Phenytoin Flashcards
What type of drug is Phenytoin?
An anticonvulsant
How does phenytoin work?
Binds to neuronal sodium channels in their inactive state preventing the influx of sodium into the neuron. This keeps the resting membrane potential lower so the threshold is not met.
Resting membrane potential (-70mV)
Threshold (-55mV)
Overall: Reduces neurone excitability, reduced electrical conductance, prevents the spread of seizure activity.
A similar effect in cardiac Purkinje fibres may account for both antiarrhythmic and cardiotoxic effects of phenytoin.
What effect does phenytoin have outside the CNS?
A similar sodium channel blockage is had in cardiac Purkinje fibres which may account for both antiarrhythmic and cardiotoxic effects of phenytoin.
What are the common uses for Phenytoin?
- Status Epilepticus: when benzodiazepines are ineffective
2. Epilepsy: focal, general and tonic clonic seizures (valproate preferred due to less side effects and interactions)
What are the contra-indications of using phenytoin?
Pregnancy
Hepatic impairment
Porphyria
People with prior Antiepileptic hypersensitivity
Why shouldn’t you give phenytoin in pregnancy?
In utero phenytoin exposure is associated with craniofacial abnormalities and reduced IQ (fetal hydantoin syndrome).
What advice should you give pregnant women who have been taking phenytoin?
Women with epilepsy planning pregnancy should discuss treatment with a specialist and take high-dose folic acid before conception
Why should doses be lowered in people with hepatic impairment?
Phenytoin is metabolised by the liver with zero-order kinetics (i.e. at a constant rate irrespective of plasma concentrations) for concentrations at or above the therapeutic range. Moreover, the therapeutic index is low, implying that the safety margin between therapeutic and toxic doses is narrow.
What are the common interactions with Phenytoin
Phenytoin is an enzyme inducer, so reduces plasma concentrations and efficacy of drugs metabolised by P450 enzymes, e.g. warfarin, and oestrogens and progestogens.
Phenytoin is itself metabolised by these enzymes, so its plasma concentrations and adverse effects are increased by cytochrome P450 inhibitors, e.g. amiodarone, diltiazem and fluconazole.
Complex interactions can occur with other antiepileptic drugs as most alter drug metabolism.
The efficacy of antiepileptic drugs is reduced by drugs that lower the seizure threshold (e.g. SSRIs, tricyclic antidepressants, antipsychotics, tramadol)
Is phenytoin a CYP450 Inducer or Inhibitor?
Inducer
What are the common side effects of Phenytoin?
Long-term phenytoin treatment can cause a change in appearance:
- skin coarsening
- acne
- hirsutism
- gum hypertrophy
- Haematological disorders
- osteomalacia
- cause folic acid and vitamin D metabolism so bones and blood can’t form.
- Hypersensitivity
- Antiepileptic hypersensitivity syndrome
What are the common side effects of dose related and toxicity of phenytoin?
Dose- related neurological effects include:
- Cerebellar toxicity (e.g. nystagmus, ataxia and discoordination)
- Impaired cognition or consciousness.
Phenytoin toxicity (due to overdose or injudicious IV infusion) can cause:
- death through cardiovascular collapse
- respiratory depression.
What hypersensitivity reactions can you get from phenytoin?
From rash to the rare life- threatening antiepileptic hypersensitivity syndrome
What is Antiepileptic hypersensitivity syndrome?
Affects about 1 in 5000 people taking carbamazepine or phenytoin
Usually within 2 months of starting treatment
Clinical features include:
- Severe skin reactions (e.g. Stevens–Johnson syndrome, toxic epidermal necrolysis)
- Fever
- Lymphadenopathy
- Systemic Involvement (e.g. haematological, hepatic, renal)
- Mortality of about 10%.
**Other common adverse effects include oedema and hyponatraemia due to an antidiuretic hormone-like effect of carbamazepine
How is Phenytoin eliminated?
Hepatically metabolised
Excreted in urine and bile
