Drug Interactions

Question 1

List 5 drug related inducers of CYP450s. (5)

Answer 1

Phenytoin (anticonvulsant)
Carbamazepine (anticonvulsant)
Barbiturates (anticonvulsant)
Rifampicin (TB)
St John’s Wort

Question 2

List 5 drug related inhibitors of CYP450s. (5)

Answer 2

Omeperazole (reduces stomach acid)
Disulphiram (acetaldehyde dehydrogenase inhibitor)
Sodium Valporate (anticonvulsant)
Isoniazid (TB)
Ciprofloxacin (abx)

Question 3

Explain how alcohol use can affect drug metabolism. (4)

Answer 3

Acute alcohol use acts as an inhibitor of CYP450s, meaning drug metabolism is reduced.
Chronic alcohol use acts as an inducer of CYP450s, meaning drug metabolism is increased.

Question 4

Describe 4 common situations that can encourage DDIs. (8)

Answer 4

If drugs work at the same receptor - Beta blockers and B2 agonists
If drugs work at different receptors - warfarin and aspirin
If the drug is non-selective - antidepressants affect many receptors.
If the effect is enhanced by other means - digoxin toxicity is enhanced by hypokalaemia caused by loop diuretics.

Question 5

Describe the “usual suspects” of DDIs. (5)

Answer 5

“The 5 A’s”
Anticonvulsants
Antibiotics
Anticoagulants 
Antidepressants or antipsychotics
Antiarrhythmics.

Question 6

Describe three common drug-disease interactions. (5)

Answer 6

Renal disease with falling GFR - reduced renal clearance of drugs, further damage with nephrotoxins.
Hepatic Disease - reduces hepatic clearance of drugs due to inhibited CYP450s.
Cardiac disease - reduced renal and hepatic blood flow.

Question 7

Describe two common drug-food interactions. Name the specific enzyme they affect. (8)

Answer 7

Grapefruit juice - Inhibits CYP3A4 (among others) to reduce clearance of drugs (eg statins) leading to toxicity.
Cranberry juice - useful to treat UTIs, but inhibits CYP2C9 to reduce warfarin clearance, which increases the risk of bleeding.

Question 8

Describe the 6 types of adverse drug effect. (6)

Answer 8

Augmented - known, common and mild.
Bizarre - unpredictable, severe, and rare
Chronic treatment - prolonged exposure related
Delayed effects - in children of patient or in patient years later.
End-of-treatment effects
Failure of desired effect.

Question 9

Give an example for each of the 6 types of adverse drug effects. (6)

Answer 9

Augmented - hypoglycaemia following insulin injection
Bizarre - anaphylaxis with penicillin
Chronic treatment - iatrogenic Cushing’s following prednisolone treatment
Delayed effects - second cancers in those treated with alkylating agents for Hodgkin Lymphoma.
End-of-treatment - adrenocortical insufficiency
Failure of desired effect - correctly used pill doesn’t prevent a pregnancy.

Question 10

Describe patients at high risk of adverse drug reactions. (5)

Answer 10

Polypharmacy
Extremes of age
Multiple medical problems
Those on drugs with narrow therapeutic windows (inc toxicity risk)
Those on drug doses near to the minimum effective concentration (increased risk of treatment failure with increased metabolism’.

Question 11

Describe 7 patient factors that can influence the variability of drug response. (7)

Answer 11

Body weight
Body surface area (size) 
Age
Sex
Genetics
Condition of health
Placebo effect.

Question 12

Describe 5 administration factors that can influence the variability of drug responses. (5)

Answer 12

Dose
Formulation
Route of administration
Drug interactions
Repeated administration factors (allergy, resistance).