Pharmacokinetics

Question 1

List the inhibitors of CYP450

Answer 1

Antifungals
Cimetidine
Macrolides
Grapefruit

Question 2

List the inducers of CYP450

Answer 2

Carbamezepine
Phenytoin
Rifampicin
Ritonavir
St Johns Wort

Question 3

What characteristics of a drug require it to be monitored?

Answer 3

Zero order
Long half life
Narrow therapeutic window
Drug-drug interactions common
Known toxic effects

Question 4

How is toxicology risk increased in the presence of i) Renal disease? ii) Hepatic disease? iii) Cardiac disease?

Answer 4

i) decreased GFR so decreased clearance of renally excreted drugs.
ii) decreased CYP450 activity and so increased half lives.
iii) decreased CO so excessive response to hypotensive agents AND decreased renal and hepatic blood flow and clearance.

Question 5

What are the 5 classes of drugs that commonly have high pharmacodynamic interactions?

Answer 5

Anti convulsants
Anti biotics
Anti coagulants
Anti depressants/psychotics
Anti arrhythmics

Question 6

List some causes of variability in drug response.

Answer 6

Genetics, Sex, Age, Allergy
Dose, Route of Administration, Resistance, Placebo Effect
Formulation, Tolerance, Body Weight and Size, Health Condition, High Drug Intake = More Interactions

Question 7

Discuss the mechanism behind Digoxin poisoning and how it is treated.

Answer 7

First Order elimination. Loading doses required to reach steady state.
Digitoxic: bradycardia, xanthopsia, vomiting.
40 hours to reduce p[drug] to 50%.
Antidote required.

Question 8

Discuss the mechanism behind Paracetamol poisoning and how it can be treated.

Answer 8

Depletion of glucaronide and sulfate.
NAPQI saturates glutathione conjugation ability.
Increase in NAPQI -> Toxic.
Replace glutathione with N-acetylcysteine (Parvolex).

Question 9

Describe the interaction between warfarin and cimetidine.

Answer 9

Cimetidine binds to plasma proteins with a higher affinity than Warfarin and displaces it. This causes dangerous levels of warfarin in the blood.