GABAA Receptor Mechanism and Pharmacokinetics Quiz

• Barbiturates act on GABAA receptors: At low concentrations, they enhance the effect of GABA and decrease its dissociation rate. At high concentrations, they directly activate the opening of chloride channels and act on glutamate, adenosine, and neuronal nicotinic acetylcholine receptors.
• Barbiturates are metabolized primarily by hepatic oxidation. Their metabolism can be influenced by drugs that induce hepatic oxidative microsomes, such as barbiturates themselves.
• Barbiturates have various organ system effects:
  • Central Nervous System (CNS): They cause proportional decreases in CMRO2 and CBF, reducing intracerebral pressure. They decrease mean arterial pressure less than ICP, improving cerebral perfusion. Maximum decrease in CMRO2 is around 50-55%, which requires hypothermia.
  • Cardiovascular: Barbiturates induce peripheral vasodilation and decreased contractility, increasing heart rate and decreasing cardiac output.
  • Respiratory: All intravenous induction agents except ketamine and etomidate cause dose-dependent respiratory depression, making respiratory parameters return to near normal within 15 minutes, with awakening occurring before normal respirations return.
• Barbiturates have been used in the past for neuroprotection during neurosurgery and following acute brain injuries. However, they have not been shown to be superior to other techniques for decreasing ICP following acute brain injury.
• Barbiturates were previously used for neuroprotection in procedures like carotid endarterectomy, temporary occlusion of cerebral arteries, profound induced hypotension, and cardiopulmonary bypass.
• Mechanisms of neuroprotective effect of barbiturates include reverse steal (Robin Hood) effect, free radical scavenging, and liposomal membrane stabilization. They can also block excitatory amino acids (EAA) at higher concentrations, functioning as anticonvulsants.
• Barbiturates have various contraindications: severe cardiovascular instability or shock, porphyria, and allergic reactions. Porphyria is a group of disorders with multiple subtypes, including acute intermittent porphyria, which is triggered by induction of heme synthesis.
• Barbiturate use has side effects and complications: cardiovascular and respiratory side effects are dose-dependent, and no significant differences exist between the barbiturates in terms of cardiovascular or respiratory side effects. At low blood levels, thiopental has been described as having an antianalgesic effect.
• Barbiturates have other uses: as a lethal injection combination, in truth serum, as a recreational drug, and as an intravenous induction agent.
• Thiopental, a commonly used barbiturate, has a high context sensitivity and may lead to accumulation of the active metabolite pentobarbital with multiple bolus dosing or prolonged infusion.
• Dosages for barbiturates vary for adults, children, and infants, and must be reduced in premedicated patients.
• Barbiturates can affect pregnancy, hypovolemia, obesity, females, and the elderly by decreasing the volume of the central compartment and the intermediate compartment.
• Thiopental infusions are used to treat status epilepticus and methohexital dosing is approximately 2 mg/kg.

Test your knowledge of the mechanism of action and pharmacokinetics of GABAA receptors. Explore how different concentrations affect the receptor and their metabolism. Challenge yourself with this quiz!