Barbiturates: Types and Mechanism

• Barbiturates are a class of drugs with various uses, but have a narrow safety profile.

Names of the Drugs & Mnemonics

• Phenobarbital is a long-acting barbiturate.
• Pentobarbital and Secobarbital are short-acting barbiturates.
• Thiopental is an ultra-short-acting barbiturate, administered intravenously.
• Amobarbital is also a common barbiturate.
• Mnemonic: "Barb’s PAST is Short and Long" (Phenobarbital, Amobarbital, Secobarbital, Thiopental).
• Alternative mnemonic: "The Short, Sexy Past of Phenomenal Barb" (Thiopental, Secobarbital, Pentobarbital, Phenobarbital, Barbiturates).

Mechanism of Action

• Barbiturates bind to the GABA-A receptor at a different site than benzodiazepines.
• They act as positive allosteric modulators of GABA-A receptors.
• Barbiturates, at low doeses enhance the duration of chloride (Cl⁻) channel opening when GABA is bound, leading to hyperpolarization and neuronal inhibition.
• At high doses, barbiturates mimic the effects of GABA-A receptor, even without GABA, increasing overdose risk.
• At even higher doses they can inhibit electron transport chain, causing cell death
• They also induce the metabolism of: Benzodiazepines, phenytoin, quinidine, warfarin. higher doses of these drugs may have to be given to reach desired effect
• Barbiturates suppress excitatory neurotransmission by inhibiting AMPA (glutamate) receptors.
• They depress the reticular activating system (RAS), causing sedation and hypnosis.
• CNS effects range from anxiolytic to sedative, hypnotic, anesthetic, coma, and death, depending on the dose.

Indications

• Clinical uses of barbiturates are now limited due to their safety profile.
• They are used for seizure disorders, especially phenobarbital.
• Thiopental is used for sedation and anesthesia induction.
• Historically used for insomnia, but now rare.
• Used in euthanasia and lethal injections.
• Phenobarbital can be used as a backup for status epilepticus.
• Phenobarbital is a first-line treatment for neonatal seizures.
• Acute anxiety states

Side Effects

• Common side effects include drowsiness and sedation.
• Other common side effects are dizziness and impaired concentration.
• Cognitive dulling is a common side effect.
• Tolerance and dependence can occur.
• Respiratory depression is a serious side effect.
• Overdoses can cause severe CNS depression, coma, and death.
• Risk of respiratory depression is higher when combined with alcohol, opioids, or benzodiazepines.
• Paradoxical excitement may occur, especially in the elderly or children.
• IV forms like thiopental can cause hypotension and bradycardia.
• Withdrawal symptoms include seizures and tremors.
• Anxiety and delirium can occur during withdrawal.
• Withdrawal can be life-threatening and requires slow tapering.

Contraindications

• Avoid or use with extreme caution in patients with porphyria, as it can precipitate acute attacks.
• Contraindicated in patients with respiratory disorders like COPD or sleep apnea.
• Avoid in individuals with a history of substance use disorder.
• Use cautiously in patients with liver dysfunction, as it affects metabolism.
• Contraindicated in pregnancy due to teratogenic effects and neonatal withdrawal.
• Barbiturates induce CYP450, decreasing levels of many drugs like warfarin, oral contraceptives, and antiepileptics.
• They potentiate other CNS depressants like opioids, alcohol, and BZDs.