A patient on long-term benzodiazepine therapy abruptly stops the drug. The life-threatening withdrawal complication that can occur and the mechanism behind it is:
- A Status epilepticus due to relative GABA deficiency and compensatory glutamatergic/NMDA receptor upregulation ✓
- B Hyperthermia due to dopamine receptor upregulation in the hypothalamus
- C Respiratory alkalosis due to rebound central respiratory stimulation
- D Bradycardia due to rebound parasympathomimetic activity
Explanation
Chronic benzodiazepine use leads to GABA-A receptor downregulation/desensitisation and compensatory upregulation of glutamatergic (NMDA) pathways. Abrupt cessation creates a state of relative CNS excitability with reduced inhibition and increased excitation, which can culminate in generalised seizures and life-threatening status epilepticus. This is the same principle as alcohol withdrawal (alcohol also potentiates GABA-A and blocks NMDA). Benzodiazepine withdrawal does not cause significant dopaminergic, respiratory, or significant cardiovascular life-threatening phenomena.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.