Pharmacokinetics 3

Question 1

Drug metabolism - phase I and II

Answer 1

Phase I: drug -> active, inactive or toxic; oxidation, reduction or hydrolysis
Phase II: drug solubilisation by conjugation and elimination in urine or bile

Question 2

Cytochrome P450 inhibitors

Answer 2

These can cause overdose for certain drugs, as cytochrome P450 helps break down drugs in the liver.
Inhibitors include amiodarone, alcohol, grapefruit juice
This is a rapid process

Question 3

Cytochrome P450 inducers

Answer 3

These break down drugs too much so don’t have enough of an effect
Include: alcohol, rifampicin

Question 4

Narrow therapeutic index of cytochrome P450

Answer 4

Drug metabolised by CYP45- with narrow therapeutic window (warfarin/aminophylline) + cytochrome P450 inhibitor = potential for adverse drug interaction

Question 5

Genetics and drug metabolism

Answer 5

Genetic polymorphisms are multiple genetic variants which result in different phenotypes
These can affect drug handling
Extensive metaboliser = two active normal alleles
Intermediate metaboliser = one normal and one abnormal allele
Poor metaboliser = two abnormal alleles
Ultrarapid metabolisers = duplication of normal alleles

Question 6

Drugs effected by genetics

Answer 6

Codeine phosphate (CYP2D6 polymorphism)
Activity of N-acetyltransferase is genetically determined

Question 7

Drug clearance

Answer 7

The sum of all the drug-eliminating processes, principally determined by hepatic metabolism and renal excretion
It can also be defined as the theoretical volume of fluid from which a drug is completely removed in a given period of time

Question 8

Other excretory methods

Answer 8

Bile (faeces)
Sweat
Exhaled air
Saliva
Breast milk

Question 9

Causes of low drug clearance

Answer 9

Normal variation
Renal impairment
Liver impairment
Enzyme inhibition
Genetic poor metabolizer
Neonate
Old age

Question 10

Causes of high drug clearance

Answer 10

Normal variation
Increased renal blood flow
Genetic hypermetabolism
Enzyme induction

Question 11

Half life provides information on

Answer 11

Time course of drug elimination
Time course of drug accumulation
Choice of dose interval

Question 12

Dosing of drugs

Answer 12

Half life = volume of distribution/clearance
Loading dose is determined by the volume of distribution
Maintenance dose is determined by the clearance
Dose interval is determined by the half life