Paul (Drug interactions and AEDs)

Question 1

Anti-epileptic drugs (AEDs)

Answer 1

Many patients benefit from combination therapy.
Narrow therapeutic index.
Many are CYP450 and glucothione inducers and some are inhibitors- AEDs have prominent effects on enzymes that metabolise the majority of other drugs.
Often administered for a lifetime.
Most AEDs are substrates for the same enzymes- stimulate their own degradation.
Can also be used as mood stabilisers in bipolar disorder as it lowers brain stimulation

Question 2

Mechanisms (main)

Answer 2

Enzyme induction:
- Many AEDs can stimulate SYP1A2, CYP2C9, CYP2C19, CYP3A4, GT (glucothione)
- Doses of concomitant drugs may need to increase
- Older AEDs have a broader spectrum
- Many AEDs are metabolised by these enzymes

Enzyme inhibition:
- Not as common
- e.g. Sodium Valproate

Others:
- Transporters e.g. P-glycoprotein
- Plasma proteins

Question 3

Important examples

Answer 3

Oral contraceptives
- Common
- Often missed
- Induce metabolism of COC
- e.g. carbamazepine, phenytoin, primidone, topiramate

Anticoagulants
- Older AEDs
- Induce metabolism of warfarin
- INR and tailored dose
- Stopping or changing AEDs