Variability in human responses to drugs

Question 1

What might cause absolute differences in the dose administered?

Answer 1

errors in prescription/dispensing
patient non-compliance
drug formulation

Question 2

What might cause relative differences in the dose administered?

Answer 2

because patient varies from text book standard due to environmental factors, food intake, fluid intake, age, disease

Question 3

What is the most important factor affecting drug handling in the elderly?

Answer 3

changes in renal function:

• reduced renal mass
• reduced renal perfusion
• reduced GFR
• reduced tubular excretion

Question 4

What pathophysiological changes can congestive heart failure cause?

Answer 4

• reduced splanchnic blood flow
• intestinal mucosal oedema
• reduced hepatic clearance

Question 5

What pathophysiological changes can liver failure lead to?

Answer 5

• reduced metabolism
• reduced 1st pass met (=increased bioavailability)
• decreased biliary secretion, hence removal
• decreased albumin synth, hence reduced plasma protein binding

Question 6

How does warfarin work?

Answer 6

inhibits vitamin K reductase which is necessary to carboxylate clotting proteins –> inhibits factors 2,7,9,10

Question 7

What is the effect of clarithromycin on warfarin?

Answer 7

clarithromycin increases potency of warfarin

Question 8

Give some examples of cytochrome p450 inhibitors

Answer 8

macrolides eg. clarithromycin
quinolones eg. ciprofloxacin
anti-fungals eg. fluconazole
proton-pump inhibitors eg. omeprazole
anti-HIV drugs eg. protease inhibitors

Question 9

What is INR and how is it measured?

Answer 9

international normalised ratio
measured using PT test:
take blood –> add citrate buffer –> add tissue factor –> converts prothrombin to thrombin –> time how long it takes for blood to clot –> compare with standard plasma
INR = (test PT/normal PT)^ISI
(N.B. ISI = international sensitivity index)
normal range = 0.9-1.2

Question 10

Give some examples of cytochrome p450 inducers + what they are used for

Answer 10

St John’s Wort –> antidepressant activity:
- Hypericin –> weak MAO activity –> acts on seretonin
- Hyperforin –> inhibits seretonin reuptake
Rifampicin –> TB therapy
Phenytoin –> anti-epileptics
Griseofulvin –> anti-fungal

Question 11

What physiological change can increase the activity of digoxin?

Answer 11

hypokalaemia –> frees up space for digoxin to bind