Emetics & Anti-emetics presentation for pharmacy students

Emetics and antiemetics are drugs used to induce and prevent vomiting, respectively. Emetics, such as ipecac syrup and apomorphine, stimulate the vomiting center in the brain or irritate the stomach lining to induce vomiting, often used in cases of poisoning. Antiemetics, including drugs like ondansetron, metoclopramide, and promethazine, work by blocking neurotransmitters like serotonin, dopamine, and histamine, which are involved in triggering the vomiting reflex. They are commonly used to treat nausea and vomiting caused by conditions such as motion sickness, chemotherapy, and postoperative recovery. Understanding the mechanisms and applications of these drugs is crucial for effectively managing emesis in various clinical scenarios.

1. EMETICS & ANTI-EMETICS Lokesh Patil B. Pharmacy, 3 rd year, 6 th semester

2. Nausea and vomiting are unwanted side effects of many clinically used drugs, notably those used for cancer chemotherapy but also opioids, general anaesthetics and digoxin. They also occur in motion sickness, during early pregnancy and in numerous disease states (e.g. migraine) as well as bacterial and viral infections. VOMITING

3. Reflex Mechanism Of Vomiting Enterochromaffin cells Sense toxic chemicals or toxins in gut Vagal Afferents Convey signals from gut to brainstem Vomitting centre Integrates incoming signals, coordinates emesis CTZ Main site for sensing emetic stimuli HIGHER CORTICAL CENTRES Pain, repulsive sights and smells and emotional factors Vestibular nuclei Input from the labyrinth

4. EMETICS Emetics are the drugs that produce vomiting. When noxious substance is ingested, vomiting has to be induced. Emetics may act directly by stimulating the CTZ or reflexly by irritating the stomach mucosa. Mustard powder (1 teaspoon) with water or hypertonic salt solution can evoke vomiting reflexly .

5. 1. Centrally acting Emetics APOMORPHINE Apomorphine is a derivative of morphine given SC/IM. It induces vomiting in 5-10 minutes. It acts by stimulating the dopaminergic receptors in the CTZ. NOTE Apomorphine can depress respiration and should therefore, avoided in presence of respiratory depression

6. IPECACUANHA Ipecacuanha is obtained from the dried root of Cephalis ipecacuanha , contains alkaloid of emetine. Given as syrup (15-20 ml), produces vomiting in 15 minutes NOTE Acts both directly on CTZ and reflexly by irritating gastric mucosa & is safe even is childrens .

7. 2. Locally acting Emetics They cause vomiting by their irritant action on Gastric Mucosa Copper sulphate Zinc Sulphate NaCl – (2 tablespoon) Black mustard CONTRAINDICATIONS During heart disease Advanced pregnancy Hernia Peptic ulcer

8. Pathophysiology of drug induced emetics

9. Pathways stimulating Emesis

10. ANTI-EMETICS Antiemetics are the drugs used in the prevention and treatment of vomiting. Vomiting is a protective mechanism aimed at eliminating the unwanted harmful material from the stomach.

11. 5-HT 3 Antagonists Anticancer drugs, radiation therapy and infection of gastrointestinal mucosa induce the release of 5HT in the gut which initiates emetics reflex through 5HT3 receptors present in gut, NTS,& CTZ Ondansetron blocks 5HT3 receptors gut, NTS, CTZ and prevents vomiting. MOA

12. Pharmacokinetics Ondansetron is powerful antiemetic and can be administered orally or intravenously (4-8 mg). It has an oral bioavailability of 60-70%, t ½ of 3-5 hours and a duration of action of 4-12 hours. They are well absorbed from the gut, metabolized by the liver and are excreted from the kidneys and partly through the gut. Requires dose reduction in Renal dysfunction

13. USES To control vomiting induced by anticancer drugs or radiotherapy. Should be given IV 30 min before or orally 1 hr before starting chemotherapy. Also useful in prevention of postoperative vomiting and other drug induced vomiting. (Dose- 4-8 mg)

14. Adverse effects Headache Constipation Abdominal discomfort Rashes Dolasetron may prolong QT interval and should be avoided in patients with prolonged QT interval.

15. Dopamine Antagonists Drugs such as chlorpromazine, prochlorperazine are effective emetics commonly used for treating more severe nausea and vomiting associated with cancer, radiation therapy and other drugs. They can be administered orally, IV, or by suppository.

16. MOA Chlorpromazine, prochlorperazine Antagonizes dopamine D2 receptors in the CTZ. They also block the histamine and muscarinic receptors.

17. Adverse reactions Sedation Hypotension Dystonias Tardive dyskinesia

18. Anticholinergics Hyoscine is a labyrinthine sedative very effective in motion sickness or travelling sickness is due to over stimulation of the vestibular apparatus along with psychological and environmental factors. Hyoscine also relaxes the GIT smooth muscle. It should be taken 30 mins before journey, it acts for 6 hrs. A transdermal patch delivers hyoscine constantly over 3 days and is applied behind the year Adverse Effects Sedation Dry mouth

19. Neurokinin Receptor Antagonists These drugs bind to neurokinin ( NK1 ) receptor in CTZ acts as anti-emetics . Aprepitant has recently completed clinical trials and is available for oral use while fosaprepitant is given IV and gets converted to aprepitant in body. Aprepitant half life of 12 hrs , it is metabolized by liver by CYP3A4 and may compete with other drugs metabolized by same enzyme. NK1 antagonist may cause dizziness, weakness and diarrhoea . Aprepitant is used in combination with 5HT3 antagonists and glucocorticoid. Efficacy of combined regimen is more than individual drugs.

20. Prokinetic Agents Drugs that enhance gastroduodenal motility and hasten gastric emptying are called gastric emptying are called prokinetic agents. Metoclopramide Domperidone Cisapride Mosapride Itopride

21. Metoclopramide Metoclopramide was introduced in 1970’s. It is structurally related to Procainamide but it is not local anaesthetic .

22. Pharmacological actions GIT :- Metaclopramide promotes forward movement of contents of the upper GI tract, increases oesophagal and gastric peristalsis. It raises lower oesophagal sphincter pressure, speeds up the gastric emptying and prevents reflux of stomach contents into oesophagus . Prokinetics have no significant effects on motility of small intestine and colon. CNS :- Metoclopramide acts as an antiemetic by blocking D2 dopamine receptors on the CTZ . It also contributes to gastric emptying.

23. Mechanism of action 1. D2 blockade:- Stimulation of dopamine receptors is gut particularly upper GIT. Inhibits cholinergic stimulation of GIT smooth muscle- relaxes the stomach, lower oesophagal sphincter (LES) and delays gastric emptying. Blocking if D2 receptors in CTZ is responsible for anti-emetic actions.

24. Mechanism of action 2. Seratonergic receptors:- 5HT4 agonist- metoclopramide stimulates 5HT4 receptors on the excitatory interneurons of the gut which enhances the release of acetylcholine myentric motor neurons . 5HT3 antagonist- in high doses metoclopramide blocks 5HT3 receptors on inhibitory myentric interneurons which can enhance Ach release in the GUT . Blockade of NTS and CTZ adds to anti-emetic action.

25. Pharmacokinetics Metoclopramide is rapidly absorbed on oral administration . It crosses the BLOOD BRAIN BARRIER, placenta and is also secreted in milk . It has a half life of 3-6 hours . Onset of action is almost immediate (1-2 mins) after IV injection while it takes 30-60 mins following the oral intake.

26. Adverse effects Sedation Restlessness Anxiety Diarrhoea D2 receptor blockade results in GYNAECOMASTIA and extrapyramidal symptoms with dystonia and tardive dyskinesia. On long term use symptoms of parkinsonism can occur.

27. Drug interactions Metoclopramide blocks the D2 receptors hence blocks the effects of levodopa . Hastens gastric emptying and thereby hastens absorption of drugs like diazepam.

28. Uses Gastro- oesophageal reflux disease. As anti-emetics As preanaesthetic medic ation In endoscopy Delayed gastric emptying

29. In case of hill journey, antimotion sickness drugs are best administered at: A. Twelve hours before commencing journey B. One hour before commencing journey C. Immediately after commencing journey D. At the first feeling of motion sickness The most effective antimotion sickness drug suitable for short brisk journies is: A. Promethazine theoclate B. Cinnarizine C. Prochlorperazine D. Hyoscine

30. Choose the phenothiazine compound which has selective labyrinthine suppressant action, is used for vomiting and vertigo, but not in schizophrenia: A. Triflupromazine B. Prochlorperazine C. Trifluoperazine D. Thioridazine The most dependable emetic used to expel ingested poisons is: A. Intramuscular emetine B. Oral syrup ipecacuanha C. Intramuscular apomorphine D. Oral bromocriptine

31. Select the prokinetic-antiemetic drug which at relatively higher doses blocks both dopamine D2 as well as 5-HT3 receptors and enhances acetylcholine release from myenteric neurones : A. Cisapride B. Prochlorperazine C. Metoclopramide D. Domperidone Metoclopramide blocks apomorphine induced vomiting, produces muscle dystonias and increases prolactin release indicates that it has: A. Anticholinergic action B. Antihistaminic action C. Anti 5-HT3 action D. Antidopaminergic action

32. Cancer chemotherapy induced vomiting that is not controlled by metoclopramide alone can be suppressed by combining it with: A. Amphetamine B. Dexamethasone C. Hyoscine D. Cyclizine Select the drug(s) which afford(s) relief in gastroesophageal reflux by increasing lower esophageal sphincter tone and promoting gastric emptying, but without affecting acidity of gastric contents: A. Sodium alginate B. Metoclopramide C. Cisapride D. Both ‘B’ and ‘C’

33. Ondansetron blocks emetogenic impulses at the following site(s): A. Vagal afferents in intestines B. Nucleus tractus solitarius C. Chemoreceptor trigger zone D. All of the above Granisetron is a: A. Second generation antihistaminic B. Drug for peptic ulcer C. Antiemetic for cancer chemotherapy D. New antiarrhythmic drug