Medicine & USMLE

Barbituates (Phenobarbital, Thiopental)

  1. Valproic Acid (Valproate)
  2. Carbamazepine
  3. Ethosuximide
  4. Gabapentin
  5. Lamotrigine
  6. Levetiracetam
  7. Barbituates (Phenobarbital, Thiopental)
  8. Topiramate
  9. Vigabatrin


Barbiturates are a class of drugs that include phenobarbital, secobarbital, pentobarbital, and thiopental. These drugs work by increasing GABA signaling in the brain. After binding to the GABA-A receptor, they prolong the duration that chloride channels stay open after binding by GABA. In general, an increase in GABA signaling causes depressant effects on the brain as GABA is an inhibitory neurotransmitter. As such, Barbiturates are clinically used to treat seizures, especially in neonates. Barbiturates may also be used to induce sedation, which is helpful in treating insomnia, anxiety, and for inducing anesthesia. Notably, barbiturates induce CYP or cytochrome P450 enzymes, so be on the lookout for drug interactions. Barbiturates are also associated with significant CNS and cardiorespiratory depression that can be fatal, and must be treated with supportive ventilatory support and oxygen. Additionally, there is a risk of developing tolerance or dependence with continued use of barbiturates. Finally, barbiturates can cause acute intermittent porphyria and should be avoided in patients with this condition.

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