Pharmacology Principles ( 15% ) Flashcards

Question 1

Q

receptors determine

a) concentration of drug required
b) limit maximal effect of a drug
c) selectivity of drug action
d) mediate actions of antagonists
e) all of the above

Answer

A

e) all of the above

a) concentration of drug required
b) limit maximal effect of a drug
c) selectivity of drug action
d) mediate actions of antagonists

Question 2

Q

The receptor affinity for binding a drug is high if

a) Emax is high
b) Emax is low
c) KD is low
d) KD is high
e) EC50 is high

Answer

A

c) KD is low
- a) Emax is high
b) Emax is low
d) KD is high
e) EC50 is high

Question 3

Q

Spare receptors

a) Are different from non-spare receptors
b) Not present in heart muscle
c) Increase the EC50.
d) Increase the sensitivity to a drug
e) Increase the KD

Answer

A

d) Increase the sensitivity to a drug
- a) Are different from non-spare receptors
b) Not present in heart muscle
c) Increase the EC50. (Decrease it)
e) Increase the KD

Question 4

Q

The effects of a non-competitive antagonist :

a) Can be overcome by increasing agonist concentration.
b) Reduce Emax
c) Reduce EC50.
d) Emax remains the same
e) None of the above

Answer

A

b) Reduce Emax
- a) Can be overcome by increasing agonist concentration. (Applies only to competitive antagonism)
c) Reduce EC50. (Remains the same)
d) Emax remains the same
e) None of the above

Question 5

Q

Clinical effectiveness of a drug depends most on

a) Potency
b) Maximal efficacy
c) KD
d) Quantal dose-effect curve
e) None of the above

Answer

A

b. Maximal efficacy

Question 6

Q

Therapeutic index is

a) EC50:TD50
b) KD:TD50
c) ED50:TD50
d) Emax:TD50
e) KD:Emax

Answer

A

c) ED50:TD50
- a) EC50:TD50
b) KD:TD50
d) Emax:TD50
e) KD:Emax

Question 7

Q

Which is false

a) Drug A with a higher potency can have a lower efficacy than drug B
b) Drug A with a higher affinity for its receptor has a higher potency
c) Drug A with a lower potency must have a lower efficacy than drug B
d) Drug A with a higher potency can still have the same efficacy
e) None of the above

Answer

A

c) Drug A with a lower potency must have a lower efficacy than drug B

Question 8

Q

Spare receptors

a) Do not affect the sensitivity to drugs
b) Are the result of low efficiency of receptor-effector interaction
c) Are present when the maximal response is achieved when occupancy is not full
d) Are qualitatively different from non-spare receptors
e) May be hidden

Answer

A

c) Are present when the maximal response is achieved when occupancy is not full

a) Do not affect the sensitivity to drugs
b) Are the result of low efficiency of receptor-effector interaction
d) Are qualitatively different from non-spare receptors
e) May be hidden

Question 9

Q

About potency and efficacy, the following are true except

a) Efficacy is more important than potency
b) Potency is the concentration/dose required to produce a given effect
c) Steep dose-response curves are a concern in low therapeutic index drugs
d) Low potency is not important
e) Efficacy is determined by receptors

Answer

A

d) Low potency is not important

a) Efficacy is more important than potency
b) Potency is the concentration/dose required to produce a given effect
c) Steep dose-response curves are a concern in low therapeutic index drugs
e) Efficacy is determined by receptors

Question 10

Q

Which is incorrect

a) A drug which binds to a receptor and produces a maximal response is called a full agonist
b) A drug which binds to a receptor and produces a variable response is called a quasi agonist.
c) A drug which binds to a receptor and produces a submaximal response is called a partial agonist
d) A drug which binds to a receptor and produces no response is called an antagonist
e) A drug which does not bind to receptors can still be effective

Answer

A

b) A drug which binds to a receptor and produces a variable response is called a quasi agonist.

Question 11

Q

Which is false

a) Partial agonists produce lower response at the same receptor occupancy rate
b) The concept of spare receptors refers to the fact that some receptors have alternate molecular configuration (isomers) and so are spared from producing a response to certain drugs
c) The efficacy of the receptor-effect coupling is dependent on the affinity of the drug for the receptor, the power of the agonist and the receptor concentration
d) variation in concentration of endogenous receptor ligand may be responsible for variations in drug effectiveness
e) changes in components of the response distal to the receptor are the largest and most important group of mechanisms of variability

Answer

A

b) The concept of spare receptors refers to the fact that some receptors have alternate molecular configuration (isomers) and so are spared from producing a response to certain drugs

Spare receptors refer to a drug achieving a maximal effect at <100% receptor occupancy (ie some receptors are ‘open’ aka ‘spare’)

Question 12

Q

Which is true

a) The ED50 is the dose at which the desired effect is produced in 50% target population
b) Maximal potency refers to the relative position of the plateau portion of the dose-response curve
c) A quantal dose-response curve plots the percentage of a population having a defined clinical response to a drug concentration or dose
d) Drugs with steep dose response curves have wide therapeutic windows
e) The ED50 can be used to assess the clinical efficacy of drugs

Answer

A

c) A quantal dose-response curve plots the percentage of a population having a defined clinical response to a drug concentration or dose

Either of these two options could be correct - c) seems right but might be a specific wording that is wrong that I don’t understand, but below has two meanings

a) The ED50 is the dose at which the desired effect is produced in 50% target population

or dose required to reach 50% of maximal effect (same as EC50)*
Two different meanings to ED50, depending if youre talking about dose-response curves (is same as EC50) or quantal dose-response curve (similar to TD50)*
b) Potency is just the dose at which 50% of a maximal effect is achieved - does not vary for a specific drug, but can be used to compare drugs
d) Drugs with steep dose response curves have narrow therapeutic windows (a small change in dose has a large clinical effect)
e) Efficacy can be used to assess the clinical efficacy of drugs

Question 13

Q

antagonists may be all of the following except

a) receptor antagonists
b) chemical antagonists
c) physiological antagonists
d) electrical antagonists
e) none of the above

Answer

A

d) electrical antagonists

Question 14

Q

With regard to a drug

a)LD50 is 50% of the dose necessary to kill experimental animals
b) Efficacy is the maximum response produced by a drug
c) Spare receptors are present if Kc50 = EC50
d) Potency is the same as affinity
e) TD50 is the concentration of a drug necessary to produce toxic effects 50% of the time

Answer

A

b) Efficacy is the maximum response produced by a drug

a)LD50 is 50% of the dose necessary to kill experimental animals (the dose that will kill 50% of the animals)
c) Spare receptors are present if Kc50 = EC50 (wrong - if EC50 < Kd)
d) Potency is the same as affinity (drugs with high potency will have high affinity, but potency is also affected by number of receptors available and efficiency of receptor occupation causing a response [in addition to affinity])
e) TD50 is the concentration of a drug necessary to produce toxic effects 50% of the time (in 50% of patients)

Question 15

Q

Quantal dose-response curves are

a) Used for determining the therapeutic index of a drug
b) Used for determining the maximal efficacy of a drug
c) Invalid in the presence of inhibitors of the drug being studied
d) Obtainable from the study of intact subjects but not from isolated tissue
e) Used to determine the statistical variation of the maximal response to the drug

Answer

A

a) Used for determining the therapeutic index of a drug

Question 16

Q

2 drugs, A and B have the same mechanism of action. Drug A in dose of 5mg produces the same magnitude of effect as Drug B at 500mg

a) Drug B is less efficacious
b) Drug A is 100 times more potent
c) Toxicity of Drug A is less
d) Drug A is a better drug if maximal efficacy is needed
e) Drug A will have a shorter duration of action, because less is present

Answer

A

b) Drug A is 100 times more potent

a) Drug B is less efficacious (equal efficacy as they produce the same magnitude of effect)
c) Toxicity of Drug A is less (cannot measure from the data)
d) Drug A is a better drug if maximal efficacy is needed (equally effective)
e) Drug A will have a shorter duration of action, because less is present (half-life depends on a multitude of other factors)

Question 17

Q

About potency and efficacy, the following are true except

a) Efficacy is more important than potency
b) Potency is the concentration/dose required to produce a given effect
c) Steep dose-response curves are a concern in low therapeutic index drugs
d) Low potency is not important
e) Efficacy is determined by receptors

Answer

A

b) Potency is the concentration/dose required to produce 50% of a given drugs maximal effect

a) Efficacy is more important than potency - efficacy is the maximal effect of the drug, potency is the dose required to achieve it. Can updose a drug, but cant improve efficacy with dosing
c) Steep dose-response curves are a concern in low therapeutic index drugs as small changes in dose create a large change in effect
d) Low potency is not important - can increase the dose to have the same efficacy so is able to be overcome
e) Efficacy is determined by receptors

Question 18

Q

What is antagonist?

Answer

A

Receptor antagonists bind to receptors but do not activate them. The primary action of antagonists is to prevent agonists activating receptors.

(Bold required to pass)

Question 19

Q

What is the difference between a competitive and non-competitive antagonist?

Answer

A

Competitive antagonist: In the presence of increasing doses of antagonist, higher concentations of agonist will produce a given effect

eg propranolol or norad / adrenaline

Irreversible or Non-competitive antagonist: bind via covalent bonds or just binding so tightly the receptor is unavailable for the agonist. Duration of action of antagonist depends on the rate of turnover of receptor-antagonist complex

Question 20

Q

What type of competitor is naloxone?

Answer

A

Competitive

Question 21

Q

What effect does a competitive antagonist have on the dose-response curve?

Answer

A

Shifts the dose-response curve to the right. Higher doses of agonist can overcome competitive antagonist.

Question 22

Q

What is drug potency?

Answer

A

The dose or concentration of the drug required to produce 50% of maximal effect, measured by the EC50 or ED50

Question 23

Q

Draw and explain dose response curve, comparing morphine with fentanyl.

Answer

A

This graph with dose or log-dose on x-axis and response/effect on y-axis.

Fentanyl will be a left-shift of the curve as it has a higher potency (and thus a smaller dose needed for a 50% effect)

Question 24

Q

What are the pharmacokinetics of fentanyl?

Answer

A

Highly lipid soluble, half-life 5min, duration of effect 1-1.5 hours, low bioavailability, hepatic metabolism.

Question 25

Q

Define potency

Answer

A

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.

Question 26

Q

Define efficacy

Answer

A

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.

Question 27

Q

Show the difference between dose and efficacy by drawing graded dose-response curves

Answer

A

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)

Question 28

Q

Compare the potency of morphine to fentanyl

Answer

A

Fentanyl 100x more potent

0.1mg fentanyl = 10mg morphine

Question 29

Q

What is the therapeutic index?

Answer

A

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

Question 30

Q

One mechanism of transmembrane signaling uses a G protein to generate an intracellular second messenger. The following are second messengers except:

a) cGMP
b) Ca2+
c) cAMP
d) adenylyl cyclase.
e) phosphoinositides

Answer

A

d) adenylyl cyclase. (Effector)

Katzung 12th ed p.25

Question 31

Q

Nitrous oxide, steroids, vitamin D and thyroid hormone act on receptors via

a) Intracellular receptors e.g. response elements
b) Ligand regulated transmembrane enzymes
c) Ligand gated channels
d) G proteins
e) 2nd messengers e.g. cAMP

Answer

A

a) Intracellular receptors e.g. response elements

Lipid-soluble / cholesterol-derived, they can cross the cell membrane to interact with internal cellular elements.

Question 32

Q

the best characterized drug receptors are

a) regulatory proteins
b) enzymes
c) transport proteins
d) structural proteins
e) none of the above

Answer

A

a) regulatory proteins

Dont know why or how, dont understand the question.

Question 33

Q

The following act by binding transmembrane enzyme receptors except

a) Insulin
b) PDGF
c) EGF
d) ANF
e) Thyroid hormone

Answer

A

e) Thyroid hormone

Binds internal cellular elements / nuclear receptors.

Others all act on ligand-regulated transmembrane enzymes

(insulin, PDGF, EGF, ANF)

Question 34

Q

Which of the following act via cytokine receptors

a) Growth hormone
b) EPO
c) IFN
d) All of the above
e) None of the above

Question 35

Q

The following use cAMP 2nd messenger except

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

Answer

A

a) Catecholamines via α1 receptor

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

Question 36

Q

The following have serpentine receptors except

a) α2 adrenergic amines
b) ACh muscarinic
c) ACh nicotinic.
d) Β adrenergic amines
e) Glucagon

Answer

A

c) ACh nicotinic.

Ion channel for neuromuscular transmission.

(Serpentine receptor is another name for GPCR)

Question 37

Q

Which of the following receptor ligand pathways is true:

a) Insulin and G receptor protein.
b) Mineralocorticoid and tyrosine kinase receptor.
c) Vitamin D and intracellular receptor
d) Adrenaline and ligand gated channel receptor.
e) PDGF and cytokine receptor.

Answer

A

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)

Question 38

Q

of the secondary messengers:

a) compared to cAMP, cGMP is more versatile and ubiquitous carrier of diverse messages
b) phosphoinositides act independently of PLC (phospholipase C)
c) upregulation of cAMP degradation is one way theophylline produces its effects
d) cAMP’s effector is adenylyl cyclase
e) all of the above

Answer

A

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

Question 39

Q

which of the following are antagonist and agonist pairs for the same receptor

a) butoxamine, terbutaline
b) phenyoxybenzamine, cyclopentolate
c) pilocarpine, bethanechol
d) oxymetazoline, dobutamine
e) bromocriptine, pranipexole

Answer

A

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

Question 40

Q

which of the following adrenoreceptors use phospholipase as a 2nd messenger

a) α1
b) α2
c) β1
d) β2
e) DA

Answer

A

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

Question 41

Q

Which statement regarding hepatic enzyme induction is INCORRECT

a) Induction takes 7-10 days to reach maximum.
b) Inhibition occurs more rapidly than induction
c) Induction ceases within a few days of withdrawal of drug
d) Suicide inhibitors are metabolized to products which inhibit the metabolizing enzymes
e) Induction is associated with an increase in hepatic smooth ER

Answer

A

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

(Several days)

Question 42

Q

Which of the following drugs exhibit flow-dependent elimination (i.e. ‘high extraction drugs)

a) Lignocaine
b) Morphine
c) Phenytoin
d) Propranolol
e) Verapamil

Answer

A

c) Phenytoin

Question 43

Q

Regarding elimination kinetics which is false

a) In 1st order kinetics, the rate of elimination is directly proportional to drug concentration
b) Ethanol displays dose dependent kinetics
c) In zero order kinetics the rate of elimination is constant
d) Most drugs display 1st order kinetics
e) Phenytoin can display zero order kinetics

Answer

A

b) Ethanol displays dose dependent kinetics

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

Question 44

Q

Which of the following is not an inducer of hepatic drug-metabolising enzymes

a) Cigarette smoke
b) Phenytoin
c) Charcoal broiled beef
d) Chloramphenicol
e) Spironolactone

Answer

A

d) Chloramphenicol

(is an inhibitor of 2C19)

Cigarette smoke induces 1A2

Phenytoin induces all except 1A2

??Spironolcatone is a suicide-inhibitor though

Question 45

Q

Which of the following drugs has a high bioavailability

a) Acyclovir
b) Cyclosporine
c) Metoprolol
d) Diazepam
e) Verapamil

Answer

A

d) Diazepam

Question 46

Q

Which of the following is not an inhibitor of hepatic drug-metabolising enzymes

a) Metronidazole
b) Cimetidine
c) Isoniazid
d) Allopurinol
e) Rifampicin

Answer

A

e) Rifampicin

(Induces all P450 subtypes)

Question 47

Q

The most important factor limiting drug permeations is

a) Aqueous diffusion
b) Lipid diffusion
c) Special carriers
d) Endocytosis
e) Exocytosis

Answer

A

b) Lipid diffusion

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

Question 48

Q

lipid diffusion is most dependent on

a) area
b) permeability coefficient
c) concentration gradient
d) thickness of the membrane
e) lipid:aqueous partition coefficient

Answer

A

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”

Question 49

Q

excretion of salicylic acid pKa=3.0 will be increased by

a) acidifying the urine
b) alkalinising the urine
c) increasing the unprotonised form
d) decreasing the ionized form
e) none of the above

Answer

A

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

Question 50

Q

In Zero-order kinetics

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

Answer

A

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.

Question 51

Q

Question 52

Q

bioavailability is not reduced by

a) first pass metabolism
b) P glycoprotein
c) Ionization of drug
d) Drugs highly extracted by liver
e) Enteric coating

Answer

A

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)

Question 53

Q

Drugs highly extracted from the liver include all except

a) Isoniazid
b) Morphine
c) Propranolol
d) Verapamil
e) Diazepam

Answer

A

e) Diazepam

Question 54

Q

Drugs poorly extracted from the liver include all except

a) TCA
b) Chlorpropramide
c) Phenytoin
d) Theophylline
e) Warfarin

Question 55

Q

1st pass effect can be avoided by all of the following except

a) sublingual tablets
b) transdermal patch
c) IV administration
d) Rectal suppositories
e) None of the above

Answer

A

d) Rectal suppositories

(about 50% undergoes first pass metabolism)

Question 56

Q

Maintenance dose depends on all except

a) Clearance
b) Target concentration
c) Oral bioavailability
d) Dosing interval
e) VoD

Answer

A

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)

Question 57

Q

Clearance depends on all except

a) Dose
b) Blood flow
c) Function of liver
d) VoD
e) Function of kidneys

Answer

A

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

Question 58

Q

The VoD is apparently smaller when there is

a) Binding to tissues
b) Binding to plasma proteins
c) Ascites
d) Obesity
e) Pleural effusion

Answer

A

b) Binding to plasma proteins

(Will have a high serum concentration, and thus seem to have a low VoD)

Question 59

Q

The rate limiting step in drug oxidation is

a) cP450 heme reduction
b) cP450 oxidation
c) flaviprotein reduction
d) flaviprotein oxidation
e) formation of NADPH

Answer

A

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)

Question 60

Q

Phase I reactions producing polar metabolites – include all except

a) Oxidation
b) Reduction
c) Hydrolysis
d) Deanimation
e) Acetylation

Answer

A

e) Acetylation

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

Question 61

Q

Phase II reactions include all except

a) Glucuronidation
b) Glutathione conjugation
c) Sulfate conjugation
d) Methylation
e) Epoxidation

Answer

A

d) Epoxidation

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

Question 62

Q

The following are enzyme inducers except

a) Chloramphenicol
b) Isoniazid
c) Ethanol
d) Steroids
e) Phenobarbital

Answer

A

a) Chloramophenicol

Is an inhibitor of 2C19

Question 63

Q

The following are enzyme inhibitors except

a) Cimetidine
b) Ketoconazole
c) Isoniazid
d) Chloramphenicol
e) Erythromycin

Answer

A

c) Isoniazid

Cimetedine - potent inhibitor

Ketoconazole - potent inhibitor

Chloramphenical - inhibits 2C19

Erythromycin - inhibits 3A4

Question 64

Q

The majority of drugs are metabolized by cP450

a) 3A4
b) 1A2
c) 2AG
d) 2C19
e) 2E1

Answer

A

a) 3A4

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

Answer 62

A

d) Procainamide

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

Answer 63

A

c) paracetamol

Answer 64

A

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 65

A

??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 66

A

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 67

A

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 68

A

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 69

A

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 70

A

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 71

A

c) Verapamil

Other agents with high first-pass metabolism include:

beta agonists and antagonists (salbutamol, metoprolol, propranolol)
Morphine
Lignocaine
Aspirin
GTN

Answer 72

A

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 73

A

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 74

A

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 75

A

a) Phenytoin

AKA zero-order

Other examples include aspirin, omeprazole, ethanol

Answer 76

A

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 77

A

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 78

A

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 79

A

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 80

A

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 81

A

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 82

A

??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 83

A

c) Phenytoin

Zero-order kinetics (aka capacity-limited)

Most first order kinetics are flow-dependent (eg GFR, hepatic enzymes)

Answer 84

A

b) ETOH displays dose dependant kinetics

EtOH has zero-order kinetics as alcohol dehydrogenase is rapidly saturated

Answer 85

A

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 86

A

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 87

A

b) Phenytoin

Answer 88

A

c) 5

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

Answer 89

A

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 90

A

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 91

A

b) Clearance

Others all affect the total body water

Answer 92

A

b) At high doses alcohol has 1st order kinetics

Alcohol usually has zero-order, except at very low doses

Answer 93

A

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 94

A

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 95

A

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 96

A

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

Answer 97

A

a) acetylation

This is conjugation, a phase II reaction

Answer 98

A

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 99

A

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 100

A

e) Polyethylene glycol

Answer 101

A

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 102

A

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 103

A

e) Of midazolam is greater than that of Warfarin

Warfarin is bound to plasma proteins

(Vd warfarin is 10L/70kg)

Answer 104

A

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 105

A

C) oxidation

Others are all conjugation (type II)

Answer 106

A

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 107

A

a) aspirin - tolbutamide

Answer 108

A

b) less lipid soluble than the original

Phase 1 rections typically make them more polar

Answer 109

A

a) Results in increased smooth ER

d) Requires 3 – 4 months to reach completion (several days)
e) Is irreversible (opposite)

Answer 110

A

b) aqueous hydrolysis

Answer 111

A

a) Urinary excretion would be accelerated by administering NH4Cl

Acidic urine excretes weak bases faster, opposite is also true.

Answer 112

A

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 113

A

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 114

A

Dosing regimens

Decay afterdose/overdose

Time to steady state after dose change

(2 to pass)

Answer 115

A

Liver - cirrhosis, carcinoma

Renal - CKD

Cardiac disease

(one organ to pass)

Answer 116

A

Kidney

Liver

One to pass

Answer 117

A

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 118

A

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 119

A

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 120

A

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 121

A

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 122

A

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 123

A

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 124

A

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 125

A

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 126

A

b. Diazepam

Answer 127

A

d. Chloroquine

Thousands of litres

Answer 128

A

c. Aspirin

But prolonged duration of effect

Answer 129

A

a. Reduction

Answer 130

A

e. Phenytoin

aka zero-order elimination

Answer 131

A

Protamine - heparin

Answer 132

A

First order kinetics generally apply to high plasma concentrations (>20 mg / 100ml) of ethanol

Alcohol dehydrogenase saturated at relatively low levels

Answer 133

A

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

Answer 134

A

e. Propranolol

Answer 135

A

10 hours

T1/2 = 0.7 (Vd/Cl)

Answer 136

A

Skin is an organ involved in drug biotransformation

Answer 137

A

Vitamin D - intracellular receptor

Answer 138

A

Reduction in creatinine clearance in 2/3 population

Decreased muscle and water, increased fat

Phase 1 reactions reduce much more than phase 2

Answer 139

A

Cytochrome p450 dependent glutathione conjugation

Answer 140

A

e) 75mg

100% = 1000mg/ml

1% = 10mg/ml

0.5%=5mg/ml

(ie multiply your % by 10 to get mg/ml)

Answer 141

A

Ketoconazole

Potent inhibitor

Rifampicin phenobarbital, phenytoin are potent inducers

Answer 142

A

Heparin

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

Answer 143

A

Efficacy is the maximum response produced by a drug

Answer 144

A

Treatment of these patients with ketoconazole

A common inhibitor of drug metabolism

Answer 145

A

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

Answer 146

A

b. Efficacy is the maximum response produced by a drug

Answer 147

A

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

1% = 10mg/ml

Answer 148

A

d) acetylation

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

Answer 149

A

c. Causes increase in smooth endoplasmic reticulum

Answer given is d) but im sure its c)

Answer 150

A

d. Efficacy is the maximum response produced by a drug

Answer 151

A

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 152

A

b) 100mg

2% = 20mg/ml

Answer 153

A

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 154

A

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 155

A

e. Trimethoprim

(renally excreted - thats how it works for UTIs)

Answer 156

A

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 157

A

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 158

A

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

Answer 159

A

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

Answer 160

A

b. Ethanol displays dose-dependent kinetics

Zero-order for EtOH

Answer 161

A

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 162

A

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

Answer 163

A

b. Acetylations of amines

Answer 164

A

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 165

A

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

Answer 166

A

d. Hydroxylation and deamination are examples of phase I reactions

Answer 167

A

b. Depends on the efficiency of drug-receptor interaction

Answer 168

A

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 169

A

b. Cytochrome P-450 dependent oxidations

Phase 1

Answer 170

A

b. Tubulin

Answer 171

A

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

Answer 172

A

e. Inhibit receptors to a degree proportionate to antagonist concentration

Answer 173

A

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 174

A

c. Oxidation

Answer 175

A

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 176

A

Digoxin.

Exported by PGP from placental to maternal tissue

Carbamazepine - congenital malformations
Streptomycin - foetal ototoxicity
MTX - used for medical abortions
PTU -

Answer 177

A

heparin

Answer 178

A

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 179

A

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 180

A

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 181

A

Increased body fat.

Decreased lean body mass, cardiac index, total body water, and hepatic blood flow

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