groups instead." ("Kruskal-Wallis one-way analysis of variance." (Wikipedia. Wikipedia, 2007. Answers.com 15 Jun. 2007. http://www.answers.com/topic/kruskal-wallis-test) Background: Chi square = "Pearson Chi-square test" = significance test used for comparing groups of categorical data. It compares frequencies and tests whether the observed rate differs signficantly from that expected if there were no difference between group s(ie, the null hypothesis). In practice, you get the pearson statistic and then look up P value. Mann whitney U test = If a group response is affected by more than one variable, then it may be of interest to evaluate thee relative impact that each of the individual variables have on a group outcome. This test is used to analyse several grouping variables (ie, it is a multivariate test) and so can adjust for confounding. It can therefore calculate an adjusted odds ratio. Wilcoxon signed ranks sum test is a non-parametric test that is equivalent to the (parametric) paird student's t-test. Spearman rank coefficient is the non-parameteric version of the (parametric) pearson correlation coefficient (r) Kruskall Wallis ANOVA tests the null hypothesis that k independent groups come from populations with the same median. Answer: D. Spearman rank order - is the odd one out as it looks for an association rather than a difference. Myles & Gin (2000): multiple pages (see index)

Question 230

SP16 [Feb04] The central limit theorem states that: A. Long option mentioning mean, median and mode B. Best measure of central tendency is mean C. With repeated sampling, distribution approaches that of normal distribution D. With increasing sample size the sample means approximate a normal distribution. E. If the 95% confidence interval includes zero then it is not statistically significant (Alt: E. 95% confidence interval contains zero )

Answer 230

The central limit theorem states that, "Regardless of the shape of the frequency distribution of observations of the original population, the frequency distribution of sample means of repeat random samples of size n tends to become normal as n increases." NOTE: this is a poorly remembered question A. ? B. the best measure of central tendency is mean, in a normal distribution. in a skewed distribution, the median may be a better measure. C. with repeated sampling (eg n\>100), distribution approaches that of normal distribution. This is true even if the distribution in the population the sample is taken from is not normal. D. is the best answer - "The distribution of an average will tend to be Normal as the sample size increases, regardless of the distribution from which the average is taken except when the moments of the parent distribution do not exist. All practical distributions in statistical engineering have defined moments, and thus the CLT applies."[1] E. if the 95% confidence interval includes zero then it may not be statistically significant, but it depends on the data being collected. is the bit on moments actually relevant? Erich 17:57, 21 Feb 2007 (EST) References Central Limit Theorem - Useful tutorial

Question 231

SP17 [Feb04] [Jul04] What kind of data is the ASA classification? A. Nominal. B. Ordinal C. Interval D. Ratio. E. Parametric.

Answer 231

A. No B. seems the most suitable answer C. interval data requires that the intervals be equal- this is probably not true of the ASA classification D. requirements as for interval data, but with a zero point- so this is definitely not the answer E. not really B. Is correct Ref. Myles & Gin Ref. ASA Classification: http://www.emergency-medicine.info/articles/asa-classification-grades.html

Question 232

SP18 [Feb04] [Jul04] Repeated statistical testing: A. Increases alpha (Type I) error B. Increases beta (Type II) error C. Decreases power D. ?

Answer 232

A is correct Repeated testing increases the likelihood of finding a difference due to chance alone, and incorrectly rejecting the null hypothesis. Thus it increases the chance of a type I error.

Question 233

SP19 [Jul04] Question about study power A. Refers to the ability of study to detect a difference if one exists. B. ? C. ? D. ?

Answer 233

Power is the likelihood of detecting a specified difference if it exists and is equal to 1-beta. A type II error is made when one accepts the Ho incorrected and the probability of that is called "beta". A. True Refs: Myles & Gin, p.25,22.

Question 234

SP20 SP19 SP21 A drug that has completed phase I trials : A. Has been tested on humans. I actually thought it said something like: A. has not been tested on humans B. next will be tested in target group C. nothing known about PK D. can be used in large teaching hospitals

Answer 234

Ignoring first A statement (obviously remembered incorrectly), answer is B. A. incorrect- phase 1 trials involve small numbers of healthy human volunteers B. correct- phase 2 trials involve patients suffering from the condition the drug is meant to treat, to determine effectiveness and appropriate doses. C. incorrect- PK are determined from phase 1 trials D. incorrect- use is not widespread or unrestricted within teaching hospitals and pertains only to patients enrolled in phase 2 of the study. Certain teaching hospitals and patients who fulfil inclusion criteria, consent etc will be involved in phase 3 RCTs but use is not unrestricted or commonplace in teaching hospitals until phase 4, postmarketing. Reference: Katzung Basic and Clinical Pharmacology p71, http://en.wikipedia.org/wiki/Clinical\_trial