CLINICAL PHARMACOLOGY; EXPECTED EXAM QUESTIONS AND THEIR ANSWERS

CLINICAL PHARMACOLOGY;
EXPECTED EXAM QUESTIONS AND
THEIR ANSWERS


Pharmacokinetics vs pharmacodynamics definitions
PK - what the body does to the drug (drug, conc)
- use concentration/time
- the study of time-course of drug concs in body and
factors affecting this

PD - what the drug does to the body (effects)
- use response/concentration
- the study of drug effects and moa
Possible reasons for overdose of a drug (exceeding
maximum toxic conc)
renal impairment
reduced metabolism
- liver imp
- enzyme inhibition
- pharmacogenetics
Possible reasons for not getting enough of a drug
(below minimum effective conc)
non-adherence
under prescribing
increased metabolism
- enzyme infuction
- pharmacogenetics

,How is drug half-life calculated and what is 'first order'
elimination?
- calculated from plasma concentration (Cp) versus time
graph
- it is the time taken for the conc to halve
- curve shape after IV injection - this is first order
elimination curve and applies to most drugs
- half life is same at all concs
What does the conc/time curve look like when using
log graph?
graph looks linear and half life more obvious
How can you work out k with a conc/time graph? (both
log and non-logged graphs)
lnCpt = lnCp0 - kt

OR

Cpt = Cp0.e^(-kt)
What is k?
- fraction of drug removed from the body per unit time
- units: time^-1 (usually per hour) e.g. 0.33 per hr
(lignocaine)
What is the half life?
t1/2

time for conc of drug in body to halve
units: time (usually hours)
e.g. 36 hours (digoxin)
What is the relationship of t1/2 and k?
K = (ln(Cp0/0.5Cp0))/(t1/2)
= ln2/t1/2

,= 0.693/t1/2

or half life = 0.693/k
Why is t1/2 important?
- time course of elimination
- time course of accumulation
- choice of dose interval
Why are Vd and CL useful clinically (individualising
dosage)?
CL: allows determination of rate of elimination and hence
the maintenance dosing
i.e. M.Dose = CL x Cpss

Vd: allows determination of amount of drug in body
required to achieve a target concentration and hence
loading dose
i.e. L.Dose = Vd x Cptarget
How do you calculate maintenance dose?
MDose = CL x Cpss
How do you calculate loading dose?
LDose = Vd x Cptarget
How do Vd and CL change in renal dysfunction?
CL
- for drugs that are renally cleared unchanged (fu = 1), CL
is reduced
- for drugs metabolised, CL not affected

Vd
- protein binding is reduced in renal disease
- for highly protein bound drugs, Vd is increased
(when more protein is lost, the apparent Cp drops so Vd is

, increased)
- for low protein bound drugs, Vd is reduced
(losing protein makes Cp greater? either way Vd is down.
Think of it like there's more drug in plasma to be cleared...)
How do Vd and CL change in the elderly?
Vd
- elderly have less muscle and more fat mass
- lipophilic drugs will have a higher Vd and hydrophilic
drugs will have a lower Vd

CL
- reduced for both renal and metabolised drugs
How do Vd and CL vary in relation to
pharmacogenetics?
CL
- if drugs metabolised by pathways subject to
polymorphisms (e.g. warfarin), then dependent on
particular genotype of pt
- Poor metabolisers (dysfunctional alleles) will have a
reduced clearance and too much drug in system so risk of
toxicity if dose not reduced
- EM (wild type) have normal clearance
- UM (ultrarapid metabolisers have duplication of
functional alleles), CL will be higher so will need higher
dose to get effect
- no effect is expected for drugs excreted renally
unchanged

Vd
- no effect
How do Vd and CL vary in obesity?