Benzos Mechanisms and Side Effects

Summary

Benzodiazepines, or benzos for short, are a class of drugs that work by increasing GABA-A signaling. This increases the frequency of chloride channel opening, which leads to a decrease in brain activity. This can also decrease REM sleep.

Side effects of benzodiazepines include CNS depression, which can manifest as drowsiness or sedation. Importantly, the CNS depressant effects can be exacerbated by taking them in combination with alcohol or barbiturates. Other side effects of these drugs include tolerance, dependence, and respiratory depression. It’s worth noting that benzodiazepines are generally considered to be safer than barbiturates, with less risk of causing severe respiratory depression and coma. 

The antidote to reverse the effects of benzodiazepines is flumazenil, which works by blocking GABA-A receptors. However, in patients who are physically dependent on benzodiazepines, flumazenil can cause acute withdrawal symptoms, including seizures.

Key Points

• Benzodiazepine Mechanisms and Side Effects
  • Mechanism
    • Increase GABAA signaling
      • Increasing frequency of Cl- channel opening
        • Increased influx of negatively charged chloride ions in response to GABA binding leads to hyperpolarization of the postsynaptic neuron and suppression of action potential firing
      • As opposed to increasing the duration of Cl- channel opening, which is the mechanism of barbiturates
    • Decreases REM sleep
  • Side Effects
    • CNS depression (sedation)
      • Exacerbated by alcohol
      • Exacerbated by barbiturates
      • Severe CNS depression is dangerous and potentially fatal
      • Should be avoided in elderly (fall risk), or patients taking other sedative drugs (barbiturates, alcohol, neuroleptics, 1st-generation antihistamines) due to additive effects
    • Respiratory depression
      • Via suppression of medullary breathing centers
    • Safer than barbiturates
      • Less risk of respiratory depression and coma
    • Tolerance
    • Dependence
      • May induce withdrawal syndrome similar to alcohol withdrawal (e.g. seizures)
      • Especially with rapid-acting benzos; quick onset but short duration increases withdrawal symptoms and increases abuse potential
  • Reversal (Treatment of Overdose)
    • Flumazenil
      • Competitive antagonist at GABAA (blocks GABAA)
      • Can cause acute withdrawal (seizures)