2. Prokinetics & Antiemetic agents - Pharm

• 5-HT3 antagonist - name?

  ends in setron
• 5-HT3 antagonist MOA

  • competitively block 5-HT3 receptor of
  • visceral afferent neuron of GIT
  • solitary tract nucleus
  • CTZ center
  • block peripheral and central stimulation of vomiting center
• Ondan - (ondansetron) - 5HT3 antagonist

  • eliminated via hepatic metabolism
  • lower dose in pts with liver disease
• Alosetron - 5HT3 antagonist

  • C/I in male
  • used in female with IBS who have diarrhea
• 5HT3 antagonist uses

  • DOC in chemotherapy induced N/V
  • combine - Ondan + Dexameth + NK1 receptor antagonist
  • postoperative N/V
  • post-radiotherapy N/V
  • IBS with diarrhea
• Alosetron is used in women with IBS with diarrhea predominant
• alosetron cause ischemic colitis
• high dose of ondan can cause QT prolongation --> TDP
• 5HT3 antagonist is not effective in motion sickness
• 5HT antagonist - can cause serotonin syndrome
• 5HT3 antagonist - not used in pregnancy during 1st trimester

  • cause cleft lip or palate
• metoclo (metoclopramide) - prokinetic due to

  • enhance release of ACh
  • D2 antagonism and 5HT4 agonism
  • D2 antagonism - increase tone of LES --> increase gastric emptying
  • 5HT4 agonism - enhance Ach release
  • 5HT3 antagonist (high conc.) - block inhibitory myenteric interneuron
• Effect of metoclopramide on upper GI tract

  1. increase tone of LES
  2. increase tone and amplitude of antral contraction
  3. relax pyloric sphincter
  4. increase gastric emptying and peristalsis of small intestine
• Metoclopramide does not have significant effect on motility of colon
• metoclo (metoclopramide) uses as antiemetic
• metoclo used as prokinetic in pts with

  • impaired gastric emptying - diabetic gastroparesis
  • GERD
  • for rapid gastric emptying
  • intractable hiccups
• metoclo adverse effects

  • extrapyramidal effect
  • tardive dyskinesia - due to prolong use
  • super-sensitivity of D2 receptor
  • Hyperprolactinemia
  • Oculogyric crisis - upward deviation of eyeball
  • in children
• Domper (domperidone) MOA

  • dopamine (D2) receptor antagonist
  • less extrapyramidal effects
• Domper (domperidone) ADE - cause cardiac arrhythmias
• erythromycin - stimulate motilin receptor of GI smooth muscles

  • promote onset of MMC
  • use in pts with acute upper GI hemorrhage to promote gastric emptying
• Substance P/Neurokinin 1 receptor antagonist - name?

  -pitant
• Substance P/Neurokinin 1 receptor uses

  • use with 5HT3 antagonist and corticosteroid
  • treatment of CINV
  • useful for cancer chemotherapy - N/V
• Substance P/Neurokinin-1 receptor antagonists - useful in Refractory hyperemesis.

  • don't use alone
• Doxylamine/Pyridoxine (Vitamin B6) combination DOC for N/V during 1st trimester of pregnancy
• Hyoscine (scopolamine) - Muscarinic receptor antagonist

  • prevent motion sickness