A patient with a history of seizure disorder is prescribed tramadol for chronic back pain. The physician is concerned about tramadol lowering the seizure threshold. The mechanism by which tramadol predisposes to seizures is:

• A Its mu-opioid receptor agonist activity directly causes neuronal hyperexcitability
• B Its inhibition of serotonin and norepinephrine reuptake lowers the seizure threshold ✓
• C Its metabolite O-desmethyltramadol directly damages neurons
• D It inhibits GABA-A receptors, reducing inhibitory neurotransmission

Explanation

Tramadol lowers the seizure threshold through its inhibition of serotonin and norepinephrine reuptake, independent of its weak mu-opioid activity. The risk is increased with higher doses, history of epilepsy, and concurrent use of SSRIs, SNRIs, or MAOIs. This dual mechanism (opioid plus monoamine reuptake inhibition) distinguishes tramadol from pure opioids in terms of seizure risk.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.