Pharmacokinetics

Question 1

6 rights of prescribing

Answer 1

right patient, drug, route, dose, time, outcome

Question 2

what does ADME stand for

Answer 2

Absorption
Distribution
Metabolism
Excretion

Question 3

Routes of drug administration

Answer 3

Enteral: oral, rectal, sublingual, buccal

parenteral: intramuscular, subcutaneous, intravenous, intradermal

topical, transdermal, inhalational, intrathecal

Question 4

the first journey of a medicine for it to reach the market

Answer 4

discovery
development
evaluation
registration
distribution
monitoring

Question 5

factors that influence enteral absorption

Answer 5

GI motility
GI blood flow
Drug particle size and formation
Drug physiochemical properties

Question 6

What is bioavailability and what is equation for it

Answer 6

fraction of administered (oral) dose of a drug that reaches systemic circulation

oral AUC divided by IV AUC

Question 7

What is the first pass effect

Answer 7

Metabolism of drug prior to reaching systemic circulation

Question 8

Drug distribution

Answer 8

process by which the drug is transferred reversibly from systemic circulation into the tissues as concentrations in the blood increase, and from tissues into blood when the blood concentrations decrease during elimination

distribution of the drug into intracellular, interstitial and vascular compartments

Question 9

drugs bind non-specifically to which protein in the blood

3 examples of highly protein bound drugs

Answer 9

albumin

warfarin, aspirin, ibuprofen, heparin, furesomide

Question 10

Factors which influence drug distribution

Answer 10

drug lipid and water solubility
drug particle size
durg protein binding
the environment - blood flow, pH

Question 11

Volume distribution definition

equation

Answer 11

volume into which a drug appears to be distributed with a conc equal to that of the plasma

drug dose (mg) divided by plasma concentration (mg/L)

Question 12

what do we mean if a drug has a low Vd
what do we mean if a drug has a middle Vd
what do we mean if a drug has a high Vd

include Vd values for each and an example

Answer 12

a) <10L Vd = highly protein bound drug retained in plasma eg warfarin
b) Vd 10-30L = water soluble drugs, low lipid solubility, distributes to interstitial fluid but not cells eg gentamicin
c) Vd >100L = lipid soluble drug distributes into tissues. higher dose needs to be given. eg amiodarone

Question 13

by what processes are drugs metabolised in phase I , mention the 3 outcomes

what is purpose of phase II and what are processes involved in this

Answer 13

outcomes: active (pro-drug), inactive or toxic. Drugs are metabolised by oxidation (cytochrome P450), reduction, hydrolysis

phase II: drug solubilisation by conjugation. Processes: glucuronidation, acetylation, sulfation, methylation

for elimination in urine or bile

Question 14

definition of prodrug

3 examples of prodrugs and their active metabolites

Answer 14

a drug or compound that is metabolised into a pharmacologically active drug eg

enalapril to enalaprilat
codeine into morphine
levodopa to dopamine

Question 15

3 CYP450 inhibitors and inducers

Answer 15

inhibitors: amiodarone, cirpofloxacin, erythromycin/clarithromycin, metronidazole, flucanazole, isoniazid, alcohol (acute), grapefruit juice
inducers: carbamazepine, phenytoin, rifampicin, alcohol (chronic)

Question 16

therapeutic index

Answer 16

ratio of concentration associated with toxicity vs concentration associated with efficacy

Question 17

what are the 4 types of genetic metabolisers and what are the allele combinations for each

Answer 17

extensive metaboliser: two active ‘normal’ alleles

intermediate metaboliser: one normal and one abnormal allele

poor metaboliser: two abnormal alleles

ultrarapid metaboliser: duplication of normal alleles

Question 18

using codeine phosphate and CYP2D6 as an example, give the effect of having an ultrarapid metaboliser polymorphism vs having a poor metaboliser polymorphism

Answer 18

CYP2D6 polymorphism with ultrarapid metaboliser effect: causes opiate toxicity even at low dose, causing exaggerated response to codeine

CYP2D6 polymorphism with poor metaboliser effect: causes inadequate pain relief by codeine in some individuals

Question 19

in phase II of metabolism, activity of N-acetyltransferase is genetically determined

a) what causes inc risk of isoniazid hepatotoxicity
b) what causes inc risk of isoniazid neuropathy
c) what causes inc risk of drug-induced lupus with hydralazine

Answer 19

a) fast acetylators
b) slow acetylators
c) slow acetylators

Question 20

describe non-saturable metabolism (first-order kinetics)

describe saturable metabolism (zero-order kinetics), give some examples of drugs which undergo this type of metabolism

Answer 20

rate of drug metabolism proportional to drug concentration

rate of drug metabolism independent of drug concentration eg phenytoin, alchohol, aspirin, fluoxetine

Question 21

Excretion out of urine via kidneys is most common method of excretion
other methods ?

Answer 21

bile (faeces)
sweat
exhaled air
saliva
breast milk

Question 22

a) causes of low drug clearance

b) causes of high drug clearance

Answer 22

a) normal variation, renal impairment, liver impairment, enzyme inhibition, genetic poor metabolizer, age (neonate/ old age), reduced blood flow
b) normal variation, inc renal blood flow, genetic hypermetabolism, enzyme induction

Question 23

How many half lifes does it take for a drug to reach steady state

Answer 23

5

Question 24

Half life definition

Answer 24

time it takes for conc of drug in plasma to half

Question 25

loading dose is determined by
maintenance dose is determined by
dose interval is determined by

Answer 25

volume of distribution (Vd)
clearance
half life