Anticonvulsants - Phenytoin

Question 1

When is phenytoin used?

Answer 1

• to control siezures in status epilepticus where benzodiazepines are innefective.
• to reduce frequency of siezures in epilepsy

Question 2

What drugs are usually preferred to reduced the frequency of siezures in epilepsy rather than phenytoin

Answer 2

• valproate
• Iamotrigine
• levetracetam

*due to less side effects and interactions than phenytoin

Question 3

How does phenytoin inhibit the spread of seizure activity?>

Answer 3

• Phenytoin reduced neuronal excitability and electrical conductance by:
• binding to neuronal Na+ channels
• stops influx of Na+ into neurone
• so threshold for action potential not reached

Question 4

What are the side effects of phenytoin?

Answer 4

1) Change in appearance:
- skin coarsening
- acne
- hirsutism
- gum hypertrophy

2) Neurological effects:
- nystagmus
- ataxia
- discoordination
- impaired cognition / consciousness

3) Haematological disorders as it causes folate / b12 metabolism
4) Osteomalacia
5) Allergic reaction
6) Phenytoin toxicity —> death via cardiovascular collapse, respiratory depression

Question 5

Phenytoin is metabolised by the Liver with zero-order kinetics - what does this mean?

Answer 5

Phenytoin is metabolised by the liver at a constant rate irrespective of plasma concentrations, this is for concentrations at or above the therapeutic range.

Question 6

What are the warnings of phenytoin?

Answer 6

-low therapeutic index (safety margin between therapeutic and toxic doses is narrow)

Question 7

When should phenytoin dose be reduced?

Answer 7

hepatic impairment

Question 8

What is in utero phenytoin exposure associated with?

Answer 8

• craniofacial abnormalities

- reduced IQ

Question 9

What are the drug interactions of phenytoin?

Answer 9

1) Drugs metabolised by P450 enzymes e.g. warfarin, oestrogens , progestogens
2) Drugs that inhibit cytochrome P450 enzyme e.g. amiodarone, diltiazem and fluconazole

Question 10

Why should phenytoin be avoided with warfarin, oestrogen and progestogen

Answer 10

• Warfarin, Oestrogen and Progestogen are metabolised by P450 enzymes
• Phenytoin is an enzyme inducer, so increases the activity of these P450 enzymes.
• So the drugs get broken down more quickly leading to decreased plasma concentrations and efficacy of the drugs.

Question 11

What enzyme metabolises phenytoin?

Answer 11

P450 enzymes

Question 12

Why should phenytoin be avoided with amiodarone, diltiazem and fluconazole?

Answer 12

• Phenytoin is metabolised by P450 enzymes
• These drugs inhibit Cytochrome P450
• so the plasma concn and efficacy of phenytoin is increased when used alongside amiodarone, diltiazem, fluconazole.

Question 13

What drugs reduce the efficacy of antiepileptic drugs?

Answer 13

The efficacy of antiepileptic drugs (such as phenytoin) is reduced by drugs that lower the seizure threshold e.g. SSRI, tricyclic antidepressants, antipsychotics, tramadol.

Question 14

What is the loading dose of phenytoin, and how is it given?

Answer 14

IV Phenytoin loading dose if 20mg/Kg then 100mg every 6 to 8 hrs.

Oral phenytoin , daily for chronic epilepsy

Question 15

Why should treatment with phenytoin not be stopped suddenly but withdrawn slowly?

Answer 15

risk of siezure recurrence

Question 16

Why would a trial of phenytoin in an elderly confused person be useful in confirming diagnosis?

Answer 16

• Sometimes a reduced level of consciousness in elderly people can be caused by non-convulsive status epilepticus.
• When EEG is not readily available a trial of phenytoin can confirm this diagnosis .
• there may be dramatic improvement in consciousness.