CNS pharmacology
Practice questions with explanations

D. 5-HT1B and 5-HT1D agonism causing cranial vasoconstriction and inhibition of neuropeptide release from trigeminal terminals

Because 5-HT1B receptors are present in coronary vessels, triptans are contraindicated in ischaemic heart disease, uncontrolled hypertension and previous stroke. They abort attacks rather than preventing them, and using them more than about ten days a month risks medication overuse headache, which is a common and reversible cause of chronic daily headache.

D. They increase the frequency of chloride channel opening in the presence of GABA

Benzodiazepines are positive allosteric modulators: they bind at the interface between alpha and gamma subunits and increase how often the channel opens when GABA is present, so they cannot act without endogenous GABA. That ceiling is why they are relatively safe in overdose alone. Barbiturates prolong opening and at high concentrations open the channel directly, which is why their overdose is far more dangerous.

D. Chronic alcohol suppresses NMDA activity and enhances GABA, so withdrawal produces glutamate excess with tremor, seizures and delirium

Alcohol potentiates GABA-A and inhibits NMDA receptors; the brain adapts by downregulating GABA-A and upregulating NMDA. Remove the alcohol and the adaptation is unopposed, producing autonomic hyperactivity, seizures and, at its worst, delirium tremens. Benzodiazepines substitute at the GABA-A receptor and are the treatment of choice, with thiamine given before glucose to prevent Wernicke encephalopathy.