Phenytoin; Uses, Dosage, Side Effects, Drug Interactions

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Phenytoin is a hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin potentially acts by promoting sodium efflux from neurons located in the motor cortex reducing post-tetanic potentiation at synapses. The reduction of potentiation prevents cortical seizure? foci from spreading to adjacent areas, stabilizing the threshold against hyperexcitability. In addition, this agent appears to reduce the sensitivity of muscle spindles to stretch causing muscle relaxation.

An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.

Mechanism of Action of Phenytoin

Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.

Indications of Phenytoin

• Complex Partial Seizures
• Grand mal Generalized? tonic-clonic seizure
• Seizures
• Tonic-clonic seizures – Mainly used in the prophylactic management of tonic-clonic seizures with complex symptomatology (psychomotor seizures). A period of 5–10 days may be required to achieve anticonvulsant effects.
• 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 in treatment of pure absence seizures due to risk for increasing frequency of seizures. However, can be used in combination with other anticonvulsants during combined absence and tonic-clonic seizures.
• Seizures during surgery – Used as prevention and treatment of seizures occurring during and after neurosurgery.
• Status epilepticus – Considered after failed treatment using a benzodiazepine due to slow onset? of action.
• Abnormal heart rhythms – may be used in the treatment of ventricular tachycardia? and sudden episodes of atrial tachycardia? after other antiarrhythmic medications or cardioversion has failed. It is a class 1b antiarrhythmic.
• Digoxin toxicity – IV formulation is the drug of choice for arrhythmias caused by cardiac glycoside toxicity.
• Trigeminal neuralgia – Second choice drug to carbamazepine.

Contra-Indications of Phenytoin

• Thyroid? Problems
• Diabetes
• Softening of Bones
• Porphyria
• Megaloblastic Anemia
• acquired decrease of all cells in the blood
• Decreased Blood Platelets
• Deficiency of Granulocytes a Type of White Blood Cell
• Decreased White Blood Cells
• Low Level of Granulocytes in the Blood
• Having Thoughts of Suicide
• The habit of Drinking Too Much Alcohol
• Alcohol Intoxication
• Depression
• Myasthenia Gravis
• Overgrowth of Gums Onto Teeth
• Liver? Problems
• kidney? disease with a reduction in kidney function
• Systemic Lupus Erythematosus?
• Osteoporosis
• Decreased Calcification or Density of Bone
• Body Temperature More Than 101 Degrees F
• Swollen Lymph Nodes?
• High Blood Sugar?
• Pregnancy

Dosage? of Phenytoin

Strengths: 50 mg/mL; 50 mg; 100 mg; 30 mg; 25 mg/mL; 200 mg; 300 mg;

Seizures

• Initial dose (in patients not previously treated with this drug): 1 capsule orally 3 times a day; dosage then adjusted to suit individual requirements
• Maintenance dose: For most adults, the satisfactory maintenance dosage will be 1 capsule 3 to 4 times a day; for others, an increase up to 2 capsules 3 times a day may be made, if necessary

Status Epilepticus

IV: Treatment can be initiated either with a loading dose or an infusion

• 10 to 15 mg/kg by slow IV infusion, not exceeding 50 mg/min; infusion must be completed within 1 to 4 hours
• Maximum rate: 50 mg/min

Side Effects of Phenytoin

The most common

• Decreased coordination
• mental confusion
• nervousness
• slurred speech
• the trouble with breathing, speaking or swallowing
• unsteadiness, trembling, or other problems with muscle control or coordination

Rare

• Inability to move the eyes
• increased blinking or spasms of the eyelid
• shakiness and unsteady walk shakiness in the legs, arms, hands, or feet
• sticking out of the tongue
• trembling or shaking of the hands or feet
• twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• uncontrolled twisting movements of the neck, trunk, arms, or legs
• unusual facial expressions

Rare/Less common

• Confusion
• Fever or a sore throat
• Rash
• Slowed breathing or breathing difficulties
• Sores in the mouth
• Broken blood vessels under the skin
• Easy bruising? or bleeding
• Swelling of the eyes, lips, or cheeks
• Blistering or peeling of the skin
• Restless muscle movements in the eyes, tongue, jaw, or neck

Drug Interactions of Phenytoin

Phenytoin may interact with following drug, supplyments, & may change the efficacy of drugs

• azapropazone
• colesevelam,
• darunavir,
• delavirdine,
• dofetilide,
• etravirine,
• molindone,
• nisoldipine, 
• pyridoxine(vitamin B6),
• rilpivirine,
• sucralfate,
• telithromycin.
• azole antifungals (such as itraconazole),
• macrolide antibiotics (such as erythromycin),
• estrogens, isoniazid, rifamycins (such as rifabutin),
• other anti-seizure medicines (such as valproic acid), among others.
• some drugs to treat cancer (such as imatinib, irinotecan), cobicistat,
• corticosteroids (such as prednisone),
• felodipine, 
• quetiapine, 
• quinidine, 
• theophylline, 
• vitamin D

Pregnancy & Lactation of Phenytoin

 FDA Pregnancy Category D

Pregnancy

Administration of this drug to pregnant animals resulted in teratogenicity (increased incidences of fetal malformations) and other developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple animal species at clinically relevant doses. There are no controlled data in human pregnancy.

Lactation

Because of the low levels of phenytoin in breastmilk, amounts ingested by the infant are small and usually cause no difficulties in breastfed infants when used alone except for rare idiosyncratic reactions. Breastfeeding during phenytoin monotherapy does not appear to adversely affect infant growth or development, and breastfed infants had slightly higher IQs and enhanced verbal abilities than nonbreastfed infants at 6 years of age in one study.

References