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Vomitting : Forceful expulsion of the contents of the stomach and upper intestinal tract through the mouth.
Higher cortical centres
Histamine antagonists Muscarinic antagonists Dopamine antagonists Cannabinoids Chemotherapy Anaesthetics Opioids
Benzodiazepines
Vomiting Reflex
Histamine antagonists Muscarinic antagonists
Sphincter modulators
Labyrinths
Surgery Neuronal pathways Factors which can cause nausea & vomiting Sites of action of drugs
Vomiting is a complex reflex coordinated by a region in the brainstem medulla oblongata, known as vomitting centre. Neural input/Impulses from receptors in many region of the body can initiate the vomiting reflex.
The region include:
1. 2. 3. 4.
Chemoreceptor trigger zone (CTZ) outside BBB (area postrema) Higher cortical centres refer to cerebral cortex Peripheral tissues (GIT) stomach, intestine Vestibular apparatus/ labyrinths A system of interconnecting canals or channels in the inner ear. (motion sickness)
* cerebral cortex is responsible for sensing and interpreting input from various sources and maintaining
cognitive function. Sensory functions interpreted by the cerebral cortex include hearing, touch, and vision. Cognitive functions include thinking, perceiving, and understanding language.
Antiemetics agent Antiemetics agent : Drug that prevents vomiting. Class 5-HT3 R antagonists Dopamine antagonists Antimuscarinics Anti-histamines Cannabinoids Antacids H2 receptor antagonist Miscellaneous Drug Ondansetron, Granisetron Metoclopramide, Domperidone Scopolamine (l-hyoscine) Cyclizine, Promethazine, Doxylamine Nabilone, Dronabinol Magnesium hydroxide and aluminium hydroxide Ranitinidine, famotidine etc. Dexamethasone, Diazepam, antipsychotic (droperidol)
5-HT3 R antagonists (Oral, IV) MOA - Block serotonergic (5-HT3) receptors in the centre & periphery - gut. Uses - For prevention & treatment of vomiting due to anticancer agents, radiation & postoperative vomiting. *** ADR: well tolerated but can cause headache, constipation & in some patients QT prolongation Dopamine antagonists MOA - Block DA2 receptors in CTZ Uses - Anti-emetics (not for motion sickness), gastro-esophageal reflux disorder (GERD) ***ADR: Hyperprolactinemia, Extra pyramidal syndrome (EPS) only with metoclopramide.
(Domperidone does not cross BBB & hence, no EPS)
Antimuscarinics MOA - Block muscarinic (M1) R in vestibular apparatus Uses - for prevention and treatment of motion sickness, sea sickness ***ADR : drowsiness, dryness of mouth, blurred vision & other atropine like side effects
Anti-histamines MOA : Block H1 & M1 (atropine like action) receptors Uses : similar to hyoscine ***ADR : similar to hyoscine Cannabinoids MOA - prevents stimulation of CTZ Uses - Reserved drug for anticancer drug induced vomiting and radiation sickness ***ADR: Mood changes, drowsiness, psychotic reactions,& drug dependence Antacids MOA : from first to last gastric acid neutralization Uses : 15 to 30ml doses of single or multiple agents may provide relief from simple nausea and vomiting associated H2 receptor antagonist May be used in low doses to manage simple nausea and vomiting associated with heartburn or gastroesophageal reflux. Miscellaneous a. Corticosteroids : Dexamethasone Mechanism not known. May inhibit prostaglandin synthesis. Uses: synergistic with other antiemetics in anticancer drug induced vomiting b. Diazepam, Lorazepam May control anticipatory vomiting by sedative & antianxiety action. Uses: synergistic with other antiemetics in anticancer drug induced vomiting
Other uses Vomiting in pregnancy - Reassurance. Pyridoxine alone or Promethazine + Pyridoxine or pyridoxine + doxylamine only if absolutely necessary Vomiting in children - pediatric gastroenteritis - rehydration measures. Children receiving chemotherapy a corticosteroid plus 5-HT 3 receptor antagonist may be preferred.