Generic Name : Phenobarbitone.

Trade Name     : phenobarbital, Phenobarbitone.

Drug Class       : Barbiturates (Anticonvulsants).

Forms of The Drug

  1. Tablet: 15mg, 16.2mg, 30mg, 32.4mg, 60mg, 64.8mg, 97.2mg, 100mg.
  2. Injectable solution: 65mg/mL, 130mg/mL.

Mechanism of Action

Its mechanism of action involves enhancing the activity of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS). Here’s a detailed overview of the mechanism of action of phenobarbital:

  1. Enhancement of GABAergic Transmission: Phenobarbital acts as a positive allosteric modulator of the GABA-A receptor, a ligand-gated chloride ion channel. GABA-A receptors are widely distributed throughout the CNS and mediate inhibitory neurotransmission by allowing the influx of chloride ions into neurons, leading to hyperpolarization and suppression of neuronal excitability.
  2. Binding to GABA-A Receptors: Phenobarbital binds to specific sites on the GABA-A receptor complex, distinct from the GABA-binding site, known as the barbiturate-binding site. By binding to these allosteric sites, phenobarbital potentiates the effects of GABA, increasing the frequency of chloride channel opening and prolonging the duration of inhibitory postsynaptic currents (IPSCs). This enhances the inhibitory effects of GABA on postsynaptic neurons, leading to neuronal hyperpolarization and inhibition of excitatory neurotransmission.
  3. Enhanced Chloride Influx: Upon binding to the GABA-A receptor, phenobarbital increases the influx of chloride ions into neurons, primarily through the opened chloride channels. This hyperpolarizes the neuronal membrane potential, making it more resistant to depolarization and reducing the likelihood of action potential generation.
  4. Suppression of Neuronal Excitability: By enhancing GABAergic transmission and promoting chloride influx, phenobarbital suppresses neuronal excitability within the CNS. This leads to a reduction in the firing rate of neurons, dampening the spread of abnormal electrical activity and reducing the likelihood of seizures.
  5. Effects on Glutamate Transmission: In addition to enhancing GABAergic transmission, phenobarbital may also modulate glutamatergic neurotransmission, albeit to a lesser extent. Glutamate is the primary excitatory neurotransmitter in the CNS, and its activity is counteracted by GABAergic inhibition. Phenobarbital may indirectly inhibit glutamatergic neurotransmission by enhancing GABAergic inhibition, further contributing to its anticonvulsant effects.
  6. Induction of Cytochrome P450 Enzymes: Phenobarbital is known to induce hepatic microsomal enzymes, particularly cytochrome P450 (CYP450) enzymes, which are responsible for the metabolism of numerous drugs and endogenous substances. Chronic administration of phenobarbital can lead to the upregulation of CYP450 enzymes, accelerating the metabolism and clearance of various medications, including other antiepileptic drugs and certain hormones.

Indications

  1. Epilepsy and Seizure Disorders.
  2. Status Epilepticus.
  3. Sedation and Anxiolysis: such as preoperative sedation, procedural sedation, or treatment of acute agitation or anxiety disorders.
  4. Alcohol Withdrawal Syndrome.
  5. Neonatal Seizures.
  6. Insomnia

Contraindications

  1. Hypersensitivity or Allergy.
  2. Porphyria
  3. Intermittent Porphyria.
  4. Respiratory Depression.
  5. Acute Intermittent Porphyria.
  6. Severe Liver Disease.
  7. Severe Renal Impairment.
  8. Pregnancy and Breastfeeding.

Side effects

  1. Respiratory depression.
  2. Respiratory depression.
  3. Ataxia.
  4. Dizziness.
  5. Drowsiness.
  6. Dysarthria.
  7. Fatigue.
  8. Headache.
  9. Irritability.
  10. Nystagmus.
  11. Paresthesia restlessness.
  12. Vertigo.
  13. Geriatric patients: Excitement, confusion, depression.
  14. Pediatric patients: Paradoxical excitement/hyperactivity

Drug Interaction

  1. Antiepileptic Drugs (AEDs): such as carbamazepine, phenytoin, and primidone.
  2. Central Nervous System (CNS) Depressants: Concurrent use of phenobarbital with other CNS depressants, such as benzodiazepines, opioids, sedatives, or alcohol.
  3. Oral Contraceptives.
  4. Warfarin and Other Anticoagulants.
  5. Corticosteroids: such as prednisone or dexamethasone.
  6. Digoxin
  7. Theophylline
  8. Hormonal Therapy: Phenobarbital may reduce the efficacy of hormonal therapies, such as hormone replacement therapy (HRT) or thyroid hormone replacement therapy.

Precautions

  1. Pregnancy: category
  2. Lactation: Phenobarbital, a medication commonly used to treat seizures and certain other conditions, including neonatal jaundice, can pass into breast milk.

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