antiemetic (1).pptx

antiemetic

1. Antiemetics & Prokinetics  Dr. Hassam Zulfiqar  Moderator: Dr. George Sam joseph

2. No Conflict Of Interest To Declare 

3. Definitions Nausea ,: T he unpleasant sensation of being about to vomit, can occur alone or can accompany vomiting , dyspepsia, or other gastrointestinal symptoms. Vomiting ( Emesis ) T he involuntary forceful expulsion of gastric contents through the mouth Antiemetics : Drugs used to treat or prevent nausea and vomiting

4. PONV Why is it Important? One of the most unpleasant memories associated with p atient ’s hospital stay. Patient satisfaction with their anaesthetic is highly linked to their experience of PONV. When severe it can lead to increased length of hospital stay, increased bleeding, incisional hernias and even life threatening aspiration pneumonia.

5. Risk Stratification Multifactorial

6. Risk Stratification

7. Apfel score

8. Physiology

9. Schematic of pathways involved in Postoperative nausea and vomiting 5-HT: 5-hydroxytriptamine 5-HT3: 5-hydroxytriptamine type 3 receptor AP : area Postrema NTS :nucleus tractus solitarius

10. Classification H1 antihistamines cinnarizine ,cyclizine , Diphenhydramine dimenhydrinate ,Promethazine Muscarinic antagonist hyoscine (scopolamine ) Selective 5HT3 antagonist : Ondanseteron , granisetron Glucocorticoids dexamethasone ,methyl prednisolone

11. Classification 5. D2 antagonist a- substituted benzamide- metoclopramide,trimethobenzamide b- Butyrophenones – domperidone,droperidol c- phenothiazine – procloperazine,promethazine Cannabinoids –dronabinol ,nabilone Neurokinin 1 antagonist – apripitant,fosapipretant

12. H1 Antihistamine (Cyclizine ) Cyclizine is a piperazine derivative. • Anticholinergic Tachycardia Dry mouth constipation urinary retention blurry vision prepared with lactic acid ,so IV, IM may be particularly painful .

13. 5-HT3 antagonists

14. substituted benzamide Metoclopramide Trimethobenzamide Domperidone Butyrophenones Droperidol Benperidol Haloperidol phenothiazine Procloperazine C hlorpromazine Promethazine D2 Antagonist

15. Extrapyramidal effects

16. Butyrophenones ( Droperido l ) Uses: prevention and treatment of PONV at doses from 0.25 to 5 mg. Mechanism of action antagonizes central dopamine (D2) receptors at the CTZ. Effects • CNS -S edation -E xtrapyramidal effects incidence increases with higher doses. up to 25% of patients may experience anxiety up to 48 hours after administration. Metabolic hyper- prolactinaemia . •CVS : - hypotension resulting from peripheral adrenoceptor blockade - concerns of QT prolongation & VT

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18. Prochlorperazine -

19. Steroids - Dexamethasone is a synthetic glucocorticoid - prevention of PONV when given at the start of anesthesia. - not effective in established vomiting. - Low-dose regimes (4 mg) appear to be as effective as higher doses. - MOA?? 1) prostaglandin antagonism or release of endorphins , resulting in elevated mood and appetite stimulation. 2) anti-inflammatory effects may also reduce 5-HT release within the gut.

20. Cannabinoids Nabilone , dronabinol mechanism of action not understood. act at central cannabinoid receptors. Used in vomiting due to cytotoxic anticancer drugs. Not commonly used. Side effects: Euphoria Dysphoria Sedation hallucination.

21. Neurokinin 1 (NK1) receptor antagonists - block the actions of substance P in the brain stem - control of delayed chemotherapy induced N&V - potentiate the effects of other antiemetics (ondansetron and dexamethasone ) Examples : Aprepitant - O ral fosaprepitant - IV

22. Acupuncture Acustimulation to point P6 (pericardium 6, which is 2.5–5 cm proximal to the distal crease of the wrist) has been shown to reduce the incidence of PONV. • Studies have shown that it can provide a further 30% reduction in PONV when used in combination with ondansetron. • Special wrist bands that exert pressure at this point can be purchased to reduce the incidence of travel sickness. Free from side effects

23. Other drugs effecting on GIT Increase gastric motility Inhibit gastric motility Metoclopramide Domperidone Erythromycin Neostigmine Cisapride Opioid Antimuscarinic agents Atropine Hyoscine

24. Erythromycin: Mimics the effect of the gut peptide motilin acts as an agonist at the motilin receptors found mainly in the gastric antrum and proximal duodenum. It increases gastric emptying used for the short-term treatment of gastroparesis orally >intravenously Side effects include: - Abdominal cramps D iarrhoea N ausea and vomiting R arely, tornado de pointes.

25. Neostigmine: This acetylcholinesterase inhibitor increases the availability of acetylcholine ( ACh ) at the myenteric plexus Which increase >> gut motility >> salivation >> gastric secretions >>sphincter tone. It is occasionally used on the ICU to treat refractory constipation. Cisapride : This prokinetic agent acts at 5-HT4 receptors enhancing ACh release at the myenteric plexus. This increases sphincter tone , peristalsis prescribed for reflux oesophagitis . Side effects : long Q-T syndrome, VT, VF and torsades de pointes.

26. Antimuscarinic agents : ( Atropine , Hyoscine) An increase in parasympathetic tone in the GIT promotes ‘resting and digesting’. Antimuscarinic drugs antagonise the muscarinic M3 receptors Decrease GIT motility Decrease saliva production Decrease gastric secretions Decrease lower oesophageal sphincter tone. Hyoscine Uses : - reduce PONV. - motion sickness \hypersalivation - sedative and amnesic agent.

27. Anticholinergics

28. Question A 78-year-old patient with Parkinson disease undergoes a cataract operation under general anesthesia. In the recovery room, the patient has two episodes of emesis and complains of severe nausea. Which of the following antiemetics would be the best choice for treatment of nausea in this patient? A. Droperidol B. Promethazine C. Ondansetron D. Metoclopramide

29. Question A 60-year-old patient with Parkinson disease undergoes a  laparascopic  cholecystectomy under general anesthesia. In the recovery room, the patient has two episodesof emesis and complains of severe nausea. Which of the following drug can be used safely in this patient? A.  Droperidol B. Prochlorperazine C. Domperidone D. Metoclopramide 

30. Question Which of the following antiemetics does not produce a significant dose-dependent prolongation of the QTc interval? A. Ondansetron B. Droperidol C. Haloperidol D. Scopolamine E. Prochlorperazine

31. explanation Scopolamine is a centrally acting anticholinergic and is efective in ameliorating motion sickness. Preoperative placement of a transdermal patch has been shown to reduce the incidence of severe postoperative nausea and vomiting in outpatient gynecologic laparoscopic procedures. Adverse effects of transdermal scopolamine include a high incidence (95% vs. 45% with placebo) of dry mouth, somnolence, mydriasis, and dizziness. However, the scopolamine patch has not been demonstrated to significantly increase the QTc interval. Antiemetics, including butyrophenone neuroleptic drugs ( droperidol and haloperidol), 5-HT 3 receptor antagonists (ondansetron, granisetron , and dolasetron ), phenothiazines (chlorpromazine and promethazine), and metoclopramide are known to prolong the QTc interval. In most cases, prolongation of the QTc interval is dose related

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