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Emetics and Anti Emetics ppt
The document provides an extensive overview of emetics and anti-emetics, detailing their pharmacology, classification, and clinical applications in treating nausea and vomiting. It explains the mechanisms of vomiting, receptor interactions, and lists various drugs used to induce or alleviate vomiting based on specific circumstances. The document also highlights drug contraindications and includes information on newer anti-emetic therapies and alternative treatments.
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Emetics and Anti Emetics ppt
- 1. BY , HARINI.M &MAHENDAR .S M.Pharm. EMETICS AND ANTI EMETICS
- 2. ï Introduction ï Pathophysiologyof vomiting ï Emetics ï Anti emetics classification pharmacology ï Drug treatment in selected circumstances
- 3. ï Nausea andvomiting are basic human protective reflexes against the absorption of toxins, as well as responses to certain stimuli ï Nausea â greek nautia : sea sickness ï Vomiting- latin vomere: discharge ï Nausea is defined as a subjectively unpleasant wavelike sensation in the back of the throat or epigastrium associated with pallor or flushing, tachycardia, and an awareness of the urge to vomit. Sweating, excess salivation, and a sensation of being cold or hot may occur. ï Vomiting, or emesis, is characterized by contraction of the abdominal muscles, descent of the diaphragm, and opening of the gastric cardia, resulting in forceful expulsion of stomach contents from the mouth. ï Retching involves spasmodic contractions of the diaphragm and the muscles of the thorax and abdominal wall without expulsion of gastric contents, the so-called dry heaves.
- 6. ï complex interactions betweencentral and peripheral pathways occurs Peripheral areas : ï gastric mucosa ï Smooth muscle ï Afferent pathways of vagus and sympathetic nerves Central areas: ï Area postrema ï Chemotrigger zone( CTZ) ï The nucleus tractus solitarus (NTS) ï Vomiting centre
- 7. CTZ: ï The areapostrema in the floor of the 4th ventricle contains CTZ ï Sensory organ containing dopaminergic(D2), serotonergic(5HT3),histaminer gic (H1) and muscarinic (M1) receptors ï Located outside BBB VOMITING CENTRE: ï Situated in the dorsolateral reticular formation close to respiratory centre ï It contains many brain stem nuclei which integrates the
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- 9. ï These aredrugs which evoke vomiting ï They are life savers when toxic substances are ingested ï Powdered mustard suspension/strong salt solutions used in emergency( act by reflexly irritating stomach) ï Drugs are: 1. Act on CTZ: Apomorphine 2. Act reflexly and on CTZ: Ipecacuanha
- 10. ï Semi syntheticderivative of morphine ï Acts as a Dopaminergic agonist on CTZ ï Injected IM/SC ( not orally as dose required is high and acts slowly) ï Dose :6mg (IM) âinduces within 5 min ï Has therapeutic effect in parkinsonism( not used due to side effects) ï Contraindicated in respiratory and CNS depressants
- 11. ï Extract ofdried root of cephalis ipecacuanha (emetine) ï Acts by irritating gastric mucosa as well as through CTZ ï Syrup ipecac: 15-30ml in adults,10-15ml in children,5ml in infants ï Safer drug than apomorphine
- 12. Emetics Contraindicated in: ï Acid or alkali poisoning: perforation & esophageal injury ï CNS stimulant poisoning : convulsions. ï Kerosene (Petroleum) poisoning: aspiration Pneumonia. ï Unconscious patients :aspiration of vomitus. ï Morphine or Phenothiazine poisoning: Ineffective.
- 13. ï Emesis istreated mainly by antagonising the receptors CLASSIFICATION âą Anticholinergics Hyoscine, Dicyclomine âą Antihistaminics: Promethazine, DiphenhydramineDimenhydrinate, Cyclizine, Meclozine âą Neuroleptics: Chlorpromazine, Prochlorperazine , Haloperidol âą Prokinetic agents: Metocloperamide, Domperidone, Cisapride, Mosapride âą 5HT3 receptor antagonist: Ondansetrone, Granisetrone, Topisetrone âą Adjuvant antiemetics: Corticosteroids ,Cannabinoids ,Benzodiazepines
- 15. ANTICHOLINERGICS ï Act byinhibition of cholinergic transmission from the vestibular nucei to higher centres with in the cerebral cortex ï Hyoscine ï Dicyclomine ï SE: drowsiness, drymouth, dilated pupils and blurred vision, decreased sweating, gastrointestinal motility, gastrointestinal secretions and difficulty with micturition, may precipitate closed angle glaucoma
- 16. Hyoscine: ï Dose: 0.2-0.4mg ï Oral/IM ï Short DOA ï AE: sedation ï Used in motion sickness ï Transdermal patches ( applied behind pinna) with mild side effects DICYCLOMINE: ï dose -10-2-mg ï Oral ï Used for prophylaxis of motion sickness and for morning sickness
- 17. ANTIHISTAMINICS ï Motion sickness,morning sickness, PONV ï Anticholinergic, Antihistaminic & Sedative action Promethazine: ï Afford protection of motion sickness for 4-6 hrs ï Sedation, dryness of mouth Doxylamine: ï Sedative H1 anti histaminic ï Morning sickness (combined with vit B6) ï Oral absorption is slow ï T1/2 : 10 hrs ï SE: drowsinees ,drymouth, vertigo, abdominal upset ï Dose :10-20 mg
- 18. Cyclizine/meclizine: ï Les sedativeand less anti cholinergic ï Meclizine long acting, protects against sea sickness for 24 hrs Cinnarizine: ï Anti vertigo drug ï Protective for motion sickness ï Inhibits influx of Ca+2 from endolymph into the vestibular sensory cells which mediates labyrinthine refluxes
- 19. NEUROLEPTICS ï Broad spectrumantiemetics ï Acts by blocking D2 receptor in CTZ ï Useful for - drug induced - disease induced - malignancy associated - radiation induced vomiting Avoided in morning sickness except hyperemesis gravidarum ï SIDE EFFECTS :- ï Significant degree of sedation ï Acute muscle dystonia ï Extrapyramidal effects NOT EFFECTIVE FOR :- ï Motion sickness as vestibular pathway does not involve dopaminergic pathway Prochlorperazine: ï D2 blocking phenothiazine ï Labyrinthine supressant,selective anti vertigo and antiemetic action ï SE:acute dystonia,tardive dyskinesia,parkinsonism
- 20. PROKINETIC DRUGS ï Increasegastric peristalsis ï Relaxes pylorus & 1st part of duodenum ï Hastens gastric emptying ï Lower esophageal sphincter tone is increased ï Gastro esophageal reflux is opposed Metoclopramide: âą Acts through D2, 5HT4 & 5HT3 receptors âą D2 antagonism leads to - increased gastric emptying -enhances LES tone âą Central D2 antagonism leads to - extrapyramidal effects - hyperprolactinemia
- 21. âą 5HT3 antagonismleads to - minor increase in Ach release( Central action appears only in large doses) âą 5HT4 antagonism leads to increased release of Ach leading to - gastric hurrying - LES tonic effects Pk:âą Rapidly absorbed orally âą Enter brain , crosses placenta, secreted in milk so leads to - Sedation, Dizziness,Parkinsonism, Galactorrhea,Gynecomastia,Loose motions, dystonia & myoclonus insuckling infants USES :- âą Antiemetic âą Gastrokinetic - in emergency - post vagotomy or diabetes associated gastric stasis - to facilitate duodenal intubation âą Dyspepsia âą Gastroesophageal reflux
- 22. Domperidone: âą D2 antagonistwith low antiemetic & prokinetic actions âą Poorly crosses BBB( Rare extrapyramidal effects) âą Hyperprolactinemia can occur Pk: âą Absorbed orally âą Low bioavailability due to first pass metabolism T1/2 : 7.5 hrs Dose :10-40mg SE: dry mouth, loose stools, head ache,rashes,galactorhoea,cardiac arrythmia (rapid IV ) Used: CINV &drug induced
- 23. Cisapride: âą Mainly has5HT4 activity(Acts by releasing Ach), Also has 5HT3 antagonistic effects âą No effects on D2 receptors âą Restores & facilitate motility throughout GIT including colon therefore used for chronic constipation âą Used for - non-ulcer dyspepsia - impaired gastric emptying - chronic constipation âą Serious drug interaction with CYP3A4 (antifungals, macrolideantibiotics, etc.) leads to ventricular arrhythmias & death (Withdrawn in USA & other countries) MOSAPRIDE : (same as Cisapride ) ï No arrythmia Tegaserod: selective 5HT4 partial agonist ï Colonic motility, promotes gastric emptying,Intestinal transit ï Colonic Cl- & water secretion
- 24. 5HT3 Antagonists âą Blocksthe depolarising action of serotonin through 5HT3 receptors on vagal afferents in GIT as well as NTS & CTZ âą Useful for - cytotoxic drug induced - radiation induced - inflammation induced vomiting ï SE: Well tolerated with minor side effects like headache, constipation or diarrhoea, abdominal discomfort & rash on iv injection Ondansetron: oral BA is 60 -70 % ï Eliminated in urine ï T1/2 :3-5 times ï DOA: 4-12 hrs ï Week 5HT4 blockade ï First choice of antiemetic Granisetron: 10-15 times more potent , plasma T1/2 is: 8-12 hrs Doses:Ondansetron 32 mg / day Granisetron 10 mg / kg / day Dolasetron 1.8 mg / kg / day
- 25. ADJUVANT ANTI EMETICS Corticosteroids: ï may act on steroid receptors in area postrema ï Dexamethasone (8-20mg) ï Augment metachlopramide & ondansetron for cisplatin induced delayed emesis ï Reduces side effects of 10 anti emetics Benzodiazepenes: ï Week anti emetics ( sedation) ï Adjuvant to metachlopramide and ondansetron ï Diazepam/lorazepam ( oral/IV) ï Relieve anxiety, anticipatory vomiting and produce amnesia for the unpleasant procedure , supress dystonic SE of metachlopramide
- 26. Cannabinoids: ï â9 tetrahydro cannabinol(â9THC) active principle of cannabis indica ï Acts at higher centres /VC by activating CB1 receptors ï Dronabinol: (synthetic â9THC) ï Less hallucinogenic ,More anti emetic ï CINV ï Used as apetite supressant in AIDS patient ï SE: drowsiness ,dizziness,drymouth,mood changes,postural hypotension ï Nabilone is a closely related THC analog that has been available in other countries and is now approved for use in the USA
- 27. NEWER ANTI EMETIC THERAPY Neurokininantagonist: ï NK1 receptors in area postrema & NTS ï The tachykinin substance P is localized within both the gastrointestinal vagal afferent nerve fibers and in the neural pathways ï Adjuvant to dexamethaone & 5HT 3 antagonist ï oral aprepitant 125 mg ï The drug is metabolized by CYP3A4 and may inhibit the metabolism of other drugs metabolized by the CYP3A4 pathway
- 28. ALTERNATIVE THERAPY ï Stimulatewrist accupuncture point p6 ( PONV) ï Ginger ( 1g pre operatively ) Motion sickness and pregnancy induced N & V
- 29. DRUG TREATMENT INSELECTED CIRCUMSTANCES PONV ï prophylactic : dexamethasone before surgery. 5HT3, H1 antagonist,phenothiazines at end. Opioid â atropine/hyoscine CINV ï acute â 5HT3 antagonist(high) , metachlopramide (low) ï Delayed -5HT3+dexa ,Meta +dexa ï Anticipatory-low doses of benzodiazepine ( avoid previous cycles)
- 30. PREGNANCY: ï CHO richmeal ï Ginger /acupuncture ï Severe âpromethazine ,second line prochlorperazine,metachlopramide ï USA: vitB6 + doxylamine ï Hyperemesis gravidarum: fluid and electrolyte replacement MIGRAINE: metachlopramide LABYRINTHITIS: anti cholinergic ,anti histaminic,benzodiazepines,phenothiazines ï Severe meclozine MOTION SICKNESS: anti cholinergic (hyoscine)
- 31. REFERENCES ï Essential medicalpharmacology by K.D.TRIPATHI,6th edition (639- 647) ï Rang & daleâs pharmacology by H.P.RANG,M.M.DALE,J.M RITTER,R.J FLOWER,6th edition (390-393) ï Clinical pharmacology & therapeutics by ROGER WALKER