Stadium Vomitorium Anti-Emetics

1.1 "Stadium Vomitorium": Anti-emetics Ondansetron, metoclopramide, H1 receptor antagonists, scopolamine, aprepitant The Nucleus Tractus Solitarius (NTS, or vomiting center), located in the medulla, receives inputs from the Gl tract (white lines connecting stomach to track), vestibular system (semi-circular canal running outside the track), & area postrema. NTS neurons project to other medullary nuclei to coordinate vomiting response (vomiting on track directly in front of NTS sign). The stomach communicates directly with the NTS via vagal stimulation (white lines run underneath "Vegas" sign). Gl irritation for any reason (e.g. infection, chemo, distention) causes mucosal serotonin release (stomach competitor throwing serotonin smiley face weights). Serotonin activates 5-HT-3 receptors on vagus afferents, relaying signal to NTS (1-2-3 sign). Vestibulocochlear system is responsible for vertigo & motion sickness (vestibular nausea); CN VIII communicates directly with NTS (seasick sailors racing vest-wearers; semicircular canal directly behind NTS track). Area postrema is the chemoreceptor trigger zone, located outside the BBB in the 4th ventricle, immediately adjacent to the NTS. Responds to emetogenic substances including chemo agents (gymnast doing "extreme postures" on exposed pommel horse immediately adjacent to NTS track). Contains D₂ dopamine receptors (gymnast on two D-rings). Triggered by Neurokinin 1 receptors bringing substance P (plaNK1 pommel horse bound by competitors; competitors must first have their pee checked). Antagonized by Aprepitant (participants). Crosses BBB. Often combined with serotonergic Rx. No impact on dopamine, serotonin, muscarinic receptors, limiting adverse effects compared with other antiemetics. This is a very new drug, so side effect profile is not well-established. Antiemetics Ondansetron (out-of-bounds dancer) locks vagal afferent 5HT-3 receptors in the Gl tract (distracting from the accurate throw of serotonin hammer). Highly effective in post-op or chemo-induced nausea/vomiting. Used off-label for other n/v; effective for any cause involving vagal stimulation. Side effects: Constipation (hammer wrapping around runner's stomach, tightening gut) Headache, dizziness (hammer hitting head). Rarely: QT interval prolongation, increasing risk of torsades des pointes (dancer with twisting ribbon) Rarely: Serotonin syndrome; usually only occurs if combined with other serotonergic agents (pile of smiley-face hammers seems like an overload) Antihistamines Histamines are involved in vestibular system, specifically H1-receptors coupled to GPCR (allergenic dandelions shaped like Qs along canal). Histamine receptor blockers (bee swatters) effective to treat motion sickness (sailor uniforms) include diphenhydramine, meclizine. Also Africanized bees add adventure to the race! Side effects a result of crossing BBB Sedation Antimuscarinic properties (recall the tea party sketch) d/t M1 receptor antagonism (motorcycle parked in spot M1) Scopolamine-a muscarinic agonist can be used to minimize these effects (telescope) Other effects of antihistamines are described in respective sketches Metoclopramide (cheating tickling gymnast-me tickle-pyramid) Da receptor antagonist in the area postrema; used for treatment of chemo induced vomiting (cheater is antagonizing gymnast on two D-rings). Also has upper Gl prokinetic effects, useful for treatment gastroparesis & delayed gastric emptying post- surgically or d/t diabetes (second gymnast has fallen off D-rings onto stomach-shaped cushion). Can cause diarrhea for same reason (mud beyond the gastric cushion). Contraindicated in small bowel obstruction d/t stimulation of motility ("do not obstruct" sign by ring-set) Side effects: d/t central D₂ blockade Drowsiness (sleeping judge) Depression (crying coach) Extrapyramidal effects, including dystonia, akathisia, Parkinsonian features (judge wearing a pyramid shaped "EXTRA" hat). With chronic use, may cause tardive dyskinesia (judge sticking out tongue). Long term used should be avoided, especially in the elderly. Neuroleptic malignant syndrome (judge eating "Now More Spicy!" chicken); symptoms include fever (man is flushed), rigidity, mental status changes, autonomic instability, rhabdomyolysis (bite out of drumstick). Usually seen with higher potency D, blockers, but may occasionally be seen here too Elevated prolactin galactorrhea, gynecomastia, menstrual disruption (judge laughing so hard, milk is coming out his nose) Prolonged QT (twisted torsades streamers)