Phenytoin

Question 1

Indications of phenytoin

Answer 1

• Effective in all types of seizures except absence seizures
• Used for neuropathic pain when carbamazepine is not appropriate

Question 2

Therapeutic index for phenytoin

Answer 2

10-20mg/L
40-80micromol/L

Question 3

Toxic effects of phenytoin

Answer 3

Nystagmus (involuntary movements of the eye)
Ataxia (Loss of balance/co-ordination)
Dysarthria (Slurred speech due to loss of muscle control)
Tremor, hyperreflexia, lethargy, nausea and vomiting

Patient may become comatose and hypotensive

Death occurs due to respiratory and circulatory depression

Question 4

Monitoring parameters of Phenytoin

Answer 4

• ADR’S - toxicity, gingival hyperplasia, hirsutism (in women growth of men-like hair), and aggravation of acne.
• Blood or skin disorders - skin rash should result in immediate withdrawal to avoid exfoliative dermatitis and Steven-Johnson syndrome
• Full blood count - Can produce rare blood dyscrasias such as agranulocytosis and aplastic anaemia
• LFT’s

Question 5

Acute ADR’s

Answer 5

Dizziness
Diplopia (double vision)
Nystagmus
Dysarthria
Ataxia

Question 6

Chronic ADR’s

Answer 6

Gingival hyperplasia
Hirsutism
Coarsening of facial features
Drowsiness
Megaloblastic anaemia (due to altered folate metabolism)

Question 7

Idiosyncratic ADR

Answer 7

Fever
Rashes
Inducing severe reactions

Question 8

Teratogenic ADR

Answer 8

Associated with cleft palate and congenital heart disease

Question 9

Enzyme inducers

Answer 9

These will decrease phenytoin serum levels:
- Smoking
- Carbamazepine
- Rifampicin
- Alcohol (chronic)
- Griseofulvin
- Phenobarbital
- St. John’s wort
(- Phenytoin)

Question 10

Enzyme inhibitors

Answer 10

These will increase phenytoin serum levels:
- Clarithromycin
- Amiodarone
- Cimetidine
- Azole antifungals (miconazole, fluconazole)
- Alcohol (binge)
- Metronidazole
- Omeprazole
- Verapamil/Diltiazem
- Isoniazid
- Erythromycin
- Chloramphenicol
- Fluoxetine

Question 11

Phenytoin and Alcohol

Answer 11

• Acute alcohol will increase phenytoin levels
• Alcoholism will decrease phenytoin levels

Question 12

Phenytoin and antipsychotics

Answer 12

Anticonvulsant effects may be antagonised
Lowering convulsive threshold
Phenytoin dose may need adjustment

Question 13

Phenytoin and tricyclic antidepressants

Answer 13

Phenytoin reduces plasma conc. of tricyclics

Question 14

Phenytoin as an enzyme inducer

Answer 14

It impairs the activity of a number of drugs
- Ciclosporin
- Corticosteroids
- Oral contraceptives
- Theophylline
- Digoxin
- Warfarin
- Itraconazole, ketoconazole