Phenytoin (PHT) is an anti-seizure medication.



Dilantin is the major tradename. 



It is useful for the prevention of tonic-clonic seizures and focal seizures, but not absence seizures.



It is believed to protect against seizures by causing voltage-dependent block of voltage gated sodium channels.



Dilantin  blocks sustained high frequency repetitive firing of action potentials by reducing the amplitude of sodium-dependent action potentials through enhancing steady state inactivation. 



The intravenous form is used for status epilepticus that does not improve with benzodiazepines.



Also be used for certain heart arrhythmias or neuropathic pain.



It can be taken intravenously or by mouth.



The intravenous form generally begins working within 30 minutes and is effective for 24 hours.



Blood levels of this drug can be used to determine the proper dose.



Pregnanc category US: D (Evidence of risk)





70–100% oral, 24.4% for rectal administration.



Protein binding 95%.



Metabolism in the liver.



Onset of action 10 to 30 min (IV)



Elimination half-life 10–22 hours.



Duration of action 24 hours



Excretion is primarily through the bile, urinary tract.



Side effects include: nausea, stomach pain, loss of appetite, poor coordination, increased hair growth, and enlargement of the gums.



Serious side effects include: sleepiness, self harm, liver problems, bone marrow suppression, low blood pressure, and toxic epidermal necrolysis.



Safe to use when breastfeeding.



Alcohol may adversely interfere with its effects.






Mainly for the prophylactic management of tonic-clonic seizures with complex symptomatology



Focal seizures: Mainly used to protect against the development of focal seizures with complex symptomatology-psychomotor and temporal lobe seizures.



Also effective in controlling partial seizures with autonomic symptoms.



Absence seizures: Not used for pure absence seizures due to risk for increasing frequency of seizures, but can be used in combination with other anticonvulsants during combined absence and tonic-clonic seizures.



Seizures during brain surgery.



Status epilepticus: Considered after failed treatment using a benzodiazepine due to slow onset of action.



It may take 5–10 days to achieve anticonvulsant effects.



It is a class 1b antiarrhythmic:


It may be used in the treatment of ventricular tachycardia and sudden episodes of atrial tachycardia after other antiarrhythmic medications or cardioversion has failed. 



Its IV formulation is drug of choice for arrhythmias caused by cardiac glycoside toxicity.



For trigeminal neuralgia it is a second choice drug to carbamazepine.



Dilantin has a narrow therapeutic index, and monitoring plasma concentrations is advised.



Anticonvulsant effect: 10–20 µg/mL; Antiarrhythmic effect: 10–20 µg/mL.



Avoiding intramuscular formulation due to skin cell death and local tissue destruction.



The elderly: May show earlier signs of toxicity.



Ideal body weight is used for  dosing calculations.



Pregnancy Category D due to risk of fetal hydantoin syndrome and fetal bleeding. 



During pregnancy the drug may be continued if benefits outweigh the risks. 



It is not recommended during breast feeding as  low concentrations of phenytoin are excreted in breast milk.



IV use is contraindicated in patients with sinus bradycardia, SA block, second- or third-degree AV block, Stokes-Adams syndrome, or hypersensitivity to phenytoin.



Hypotension and abnormal heart rhythms can be seen with rapid infusion of IV phenytoin. 



IV infusion should not exceed 50 mg/min in adults or 1–3 mg/kg/min in children. 



Heart monitoring should occur during and after IV infusion.



Phenytoin may produce nystagmus on lateral gaze. 



At toxic doses, patients experience neurological findings of vertical nystagmus, double vision, sedation, slurred speech, cerebellar ataxia, and tremor.



The sudden cessation of phenytoin may result in increased seizure frequency, including status epilepticus.



Phenytoin may accumulate over long periods of time and can cause atrophy of the cerebellum.



Phenytoin is a causal factor in the development of peripheral neuropathy.



Folate is present in food in a polyglutamate form, which is then converted into monoglutamates by intestinal conjugase to be absorbed by the jejunum. 



Phenytoin acts by inhibiting the enzyme intestinal conjugase thereby causing folate deficiency, and thus megaloblastic anemia..



Other side effects may include: agranulocytosis, aplastic anemia, decreased white blood cell count,and a low platelet count.



It is a known teratogen:  craniofacial anomalies with broad nasal bridge, cleft lip and palate, smaller than normal head, and a mild form of mental retardation.



Gingival enlargement is probably due to folate deficiency.



Gingival overgrowth develops in approximately half the patients taking phenytoin. 



Folic acid supplementation can prevent gingival enlargement in children who take phenytoin.



Phenytoin associated with: 


hypertrichosis, Stevens–Johnson syndrome, purple glove syndrome, rash, exfoliative dermatitis, itching, excessive hairiness, and coarsening of facial features.



These skin conditions are significantly more common in patients with a particular HLA-B*1502.



HLA-B*1502 allele occurs almost exclusively in patients with Asian ancestry.



Primarily metabolized to its inactive form by the enzyme CYP2C9. 



Variations within the CYP2C9 gene that decrease  enzymatic activity have been associated with increased phenytoin concentrations, and drug toxicities



Strong evidence exists linking HLA-B*1502 with the risk of developing Stevens Johnson Syndrome or toxic epidermal necrosis in patients taking carbamazepine.



Can cause drug-induced lupus, and 


is aassociated with reversible IgA deficiency.



It may increase risk of suicidal thoughts or behavior. 



Chronic use is associated with decreased bone density and increased bone fractures. 



Phenytoin induces metabolizing enzymes in the liver, and is associated with increased metabolism of vitamin D, and  decreased vitamin D levels. 



It induces CYP3A4 and CYP2C9 families of the P450 enzyme responsible for the liver’s degradation of various drugs.



It alters the extent of absorption of antacids.



Antacids may decrease the AUC of phenytoin, and concomitant use of antacids and phenytoin should be avoided.



Warfarin and trimethoprim increase serum phenytoin levels, prolonging  the serum half-life of phenytoin by inhibiting its metabolism. 



It binds preferentially to the inactive form of the sodium channel. 



The  binding to the inactive state by phenytoin sodium can produce voltage-dependent, use-dependent and time-dependent block of sodium-dependent action potentials.



Phenytoin’s primary site of action appears to be the motor cortex where spread of seizure activity is inhibited.



By promoting sodium efflux from neurons, it tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. 



It reduces post-tetanic potentiation at synapses which prevents cortical seizure foci from detonating adjacent cortical areas. 



It  reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures.



A small increase in dose may lead to a large increase in drug concentration.



 The time to reach steady state is often longer than 2 weeks.



Topical phenytoin is useful in wound healing in people with chronic skin wounds.

Exhibits nonlinear kinetics, and saturable metabolism, so that a small dose increase can lead to a larger than expected increase in drug levels with potential toxicity.

90-95% protein bound and follows the Michaelis-Menten or saturable pharmacokinetics.

A Class 1b antiarrhythmic agent that blocks the sodium ion channel in both neural and cardiac tissue.

In the bloodstream largely bound to proteins such as albumin, making it physiologically inactive.

Renal failure can greatly increase unbound fraction of phenytoin.

Metabolized by cytochrome P450 system.

The free fraction phenytoin that is pharmacologically active his primarily metabolized via the cytochrome P450 enzymes 2C9 and 2C19.

An inducer of the CYP 450 enzymes 3A4, 2C9, 2C19, and 2B6.

Can cause widened QRS complexes.

Phenytoin has the ability to induce it so metabolism as well as metabolism of other drugs, creating into patient variability and requiring pharmacokinetic monitoring.


Gingival overgrowth develops in approximately half the patients taking phenytoin. 


Leave a Reply

Your email address will not be published. Required fields are marked *