USMLE Step 1






Barbituates (Phenobarbital, Thiopental)

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Key Points

  • Barbiturates
    • Drug Names
      • -barbital drugs (phenobarbital, secobarbital, pentobarbital)
      • Thiopental
    • Mechanism
      • Increases GABA-A receptor activity by increasing duration of Cl- channel opening in response to GABA binding
        • Increased chloride influx increases the hyperpolarization of postsynaptic neuron, accentuating the  inhibitory effects of GABA on neuronal firing
        • Contrast vs. Benzodiazepines, which increase the frequency of Cl- channel opening
    • Clinical Use
      • Treats seizures (antiepileptic)
        • First-line in neonates 
        • 3rd line for status epilepticus
          • After lorazepam and phenytoin comes phenobarbital
        • Narrow-spectrum antiepileptic that is preferred in special populations (e.g. babies, children, pregnant women)
      • Sedative for anxiety, insomnia, induction of anesthesia
    • Adverse Effects
      • Induces cytochrome P-450
        • May cause drug interactions with warfarin, theophylline, etc.
        • Can indirectly cause osteoporosis by increasing catabolism of vitamin D
      • Acute intermittent porphyria
      • Sedation (CNS depression)
        • Obvious given inhibitory effects on neuronal signaling
      • Cardiorespiratory depression
      • Tolerance/dependence