SCRIPT: drug interactions

Question 1

Pharmacodynamic interactions.

a) What are they?
b) Example - sildenafil and GTN

Answer 1

a) - Drugs amplify (additive effects) or negate each other’s pharmacological effects
- These interactions occur at the level of the receptor, tissue, and organ

b) - Both drugs increase cyclic GMP
- Both lead to hypotension
- Co-adminstration amplifies these effects and can lead to fatal hypotension or MI

Question 2

Pharmacokinetic interactions

Answer 2

When one drug affects the Absorption, Distribution, Metabolism or Excretion (ADME) of another drug

Question 3

Cytochrome P450.*

a) Inducers
- effects on most drugs (eg. warfarin, COCP)
- effects on prodrugs (eg.

b) Inhibitors
- effects on most drugs (eg. warfarin)
- effects on prodrugs (eg.

c) Examples of enzyme inducers (PC BRAS) and inhibitors (AO DEVICES)
* Enzyme inhibitors and inducers (if required) must be considered when adding, removing, increasing/reducing dose if patients are on a drug which uses CYP450 as a substrate (eg. warfarin)

Answer 3

a) Enzyme inducers.

Effect on most drugs:

• Increase the metabolism of drugs that are substrates to a CYP450 enzyme (eg. warfarin, COCP)
• This results in reduced concentration and therefore reduced efficacy of these drugs
• CYP450 inducers may reduce warfarin efficacy, leading to lower INR and predisposing to CLOTTING
• CYP450 inducers may reduce COCP efficacy, thereby leading to unplanned pregnancy

Effect on prodrugs:

• Increased conversion to active form
• Increased efficacy/ toxicity

Enzyme inducer drugs (PC BRAS)

• Phenytoin
• Carbamazepine
• Barbiturates
• Rifampicin
• Alcohol excess
• St John’s Wort, sulfonylureas, smoking

b) Enzyme inhibitors.

Effect on most drugs:

• Reduce the metabolism of drugs that are substrates to a CYP450 enzyme
• This results in elevated concentrations and therefore increased toxicity from these drugs
• CYP450 inhibitors may result in warfarin toxicity, leading to higher INR and predisposing to BLEEDING

Effect on prodrugs:

• Reduce conversion to active form
• Reduced efficacy

Examples of enzyme inhibitors (AO DEVICES)

• ‘Azole’ antifungals (eg. miconazole, fluconazole)
• Omeprazole
• Disulfiram
• Erythromycin, clarithromycin
• Valproate
• Isoniazid
• Ciprofloxacin
• Ethanol (acute)
• Sweet juice - cranberry, grapefruit

Question 4

Aminoglycosides have a greater risk of causing ototoxicity when given in combination with which other class?

Answer 4

Loop diuretics

Question 5

Renally-excreted drugs can accumulate if given with which class of drugs?

Answer 5

ACE inhibitors (as they reduce the GFR)

Question 6

Warfarin.

a) Pharmacodynamic interactions - drugs to avoid
b) Pharmacokinetic interactions - drugs to avoid
c) Food interactions

Answer 6

a) Additive bleeding effects:
- NSAIDs (increase bleeding risk 10-fold)

b) CYP450 inducers
- reduce concentration of warfarin (lower INR)
- reduced efficacy = increased risk of clotting

CYP450 inhibitors

• increase concentration of warfarin (higher INR)
• increased toxicity = increased risk of bleeding

c) - Vitamin K-rich foods may reduce efficacy of warfarin (but patients should not radically alter diet)
- Avoid grapefruit juice, cranberry juice and limit alcohol

Question 7

Contraceptives and CYP450.

a) Enzyme inducers - effect?
b) Emergency contraception - guidance

Answer 7

a) Reduce efficacy of COCP/ emergency contraceptives

b) - If taken enzyme inducer in last 4 weeks, patient should use non-hormonal contraceptive if possible (eg. copper IUD)
- If hormonal contraception must be taken, patient should take DOUBLE the normal dose

Question 8

Efflux pump systems.

a) Which is the most common?
b) How it protects cells?
c) Drugs that are flushed out by this system?
d) Drugs that inhibit this pump, and therefore can lead to toxicity to certain drugs
e) Cancer expression- explain

Answer 8

a) P-glycoprotein pump
b) Flushes drug out of cell and back into the lumen of the bowel so cannot be absorbed into blood
c) Digoxin

d) Verapamil, atorvastatin, amiodarone
- if these are taken with digoxin, can lead to digoxin toxicity

e) - Over-expression, leading to resistance to certain anti-cancer drugs

Question 9

Drugs that affect iron absorption/ are affected by iron absorption

a) Give examples
b) If interaction, what should you do?

Answer 9

a) - Thyroxine
- Some antibiotics - quinolones, tetracyclines, chloramphenicol
- Some Parkinsonian medications
- Some salts (eg. calcium carbonate, magnesium carbonate)

b) Space doses out:
- Usually 1 - 2 hours apart
- For thyroxine, give 4 hours apart