Pharmacology Principles ( 15% ) Flashcards

Question

Define potency

Answer 1

The **amount of drug required to produce an effect** of a certain intensity**.** Concentration or dose required to produce 50% of maximal effect, measured by ED50 or EC50. Dependent on affinity of drug for receptor and number of receptors available.

Answer 2

Maximum effect a drug can produce when all receptors are occupied, irrespective of concentration or dose required to achieve that response. Determined by the drugs mode of interaction with the receptor or by characteristics of the receptor-effector system involved.

Answer 3

A and B have similar potency. A and B are more potent than C which is more potent than D for mild-mod effects. A, C, & D have similar efficacy and greater efficacy than B. B is a partial agonist (produces less than maximal response despite full receptor occupancy)

Answer 4

Fentanyl 100x more potent 0.1mg fentanyl = 10mg morphine

Answer 5

dose required to produce desired effect vs dose required to produce undesired effect. (TD/effective dose)

Answer 6

d) adenylyl cyclase. (Effector) Katzung 12th ed p.25

Answer 7

a) Intracellular receptors e.g. response elements Lipid-soluble / cholesterol-derived, they can cross the cell membrane to interact with internal cellular elements.

Answer 8

a) regulatory proteins Dont know why or how, dont understand the question.

Answer 9

e) Thyroid hormone Binds internal cellular elements / nuclear receptors. Others all act on ligand-regulated transmembrane enzymes (insulin, PDGF, EGF, ANF)

Answer 10

a) Catecholamines via α1 receptor * b) Catecholamines via β receptor * c) Glucagons * d) FSH * e) Vasopressin (V2 receptor)

Answer 11

c) ACh nicotinic. Ion channel for neuromuscular transmission. (Serpentine receptor is another name for GPCR)

Answer 12

c) Vitamin D and intracellular receptor * a) Insulin and G receptor protein. (Tyrosine kinase) * b) Mineralocorticoid and tyrosine kinase receptor. (Intracellular) * d) Adrenaline and ligand gated channel receptor. (GPCR) * e) PDGF and cytokine receptor. (Cytokine rec.s are a subset of ligand regulated transmembrane enzymes whose mechanism is similar to tyrosine kinases. They bind EPO, growth hormone and several interferons)

Answer 13

d) cAMP’s effector is adenylyl cyclase * a) compared to cAMP, cGMP is more versatile and ubiquitous carrier of diverse messages * (cAMP is more versatile and wide-spread throughout the body; cGMP only has a few specific roles eg relaxes smooth muscle) * b) phosphoinositides act independently of PLC * IP3 is a phosphoinositide. PLC interacts with DAG and IP3 to causes a rise in Ca2+ * c) upregulation of cAMP degradation is one way theophylline produces its effects * Theophylline is a phosphodiesterase inhibitor, causing an increase in cAMP

Answer 14

a) butoxamine, terbutaline (ß2 adrenergic receptors; antagonist and agonist respectively) * b) phenyoxybenzamine, cyclopentolate * Irreversable alpha blocker / muscarinic antagonist * c) pilocarpine, bethanechol * muscarinic (M3) agonist / muscarinic agonist * d) oxymetazoline, dobutamine * alpha 1 agonist + alpha 2 partial agonist / beta-1 agonist * e) bromocriptine, pranipexole * dopamine agonist / dopamine agonist

Answer 15

a) α1 Gq -\> phospholipase C activation -\> DAG + IP3 -\> Ca2+ * b) α2 * Gi -\> adenalate cyclase inhibition -\> reduced cAMP * c) β1 * Gs -\> adenalate cyclase activation -\> increase cAMP * d) β2 * Gs + Gi * e) DA

Answer 16

a) Induction takes 7-10 days to reach maximum. (Several days)

Answer 17

c) Phenytoin

Answer 18

b) Ethanol displays dose dependent kinetics (Ethanol has zero-order kinetics - it quickly saturates alcohol dehydrogenase, and recreational doses are relatively very large)

Answer 19

d) Chloramphenicol (is an inhibitor of 2C19) Cigarette smoke induces 1A2 Phenytoin induces all except 1A2 ??Spironolcatone is a suicide-inhibitor though

Answer 20

d) Diazepam

Answer 21

e) Rifampicin | (Induces all P450 subtypes)

Answer 22

b) Lipid diffusion (due to the large number of lipid barriers in the body)

Answer 23

e) lipid:aqueous partition coefficient Area, permeability coefficient, concentration gradient, membrane thickness are all components of Fick's law: “The magnitude of the diffusing tendency from one region to another is directly proportional to the cross-sectional area across which diffusion is taking place and the concentration gradient, or chemical gradient, which is the difference in concentration of the diffusing substance divided by the thickness of the boundary”

Answer 24

b) alkalinising the urine Aspirin is a weak acid H-drug (weak acid in unionised form) + OH- (alkali urine) ←→ drug- (ionised form) + H2O More alkali urine will push the equation to the right, creating more ionised aspirin. Polar molecules are poorly reabsorbed in the renal tubules and hence have increased excretion

Answer 25

e) Drugs exhibit capacity limited elimination * a) Rate elimination is proportional to concentration (first order) * (Clearance has no real meaning in zero-order kinetics as elimination approximates Vmax) * b) Clearance can be calculated from AUC * c) Clearance does not depend on drug concentration * d) Clearance is always constant.

Answer 26

e) Enteric coating * a) first pass metabolism * b) P glycoprotein (reverse transports drugs out of cells) * c) Ionization of drug (cannot cross cell membranes or basement membrane depending on polarity) * d) Drugs highly extracted by liver (same as first pass metabolism)

Answer 27

e) Diazepam

Answer 28

d) Rectal suppositories (about 50% undergoes first pass metabolism)

Answer 29

e) VoD * a) Clearance (Most important factor that impacts dosing; dosing rate = clearance x target concentration) * b) Target concentration (higher target = higher dose needed; concentration wanted can vary between indications for same drug) * c) Oral bioavailability (dosing needs to acount for bioavailability - dosing rate is divided by bioavailability to give final dosing rate) * d) Dosing interval (shorter interval = lower dose needed)

Answer 30

d) VoD Elimination (or maintenence dose) = clearance x concentration Clearance = elimination (or MD) / concentration dose will affect concentration; blood flow and liver/renal function will affect elimination rate

Answer 31

b) Binding to plasma proteins (Will have a high serum concentration, and thus seem to have a low VoD)

Answer 32

a) cP450 heme reduction Cytochrome P450 is a type of heme protein whose purpose is to oxidise molecules in phase 1 metabolic reactions In order to oxidise molecules, it must first be reduced, creating the limiting step NADPH-P450 reductase is a flaviprotein whose role is as an electron doner (ie it reduces other molecules, and is itself oxidised)

Answer 33

e) Acetylation "Other phase I reactions include other oxidation reactions (eg alcohol dehydrogenase), reduction reactions, deamination, and hydrolysis reactions (eg esters and amides, aspirin)"

Answer 34

d) Epoxidation ## Footnote Phase 2: Conjugation system that adds a large polar molecule to the reactive side-group formed in Phase I Examples of groups added: glucuronyl, sulfate, methyl, ethyl, glycyl, glutathione

Answer 35

a) Chloramophenicol Is an inhibitor of 2C19

Answer 36

c) Isoniazid Cimetedine - potent inhibitor Ketoconazole - potent inhibitor Chloramphenical - inhibits 2C19 Erythromycin - inhibits 3A4

Answer 37

a) 3A4 75% of all drugs are metabolised by 3A4 (and 3A5 which is the same but slower actioning) and 2D6

Answer 38

d) Procainamide Procainimide is acetylated at a rate which is genetically determined (ie not hepatic blood flow determined)

Answer 39

c) paracetamol

Answer 40

d) Amount of drug in the body/concentration of drug in plasma * a) Is always a real volume (false - it is an *apparent* volume) * b) Amount of drug in plasma/concentration in body (wrong - practically you can measure the concentration in the plasma but not the total amount) * c) Concentration of drug in plasma/amount of drug in blood (wrong) * e) AUC/dose (wrong)

Answer 41

??d) A greater reduction in conjugation compared to oxidation Phase 1 metabolism (oxidation) reduces compared to Phase 2 (conjugation) Body fat increases (40% vs 25%) and body water decreases (50% vs 60%) with reducing muscle mass (10% vs 20%) Absorption does not change (unless drug eg antacid or illness induced) Answer is noted as d) but perhaps is a) (unsure of proportion of people who have a reduced CrCl in age but 2/3rds *seems* reasonable)

Answer 42

b) Grapefruit juice inhibits cyclosporin metabolism (grapefruit also inhibits statins, CCBs, R-warfarin, fentanyl, diazepam) * a) ETOH enhances methanol metabolism (reduces it - competitive ligands for alcohol dehydrogenase) * c) Phenytoin inhibits Theophylline metabolism (phenytoin is a potent *inducer* of all except 1A2) * d) Rifampicin inhibits OCP metabolism (rifampicin is a potent inducer of all) * e) Griseofulvin inhibits Warfarin metabolism (I dont know what this drug is - feel free to update)

Answer 43

e) is equivalent to absorption minus the extraction rate for an orally administered drug * a) less than 100% by any route (100% via IV by definition - ie proportion that gets to the blood stream) * b) is the percentage of a drug formulation that is absorbed (needs to also get past hepatic metabolism) * c) is not affected by first pass metabolism (is very much affected) * d) is close to 80% for oral verapamil (20-35% - undergoes a lot of first pass metabolism) *Bioavailability = fraction of unchanged drug reaching the systemic circulation following administration by any route*

Answer 44

a) its effect on bioavailability is expressed as the extraction ratio where ER = CL (liver)/Q (liver) * b) it affects the volume of distribution * c) it reduces the bioavailability of oral morphine to 15% (33% [100% absorption, 2/3rds first pass metabolism]) * d) the extraction ratio of phenytoin is higher (E = 0.03; cf 0.66 for morphine ie morphine undergoes more 1st pass metabolism) * e) it makes it impossible to attain therapeutic levels of lignocaine using oral dosage (oral bioavailability of lignocaise is 35%)

Answer 45

a) Is the amount of drug eliminated / concentration of the drug Clearance (L/h) = elimination (mg/h) / concentration (mg/L) Elimination (mg/h) = clearance (L/h) x concentration (mg/L) * b) Is constant for most drugs in the clinical setting at therapeutic levels * c) Is very high for lithium (\<2.4L/h - cf morpine at 60L/h) * d) Is independent of concentration for phenytoin (phenyotin undergoes zero-order kinetics, so *elimination* is independent of concentration) * e) Is inversely proportional to volume of distribution (don't think these two relate to each other) \*\*Unclear about this answer - a) is definitely correct. However, *clearance* remains constant for first order kinetics (which 95% of therapeutic drugs obey) as it is an abstract ideal. *E**limination* varies with concentration, so strictly speaking b) is also correct unless they have confused clearance with elimination (as would also seem to be the case with d)\*\*

Answer 46

e) Is proportional to half life ( T1/2 = 0.7 [Vd / Cl] ) * a) Is inversely proportional to clearance (proportional in Varea) * b) Is measured in mg/L (is a volume, measured in L) * c) Is used to work out the maintenance dose (loading dose) * d) Is high in Warfarin (10L; low as it is plasma-protein bound)

Answer 47

c) Verapamil ## Footnote Other agents with high first-pass metabolism include: - beta agonists and antagonists (salbutamol, metoprolol, propranolol) - Morphine - Lignocaine - Aspirin - GTN

Answer 48

**b) Is proportional to accumulation factor** * LD = Maintenence dose x accumulationo factor* * LD = C x Vd will only reach the average steady state concentration, to reach peak steady state you need to use the top equation* * a) Is *proportional* to volume of distribution * c) Is *dependent on* rate of administration to multicompartment pharmacokinetics * *If a loading dose is calculated, but given as a rapid push, it can lead to a transient toxicity, as absorption will be immediate if given IV (eg lidocaine), so need to give a slower push to avoid this whilst the drug distributes* * d) *Ld = target concentration x Vd* * *MD = target concentration x clearance* * e) Of Theophylline administered IV in a normal 70kg man*= 350mg (35L x 10mg/L)*

Answer 49

b) Depends on the volume of distribution and the clearance of a drug (T 1/2 = 0.7 (Vd / Cl) * a) Is not a useful parameter in drug dosage (very useful in maintenence dosing) * c) Is defined as the time required for a third of the drug to be eliminated (shouldn't need to explain why this is wrong) * d) Does not vary with age (half-lives of benzos and barbituates can double after 60yo) * e) Is not altered with certain disease states (is related to both Vd and Cl which can change in disease states - eg dehydration/oedema, or renal/hepatic failure)

Answer 50

c) Can vastly exceed any physical volume in the body (true - eg chloroquine has a Vd of thousands of litres) * a) Is directly proportional to concentration (indirectly) * b) May be defined only in respect to blood (plasma) * d) Is not influenced by plasma binding (hugely affected) * e) Has no influence on the half life ( T1/2 = 0.7 [Vd / Cl]) **Vd = dose (mg) / concentration (mg/L)**

Answer 51

a) Phenytoin AKA zero-order Other examples include aspirin, omeprazole, ethanol

Answer 52

**b) Skin is an organ involved in biotransformation of drugs** "WHERE DO DRUG BIOTRANSFORMATIONS OCCUR? *...the liver is the principal organ of drug metabolism. Other tissues that display considerable activity include the gastrointestinal tract, the lungs, _the skin_, the kidneys, and the brain" - Katzungs* * a) Phase I reactions *often but not always* precede phase II - *historical convention which admittedly had many exceptions even at the time* * c) Water conjugation is *phase II* biotransformation * d) *CYP3A4* accounts for the majority of P450 activity *(~30%)* * e) Epoxidation is phase *_I_* biotransformation *- this is the process warfarin blocks in Vitamin K*

Answer 53

b) In flow dependent elimination the limiting factor is the volume of distribution This seems correct, as a large Vd will cause less drug to be delivered to the liver/kidneys However c) is listed as the right answer although almost certainly wrong * a) For most drugs the rate of elimination = clearance X half-life (elimination = clearance x concentration) * c) Capacity limited elimination is also known as Michaelis-Menton elimination (capacity-limited elimination is zero-order; michaelis-Menton is mixed-order) * d) Most drug pathways are not saturated at very high doses (most probably are at very high doses, but not therapeutic doses) * e) The 2 major sites of drug elimination are the kidneys and the lungs (kidneys and liver)

Answer 54

**c) Is the amount of drug cleared by the body per unit time** * Helps work out the relationship between concentration and elimination - its is the theoretical volume of plasma/blood that is cleared of drug in a given time.* * Used to work out maintenence dosing.* * Elimination is the removal of drug from the body. Katzungs unclear - it describes elimination unchanged in the urine as 'renal clearance'. Just try to hope wording isnt too specific, and know the general principle I guess.*

Answer 55

a) Of a drug cannot be smaller than the body’s blood volume (by definition, unless there is a distinction with plasma) Though b) is listed as correct * b) Of imipramine is 2100 L (650-1100L as per google) * c) Can be used to calculate the maintenance dose (loading dose = Vd x target conc) * d) Of a drug varies inversely with its half life (apparently not) * e) Cannot be easily calculated (easy - plasma concentration extrapolated)

Answer 56

c) Is a composite pharmacokinetic parameter Can't say why its right, but the others are all wrong * a) Is not affected by a drug’s lipid solubility (affects its Vd which affects half-life) * b) Refers to half the time taken for a drug to be eliminated (time taken to elimate half the drug) * d) Has no bearing on dosing frequency (only useful to calculate dosing regimes - but does not tell us about duration of effect) * e) Of phenytoin is constant (zero-order kinetics so rate eliminated is constant, half-life will vary with concentration)

Answer 57

c) Can help to determine the need to treat a patient who presents following an OD I think e) study of metabolism of a drug is partially correct only - also concerns absorption, dosing etc.

Answer 58

??c) 2 g/min MD = clearance x conc. = 1000ml/min x 2mg/ml =2000mg/min =2g/min Although if oral dosing is used, also need to know the absorption fraction to calculate bioavailability to adjust dose

Answer 59

c) Phenytoin Zero-order kinetics (aka capacity-limited) Most first order kinetics are flow-dependent (eg GFR, hepatic enzymes)

Answer 60

b) ETOH displays dose dependant kinetics EtOH has zero-order kinetics as alcohol dehydrogenase is rapidly saturated

Answer 61

a) Half-life is inversely proportional to volume of distribution Not sure about the molecular weight thing, but a) is definitely correct T1/2 = 0.7 x (Vd/Cl)

Answer 62

a) pKa of the drug Vd = dose / concentration pKa is a measure of strength of an acid in solution Plasma protein binding decreases Vd Tissue binding increases Vd Fat absorption increases Vd

Answer 63

b) Phenytoin

Answer 64

c) 5 95% is eliminated after 4 (so another half-life removes half of the remaining 5%)

Answer 65

a) Dose (Nicks notes say c) but genetic polymorphisms affecting liver function can impact on clearance, or reduced renal function causing a reduction in clearance) Clearance is a constant theoretical value and should not be affected by dose given (elimination is)

Answer 66

c) If high, implies increased concentration of drug extravascularly (as plasma concentrations will be low) * a) Relates dose to clearance ( dose x conc ) * b) Is not an apparent volume (it is an apparent volume) * d) If high, implies increased plasma protein binding (opposite) * e) If high, implies easier clearance of the drug by haemodialysis (unsure, but probably the opposite as more will be filtered)

Answer 67

b) Clearance Others all affect the total body water

Answer 68

b) At high doses alcohol has 1st order kinetics Alcohol usually has zero-order, except at very low doses

Answer 69

b) Relates loading dose to the target concentration loading dose = Vd x target conc. * a) Never exceeds total body volume (often can) * c) If high, suggests the drug is highly protein bound (opposite) * d) If low suggests the drug is hydrophobic (opposite) * e) Relates clearance to the plasma concentration (wrong - Vd and Cl involved in half-life calculation though; maintence dose = Cl x conc)

Answer 70

**b) is limited by blood flow if a tissue has a high extraction ratio** ER = Cl organ / blood flow organ *High ER is the same principle as a high-first pass metabolism - that is most of the drug is taken out with one pass, and the clearance is not saturated, so only by increasing blood flow can you increase extraction* * a) is the amount of *plasma cleared per unit time (units are L/H, or ml/min)* * c) is required to calculate the *maintence dose (= Cl x C)* * d) *Varies* for all the doses of phenytoin - *capacity-limited (zero-order aka clearance-dependent) elimination, so clearance varies with concentration* * *First order elimination is* constant for all doses as it will be elimination that varies with concentration/dose * e) in the kidney is determined by the GFR*, tubular secretion and passive diffusion across the tubules*

Answer 71

a) dose / plasma concentration (usually referred to as dose / conc., but amount of drug *in the body* has also been noted. Unclear which they mean here) b. is listed as answer. Deranged physiology uses "dose / conc"

Answer 72

d) The time taken for the plasma concentration to fall to 50%

Answer 73

a) acetylation This is conjugation, a phase II reaction

Answer 74

d) important because it determines the fraction of the dose administered which can be found in the systemic circulation * a) 100% for IM (75-\> \<100%) * b) 100% for PO which are not metabolized by the liver (5- \<100%) * c) equal to the amount of drug in the body at the time of peak plasma concentration relative to the amount administered (= fraction of unchanged drug reaching the systemic circulation following administration by any route) * e) less than 100% only in orally administered drugs (less than 100% in most routes of administration)

Answer 75

**e) Administration of NH4Cl will increase urinary excretion** *Is used as a urinary acidifying agent. In acidic urine, a basic drug will be more in the ionised (RH+) form, and thus unable to cross the tubular cells by diffusion.*

Answer 76

e) Polyethylene glycol

Answer 77

**c) in general, changes in protein binding do not cause clinically important drug interactions** *As per Katzungs (paraphrased) - there are no meaningful clinical interactions that come with increasing or decreasing a drugs protein binding in the body. The degree of protein binding is only useful to help interpret measured blood concentrations. Partly this is because increasing the fraction of unbound drug increases elimination, but also that even highly bound drugs (eg warfarin) only have about 1/3rd bound at any one time, and any small reduction in binding has very minimal change on the amount of active drug at the site of interaction.*

Answer 78

d) For drugs which exhibit capacity limited elimination, clearance will be constant capacity-limited = zero order * a) Zero order kinetics refers to situations where a constant proportion of the drug in the body is eliminated per unit time (constant amount not proportion) * b) Non-linear kinetics are best described in situations where no matter how much drug is in the body a constant amount of drug is eliminated per unit time (aka Michaelis-Menod, i think) * c) Variations in the dose of ETOH will not effect its half life (zero-order so half-life will change with dose) * e) If drug doses are repeated, the drug will accumulate in the body only if the dosing intervals is less than 3 half lives (4)

Answer 79

e) Of midazolam is greater than that of Warfarin Warfarin is bound to plasma proteins (Vd warfarin is 10L/70kg)

Answer 80

e) Is 70% for oral digoxin (because the others are wrong) * a) Must be 100% if given by inhalation (5-\<100%) * b) Is typically 75% for IV (100% by definition) * c) Is high if the drug is hydrophilic (low - it cannot cross the cell membrane) * d) Is equal to 1 – extraction rate (bioavailibility = f x (1-ER)

Answer 81

C) oxidation Others are all conjugation (type II)

Answer 82

b) Efficacy is the maximum response produced by a drug * a) LD50 is 50% of the dose necessary to kill experimental animals (LD50 will kill 50% of the animals) * c) Spare receptors are present if Kc50 = EC50 (if EC50 is \< Kd) * d) Potency is the same as affinity (high potency will have high affinity, but is also affected by number of receptors and efficiency of receptor occupation) * e) TD50 is the concentration of a drug necessary to produce toxic effects 50% of the time (in 50% of people)

Answer 83

a) aspirin - tolbutamide

Answer 84

b) less lipid soluble than the original Phase 1 rections typically make them more polar

Answer 85

a) Results in increased smooth ER * d) Requires 3 – 4 months to reach completion (several days) * e) Is irreversible (opposite)

Answer 86

b) aqueous hydrolysis

Answer 87

a) Urinary excretion would be accelerated by administering NH4Cl Acidic urine excretes weak bases faster, opposite is also true.

Answer 88

4) 90% Weak acids (or bases) are more lipophilic in an acidic environment (or basic for bases). The opposite is also true, and weak acids will be more hydrophilic in a basic environment (and vice versa for weak bases) Not sure about working the numbers, though they probably relate to Henderson-Hasselbach: pH - pKa = log [ionized]/[unionized]

Answer 89

The time taken to change the amount of drug in the body by one half during elimination ***T1/2 = 0.7 (Vd/Cl)*** 50% after 1, \>90% after 4

Answer 90

Dosing regimens Decay afterdose/overdose Time to steady state after dose change (2 to pass)

Answer 91

Liver - cirrhosis, carcinoma Renal - CKD Cardiac disease (one organ to pass)

Answer 92

Kidney Liver One to pass

Answer 93

Clearance is the volume of blood cleared of drug per unit time Measure of the ability of the body to eliminate a drug Rate of elimination in relation to drug concentration Clearance = elimination / concentration (reasonable definition)

Answer 94

Concentration - **Dose** and **Bioavailability** Elimination - **Specific organ function / blood flow** & **protein binding** Major organs are kidneys and liver, therefore factors affecting these organs function and blood flow will have the most effect (one for each element)

Answer 95

- **Capacity-limited (aka zero-order) is saturable** so the rate of elimination is constant despite the concentration of the drug ie a certain *amount* will be eliminated per unit time eg phenyotin, aspirin, ethanol - **Flow-dependent (aka first order) elimination is non-saturable** and is proportional to the amount of drug in the plasma ie a certain *proportion* will be eliminated per unit time eg verapamil, labetalol, morphine (bold to pass)

Answer 96

Drug metabolism to allow drugs to become **inactive or by increasing extraction** by making them more hydrophilic, or by metabolising them to a less active agent (bold to pass)

Answer 97

Phase 1 - **unmasking functional group** (-OH, NH2, -SH) by making the substance more polar metabolite. Includes oxidation, reduction, deamination, hydrolysis Phase 2 - **conjugation with endogenous substrate** to become highly polar conjugate (bold to pass)

Answer 98

**Rapid phase 1 hydrolysis** by **butyrycholinesterase and pseudocholinesterase** in plasma and liver Genetically deficient in BCHE so slowed metabolism (one of the bold to pass)

Answer 99

Measure of the body to eliminate a drug Volume of plasma cleared of the drug per unit time, or rate of elimination in relation to the concentration Clearance = elimination / conc

Answer 100

Concentration - dose and bioavailability Elimination - specific organ function / blood flow / protein binding Major sites of elimination are the liver and kidneys, therefore factors affecting these organs and their blood flow will have the most effect (one for each element)

Answer 101

**Capacity-limited is saturable (zero-order)** Constant amount of drug elimination eg aspirin, phenyotin, ethanol **Flow-dependent is non-saturable (first-order).** Most drug is eliminated on first pass, so rate of elimination is limited by blood flow to the organ eg verapamil, morphine, labetalol (bold to pass)

Answer 102

b. Diazepam

Answer 103

d. Chloroquine Thousands of litres

Answer 104

c. Aspirin But prolonged duration of effect

Answer 105

a. Reduction

Answer 106

e. Phenytoin aka zero-order elimination

Answer 107

Protamine - heparin

Answer 108

First order kinetics generally apply to high plasma concentrations (\>20 mg / 100ml) of ethanol Alcohol dehydrogenase saturated at relatively low levels

Answer 109

The proportion of the drug in a formulation that is found in the systemic circulation

Answer 110

e. Propranolol

Answer 111

10 hours T1/2 = 0.7 (Vd/Cl)

Answer 112

Skin is an organ involved in drug biotransformation

Answer 113

Vitamin D - intracellular receptor

Answer 114

Reduction in creatinine clearance in 2/3 population Decreased muscle and water, increased fat Phase 1 reactions reduce much more than phase 2

Answer 115

Cytochrome p450 dependent glutathione conjugation

Answer 116

e) 75mg 100% = 1000mg/ml 1% = 10mg/ml 0.5%=5mg/ml (ie multiply your % by 10 to get mg/ml)

Answer 117

Ketoconazole Potent inhibitor Rifampicin phenobarbital, phenytoin are potent inducers

Answer 118

Heparin Large macromolecule that cannot cross the glomerular filter (and hence maybe the placenta?)

Answer 119

Efficacy is the maximum response produced by a drug

Answer 120

Treatment of these patients with ketoconazole A common inhibitor of drug metabolism

Answer 121

e. A patient with oedema will have an increased volume of distribution of tobramycin

Answer 122

b. Efficacy is the maximum response produced by a drug

Answer 123

b) 10mg 0. 5% = 5mg/ml 1% = 10mg/ml

Answer 124

d) acetylation ## Footnote The phase II rections are glucuronidation, acetylation, glutathione conjugation, glycine conjugation, sulfation, methylation, (??water conjugation)

Answer 125

c. Causes increase in smooth endoplasmic reticulum Answer given is d) but im sure its c)

Answer 126

d. Efficacy is the maximum response produced by a drug

Answer 127

e. Is proportional to half life T1/2 = 0.7 (Vd/Cl) * a. Is *proportional* to clearance * If above rearranged to Vd = (T1/2 x Cl)/0.7 * b. Is measured in *litres* * c. Is used to work out the *loading dose* * d. Is *low* in warfarin as highly bound to plasma proteins

Answer 128

b) 100mg 2% = 20mg/ml

Answer 129

e. Of midazolam is greater than that of warfarin Warfarin is 98% bound to plasma proteins so very low Vd * a. Is calculated by dividing the amount of drug by its *concentration* * High Vd suggests lipophilic and accumulating elsewhere, low Vd suggets it is accumulating in the plasma. Moderate would suggest homogenous distribution. * d. Of aspirin is greater than that of pethidine

Answer 130

**d. Is about 5L/kg for pethidine** (4L/kg as per google) * *Fluoxetine is 30-40L/kg* * *Independent of route of admin* * *Proportional to halflife (T1/2 = 0.7 [Vd/Cl])* * *Calculated by diving dose or amount of drug by concentration in plasma* * *eg lookimg at the units: (mg / mg/L) = L*

Answer 131

e. Trimethoprim (renally excreted - thats how it works for UTIs)

Answer 132

e. Is 70% for orall administered digoxin Bio = f (1-ER) Hydophilic drugs struggle to cross cell membranes Is 100% for IV admin, less for every other route

Answer 133

**d. Drug A has a lower ED50 than drug B** * Because it will produce 50% of its maximal effect at a lower dose than drug B - the definition of potency* * We cannot make assertions about efficacy (or by extension partial agonism) as these are not directly related to potentcy*

Answer 134

c. If high, implies greater concentration of drug in extravascular tissue

Answer 135

e. Spare receptors produce effect without the need for a drug

Answer 136

b. Ethanol displays dose-dependent kinetics Zero-order for EtOH

Answer 137

**d. All of the above may be true depending on the drug** 'The time course of effect is linear, initially' is given as the answer but I think it is wrong. Time course of effect could be linear or exponential depending on spare receptors etc, and at a 4x higher dose than EC50 could definitely get toxic effects if it was a low TI

Answer 138

d. Spare receptors activate the effector machinery of the cell without the need for a drug

Answer 139

b. Acetylations of amines

Answer 140

d. Second messengers explain “spare receptors” as the Duration of effector activation is much longer than the duration of drug-receptor interaction * *pharmacologic antagonism* – they compete for the same receptor. * *Physiologic antagonism* is where drugs act on different receptors to stimulate different endogenous regulatory pathways with opposing effects – more difficult to control (e.g. glucocorticoids vs. insulin) * *chemical antagonism -* the antagonist will react directly with the drug (protamine +ve change binds to heparin –ve charge to counteract)

Answer 141

d. Is reduced in digoxin when given orally because of bacterial metabolism

Answer 142

d. Hydroxylation and deamination are examples of phase I reactions

Answer 143

b. Depends on the efficiency of drug-receptor interaction

Answer 144

c. Is a measure of the apparent space available in the body to contain a drug * a. Is *inversely* proportionately related to the concentration of crug in the body * b. Is *low* for those drugs retained in the vascular compartment * d. For chloroquine is much *larger* than that of digoxin * e. None of the above

Answer 145

b. Cytochrome P-450 dependent oxidations Phase 1

Answer 146

b. Tubulin

Answer 147

a. Related the amount of a drug in the body to its plasma concentration

Answer 148

e. Inhibit receptors to a degree proportionate to antagonist concentration

Answer 149

b. cAMP exerts most of its effects by stimulating cAMP-dependent protein kinases adenylyl cyclase activation causes increased cAMP Widespread throughout the body, roles include regulating inotropy, calcium homeostasis via PTH, and aquaporin insertion by ADH

Answer 150

c. Oxidation

Answer 151

**A single intrauterine exposure to a drug can be teratogenic** * Transfer of drugs across the placenta is *dependent* of its lipid solubility and charge - *ionised doesnt cross, lipid soluble does* * Foetal proteins have a *low* binding affinity for drugs. * Pregnant women have a smaller volume of distribution. Increased TBW, so generally bigger Vd * Gastric emptying time is shortened in the first day of life. Longer

Answer 152

**Digoxin.** *Exported by PGP from placental to maternal tissue* * **Carbamazepine - *congenital malformations* * Streptomycin - *foetal ototoxicity* * MTX - *used for medical abortions* * PTU -

Answer 153

**heparin**

Answer 154

**None of the above** * They have a *lower* glomerular filtration rate in adults *(40% the rate of adults)* * Their liver enzyme systems are *less* active in adults * All their renal mechanisms (filtration, secretion and reabsorption) are decreased compared to adults * They have *lower* gastric acidity and *increased* gastric emptying time than adults *(gastric acid productin starts on day 4 of life)*

Answer 155

**S/E are proportional to the amount of medication** * The dose of lithium should be *decreased (due to reduced TBW)* * Their phase *I* biotransformation is much poorer *(phase I reduced more than phase II -* *Enzyme function mostly the same but blood flow may be less)* * They have *decreased* lean body mass *(and increased fat)* * They have *decreased* serum albumin.

Answer 156

**respond better to diuretics and calcium channel blockers than to ACE inhibitors as anti-hypertensive treatment.** * have *decreased* lean body mass. * *most* have an age related decline in creatinine clearance, *but this is a population trend and is not universal* * have *decreased* serum albumin and α acid glycoprotein. * are *more* sensitive to respiratory effects of opioid analgesics, *due to age-related reduction in respiratory function*

Answer 157

**Increased body fat.** * *Decreased* lean body mass, cardiac index, total body water, and hepatic blood flow

Pharmacology Principles ( 15% ) Flashcards

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