CNS Flashcards

Question

Which of the following opiates is associated with seizures when given in high dose to patients with renal failure? A Morphine B Fentanyl C Pethidine D Codeine E Methadone

Answer 1

C Explanation Pethidine metabolite via liver cytochrome oxidases to Norpethidine and via liver carboxyesterases to Pethidinic acid and excreted by the kidneys Norpethidine is neurotoxic and thus build up of metabolites in the setting of repeated dosing and renal failure could lead to seizures Note: Morphine-3-glucuronide is a metabolite of morphoine produced by UGT2B7. It is not active as an opioid agonist but does have some action as a convulsant, which does not appear to be mediated through opioid receptors. It is mediated by GABA/glycinergic system. As a polar compound, it has a limited ability to cross the blood brain barrier, but renal failure may lead to its accumulation and result in seizures

Answer 2

A Explanation Strychnine antagonizes glycine receptors. Atropine is an antagonist at the M2 (muscarinic receptor). Butyrophenones antagonize the dopamine receptor

Answer 3

A Explanation Buspirone relieves anxiety without sedation; it is a non-benzodiazapine anxiolytic. It is a partial agonist at 5HT1 and a presynaptic antagonist at D2 (also D3 and D4). It is also a partial alpha one receptor agonist. There is no rebound anxiety on stopping drug. It takes a week to work, unsuitable in acute anxiety.

Answer 4

D Explanation Potency is the dose required to produce 50% of THAT drugs effect. Phenobarbitone may have a stronger effect but it is required in much higher doses than midazolam and is therefore not as potent.

Answer 5

C Explanation Chlorpromazine (a phenothiazine) causes medium EP side effects. Risperidone (atypical antipsychotic) cause low EP side effects. Haloperidol (a butyrophenone) causes very high side effects. Clozapine (atypical antipsychotic) cause low EP side effect

Answer 6

A Explanation Propranolol is a non-selective beta receptor blocker. It has no sympathomimetic activity. It is highly lipid soluble and readily crosses the BBB. Because of its Na channel blocking activity, it causes widening of the QRS and therefore VF arrest in overdose. It also causes seizures in overdose as it crosses the BBB. Treatment is bicarbonate. Half-life 3.5-6hrs. Bioavailability 26%

Answer 7

C Explanation Aspirin overdose does present with hyperthermia and agitation but does not cause mydriasis There is a spectrum of hypertensive disease it is important to understand. This case is most likely due to ANTICHOLINERGIC toxicity. Anticholinergic: "Hot as hell (hyperthermia), dry as a chip (xerostomia, anhydrosis), blind as a bat (mydriasis), red as a beet (erythema), mad as a hatter (agitated delirium). Onset <12hrs after drug. Rx supportive, occasionally can give physostigmine (centrally acting ACh-esterase) Serotonin syndrome: Sweaty, tachycardic, hot, very increased muscle tone, hyper-reflexia and clonus, dilated pupils, diarrhoea. Drugs implicated: SSRI/SNRI/TCA/tramadol/amphetamines/St John's wort. Rx supportive, cooling and benzos. Neuroleptic Malignant Syndrome: Slower onset. Pale, sweaty, tachycardia, pyrexial, lead-pipe rigidity, bradykinesia, bradyreflexia, normal or dilate pupils. Autonomic instability is key. Dopamine antagonists (antipsychotics) associated. Rx supportive, can consider dantrolene, bromocriptine occasionally. Malignant Hyperthermia: Sweaty, mottled, tachycardia, pyrexial, pupils normal, tone rigid, bradyreflexic, agitated. Associated with inhalational anaesthetics. Rx dantrolene. Salicylate toxicity: Not classically considered with the other 4 causes of fever and coma. Classically vomiting, tinnitus, hyperventilation with respiratory alkalosis and metabolic acidosis. Rx early diagnosis (can be hard) urinary alkalinisation and dialysis are effective.

Answer 8

D Explanation Reduced sweating is a sign of anticholinergic poisoning. Others include mydriasis-blindness, delirium, flushing. Remember “Dry as a Bone, Mad as a Hatter, Hot as a Hare, Red as a Beet, Blind as a Bat” - dry mouth - hallucinations/ agitation/ delirium - peripheral thermoregulatory inhibition - hot flushed skin - mydriasis / cycloplegia

Answer 9

B Frusemide will decrease serum potassium levels Spironolactone is a potassium sparing diuretic ACE inhibitor can cause hyperkalaemia as a side effect Methyldopa does not affect K levels

Answer 10

D Explanation Benztropine is a centrally acting antimuscarinic preparation. It is an antagonist at the M receptors in the basal ganglia. Benztropine reduces tremor and rigidity. It has little effect on bradykinesia. It greatest clinical application is in the treatment of Parkinson’s disease The side effects are typical antimuscarinic side effects: mydriasis, delirium, flushing, decreased sweating (remember: blind as a bat, mad as a hatter, dry as a chip, red as a beet). The other options here represent cholinergic poisoning.

Answer 11

B Explanation St John’s wort is an enzyme inducer and has been trialed for depression. It has not trialed, and should therefore not be used for viral disease or cancers. Side effects: mania, photosensitization, autonomic arousal. It can lower the clinical concentration and efficacy of a number of drugs including benzodiazepines by induction of cytocrome p450 enzymes cyp3A4 and cyp2C19 St John's wort is associated with a serotonin syndrome-like toxidrome, which may involve hyperthermia and hypertension if used in combination with other SSRIs. Alone it is unlikely to cause this toxidrome

Answer 12

A Explanation Atracurium’s duration of action 20-35m which is the same as vecuronium. Atracurium releases histamine slightly. It is an isoquinolone derivative. And is eliminated by Hofmann (non renal/liver) elimination Please note: I am not going to change the stem or the answer of the question BUT, Katzung does say that atracurium is inactivated by the Hofmann elimination in addition to hepatic metabolism. The table of the non depolarising drugs reads that it is only Hofmann elimination. Lots of online sources do not refer to hepatic metabolism of this drug. Also- the non-renal or liver dependant mechanisms- means Hoffman elimination (spotnaeous elimination) and or liver dependant mechanism. Poorly worded stem.

Answer 13

A Explanation Pancuronium’s (a steroid derivative) duration of action >35min. >80% kidney elimination. Vecuronium’s duration of action is 20-35m

Answer 14

B Explanation Phenytoin causes gum hyperplasia (NOT HYPERTROPHY). In the prescribed texts, it is not clearly stated, but ethosuximide can cause hirsutism

Answer 15

A Explanation The side effect of methaemoglobinaemia is due to the accumulation of one of prilocaine's metabolites o-toluidine, an oxidising agent. Extra: Case reports exist of methaemoglobinaemia occurring due to lignocaine https://pubmed.ncbi.nlm.nih.gov/2563761. However, the textbook seems to only report on Prilocaine aas a cause.

Answer 16

D Explanation These benztropine side effects are typical antimuscarinic: mydriasis, delirium, flushing, lack of sweating (remember: blind as a bat, mad as a hatter, dry as a chip, red as a beet). Levodopa (dopamine precursor): GIT upset, arrhythmias, dyskinesias, behavioral disturbance, on-off phenomena. Tolcapone/Entacapone (catechol-O-methyltransferase (COMT) inhibitor used as adjunct therapy in the symptomatic management of idiopathic Parkinson's disease): hepatotoxicity. Pramipexole (dopamine agonist): nausea and vomiting, postural hypotension and dyskinesias

Answer 17

D Explanation Lignocaine, Propanolol, Mexiletine and Moricizine shorten the RP in normal cells. Adenosine, Diltiazem, Esmolol, Flecanide,Tocainide and Verapamil have no effect on the RP of normal Cells

Answer 18

B Explanation Ipratropium is a quaternary amine-charged- and therefore poorly taken up by the brain and are relatively free-at low doses-of central nervous system effects. The other drugs are tertiary amines and are able to be taken up by the brain at lower doses.

Answer 19

B Explanation L-dopa is an immediate precursor of dopamine. L-dopa is rapidly absorbed from the small intestine, but its absorption depends on the rate of gastric emptying and the pH of the gastric contents. Food will delay the appearance of L-dopa in the plasma. Adding carbidopa will reduce GIT side effects. (only 20% will suffer as opposed to 80% without carbidopa). 1-3% enters the brain unaltered, but this number will be higher if given with dopa decarboxylase inhibitor. Concomitant administration of a peripheral dopa decarboxylase inhibitor (carbidopa) may reduce the daily requirement of levodopa by approximately 75%. L-dopa causes a positive Coombs test. L-dopa has a half life of between 1-3 hours but when administered with carbidopa, the plasma half lie is longer. Suddenly stopping L-dopa will cause tremor. This side effect part of the neuroleptic malignant syndrome which may occur on abrupt stopping of the drug. L-dopa does not stop the progression of parkinsonism but its early initiation will lower mortality.

Answer 20

B Explanation Stemetil is prochlorperazine: gives dopamine (D2) receptor blockade, especially dopaminergic receptors in CTZ (chemoreceptor trigger zone) of the medulla. Also has anticholinergic, alpha blocker and NA channel blocking effects. Indications: anti emetic, migraines, not for psychotic episodes. Side effects: muscarinic (anticholinergic) blockade : dry mouth,/urinary retention, constipation, loss of accommodation, flushed (remember :red as a beet, mad as a hatter, blind as a bat, dry as a crisp). Alpha blockade: orthostatic hypotension. Another life threatening side effect is :Neuroleptic malignant syndrome (A high fever, stiff muscles, confusion, irregular pulse or blood pressure, tachycardia, sweating, arrhythmias.

Answer 21

B Explanation Direct acting cholinomimetics (Pilocarpine) and Indirect acting cholinomimetics (Physostigmine): constricts ciliary and iris circular muscle = Decrease IOP Prostaglandin analogues (Latanoprost): Relax ciliary muscle and modulate extracellular matrix = Increase uveoscleral outflow tract = Decrease IOP Beta-adrenoreceptor antagonists (Timolol): Block B adrenoreceptors on ciliary muscle = Decrease aqueous secretion = Decrease IOP Alpha-2 adrenoreceptor agonists (Brimonidine) decreases aqueous secretion and Non selective alpha agonist (adrenaline) increases uveoscleral outflow tract = Decrease IOP Carbonic anhydrase inhibitors (Acetazolamide): Decrease HCO3 formation and aqueous secretion = Decrease IOP

Answer 22

C Explanation Pralidoxime is used to reactivate acetylcholinesterase inhibited by organophosphates. It is only effective if given before irreversible binding of the OP and the acetylcholinesterase has occurred. Re-establishment of enzymic function rapidly reverses the nicotinic and muscarinic effects of OP poisoning. It is used concurrently with Atropine. Atropine is usually administered prior to pralidoxime and the effects at muscarinic receptor are synergistic. Atropine is only effective at muscarinic receptors and not at nicotinic receptors

Answer 23

A Explanation A. Lithium Carbonate is the drug treatment of choice in bipolar, especially the acute manic episodes and relapse prevention. B. Due to their high plasma protein binding, they usually have long half-lives. C. Side effects of SSRI are usually less and better tolerated than those of TCAs. D. SSRIs are indicated in major depression, obsessive-compulsive disorder (OCD), Body dysmorphic disorder (BDD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder and social phobia (social anxiety disorder).

Answer 24

D Explanation Diazepam has a half life of 20-40hrs. It is used for any seizure disorder. In contrast to barbiturates, benzodiazepines do not change hepatic drug metabolizing enzyme activity with continuous use. Benzodiazepines are widely used as sedative hypnotics They bind to the GABA-a receptor in the CNS. This receptor functions as a chloride ion channel is activated by the inhibitory neurotransmitter GABA. Benzodiazepines appear to increase the efficiency of GABAergic synaptic transmission. The benzodiazepines do not substitute for GABA but appear to enhance GABA’s effect allosterically without directly activating GABA-a receptors or opening the associated ion channel. There is an increase in the frequency of channel opening events Benzodiazepines cross the placenta. If given during the predilvery period, they may contribute to the depression of neonatal functions. They are detectable in breast milk and may exert depressing effects in the nursing infant

Answer 25

D Explanation Dantrolene has a spasmolytic function outside the CNS. It reduces skeletal muscle strength by interfering with excitation–contraction coupling in the muscle fiber. Dantrolene interferes with the release of activator calcium via the sarcoplasmic reticulm calcium channel, possible by binding to the same receptor used by ryanodine. Malignant hyperthermia results in massive calcium release, massive muscle muscle contraction, hyperthermia and lactic acid production. Triggers are often general anaesthesia and neuromuscular blockers. Dantrolene is used to stem the calcium release

Answer 26

B Explanation In acute Lithium overdoses, neurological symptoms, if they develop, are delayed reflecting slow redistribution into the CNS. The earliest and most frequent neurological sign is tremor. Other CNS neurotoxic symptoms rarely progress beyond tremor provided adequate lithium excretion is maintained. Source: Toxicology Handbook, Murray et al

Answer 27

B Explanation Tranylcypromine is a MAOI, which will inhibit the catabolism of dietary amines-prevents breakdown of tyramine in the gut. When foods containing tyramine (cheese, tap beer, soy products and dried sausage) are ingested, the patient may develop a hypertensive crisis. The mechanism is poorly understood but is thought that tyramine displaces noradrenaline from the storage vesicles and enhance peripheral noradrenergic effects, including raising blood pressure dramatically. Similarly drugs with sympathommimetic properties may cause significant hypertension when combined with MAOIs. Over-the-counter preparations that contain pseudoephedrine and phenylpropanolamine are contraindicated in patients taking MAOIs. Pethidine is associated with serotonin syndrome when given with the MAOI drug group

Answer 28

A Explanation The antipsychotics have antipsychotic properties as well as extrapyramidal (EP) toxicity, sedative action and hypotensive and anticholinergic effects. These side effects were traced to the blocking effects of alpha, 5-HT2, H1 receptors and muscarinic receptors Aripiprazole is a second generation antipsychotic drug: These drugs have complex pharmacology, but they share a greater ability to alter 5-HT2A-receptor activity than to interfere with D2-receptor action. In most cases, they act as partial agonists at the 5-HT1A receptor, which produces synergistic effects with 5-HT2A receptor antagonism. Most are also either 5-HT6 or 5-HT7 receptor antagonists. It seems that there is no demonstrable antipsychotic effect after blocking any other receptor than the D2 (dopamine). D1, D3, D4 receptors have been tested with no antipsychotic effects. Haloperidol, a butyrophenone, is the most widely used antipsychotic. It has the highest EP toxicity relative to its antipsychotic effect. Piperazine, a phenothiazine, has high EP as well. Thioridazine, a phenothiazine, has the greatest anticholinergic side effects (anti muscarinic). Atypical antipsychotics: clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine and aripiprazole. They have less EP effects. Chlorpromazine has the greatest affinity for the alpha-receptor and thus causes hypotension. The answer to this question is found in the following paragraph: Hyperprolactinemia in women results in the amenorrhea-galactorrhea syndrome and infertility; in men, loss of libido, impotence, and infertility may result. Hyperprolactinemia may cause osteoporosis, particularly in women. If dose reduction is not indicated, or is ineffective in controlling this pattern, switching to an atypical agent that does not raise prolactin levels, eg, aripiprazole, may be indicated. Katzung: Basic and clinical pharmacology, 15edition

Answer 29

B Explanation Sensitivity to block: Sympathetic postganglionic, dorsal root pain (type C fibres) and preganglionic autonomic (type B fibres)=4 + sensitive Type A fibres: Pain and temp (delta fibres)=3+ sensitive Muscle spindles (gamma fibres) and touch, pressure (beta fibres)= 2+ sensitive Proprioception and motor (alpha fibres)= 1+ sensitive Note: beginning with sympathetic transmission and progressing to temperature, pain, light touch and finally motor block. Extra: Spinal block reflects this - the most vulnerable components achieving greater dermatomal (cephalad) spread. Loss of cold sensation roughly two segments above analgesic level for pinprick (pain), which will in turn be roughly two segments above loss of light touch.

Answer 30

C Explanation TCA block the following receptors: Noradrenaline, histamine, serotonin, muscarininc, alpha receptors. They also block sodium channels and in overdose lead to ventricular tachycardia and fibrillation. Note: The MCQ option may include nicotinic receptors. A web-based search does report that TCA can block these receptors They do not block dopamine receptors. The MCQ may offer GABA receptors- according to current web sources- they do antagonize the GABA receptor Extra: Tricyclic antidepressants impose their therapeutic effects by inhibiting presynaptic reuptake of norepinephrine and serotonin in the central nervous system (CNS). This effect in the CNS can cause seizures. TCAs are weakly basic, and an acidic environment facilitates the formation of the ionized form and potentiates this effect. In cases of toxicity, TCAs block a number of receptors, including peripheral alpha-adrenergic, histaminic, muscarinic, and central serotonin receptors. Blockade of alpha-adrenergic receptors can cause hypotension. Blockade of muscarinic receptors can cause signs of anticholinergic toxicity, such as tachycardia, fever, dry mouth and skin, decreased bowel sounds, and altered mental status. Blockade of histamine receptors can also cause altered mental status. TCAs can cause cardiac toxicity. Blockade of fast sodium channels in myocardial cells slows the action potential and provides a membrane stabilizing effect. The characteristic QRS prolongation seen in TCA overdose occurs secondary to prolongation of phase “0” of the myocardial action potential. This effect can lead to heart block and bradycardia. QT prolongation seen in cases of TCA overdose occurs due to potassium channel blockade that may potentially cause torsades de pointes. TCAs can also exert a quinidine-like toxic effect on the myocardium that can cause decreased cardiac contractility and hypotension Source: Tricyclic Antidepressant Toxicity Muhammad M. Khalid; Muhammad Waseem

Answer 31

D Explanation Note: Difficult question. Not sure of the answer. A closer look at Histamine reveals that it is a neurotransmitter and a neuromodulator and in most tissues histamine is sequestered and bound in granules (vesicles) in mast cells or basophils Looking through Ganong: Norepipherine: is sequestrated into presynaptic vesicles Ach: is transported into a storage vesicle. By definition, Ach is a neurotransmitter of the parasympathetic nervous system Serotonin: is concentrated in vesicles. It is also found in the brainstem where cell bodies synthesise, store and release it Histamine: It seems to be more of a stimulant of sensory nerve endings via H1, rather than being released form vesicles. Histamine is sequestrated into vesicles of mast cells, rather than vesicles of nerve endings. H3 agonists induce the release of ACH, amine and peptide transmitters (rather than acting as vesicle bound neurotransmitters themselves) Extra: it may be noradrenaline as noradrenaline is stored as dopamine, and then converted to noradrenaline once inside the actual vesicle. I will let you decide. From a subscirber...perhaps the answer is ACh... in the current TB it says about noradrenaline "it is found in characteristic small vesicles that have a dense core (granulated vesicles") so Imaybe implies that vesicles are not in fact granules. Extra: a thorough explanation for a subscriber The answer is as you state Noradrenaline. The wording of the question is lacking, having seen this before and from the prescribed text, my feeling is that what is meant by the question is " Which of these neurotransmitters is NOT stored, preformed, in secretory granules". Grammar is everything. The answer would then be as stated. L Dopa is converted to Dopamine, dopamine is taken up into the secretory vesicle and then NA is FORMED in the vesicle itself, as opposed the the others where it is ACh, Histamine and Seretonin that are transported into the vesicle, with no additional steps whilst inside the vesicle itself. Agreed this is a poor question, however I believe your answer to be correct. I think they just got "in" and "preformed" the wrong way round in the question. Moreover, the nomenclture of granules is outdated, it is interchangeable with vesicle in this instance, it relates to chromatin granules in the adrenal medulla for example. The use of vesicle and granule are somewhat location dependent depending on nomenclature at the time of discovery and other factors. In regard neurotransmission the accepted current nomenclature in scientific text is: Small synaptic vesicles, SSV (which are clear cored) Large dense cored vesicles (LDCV) Small dense cored vesicles (SDCV) as evidenced by Merighi et al Front. Cell. Neurosci., 21 August 2018 | https://doi.org/10.3389/fncel.2018.00272 I believe, but don't quote me on this, the dense vs clear is a related to their initial identification process, where the larger MW contents of SDCV / LDCV appeared darker as they have higher MW and proteinaceous content than the smaller monoamines. ChatGPT: C Acetylcholine (ACh): Unlike the other neurotransmitters listed, acetylcholine is not stored in preformed secretory granules. It is synthesized in the cytoplasm of the nerve terminal from acetyl-CoA and choline by the enzyme choline acetyltransferase and is then transported into vesicles for release. However, the vesicles are not considered "preformed secretory granules" like those seen with other neurotransmitters. Serotonin, Histamine, Noradrenaline: These neurotransmitters are synthesized and stored in preformed secretory granules within the nerve terminal. These granules allow rapid release of neurotransmitter upon stimulation.

Answer 32

D Explanation It seems that there is no demonstrable antipsychotic effect after blocking any other receptor than the D2 (dopamine). D1, D3, D4 receptos have been tested with no antipsychotic effects. Most of the newer antispychotics agents and some of the traditional ones have a higher affinity for 5-HT2A receptor than D2, suggesting an important role for the serotonin system in the aetiology of schizophrenia and the action of these drugs.

Answer 33

B Explanation Mesolimbic-mesocortical pathway= behaviour and psychosis Nigrostriatal pathway= coordination of voluntary movement Tuberoinfundibular pathway= inhibits prolactin form the anterior pituitary Medullary-periventricular pathway= ?eating behaviour Incertohypothalamic pathway= regulates the anticipatory motivational phase of copulatory behaviour in rats

Answer 34

B Explanation Phenobarbitone is the oldest of the current anti-seizure medications available. Due to its side effects, it is considered the first choice of anti-seizure medication only in infants. pKa is similar to that of plasma pH=7.4. Mechanism of action is through enhancement of inhibitory processes and diminution of excitatory transmission. At higher doses it suppresses high frequency repetitive firing in neurons through an action on Na conductance. It also enhances GABA receptor mediated prolonged opening of the Cl channel. Finally it plays a role in suppression of glutamate-mediated excitation. It is used in the treatment of partial and generalized seizures, but there is no evidence for its use in the management of absence seizures. All barbiturates are metabolised in the liver and then excreted in the urine. With the EXCEPTION of phenobarbitone (20-30%), only insignificant quantities of barbiturates are excreted unchanged in the urine

Answer 35

E Explanation Neuroleptic malignant syndrome (NMS) is a life threatening neurologic emergency associated with the use of neuroleptic agents. The aetiology of NMS remains controversial. Although a central deficiency of dopaminergic neurotransmission at nigrostriatal, mesolimbic and hypothalamic-pituitary pathways appears pivotal. The syndrome develops in 0.02-2.5% of people taking neuroleptic medication. The onset of NMS usually occurs over 24-72 hours. It presents with a triad of CNS, neuromuscular and autonomic changes. CNS: Altered mental state (in 82% of patients) agitated delirium with confusion rather than psychosis. Catatonic signs and mutism can be prominent. Progression to stupor and eventual coma. Neuromuscular: Increased tone with ‘lead-pipe’ rigidity, generalised bradykinesia or akinesia – Mutism and staring- Dysarthria – Dystonia and abnormal postures – Abnormal involuntary movements – Incontinence Autonomic instability: Hyperthermia – Tachycardia – Hypertension – Respiratory irregularities – Cardiac dysrhythmias Management: Attention to ABC with rapid sequence intubation if coma or hyperthermia >39.5 degrees celcius. Detect and correct hyperthermia with continuous core temperature monitoring from 38.5 and RSI with neuromuscular paralysis above 39.5. Dantroline is indicated for severe muscle rigidity and fever. Bromocriptine is a dopamine agonist and can be given in moderate to severe cases to improve autonomic instability and fever. Hypertension and tachycardia may be initially treated with a parental vasodilator such as GTN or nitroprusside. Any agent with dopamine antagonist effects should be avoided.

Answer 36

B Explanation MAOIs are associated with a sever drug interaction when combined with SSRIs. Life threatening serotonin syndrome can develop. The serotonin syndrome is due to overstimulation of the 5-HT receptors in the central gray nuclei and the medulla. Symptoms range from mild to lethal and include a triad of cognitive (delirium and coma), autonomic (hypertension, tachycardia and diaphoreses) and somatic (myoclonus, hyperreflexia and tremor) effects. Most SSRI antidepressants should be discontinued for at least 2weeks before starting a MAOI. Fluoxetine, because of its long half-life, should be discontinued for 4-5weeks. Conversely, an MAOI must be discontinued for at least 2 weeks before starting a serotonin agent Note: There is a potential for drug interaction with all antidepressants, but the most serious of these involve the MAOIs and to a lesser extent the TCAs

Answer 37

A Explanation Sodium valproate (SV) inhibits the metabolism (increasing concnetration) of phenobarbitol, phenytoin, ethosuximide and carbamazepine (epoxide metabolite), leading to higher steady state concentrations of these agents. SV dramatically decreases the clearance of lamotrigine, resulting in a two-threefold prolongation of its half-life. SV may decrease the olanzapine plasma concentration-mechansim unknown-(implying a increase in metabolism). This may result in a insufficient effect of olnazapine when taken with SV

Answer 38

D Explanation Lithium is rapidly absorbed, and plasma conc. peak within one-half to three hrs following oral administrations. Gastrointestinal absorption of lithium carbonate tablets or capsules appears to be virtually complete (95% to 100%). The absorption of sustained-release lithium products is more variable, and ranges from (60% to 90%). Lithium solutions appears to be rapidly and completely absorbed and plasma conc. peak within 60 min(30min-2Hrs). The usual volume of distribution for lithium is approximately (0.7 L/kg). T1/2=20hrs, no plasma protein binding It is NOT metabolised and excreted virtually entirely in the urine

Answer 39

A Explanation Renal clearance of lithium is reduced by 25% with thiazide diuretics and the dose may need to be reduced by a similar amount. A similar reduction occurs with the newer NSAIDS. There is no issue with Aspirin however. Paracetamol is also safe. All neuroleptics with the possible exception of clozapine may produce more severe extrapyradimal side effects when combined with lithium

Answer 40

B Explanation Propofol is formulated as an emulsion containing 10% soybean oil, 2.25% glycerol and 1.2% lecithin, the major component of the egg yolk phosphatide fraction

Answer 41

A Explanation Transient neurological symptoms (TNS) is a rare but devastating neurological complication that can occur with neuraxial (spinal and epidural) administration of local anaesthetic. TNS is a syndrome of transient pain and or dysaesthesia. The pain expeirenced can often be worse than the pain induced by the surgery alone. Lignocaine seems to be the drug most likely to cause TNS. The risk of other local anaesthetic causing TNS varies. Procaine and mepivacaine reduces the risk of TNS slightly. Risk of TNS with bupivacaine, prilocaine and chloroprociane is negligible

Answer 42

B Explanation Bupivacaine requires low concentrations (<0.25%) to achieve prolonged peripheral anaesthesia and analgesia for postoperative pain control and pain control during surgery. It is often the agent of choice for epidural infusions for postoperative pain control and for labour analgesia. It is regarded as a very safe spinal anaesthetic agent, with a relatively favourable therapeutic index with respect to neurotoxicity and the development of transient neurologic symptoms.

Answer 43

B Explanation Certain vestibular disorders respond to antimuscarininc drugs (and to antihistaminic agents with antimuscarinic effects). Scopolomine is one of the oldest remedies for seasickness and is affective as most other newer agents. Not sure about this question. The textbook says both antimuscarinic drugs as well as first generation H1 antagonists are the most effective agents for motion sickness.

Answer 44

B Explanation Tramadol-central acting analgesia, mechanism of action-blockade of serotonin reuptake. Toxicity includes association with seizures and the drug is relatively contraindicated in patients with a history of epilepsy and with use of other drugs that lower the threshold for seizures. Another serious risk is the development of serotonin syndrome, especially if combined with a SSRI antidepressant Note: In Australia the most common drugs causing toxic seizure are venlefaxine, bupropion, tramadol and amphetamines

Answer 45

B Explanation Thiopentone produces dose dependent CNS depression ranging from sedation to general anaesthesia. They do NOT produce analgesia. Some evidence suggests that they cause hyperalgesia. It is a potent cerebral vasoconstrictor and produce predictable decrease in cerebral blood flow, cerebral blood volume and intracranial pressure. They decrease CMRO2. They may provide neuroprotecttion from focal cerebral ischaemia (CVA, surgical resection, temporary clips during aneurysm clipping) but not form global cerebral ischaemia (due to cardiac arrest). They suppress cerebral electrical activity-anticonvulsants

Answer 46

B Explanation Chlorpromazine has strong anti alpha and 5HT2A effects, followed by anti dopamine 2 and 1. Clinical potency is low, extrapyramidal toxicity is moderate. Orthostatic hypotensive action is high. Sedative action is also high. Other anti alpha effects include failure to ejaculate and impotence. From Katzung: chlorpromazine: many adverse side effects, especially automimic- orthostatic hypotension, impotence and failure to ejaculate.

Answer 47

A Explanation Diazepam is metablised into oxazepam (an active metabolite) Alprazolam and triazolam are metabolised into alpha-hydroxy metabolites (active) Chlordiazepoxide is metabolised into desmethylchlordiazepoxide (active) Another way the question could (or should be asked): "Which of the following benzodiazepines have inactive metabolites?" (None of the benzodiazepines listed are inactive, but lorazepam is the only one listed with inactive metabolites.)

Answer 48

C Explanation The organ system effects of propofol CNS: hypnotic effects, no analgesia. Reduction in cerebral blood flow, reduction in basal cerebral metabolic rate for oxygen, reduction in intracranial and intraocular pressure. Burst suppression of the EEG CVS: most pronounced decrease in blood pressure compared to other induction drugs. Vasodilation of both arteries and veins leading to reduction in preload and afterload. Inhibition of the baroreflex resulting in only a modest increase in heart rate Rep: respiratory depression and apnoea. Greater reduction in upper airway reflexes (than Thiopentone) allowing easier placement of a LMA Other effects: Propofol does not augment other neuromuscular blockade. Propofol has desirable antiemetic properties. Pain at site of IVI injection can be reduced with the co-administration of lignocaine, slow injection rate and larger veins. Mechanism of action: potentiation of the chloride current mediated through the GABAa receptor complex

Answer 49

B Explanation Domperidone is extremely well tolerated. Because it does not cross the blood brain barrier to a significant degree, neuropsychiatric and extrapyramidal effects are rare. Metoclopramide, the phenothiazine (prochlorperazine, promethazine) and the butyrophenones (droperidol) cause extrapyramidal side effects-restlessness, dystonia and parkinsonian symptoms.

Answer 50

A Explanation Benzodiazepines are allosteric modulators at the GABA-A receptor, where they increased chloride channel opening frequency.

Answer 51

B Explanation Phenytoin exhibits dose-dependent elimination, with a switch from first to zero order kinetics at increasing concentrations predisposing to toxicity. Carbamazepine is a CYP inducer and induces its own metabolism. Valproate undergoes hepatic metabolism with first order kinetics. Keppra is metabolized primarily in the blood and thus has minimal drug interactions. Extra: Most antiseizure drugs follow linear (first order) kinetics, in which a constant fraction per unit time of the drug is eliminated (elimination is proportional to drug concentration). In the case of phenytoin, as dose increases, there is saturation of metabolism and a shift from first order to zero order kinetics, in which a constant quantity per unit time is metabolised. A small increase in dose can result in a large increase in concentration. Orally administrated gabapentin also exhibits zero-order kinetics, but in contrast to phenytoin where metabolism can be saturated , in the case of gabapentin, gut absorption, which is mediated by the large neutral amino acid system L transporter , is susceptible to saturation. The bioavailability of gabapentin falls at high dose as the transporter is saturated so that increase in blood levels do not keep pace with increase in dose.

Answer 52

B Explanation Adverse effects of carbamazepine include CNS effects (nystagmus, diplopia, ataxia, sedation at high doses), GI upset, LFT derangement, benign leukopenia, erythematous skin rash, hyponatraemia. Overdose causes seizures and cardiac toxicity.

Answer 53

B Explanation Beta-blockers decrease aqueous humour secretion.

Answer 54

D Explanation Cyclopentolate is an anti-muscarinic which causes mydriasis (pupillary constrictor muscle depends on muscarinic cholinoceptor activation) and cycoplegia (weakened contraction of ciliary muscle) Accurate measurement of refractive error in uncooperative patients, e.g., young children, require ciliary paralysis. Also, mydriases greatly facilitates ophthalmoscopic examination of the retina. Therefore, antimuscarinic drugs, administered topically as eye drops or ointment, are very helpful in doing a complete exam. For older adults and older children, the shorter acting drugs are preferable. For younger children, the greater efficacy of atropine is sometimes necessary, but the possibility of antimuscarinic poisoning is correspondingly increased. Interesting, antimuscarinic drugs should never be used for mydriasis unless cycloplegia or prolonged action is required. Alpha-adrenoceptor stimulant drugs e.g. phenylephrine, produce a short-lasting mydriasis that us usually sufficient for fundoscopy examination. Antimuscarinic drugs (duration of effect) Atropine 5-7 days Scopolamine 3-7 days Homatropine 12-24hrs Cyclopentolate 3-6hrs Tropicamide 15-60min

Answer 55

B Explanation Hepatic metabolism accounts for the clearance of all benzodiazepines. Most benzodiazepines undergo microsomal oxidation (phase I reactions), including hydroxylation. The metabolites are subsequently conjugated (phase II reactions) to form glucuronides that are excreted in the urine

Answer 56

B Explanation In the CNS, cocaine blocks the uptake of dopamine, serotonin and noradrenaline through their receptive transporters.The block of the dopamine transporter (DAT), by increasing dopamine concentrations in the nucleus accumbens, has been implicated in the rewarding effects of cocaine.

Answer 57

C Explanation Risperidone has been shown to cause neuroleptic malignant syndrome. The initial symptom is marked muscle rigidity- a lead pipe rigidity. Muscle type creatine kinase are usually elevated, reflecting muscle damage.

Answer 58

B Explanation Amitriptyline in overdose can cause anti-cholinergic features with quinidine-like depressant effects on cardiac sodium channel (slowed conduction with a wide QRS interval and depressed cardiac contractility)

Answer 59

B Explanation The prototype SSRI, fluoxetine, differs from other SSRIs in some important respects. Fluoxetine is metabolized to an active product, norfluoxetine, which may have plasma concentrations greater than those of fluoxetine. The elimination half-life of norfluoxetine is about three times longer than fluoxetine and contributes to the longest half-life of all the SSRIs. As a result, fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered to mitigate the risk of serotonin syndrome.

Answer 60

B Explanation The most common dose-related adverse effects of carbamazepine are diplopia and ataxia. The diplopia often occurs first and may last less than an hour during a particular time of day. Rearrangement of the divided daily dose can often remedy this complaint. Other dose-related complaints include mild gastrointestinal upsets, unsteadiness, and, at much higher doses, drowsiness. Hyponatremia and water intoxication have occasionally occurred and may be dose related.

CNS Flashcards

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