Drugs for vomiting, Std copy-B29.pdf

Drugs for vomiting Dr. Nazmun Nahar Alam AIMST University  Specific learning Outcome At the end of the lecture student should be able to – Classify anti-emetics based on their action on receptors. – Describe the uses and side effects of dopamine antagonists – prochlorperazine,...

Drugs for vomiting Dr. Nazmun Nahar Alam AIMST University  Specific learning Outcome At the end of the lecture student should be able to – Classify anti-emetics based on their action on receptors. – Describe the uses and side effects of dopamine antagonists – prochlorperazine, metoclopramide and domperidone. – Describe the uses and side effects of antihistamines - cyclizine and promethazine. – Describe the uses and side effects of 5-HT3 antagonists - ondansetron and granisetron. – Describe the antiemetic uses and side effects of misc. antiemetics - diazepam, lorazepam etc. – State the pharmacotherapy of motion sickness and chemotherapy / radiation induced vomiting. Dr. Nazmun Nahar Alam@ AIMST 2 Vomiting / Emesis &Nausea ▪ It is a protective mechanism of body. ▪ Forceful contraction of abdominal muscles to cause stomach contents to come up through the mouth. ▪ Often preceded by nausea Dr. Nazmun Nahar Alam@ AIMST 3  Vomiting is regulated centrally by the vomiting center & the chemoreceptor trigger zone (CTZ), both of which lie in the medulla. Vomiting Centre does not initiate, but coordinates emesis by receiving Pathophysiology stimuli. of Emesis The chemoreceptor trigger zone (CTZ) is located in the area postrema (at the caudal end of the fourth ventricle). It is outside the blood– brain barrier. Thus, it can respond directly to chemical stimuli in the blood or cerebrospinal fluid. Dr. Nazmun Nahar Alam@ AIMST 4  The second important site, the vomiting center, which is located in the lateral reticular formation of the medulla, coordinates the motor mechanisms of vomiting. Pathophysiology The vomiting center also responds to afferent input of Emesis from the vestibular system, the periphery (pharynx and GI tract), and higher brainstem and cortical structures. The vestibular system functions mainly in motion sickness. Dr. Nazmun Nahar Alam@ AIMST 5 Dr. Nazmun Nahar Alam@ AIMST 6 Dr. Nazmun Nahar Alam@ AIMST 7  Causes Of Emesis adverse effects from medications pregnancy vestibular dysfunction hepatobiliary disorders radiation or chemotherapy gastrointestinal obstruction or infections Dr. Nazmun Nahar Alam@ AIMST 8  Drugs Used in Vomiting 1. D2 receptor antagonist/ Pro-kinetic agent: Prochlorperazine, Metoclopramide, Domperidone 2. 5-HT3 antagonists: Ondansetron, Granisetron, 3. H1 blocker/Antihistamines: Diphenhydramine, Dimenhydrinate, Meclizine 4. Antimuscarinic agents: Hyoscine 5. Corticosteroids: Dexamethasone, Methylprednisolone Dr. Nazmun Nahar Alam@ AIMST 9  Drugs Used in Vomiting 6. Benzodiazepines: Diazepam , lorazepam 7. Cannabinoids Dronabinol, Nabilone 8. Substance P /Neurokinin1 receptor blocker Aprepitant & fosaprepitant Dr. Nazmun Nahar Alam@ AIMST 10  METOCLOPRAMIDE & DOMPERIDONE Mechanism of action of Metoclopramide: Block Dopaminergic (D2) receptors within the GIT Stimulation of cholinergic smooth muscle in GIT i.e. reversal of inhibitory impulse given by D2 receptors Net results are Increase esophageal peristaltic amplitude Increase lower esophageal sphincter pressure Increase gastric emptying Thus produce anti emetic action Dr. Nazmun Nahar Alam@ AIMST 11 Mechanism of action of Domperidone Domperidon blocks D2 receptors centrally in the chemoreceptor trigger zone (CTZ) of the medulla. It results potent anti-nausea & anti-emetic effect. Dr. Nazmun Nahar Alam@ AIMST 12  INDICATIONS OF METOCLOPRAMIDE & DOMPERIDONE Uses: Gastro- esophageal reflux disease (GERD) Non-ulcer dyspepsia Impaired gastric emptying To control nausea and vomiting Postpartum lactation stimulation Dr. Nazmun Nahar Alam@ AIMST 13  ADVERSE EFFECTS OF METOCLOPRAMIDE CNS : As Metoclopramide crosses BBB significantly the most common adverse effects of it involve CNS Restlessness, drowsiness, insomnia, anxiety, agitation Extrapyramidal side effects: (more common for metoclopramide but rare for domperidone) Dystonia , akathisia, parkinsonism ,Tardive dyskinesia Common in children & young adults Due to increased prolactin level: (both Metoclopramide & Domperidone) Galactorrhea, gynecomastia, Impotence, menstrual disorder Dr. Nazmun Nahar Alam@ AIMST 14  ADVERSE EFFECTS OF DOMPERIDONE Domperidone does not cross BBB to a significant degree, neuropsychiatric and extrapyramidal effects are less. Due to increased prolactin level: (both Metoclopramide & Domperidone) Galactorrhea, gynecomastia, Impotence, menstrual disorder Dr. Nazmun Nahar Alam@ AIMST 15  5-HT3 antagonists Ondansetron, Granisetron : – Blockade of central 5-HT3 receptors in the vomiting center and chemoreceptor trigger zone (CTZ). – Blockade of peripheral 5-HT3 receptors on extrinsic intestinal vagal and spinal afferent nerve. And produces antiemetic action. Dr. Nazmun Nahar Alam@ AIMST 16  5-HT3 antagonists Uses Cancer chemotherapy induced nausea and vomiting (Anticancer treatment releases serotonin (5-HT) from enterochromaffin cells in the gut mucosa which cause emesis).so this is the best drug of choice Postoperative and post-radiotherapy induced nausea & vomiting ADRs Headache, dizziness, Constipation, prolong QT interval Dr. Nazmun Nahar Alam@ AIMST 17  Muscarinic blockers Hyoscine, scopolamine: Use: motion sickness ADRs: Anticholinergic side effects (dry mouth, blurred vision….) Route: i.m., oral , transdermal patch Dr. Nazmun Nahar Alam@ AIMST 18 Applied behind the pinna (scopolamine T/D patch) Dr. Nazmun Nahar Alam@ AIMST 19  Choice of antiemetic Morning Sickness Morning sickness is common in pregnancy. However, anti-emetics are not prescribed unless its severe situations, such as hyperemesis gravidarum or where nausea and vomiting interfere with everyday life. Most of the drugs are avoided in first trimester of pregnancy to avoid teratogenic effect. H1 blockers- Promethazine, Meclizine, Dimenhydrinate etc can be used in pregnancy. Dr. Nazmun Nahar Alam@ AIMST 20  Motion sickness Car, sea, train, or air sickness. Group of symptoms, particularly nausea, caused by movement during travel. Treatment : H 1 blockers Muscarinic blockers D2 antagonists Dr. Nazmun Nahar Alam@ AIMST 21