Phenobarbital is a medication with several applications, primarily known for its use in controlling seizures. It belongs to the class of drugs called barbiturates, which act as central nervous system depressants. This article provides a comprehensive overview of phenobarbital, including its uses, how it works, potential side effects, and essential precautions.
What is Phenobarbital Used For?
Phenobarbital is prescribed for the following conditions:
- Seizure Control: Phenobarbital is used alone or in combination with other medications to manage and reduce the frequency of seizures. By controlling abnormal electrical activity in the brain, it helps prevent harm from loss of consciousness and reduces the risk of life-threatening, repeated seizures.
- Short-Term Anxiety Relief and Sleep Aid: Phenobarbital can be used for a short period (usually up to two weeks) to help calm anxiety or induce sleep. However, it is not recommended for long-term use due to the risk of dependence and reduced effectiveness.
- Treatment for Status Epilepticus: Phenobarbital is recommended as an agent to treat status epilepticus. A study showed that intravenous phenobarbital had better clinical outcomes than valproic acid in the study population.
- Alcohol and Benzodiazepine Withdrawal: Phenobarbital's sedative and anti-seizure properties make it useful in managing withdrawal symptoms from alcohol and benzodiazepines.
- Preanesthetic: Phenobarbital is sometimes used as a sedative before surgery.
How Does Phenobarbital Work?
Phenobarbital works by controlling the abnormal electrical activity in the brain that occurs during a seizure. It mimics the effects of gamma-aminobutyric acid (GABA), a natural chemical in the brain that calms brain activity. Phenobarbital facilitates the sustained opening of chloride ion gates on GABA-A receptor subunits, increasing chloride influx into neuronal cells. This hyperpolarization of the cell membrane elevates the action potential threshold, making it more difficult for seizures to occur.
Dosage and Administration
Dosage depends on its use. Phenobarbital is available in several forms:
- Oral Elixir: 20 mg/5 mL
- Oral Tablets: 15 mg, 16.2 mg, 30 mg, 32.4 mg, 60 mg, 64.8 mg, 97.2 mg, 100 mg
- Intramuscular (IM)/Intravenous (IV) Solution: 65 mg/mL, 130 mg/mL
For seizure control, it is usually taken once daily at bedtime. The dosage is based on the patient's medical condition, phenobarbital blood levels, and response to treatment. Doctors may start with a low dose and gradually increase it to minimize side effects like drowsiness and dizziness. It may take several weeks to reach the optimal dose for complete seizure control.
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When used intravenously, phenobarbital should only be administered in emergency cases. If possible, other routes of administration should be accessed first.
Dosage Considerations
- Adult Oral Dosage:
- Daytime sedative: 30 to 120 mg daily in 2 to 3 divided doses.
- Bedtime hypnotic: 100 to 320 mg.
- Anticonvulsant: 50 to 100 mg 2 to 3 times daily.
- Preoperative: 1 to 3 mg/kg.
- Anticonvulsant use: A therapeutic anticonvulsant level of phenobarbital in serum is 10 to 25 µg/mL.
- Special patient population: Dosage should be reduced in the elderly or debilitated because these patients may be more sensitive to phenobarbital. Dosage should be reduced for patients with impaired renal function or hepatic disease.
Potential Side Effects
As with any medication, phenobarbital can cause side effects. Common side effects include:
- Dizziness
- Drowsiness
- Excitation
- Headache
- Tiredness
- Loss of appetite
- Nausea
- Vomiting
- Constipation
These side effects may occur as the body adjusts to the medication. However, some side effects can be serious and require immediate medical attention.
Serious Side Effects
- Severe Allergic Reactions: Symptoms include breathing problems, racing heart, itching, skin rash, fever, swollen lymph nodes, and swelling of the face, lips, or throat.
- Severe Skin Reactions: Phenobarbital can cause severe skin reactions called Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). Symptoms include painful red or purple skin that looks burned and peels off, flat red rash or blisters on the skin, and red, painful, watery eyes.
- Suicidal Thoughts and Actions: Phenobarbital may cause suicidal thoughts or actions in a small number of people.
- Central Nervous System (CNS) Depression: Symptoms include confusion, excessive sleepiness, memory problems, slow or shallow breathing, and slurred speech.
- Dependence and Withdrawal Reactions: Phenobarbital can cause physical dependence, leading to withdrawal symptoms if stopped suddenly.
- Heart Rhythm Changes: Phenobarbital may cause a rare, dangerous heart rhythm problem called QT prolongation and torsade de pointes.
Precautions and Warnings
Before taking phenobarbital, it is essential to consider the following precautions and warnings:
- Allergies: Inform your doctor if you are allergic to phenobarbital, other barbiturates, or any other medications.
- Porphyria: Phenobarbital should not be used if you have porphyria, a genetic disorder that affects the skin.
- Liver Problems: Phenobarbital should not be used if your liver is not functioning correctly.
- Breathing Problems: Phenobarbital should not be used if you have lung or breathing problems.
- Mental Health Conditions: Inform your doctor if you have a history of depression, mood problems, or suicidal thoughts or actions.
- Drug or Alcohol Abuse: Phenobarbital can be habit-forming, so caution is advised if you have a history of drug or alcohol abuse.
- Pregnancy: Phenobarbital can cause fetal damage when administered to a pregnant woman. Discuss the benefits and risks of using this medication during pregnancy with your doctor.
- Breastfeeding: Phenobarbital passes into breast milk and may cause excessive sleepiness or feeding problems in the nursing infant. Consult your doctor before breastfeeding.
- Older Adults: Older adults may be more sensitive to the side effects of phenobarbital, such as drowsiness and dizziness.
- Driving and Operating Machinery: Phenobarbital can impair physical and mental abilities, so avoid driving or operating hazardous machinery until you know how it affects you.
- Alcohol: Avoid drinking alcohol while taking phenobarbital, as it can worsen the side effects of the medication.
- Birth Control: Phenobarbital may decrease the effectiveness of hormonal contraceptives. Discuss alternative birth control methods with your doctor.
Drug Interactions
Phenobarbital can interact with other medications, affecting how they work or increasing the risk of serious side effects. Some notable drug interactions include:
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- Anticoagulants: Phenobarbital can lower the plasma levels of anticoagulants like warfarin, reducing their effectiveness.
- Corticosteroids: Phenobarbital may enhance the metabolism of corticosteroids, potentially requiring dosage adjustments.
- Griseofulvin: Phenobarbital may interfere with the absorption of orally administered griseofulvin.
- Doxycycline: Phenobarbital can shorten the half-life of doxycycline.
- Phenytoin, Sodium Valproate, Valproic Acid: Phenobarbital's effect on phenytoin metabolism is variable, requiring close monitoring of blood levels. Sodium valproate and valproic acid may decrease phenobarbital metabolism.
- Central Nervous System Depressants: The concomitant use of other CNS depressants, including sedatives, antihistamines, tranquilizers, or alcohol, may produce additive depressant effects.
- Monoamine Oxidase Inhibitors (MAOIs): MAOIs may prolong the effects of phenobarbital by inhibiting its metabolism.
- Estradiol, Estrone, Progesterone, and Other Steroidal Hormones: Phenobarbital may decrease the effect of estradiol by increasing its metabolism.
Overdose
An overdose of phenobarbital is a medical emergency requiring immediate attention. Symptoms of acute intoxication include unsteady gait, slurred speech, and sustained nystagmus. Mental signs of chronic intoxication include confusion, poor judgment, irritability, and insomnia.
Treatment for phenobarbital overdose includes:
- Maintenance of airway function (endotracheal intubation and mechanical ventilation)
- Correction of bradycardia and hypotension (IV fluids and vasopressors, if necessary)
- Gastric irrigation
- Forced alkaline diuresis
- Hemodialysis or hemoperfusion
Dependence and Withdrawal
Phenobarbital can be habit-forming, leading to tolerance, psychological dependence, and physical dependence, especially with prolonged use of high doses. Symptoms of withdrawal can be severe and may cause death. Minor withdrawal symptoms may include anxiety, muscle twitching, tremor, weakness, dizziness, and insomnia. Major withdrawal symptoms include convulsions and delirium.
Treatment of phenobarbital dependence involves cautious and gradual withdrawal of the drug under medical supervision.
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