PHRM 311 Lecture Notes - Motion Sickness, Amnesia, Meclizine
Document Summary
Pathophysiology and pharmacology of nausea and vomiting (part 2) Major actions: suppress nausea and prevent vomiting (central action) and/or, modulate gi motility. 5-ht3 receptors mixed cation channels found in the peripheral and cns. Found on vagal afferent fibers, and also in chemoreceptor trigger zone. Blockade reduces signals from the ctz and activation of vagal afferent fibers. Ondansetron (4, 8 mg tablets, 2 mg/ml injection) Prototypical 5-ht3 antagonist causes a non-competitive channel block. Adverse effects: constipation/diarrhea, headache, dizziness, qt prolongation (cardiac arrhythmia/arrest risk) May bind to additional sites of the receptor to induce an allosteric modulation that promotes receptor internalization. Longer half life (40 hours), 50% excreted in urine unchanged. Single iv dose of 0. 075 (post op nausea) to 0. 25 mg (chemo) Tachykinins (esp substance p) found in ens and released (along with serotonin) from enterochromaffin cells and excite vagal afferent activity. Neurokinin receptors also in ap, nts, dm. Aprepitant (netupitant and rolapitant longer half lives)
