phenobarbital

Actions and Spectrum: 

• phenobarbital is a barbiturate drug used as an anticonvulsant and sedative for over a century. Its mechanism of action involves enhancing the activity of the brain’s neurotransmitter GABA (gamma-aminobutyric acid). 
• GABA is an inhibitory neurotransmitter that helps to regulate the excitability of neurons in the brain. When GABA binds to its receptors, it opens channels in the neuron’s cell membrane, allowing negatively charged ions to flow into the cell. This hyperpolarizes the neuron, making it less likely to fire an action potential and transmit a signal. 
• phenobarbital enhances the activity of GABA by binding to a specific site on GABA-A receptors, which are ionotropic receptors that mediate the effects of GABA. This binding increases the duration of time that the GABA-A receptor channel is open, allowing more chloride ions to enter the neuron and further inhibiting its activity. 
• Regarding its spectrum of activity, phenobarbital is primarily used as an anticonvulsant to prevent or control seizures. It is particularly effective in treating partial and generalized tonic-clonic seizures but may also be used to treat other seizure types.  
• phenobarbital is also a sedative and hypnotic and may be used to treat anxiety, insomnia, and other conditions. However, due to its soothing effects, it is generally not recommended for long-term use as a sleep aid or for anxiety unless other treatments have been ineffective. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency not defined 

Common 

Dizziness 

Dysarthria 

Headache 

Irritability 

Paresthesia restlessness 

Geriatric patients: Excitement, confusion, depression 

Ataxia 

Drowsiness 

Fatigue 

Nystagmus 

Vertigo  

Less Common 

Constipation 

Nausea 

Megaloblastic (folate-deficiency) anemia 

Mental dullness 

Diarrhea 

Vomiting  

Uncommon 

Hypocalcemia 

Rash 

Hepatotoxicity 

Rare 

Rickets 

Stevens-Johnson syndrome 

Osteomalacia  

IV 

• Respiratory depression 

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: Patients who have had an allergic reaction to phenobarbital or any other barbiturate should not take this medication. 
• Porphyria: phenobarbital can exacerbate porphyria, a group of rare genetic disorders that affect heme production, a hemoglobin component. 
• Respiratory depression: phenobarbital can cause respiratory depression, especially in patients with underlying lung disease or those taking other medications that depress respiration. 
• Liver disease: phenobarbital is metabolized by the liver and can cause liver damage in patients with liver disease. 
• Pregnancy and breast-feeding: phenobarbital can cause harm to the fetus during pregnancy and can be passed through breast milk to a nursing infant. 
• Acute intermittent porphyria: phenobarbital can exacerbate acute intermittent porphyria, which affects the nervous system. 
• Severe anemia: phenobarbital can exacerbate severe anemia by increasing the breakdown of red blood cells. 
• Alcohol use: phenobarbital can increase the sedative effects of alcohol, leading to an increased risk of respiratory depression and other adverse effects. 

Caution: 

• Elderly patients: Elderly patients may be more sensitive to phenobarbital’s sedative and respiratory depressant effects and may be more likely to experience confusion, dizziness, and falls. 
• Patients with respiratory disease: phenobarbital can cause respiratory depression, and patients with underlying respiratory disease, such as chronic obstructive pulmonary disease (COPD), may be at increased risk of respiratory failure. 
• Patients with liver or kidney disease: phenobarbital is metabolized by the liver and excreted by the kidneys. Patients with liver or kidney disease may be at increased risk of toxicity and adverse effects. 
• Patients with a history of substance abuse: phenobarbital can be habit-forming and should be used cautiously in patients with a history of substance abuse. 
• Patients with a history of depression or suicidal thoughts: phenobarbital can increase the risk of depression and suicidal thoughts in some patients. 
• Patients taking other medications: phenobarbital can interact with other medications, including other sedatives, opioids, and anticoagulants, and should be used with caution in patients taking these medications. 
• Patients with a history of epilepsy: phenobarbital is used as an anticonvulsant, but long-term use can lead to tolerance and reduced effectiveness. It should be used with caution in patients with a history of epilepsy. 

Pregnancy consideration: phenobarbital can cause harm to the fetus during pregnancy 

Lactation:  

• Excretion of the drug in human breast milk is known and can be passed through breast milk to a nursing infant. 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology: 

phenobarbital enhances the activity of the neurotransmitter GABA (gamma-aminobutyric acid) in the brain, which results in the overall inhibition of neuronal activity. It binds to a specific site on GABA-A receptors. It increases the time that the receptor channel is open, allowing more chloride ions to enter the neuron and further inhibiting its activity. 

Pharmacodynamics: 

The pharmacodynamics of phenobarbital: 

• Effects on GABA: phenobarbital enhances the activity of GABA in the brain, which leads to an overall reduction in neuronal activity and CNS depression. It binds to a specific site on the GABA-A receptor. It increases the time the receptor channel is open, allowing more chloride ions to enter the neuron and further inhibiting its activity. 

• Anticonvulsant effects: phenobarbital is a potent anticonvulsant drug that prevents or controls seizures. It reduces the excitability of neurons in the brain, which helps to prevent the spread of abnormal electrical activity that can lead to seizures. 

• Sedative and hypnotic effects: phenobarbital is also used as a sedative and hypnotic to treat anxiety, insomnia, and other conditions. Its CNS depressant effects can lead to drowsiness, sedation, and hypnosis, which can help to reduce anxiety and promote sleep. 

• Respiratory depression: phenobarbital can cause respiratory depression by reducing neurons’ activity in the brainstem’s respiratory center. This can lead to decreased respiratory rate and depth, which is dangerous in patients with underlying respiratory disease or taking other medications that cause respiratory depression. 

• Tolerance and dependence: Long-term use of phenobarbital can lead to tolerance and dependence, which means that higher drug doses are needed to achieve the same therapeutic effects. Abrupt discontinuation of the drug can cause withdrawal symptoms, including seizures, anxiety, and insomnia. 

• Adverse effects: phenobarbital can cause various adverse effects, including drowsiness, dizziness, ataxia, confusion, respiratory depression, and paradoxical excitement. It can also interact with other medications and may exacerbate underlying conditions like liver disease or porphyria. 

Pharmacokinetics: 

Absorption 

phenobarbital is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 3 hours. The drug can also be administered by injection, which is less commonly used. Food can affect phenobarbital absorption, with higher plasma concentrations observed when the drug is taken on an empty stomach.  

Distribution 

phenobarbital is widely distributed throughout the body, including the brain, liver, and kidneys. It can cross the placenta and enter breast milk. The drug is highly protein-bound (up to 60-70%), primarily to albumin.  

Metabolism 

phenobarbital is metabolized by the liver, primarily through the CYP2C19 and CYP3A4 pathways. The drug is converted into several metabolites, including p-hydroxy phenobarbital and phenobarbital-N-glucuronide. These metabolites are less active than the parent compound, but they may contribute to the overall pharmacological effects of the drug.  

Elimination and Excretion 

phenobarbital is eliminated primarily in the urine as an unchanged drug and metabolite. The elimination half-life of phenobarbital is approximately 50-120 hours, which is relatively long compared to many other drugs. The drug can also be excreted in the feces and, to a lesser extent, in sweat, saliva, and breast milk. And may exacerbate underlying medical conditions like liver disease or porphyria. 

Administration: 

• Oral administration: phenobarbital is most commonly administered orally through tablets or capsules. The drug should be taken with water and can be taken with or without food. However, taking the drug on an empty stomach may increase its absorption and reduce the risk of adverse effects. 

• Injection: phenobarbital can also be administered by injection, typically as an intravenous or intramuscular solution. The injection is often used in emergencies or when oral administration is not feasible or practical. 

• Dosage: The dosage of phenobarbital will depend on the patient’s age, weight, medical condition, and other factors. The drug is typically started at a low dose and gradually increased as needed to achieve the desired therapeutic effect. The maximum recommended daily dose for adults is typically 600 mg/day, although this may be higher in certain situations. 

• Monitoring: Patients receiving phenobarbital should be closely monitored for therapeutic efficacy and adverse effects. Plasma concentrations of the drug may be monitored to ensure that the dose is within the therapeutic range and to minimize the risk of toxicity. Patients should also be monitored for signs of respiratory depression, sedation, and other CNS effects. 

• Interactions: phenobarbital can interact with other medications, including CNS depressants, anticoagulants, and hormonal contraceptives. Patients should be advised to inform their healthcare provider of all medications and supplements they are taking to avoid potential drug interactions. 

Patient information leaflet 

Generic Name: phenobarbital 

Why do we use phenobarbital? 

phenobarbital is a medication that has been used for various purposes in medicine. Here are some of the most common uses of phenobarbital: 

• Epilepsy: phenobarbital is often used as an anticonvulsant medication to control seizures in people with epilepsy. It is particularly effective for partial seizures and generalized tonic-clonic seizures. 
• Sedation: phenobarbital has solid soothing properties and can induce sleep or sedate patients for medical procedures. It is also used in veterinary medicine to sedate animals. 
• Anxiety and insomnia: phenobarbital is sometimes used to treat anxiety and insomnia, although this use has declined due to the risk of dependence and other adverse effects. 
• Alcohol withdrawal: phenobarbital is sometimes used to manage symptoms of alcohol withdrawal, particularly seizures. 
• Neonatal jaundice: phenobarbital is sometimes used to treat neonatal jaundice, a condition in which a baby’s skin and eyes appear yellow due to high bilirubin levels in the blood. The drug helps to increase the excretion of bilirubin by the liver.