Class antiemetics 3

1. ANTIEMETIC DRUGS Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC. 1

2. Receptors –in Neuro transmision of vomiting Area Type of receptors Stimulus Chemoreceptor trigger zone (CTZ) Dopamine D 2 5HT 3 Opioid H1 anti Cancer chemotherapy Opioids Morning sickness Vestibular nuclei Muscarinic Histamine H 1 Motion sickness Pharynx and GIT 5HT 3 Cancer chemotherapy Radio therapy Gastroenteritis Cerebral cortex Smell Sight Thought Anticipatory emesis

3. Antiemetics Anti- dopaminergic agents a) Phenothiazines : Prochlorperazine , Promethazine b) Butyrophenones : Droperidol Anti- 5 HT3 antagonists : Ondansetron,Granisetron Anticholinergics : Atropine, hyoscine , Glycopyrrolate Anti-histamines: Cyclizine, diphenhydramine, Cinnarizine Glucocorticoids: Dexamethazone Cannabinoids : Dronabinol , Nabilone Miscellaneous: Diphenidol , Droperidol, Trimethobenzamide

4. Prokinetic agents Substituted benzamides : Metoclopramide Benzimidazole Derivative: Domperidone Anti -5HT4 agonists : cisapride , mosopride , zacopride , renzapride , prucalopride Macrolides : motilin agonists: Erythromycin, Azithromycin , Clarithromycin CCK1 antagonist : loxiglumide

5. Phenothizines Phenothiazines are primarily antipsychotic Mechanism of the antiemetic action: inhibition of central dopamine, muscarinic and H1 histamine receptors receptors Use: Chemotherapy-induced vomiting Radiotherapy-induced vomiting postoperative nausea and vomiting

6. Butyrophenones - droperidol are primarily antipsychotic agents Mechanism of the antiemetic action: inhibition of central dopamine receptors Use: Chemotherapy-induced vomiting Radiotherapy-induced vomiting postoperative nausea and vomiting Adverse effects: droperidol may prolong the QT inter, therefore, it should not be used in patients with QT prolongation (should only be used in patients who have not responded adequately to alternative agents).

7. Serotonin 5 HT 3 Antagonist-Potent antiemetics Ondansetron , Granisetron , Dolasetron , Palonosetron Mechanism of action : Peripheral 5-HT3 receptor blockade on intestinal vagal afferents. Central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone High first pass metabolism Excreted by liver & kidney

8. Indiacations Chemotherapy induced nausea and vomiting Post radiation nausea & vomiting Vomiting of pregnancy Postoperative vomiting Adverse drug reactions Headache and dizziness Constipation or diarrhoea

9. Corticosteroids Dexamethazone Corticosteroids have antiemetic properties Mechanism of action : possibly by suppressing peritumoral inflammation and prostaglandin production. Use : to enhance efficacy of 5HT3 receptor antagonists in the treatment of chemotherapy-induced vomiting.

10. H1 receptor antagonists and Anticholinergics Use: prevention or treatment of motion sickness. Adverse effects : sedation, dizziness,confusion , dry mouth, cycloplegia , and urinary retention. . Diphen hydramine dimenhydrinate First generation H1 receptor blockers that have anticholinergic and sedating properties Meclizine First generation H1 receptor blockers that have lesser anticholinergic and sedating properties Hyoscine Muscarinic receptor blocker

11. Cannabinoids : Dronabinol , Nabilone Pharmacokinetics: Readily absorbed after oral administration It undergoes extensive first-pass metabolism with limited systemic bioavailability after single doses. Metabolites are excreted primarily via the biliary -fecal route Adverse effects: Euphoria or dysphoria , sedation withdrawal syndrome (restless, insomnia and irritability) Autonomic effects (sympathetic) in the form of tachycardia, palpitation, orthostatic hypotension. Use: For the prevention of chemotherapy-induced nausea and vomiting

12. Prokinetic agents Substituted benzamides Metoclopramide 5HT3 and 5HT4 receptor antagonist Mechanism of antiemetic action: Central dopamine-receptor blockade Prokinetic effects- activation of 5HT4 receptors Side effects : (mainly extrapyramidal ): Restlessness,Dystonias Parkinsonian symptoms Galactorrhoea and gynacomastia

13. Benzimidazole Derivative Domperidone Structurally similar to haloperidol MOA similar to metaclopramide Used to prevent emetic side effect of levodopa or bromocriptine

14. Emetics Ipecac is an OTC drug Administration Take with a glass of water or fluid, not with milk or carbonated beverage Vomiting occurs in 20 to 30 minutes and if not, repeat dose Gastric lavage may be needed if vomiting does not occur Caution: avoid vomiting if substance is caustic or petroleum Apomorphine is a morphine derive emetic, SQ/IM, Onset 15 min

15. Anti -5HT4 agonists : Cisapride , Mosopride , Zacopride , Renzapride , Prucalopride -no antiemetic effect Promote release of Ach from myentric plexus Cisapride - facilitates gastric motility , throughout the GIT Hastens gastric emptying , improves LES tone And oesophageal peristalsis .

16. Anti -5HT4 agonists : adverse reactions Abdominal cramps, diarrhoea QT prolongation Cytochrome P450 inhibition

17. Macrolides Motilin receptors Increase LES tone CCK1 receptor antagonist Loxiglumide –increase GI motility THANK YOU