Phenytoin

Drug Information: Phenytoin

Phenytoin is an anticonvulsant medication primarily used to control seizures. It belongs to the hydantoin class of drugs and works by stabilizing neuronal membranes and limiting the spread of seizure activity in the brain. Originally synthesized in 1908, it gained prominence in the 1930s as an effective treatment for various types of seizures. Phenytoin is available in both oral and intravenous formulations, allowing for flexibility in administration depending on the clinical situation. Its efficacy in managing seizures stems from its ability to modulate sodium channels, which are critical for neuronal excitability. However, careful monitoring of phenytoin levels is essential due to its narrow therapeutic range and potential for significant side effects.

Category

Neurological Drugs – Anticonvulsant

Mechanism of Action

Phenytoin exerts its anticonvulsant effects primarily by modulating neuronal voltage-gated sodium channels. These channels are essential for the generation and propagation of action potentials in neurons. Phenytoin preferentially binds to the inactivated state of the sodium channel, prolonging its inactivated state and slowing its recovery to the resting state. This reduces the ability of neurons to fire high-frequency action potentials, which are characteristic of seizure activity. By selectively inhibiting the rapid and repetitive firing of neurons in the epileptic focus, phenytoin helps to prevent the spread of seizure activity to other parts of the brain. The drug’s effect is use-dependent, meaning that it preferentially affects neurons that are firing rapidly, thus minimizing its effects on normal neuronal activity. The blockage of sodium channels also stabilizes neuronal membranes, reducing their excitability and further contributing to the anticonvulsant effect. This complex interaction with sodium channels is crucial for phenytoin’s role in controlling and preventing seizures. This action reduces the influx of sodium ions across the neuronal membrane, stabilizing the neuron and decreasing its excitability.

Clinical Uses

Phenytoin is primarily used in the treatment of various types of seizures, including:

• Generalized tonic-clonic seizures: Phenytoin is effective in controlling these types of seizures, which involve loss of consciousness and muscle convulsions.
• Partial (focal) seizures: It can be used to manage simple partial seizures, complex partial seizures, and secondarily generalized seizures.
• Status epilepticus: Intravenous phenytoin is a second-line treatment for status epilepticus, a medical emergency characterized by prolonged or repeated seizures. It is typically used after benzodiazepines (like lorazepam) have failed to control the seizures.
• Seizure prophylaxis: Phenytoin can be used to prevent seizures in certain situations, such as after head trauma or neurosurgery.

It’s important to note that phenytoin is generally not effective for absence seizures and may even exacerbate them. Its use should be guided by a qualified healthcare professional who can accurately diagnose the seizure type and assess the risks and benefits of phenytoin therapy. The drug’s narrow therapeutic index necessitates careful monitoring of serum levels to ensure efficacy and minimize the risk of toxicity.

Dosage

Dosage varies significantly depending on the individual, seizure type, and formulation (oral vs. intravenous). It is CRUCIAL to consult a healthcare professional for accurate dosing instructions. The following provides general guidelines ONLY:

Oral Dosage:

• Adults: Typically, the initial dose is 100 mg three times daily or 300 mg once daily. The dosage may be adjusted based on serum phenytoin levels and seizure control. Maintenance doses usually range from 300 to 400 mg daily.
• Children: The initial dose is typically 5-7 mg/kg/day in divided doses. The dosage may be adjusted based on serum phenytoin levels and seizure control. Maintenance doses usually range from 4-8 mg/kg/day.

Intravenous Dosage (for Status Epilepticus):

• Adults: A loading dose of 15-20 mg/kg is administered intravenously at a rate not exceeding 50 mg/minute. This should be followed by maintenance doses adjusted according to serum levels.
• Children: A loading dose of 15-20 mg/kg is administered intravenously at a rate not exceeding 1-3 mg/kg/minute. Maintenance doses are adjusted according to serum levels.

Important Considerations:

• Phenytoin follows non-linear pharmacokinetics, meaning small dose changes can lead to disproportionate changes in serum levels.
• Regular monitoring of serum phenytoin levels is essential to maintain therapeutic concentrations (typically 10-20 mcg/mL) and avoid toxicity.
• Dosage adjustments should be made gradually, based on individual response and serum levels.

Indications

Common indications for Phenytoin include:

• Treatment of generalized tonic-clonic seizures.
• Treatment of partial (focal) seizures.
• Management of status epilepticus (as a second-line agent).
• Prevention of seizures following head trauma or neurosurgery.
• Treatment of trigeminal neuralgia (less common).

Contraindications

Contraindications for Phenytoin include:

• Hypersensitivity to phenytoin or other hydantoins.
• Sinus bradycardia, sinoatrial block, second- or third-degree AV block (unless a functioning pacemaker is present).
• Acute intermittent porphyria.
• Concomitant use with delavirdine (an antiretroviral medication).
• Pregnancy: Phenytoin can cause fetal hydantoin syndrome. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

FAQ

• Q: What are the common side effects of Phenytoin?
  
  A: Common side effects include gingival hyperplasia (gum overgrowth), hirsutism (excessive hair growth), ataxia (loss of coordination), nystagmus (involuntary eye movements), drowsiness, and skin rashes.
• Q: How should Phenytoin be taken?
  
  A: Phenytoin should be taken as prescribed by your doctor. It’s usually taken orally with or without food. Consistency in timing is important.
• Q: What should I do if I miss a dose of Phenytoin?
  
  A: If you miss a dose, take it as soon as you remember. However, if it’s almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose to catch up.
• Q: Can Phenytoin interact with other medications?
  
  A: Yes, Phenytoin can interact with many other medications, including warfarin, oral contraceptives, and certain antibiotics. It’s crucial to inform your doctor about all the medications you are taking.
• Q: Why is it important to have regular blood tests while taking Phenytoin?
  
  A: Regular blood tests are necessary to monitor Phenytoin levels in your blood and ensure they are within the therapeutic range. This helps prevent toxicity and ensures the medication is effective.
• Q: Can I drink alcohol while taking Phenytoin?
  
  A: Alcohol can interact with Phenytoin and increase the risk of side effects. It’s best to avoid alcohol while taking this medication.
• Q: What is Phenytoin toxicity and what are the signs?
  
  A: Phenytoin toxicity occurs when the level of Phenytoin in the blood is too high. Signs of toxicity include nystagmus, ataxia, slurred speech, confusion, and seizures. If you experience any of these symptoms, contact your doctor immediately.
• Q: Is Phenytoin safe to take during pregnancy?
  
  A: Phenytoin can cause fetal hydantoin syndrome and is generally not recommended during pregnancy unless the benefits outweigh the risks. Discuss this with your doctor if you are pregnant or planning to become pregnant.