NEURO: PHENYTOIN

Question 1

PHENYTOIN: INDICATIONS

Answer 1

• Control seizures in SE (where Benzos are ineffective)

- Reduce frequency of generalised or focal seizures in epilepsy

Question 2

PHENYTOIN: MOA

Answer 2

• Reduces neuronal excitability and electrical conductance among neurons => REDUCING SPREAD OF SEIZURE ACTIVITY
• Bind to Na+ channels in their inactive state and preventing Na+ influx into the neuron
• Shift in resting membrane potential from -70mv, to the threshold value -50mv required to trigger a AP
• Same effect in cardiac purkinje fibres

Question 3

PHENYTOIN: ADVERSE EFFECTS

Answer 3

• Change in appearance (skin coarsening, acne, hirutism and gum hypertrophy)
• Dose related neurological effects = include cerebellar toxicity (Impaired coordination and cognition)
• Haematological disorders and ostomalacia
• FA and Vit D metabolism
• HSRxns = mild skin rash to rare life threatening antiepileptic HS syndromes
• Phenytoin toxicity (OD) = cardivascular collapse and resp depression

Question 4

PHENYTOIN: WARNINGS

Answer 4

• Zero order kinetics - theraputic index is low, so safety margin between therapeutic + toxic doses is narrow
• Dose reduced in patients with hepatic impairment
• In utero = craniofacial abnormalities, reduced IQ
• Women with epilepsy planning pregnancy should discuss tx with a specialist and take high dose folic acid before conception

Question 5

PHENYTOIN: INTERACTIONS

Answer 5

• Enzyme inducer so reduces plasma concentrations and efficacy of drugs metabolised by P450 enzymes
  (Warfarin, oestrogens and progesterones)
• Phenytoin is itself metabolised by these enzymes so its plasma concentrations and adverse effects are increased by cytochrome p450 inhibitors (amiodarone, diltazem and flucanzole)
• Complex interactions = other antiepileptic drugs
• Efficacy of antiepileptics is reduced by drugs that lower the seizure threshold (SSRIs, TCAs, ANtipsychs, Tramadol)