anti-emetics

Question 1

how does cisplatin induce nausea and vomiting

Answer 1

toxic to enterochromaffin cells -> release free radicals -> excessive 5-HT (serotonin) release -> activates 5-HT3A receptors on nerve fibres to chemoreceptor trigger zone (CTZ; midbrain outside BBB) -> activates nerve fibres to vomiting centre (VC) -> causes nausea

Question 2

2 main areas involved in pathophysiology of nausea and vomiting

Answer 2

chemoreceptor trigger zone (CTZ), vomiting centre (VC)

Question 3

triple treatment of nausea and vomiting caused by cisplatin

Answer 3

ondansetron (5-HT3A receptor antagonist), glucocorticoids (reduce free radical production), aprepitant (neurokinin-1 receptor antagonist on vomiting centre, usually activated by substance P)

Question 4

reason for triple treatment of nausea and vomiting caused by cisplatin

Answer 4

2 phases: initial vomiting (ondansetron most effective), latent vomiting (glucocorticoids and aprepitant most effective)

Question 5

how does motion sickness cause nausea and vomiting

Answer 5

labyrinth-neural mismatch -> activates histamine receptors (H1) on vestibular nuclei -> activate muscarinic receptors (M1-5) on CTZ -> activates muscarinic receptors (M1-5) on VC -> nausea

Question 6

2 treatments for nausea and vomiting due to motion sickness

Answer 6

promethazine (H1 receptor antagonist), hyoscine (scopolomine; centrally acting non-selective muscarinic receptor antagonist, so can be used in various causes of nausea and vomiting)

Question 7

how does gastroparesis (delayed emptying of stomach) cause nausea and vomiting

Answer 7

reduced stomach contraction -> releases 5-HT -> activates 5-HT3A receptors on nerve fibres to CTZ -> activates nerve fibres to VC -> causes nausea

Question 8

3 other causes of nausea and vomiting

Answer 8

seeing/smelling something disturbing, pregnancy, high dopamine levels in Parkinson’s treatment

Question 9

how do high dopamine levels in Parkinson’s treatment cause nausea and vomiting

Answer 9

activate D2 receptors on CTZ -> activate nerve fibres to VC -> nausea

Question 10

treatment for nausea and vomiting caused by D2 and 5-HT3A receptor activation

Answer 10

metoclopramide (inhibits activation of CTZ by acting as D2 receptor antagonist and 5-HT3A receptor antagonist)

Question 11

why would metoclopramide be given to patient with nausea and vomiting due to gastroparesis, as opposed to just a 5-HT3A receptor activation

Answer 11

D2 receptor antagonist has prokinetic effects, stimulating gastric emptying

Question 12

summarise physiological control of nausea and vomiting

Answer 12

CTZ (input from stomach, vestibular nuclei etc.), communicates with VC

Question 13

mechanistic triggers for control of nausea and vomiting

Answer 13

cytotoxic drugs, motion sickness, GI problems, pregnancy, other higher functions

Question 14

4 main classes of anti-emetic drugs

Answer 14

5-HT3A receptor antagonists (e.g. chemotherapy induced), H1 receptor antagonists (e.g. motion sickness), muscarinic receptor antagonists (e.g. motion sickness), D2 receptor antagonists (e.g. GI induced)

Question 15

side effects of 5-HT3A receptor antagonists

Answer 15

headaches, constipation

Question 16

side effect of H1 receptor antagonists

Answer 16

drowsiness (centrally acting)

Question 17

side effects of centrally acting muscarinic receptor antagonists

Answer 17

decreased PSNS effects (e.g. dry mouth, drowsiness as centrally acting)

Question 18

side effects of D2 receptor antagonists

Answer 18

galactorrhoea, extrapyramidal side effects (e.g. tremor)