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Uploaded byKhalid Ghaznavi
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Pro-Kinetic Agents

This document discusses pro-kinetic agents and their role in enhancing gastrointestinal motility to treat conditions like reflux esophagitis and nausea. It provides detailed information about specific drugs such as metoclopramide, domperidone, and cisapride, including their mechanisms of action, uses, and side effects. Additionally, it covers classifications of anti-emetics and their applications in managing vomiting due to various causes.

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Pro-Kinetic Agents Dr. Khalid Ghaznavi Doctor of Physiotherapy (USA)
Pro-Kinetic Agents Drugs that….  enhance gastro-duodenal motility and  hasten the gastric motility  Metoclopramide  Domperidone  Cisapride  Mosapride Dr.Khalid Ghaznavi (DPT)
--METOCLOPRAMIDE-- Actions GIT:  Promotes forward movement of upper GIT  Speeds up gastric emptying  Prevents reflex esophagitis  Slightly increase intestinal motility/peristalasis. CNS Actions: Acts as anti-emetic by  actions on CTZ and  by speeding up the gastric emptying Dr.Khalid Ghaznavi (DPT)
Mechanism of action of Metoclopramide  By Blocking dopamine receptors in the gut  By Enhancing acetylcholine release from the cholinergic neurons in the gut  By Blocking the D2 receptors in the CTZ-responsible for anti-emetic action Dr.Khalid Ghaznavi (DPT)
Adverse effects of Metoclopramide  Sedation  Dystonia  Diarrhea  Gynecomastia  Galactorrhea  Parkinsonism (extra-pyramidal symptoms) can occur on long term use due to blockade of dopamine receptors. Dr.Khalid Ghaznavi (DPT)
Uses of Metoclopramide Reflux esophagitis  Heart burn due to reflex of acid into esophagus is benefited by prokinetic agents. As anti-emetic  In post-operative period and vomiting due to anti-cancer drugs. As pre-anesthetic medication  To promote gastric emptying before induction of general anesthesia in emergency. In Endoscopy  to assist the passage of tubes into duodenum Dr.Khalid Ghaznavi (DPT)
--DOMPERIDONE-- Similar to metoclopramide;  Except it does not cross Blood Brain Barrier  Hence does not cause extra-pyramidal side effects Side effects include; ✓ Headache ✓ Dryness of mouth ✓ Diarrhea ✓ Rashes  Domperidone can be used in place of metoclopramide. Dr.Khalid Ghaznavi (DPT)
--CISAPRIDE--  Enhance gastric motility by promoting the release of acetylcholine in gut wall  Promotes colonic motility which may result in diarrhea  Used in reflux esophagitis  But not being used because of their adverse effects now a days Dr.Khalid Ghaznavi (DPT)
Emetics & Anti-emetics Dr.Khalid Ghaznavi (DPT)
Emetics “A protective reflex that serves to rid the stomach and intestine of toxic substances and prevent their further ingestion.”  Occurs due to stimulation of the emetic/vomiting center situated in the medulla oblongata Dr.Khalid Ghaznavi (DPT)
Multiple pathways can elicit vomiting  Vomiting center receives afferents impulses arising from ◼ CTZ , ◼ GI Tract, ◼ throat , ◼ vestibular apparatus and ◼ other viscera CTZ is also accessible; blood borne drugs,  mediators,  hormones,  toxins etc. Dr.Khalid Ghaznavi (DPT)
Emetics –centrally acting Apomorphine  Derivative of morphine.  Given S.C/I.M -6mg  Causes vomiting within 5-10 min  Vomiting is often accompanied by sedation  Act by stimulating CTZ Dr.Khalid Ghaznavi (DPT)
Emetics –peripherally acting Mustard:  It is safe and easily available  Dose -1 tp in water Sodium chloride  Given orally  Causes reflex emesis Dr.Khalid Ghaznavi (DPT)
Emetics –both Ipecacuanha (Emetine):  Contains an alkaloid emetine.  Given as syrup (15-20ml) it produces vomiting in 15 min.  It is safe even in children.  Acts by irritating gastric mucosa as well as through CTZ  Dried root of ipecacuanha contains emetine  Takes 15 min or more for the effect  Used as syrup ipecac for inducing vomiting 15-20ml adults 10-15ml children 5ml infants Dr.Khalid Ghaznavi (DPT)
Classification: Anti-emetics 1. Dopamine D2 Antagonists-Prokinetic drugs: Metoclopramide, Domperidone, Cisapride, Mosapride 2.Anti-cholinergics/ muscarinics: Hyoscine, Dicyclomine 3. H1 anti-histaminics: Promethazine, Diphenhydramine, Cyclizine 4. 5HT3 –Antagonists: Ondansetron, Granisetron, Dolasetron, Tropisteron. 5. Adjuvant anti-emetics: Corticosteroids, Benzodiazepines, Cannabinoids 6. Neuroleptics: Chloropromazine, Prochlorperazine, haloperidol 7. Other agents: Cisapride, Corticosteriods. Dr.Khalid Ghaznavi (DPT)
Pro-kinetic drugs DOPAMINE D2 ANATAGOINST Dr.Khalid Ghaznavi (DPT)
--Metoclopramide--  Introduced in early 1970s as a ‘gastric hurrying agent’  Widely used anti-emetic Actions  Act centrally by blocking dopamine D2 receptors on the CTZ  Increases the tone of lower esophageal sphincter  Enhance gastric peristalsis Dr.Khalid Ghaznavi (DPT)
Uses  In nausea and vomiting due to gastrointestinal disorders  Migraine  Post-operative period  Vomiting due to anti-cancer drugs and radiotherapy  Vomiting due to pregnancy Dr.Khalid Ghaznavi (DPT)
Anti-Cholinergics ANTI-MUSCARINICS Dr.Khalid Ghaznavi (DPT)
--Hyoscine--  Most effective for motion sickness/travelling sickness  Due to overstimulation of vestibular apparatus along with psychological and environmental factors Dr.Khalid Ghaznavi (DPT)
 0.4 -0.6mg oral, I.M  Take 30 min before journey  Acts for 6 hours  Suitable for short brisk journeys  Dose should be repeated if journey is longer  Produces sedation and other anticholinergic side effects  Transdermal patch 1.5mg applied behind the ear  To be delivered over 3 days  Suppresses motion sickness  Have only mild side effects Dr.Khalid Ghaznavi (DPT)
--DICYCLOMINE--  10-20mg oral  Used for prophylaxis of motion sickness and for morning sickness  It has been cleared of teratogenic potential Dr.Khalid Ghaznavi (DPT)
H1 Anti-Histamines Dr.Khalid Ghaznavi (DPT)
H1 Anti-Histamines  Some anti-histaminics are anti-emetic  They are useful mainly in motion sickness and  Lesser extent in morning sickness, post-operative and some other forms of vomiting  Their antiemetic effect appears to be based on anti-cholinergic, anti-histaminic and sedative properties  Also Used in pregnancy Dr.Khalid Ghaznavi (DPT)
Drugs available 1. Meclizine 2. Cyclizine 3. Diphenhydramine 4. Promethazine Dr.Khalid Ghaznavi (DPT)
H1 antihistamines Cont..  All antimotion drugs are more effective when taken ½ -1 hr before commencing journey  Once sickness has started, it is more difficult to control Dr.Khalid Ghaznavi (DPT)
5HT3 –Antagonists Dr.Khalid Ghaznavi (DPT)
--Ondansetron--  5-hydroxytryptamine released in the gut is an important transmitter of emesis  Ondansetron blocks 5-hydroxytryptamine 3 receptors in GIT and CTZ and prevents vomiting Dr.Khalid Ghaznavi (DPT)
Ondansetron Used in:  Postoperative period  Vomiting due to anti-cancer drugs and radiotherapy  Drug induced vomiting Dr.Khalid Ghaznavi (DPT)
Adjuvant Anti-Emetics Dr.Khalid Ghaznavi (DPT)
--Neuroleptics--  Potent antiemetics  Act by blocking D2 receptors in the CTZ  Antiemetic dose is much lower than antipsychotic doses  These agents should not be administered until the cause of vomiting has been diagnosed Dr.Khalid Ghaznavi (DPT)
Neuroleptics Cont… Broad spectrum antiemetic , effective in;  Drug induced and post-anesthetic nausea and vomiting  Disease induced vomiting  Chemotherapy induced (mildly emetogenic) Dr.Khalid Ghaznavi (DPT)
.From. Dr.Khalid Ghaznavi (DPT)