Recommended
More Related Content
Similar to Faculty Presentation- Dr Sreedevi.pptx
Similar to Faculty Presentation- Dr Sreedevi.pptx (20)
More from Dhruv Saini
Recently uploaded
Recently uploaded (20)
Faculty Presentation- Dr Sreedevi.pptx
- 1. Nausea and Vomiting in Palliative care Dr Sreedevi Warrier Pallium India
- 2. Why Is It Important. ..? Affects patient’s daily functioning. Hinders quality of life. Non compliance to treatment (cancer) Inadequate symptom control (fear or anxiety/poor absorption of medicines) Escalates distress (patient & family)
- 3. •Prevalence of nausea •Advanced cancer- 6- 68% •AIDS - 43-49% •Heart disease – 17- 48% •Renal disease – 30- 43%
- 4. Objectiv es To stop or reduce frequency To establish compliance of treatment To administer oral medications To improve quality of life
- 5. Definitions • Nausea is an unpleasant feeling of the need to vomit often accompanied by pallor, cold sweat, salivation & tachycardia • Vomiting is the forceful expulsion of gastric contents through the mouth • Retching is a rhythmic, labored, spasmodic movement of the diaphragm and abdominal muscles
- 6. Principles of Managem ent • Correct the cause • Non – pharmacological measures • Dietary modifications • Block the receptors at various sites (antiemetics)
- 7. Non – pharmacolo gic measures Avoid situations which induce nausea & vomiting (food) Calm, reassuring environment Fresh air Nurse in the upright position
- 8. Non pharmacologic measures Good oral hygiene Control of malodour (colostomy, fungating tumour, decubitus ulcer) Suitable distracters
- 9. Dietary Modificatio ns Frequent small meals. Avoid fatty / sweet / spicy food/ carbonated drinks Bland food and clear fluids tolerated better
- 12. 5 Key players Vomiting centre • Located in the lateral reticular formation of the medulla and is the final common pathway. • The VC is a diffuse, interconnecting neural network that integrates emetogenic stimuli with parasympathetic and motor efferent activity to produce the vomiting reflex. Area postrema (chemoreceptor trigger zone) • Is a circumventricular structure located at the caudal end of the fourth ventricle. • It is positioned outside the blood brain barrier and therefore is accessible to emetic substances borne in either blood or cerebral spinal fluid. • Also termed the chemoreceptor trigger
- 13. Stomach and proximal bowel Local mediators from the enterochromaffin cells Stimulate vagal and splanchnic afferent fibers within the bowel wall Signals to the brainstem either directly to nuclei within the vomiting center such as the nucleus tractus solitarius or indirectly via the area postrema initiating the emetic reflex. Cerebral cortex Vestibular nucleus Higher input from cerebral cortex Memory/Fear/Modification Input from Vestibular nucleus regarding balance/movement
- 14. Receptors andNeurotransmitter Dopamine Dopamine receptors are divided into five groups (D1–D5), the D2 receptors in area postrema and central D3 receptors were associated with the genesis of emesis. D2 receptor seen in GI Serotonin Main groups 5-HT1, 5-HT2 5-HT3 and5-HT4 receptors . 5-HT3 receptor is seen at vagal afferent fibers in gut, area postrema and in the nucleus of the tractus solitarius. 5HT4 receptor seen in GI Tachykinis and neurokinins Substance P,neurokinin A, and neurokinin B, which bind to the receptors neurokinin-1, neurokinin-2, and neurokinin- 3, respectively. Neurokinin-1 receptors are widely distributed throughout the central nervous system including the area postrema and the NTS, and in GIT. Other neurotransmitte r Histamine, acetylcholine, Endorphins, gamma-amino butyric acid and cannabinoids
- 15. Emesis pathway
- 16. CLASSIFICATION OF ANTI-EMETICS - Central nervous system Vomiting centre Antimuscuranic Antihistaminic 5HT2-receptor antagonist NK1- receptor antagonist Hyoscine Cyclizine Levomepromazine, Olanzapine Aprepitant Area postrema (chemoreceptor trigger zone) D2-receptor antagonist 5HT3-receptor antagonist NK1-receptor antagonist Haloperidol, Metoclopramide, Domperidone Granisetron, Ondansetron Aprepitant Cerebral cortex Benzodiazepine Cannabinoid Corticosteroi d NK1-receptor antagonist Lorazepam Nabilone Dexamethaso ne Aprepitant
- 17. CLASSIFICATION OF ANTI-EMETICS - Gastrointestinal System Prokinetics 5HT4-receptor agonist D2-receptor antagonist Motilin receptor agonist Metoclopramide Metoclopramide, Domperidone Erythromycin Antisecretory Antimuscuranic Somatostatin analogue Hyoscine Octreotide, Lanreotide Vagal 5HT3- receptor blockade 5HT3-receptor antagonist NK1-receptor antagonist Granisetron, Ondansetron Aprepitant Anti-inflammatory Corticosteroid Dexamethasone
- 18. 10 M (M1 to M3) Metastasis Cerebral Raised ICT - CTZ Liver Toxin build up CTZ Cerebral Steroids, Mannitol Meningeal Leptomeningeal disease -raised ICT CTZ Cerebral Steroids Medication Opioids Chemotherapy NSAIDs CTZ, Vestibular , GI CTZ , GI CTZ, GI Metoclopramide (D2, 5HT4) Haloperidol (D2) Ondansetron (5HT3) Dexamethasone Omeprazol e
- 19. 10 M (M4 to M6) Movement Vestibular stimulation – Usually Morphine associated Promethazine Mentation Cortical activity – Anxiety Lorazepam (GABA) Mechanical Luminal Wall Extra luminal Constipation Tumor ,stricture Peritone al deposits Manage constipation Manage bowel obstruction
- 20. 10 M (M7 to M10) Metabolic Hypercalcemia/Hyponatremia Liver/Renal failure - CTZ Dexamethason e, correction Ondansetron Motility Opioids, Ileus and other medications Metoclopramid e Bisacodyl Mucosal NSAIDs, APD, GERD – GI Antacids, cytoprotectives Microbes Oral cavity GI Systemic sepsis Candida, infected mouth ulcers Herpes, CMV, H.P CTZ Topical antifungal, gargles Antibiotics, Antiviral Antibiotics
- 21. Approach to a patient with nausea and vomiting Rule of thumb Assessment Correct the correctable Manage the consequence/complication Provide targeted therapy (choose appropriate anti-emetic) Appropriate route Attention to details
- 23. METOCLOPRAMIDE Metoclopramide - dysmotility, dyspepsia, delayed gastric emptying, and chronic nausea Combined D2 antagonist and 5HT4 agonist. Doses > 100mg/24 hour manifests 5HT3 antagonism. Prokinetic agent. Prokinesis is due to triggering of cholinergic system in the wall of the gut. Opioids impede this effect. D2 antagonists block the ‘dopamine brake’ on gastric emptying induced by stress anxiety and nausea from any cause 5HT4 agonists have a direct excitatory effect which in theory gives them an advantage over the D2 antagonists particularly for patients with gastric stasis or functional intestinal obstruction
- 24. METOCLOPRAMIDE Pharmacokinetics Bio-availability 50–80% PO Onset of action 10–15min IM; 15–60min PO Time to peak plasma concentration 1–2.5h PO Plasma half-life 2.5–5h Duration of action 1–2h Adverse effects Acute dystonic reactions with facial and skeletal muscle spasms and oculogyric crises occur in <5% of patients. Common in young girls and women. Other side effects include neuroleptic (antipsychotic) malignant syndrome. Occasionally drowsiness, restlessness, depression, diarrhoea.
- 25. METOCLOPRAMIDE Interactions Do not combine Metoclopramide with Antimuscuranics(Buscopan) – opposite effect Combination of IV metoclopramide and IV Ondansetron occasionally causes cardiac arrhythmias. As 5HT3-receptors influence various aspects of cardiac function, including inotropy, chronotropy and coronary arterial tone Caution Epilepsy (lowers seizure threshold) Parkinson's disease or parkinsonism (exacerbates symptoms) Pheochromocytoma (enhances catecholamine effect) GI hemorrhage and perforation, < 3 days of GI surgery (worsens symptoms) Complete bowel obstruction/bowel obstruction with presence of colic
- 26. DOMPERIDONE Domperidone is a D2 antagonist. Does not normally cross the blood-brain barrier Domperidone has a dual anti-emetic effect. Acts on dopamine receptors in the chemoreceptor trigger zone (CTZ) in the area postrema, acts on D2-receptors at the gastro-esophageal and gastro duodenal junctions, and thereby counteracts the gastric ‘dopamine brake’. The plasma half-life is increased by up to 50% in renal failure. Domperidone causes less frequent and less severe undesirable effects than metoclopramide e.g. less drowsiness and loss of mental acuity Interactions Concurrent use of CYP3A4 inhibitors (e.g. Ketoconazole, erythromycin, ritonavir, SSRIs, macrolide antibiotics and grapefruit juice) may increase the Domperidone plasma concentration, increasing the risk of QT prolongation and thus torsade de pointes
- 27. DOMPERIDONE Caution GI hemorrhage and perforation, < 3 days of GI surgery (worsens symptoms) Complete bowel obstruction/bowel obstruction with presence of colic Adverse effects Gynaecomastia, galactorrhoea, amenorrhea (secondary to increased prolactin secretion), reduced libido Colic Rarely pruritus, rash, headache Pharmacokinetics Bio-availability 12–18% PO (fasting), 24% PO (after food) Onset of action 30min. Duration of action 12–24h Time to peak plasma concentration 0.5–2h PO Plasma half-life 7–16h; increasing up to 21h in severe renal impairment
- 28. Anti-psychotics Haloperidol Typical antipsychotic. Pure D2 receptor blocker Antiemetic doses of haloperidol are 1.5–5 mg twice a day or three times a day by mouth, or 0.5–2 mg intravenously every 8 hours, and are lower than usual antipsychotic doses Olanzapine Atypical antipsychotic with high affinity for multiple dopamine (D1, D2, D4), serotonin (5HT2A, 5HT2C, 5HT3), α1-adrenergic, H1, and cholinergic (M1–5) receptors. Antiemetic dose is 5–10 mg/day by mouth Levomepromazine Levomepromazine a D2 receptor antagonist is utilized as second-line or third-line therapy for refractory nausea and vomiting in palliative care. Antiemetic dose is 6.25–25 mg twice a day, or 25–50 mg/day via continuous subcutaneous infusion
- 29. Miscellaneous Corticosteroids Antiemetic in chemotherapy-induced emesis, in the management of malignant bowel obstruction, raised intracranial pressure. second-line therapy in chronic nausea of advanced cancer Precise antiemetic mechanism of action of steroids is unknown. Possible mechanisms include depletion of GABA stores in the medulla, reduction of blood–brain barrier permeability to emetic toxins, and inhibition of enkephalin release in the brainstem Antiemetic dose of dexamethasone is 4–8 mg/day for chronic nausea and up to 16 mg/day for malignant bowel obstruction or raised intracranial pressure Octreotide Decreases Peptide Y, Neurotensin, VIP, Substance P Decreases splanchnic blood flow . 100-200mcg Q8H,Refractory V, MBO Hyoscine Antimuscuranic, Decreases GI secretions, relaxes smooth muscles 60-120mg/24h MBO Cannabinoids CB1 receptor action, Dronabinol Benzodiazepines Cerebral action, anxiolytic/amnestic –Lorazepam
- 30. Case Study 56-year-old male with carcinoma colon has persistent vomiting
- 31. Scenario1 Reports colicky pain abdomen Distension of abdomen Bilious vomiting Bowels not opened 1 week 56 year old male with carcinoma colon has persistent vomiting
- 32. Gastric Stasis or Outlet Obstruction Feels okay most of the time. Nausea depending on the severity of obstruction Feels better after vomiting. No bile in the vomitus Takes about an hour after the meal to vomit. Epigastric discomfort or pain in gastric irritation
- 33. Mechanisms... Obstruction Stretch Serotonin release from mucosal enterochromaffin cells •5HT •Neurokini n 1 •Cannabin oid •Vagal stretch receptors 2/5/2021 33 NAUSEA & VOMITING 2020
- 34. Management Obstruction Dexamethasone 8 – 12 mg od Metoclopramide 10 mg tid or qid Stasis Metoclopramide/ Domperidone 10 mg tid or qid Gastric Irritation Omeprazole 20 mg bid Metoclopramide 10 mg tid or qid Sucralfate 1 gram qid STOP the offending drug
- 35. Scenario 2 &3 Received chemotherapy 3 days ago Has come to day care for 3rd cycle of chemotherapy 56 year old male with carcinoma colon has persistent vomiting
- 36. Mechanisms... DRUGS CT agents CORTEX Anxiety, memory 2/5/2021 36 NAUSEA & VOMITING 2020
- 37. CHEMOTHERAPY Ondansetron 4 – 8mg tid or Granisetron 1 mg bd Usually given for 3 days after chemotherapy ANXIETY Lorazepam 0.5-2 mg od/ bd Drugs.... 2/5/2021 37 NAUSEA & VOMITING 2020
- 38. Scenario 4 History of severe headache and weakness of right half of the body 56 year old male with carcinoma colon has persistent vomiting
- 39. Mechanisms... CORTEX • Sensory input • Anxiety, memory • Meningeal irritation • Increased ICP 2/5/2021 39 NAUSEA & VOMITING 2020
- 40. Scenario 5 Reports dizziness and vertigo, head movement causes vomiting 56 year old male with carcinoma colon has persistent vomiting
- 41. Mechanisms Vestibular • Motion • CNS lesions • Opioids Histami ne Muscari nic 2/5/2021 41 NAUSEA & VOMITING 2020
- 42. Scenario 6 On Morphine 10mg every 4hrs for pain, early satiety and bloating sensation 56 year old male with carcinoma colon has persistent vomiting
- 43. Mechanism s... Drug s CT agents NSAIDS Opioids Digoxin Antiarrhythm ics Theophyllin Anticonvulsa nts Metabolic causes CTZ Dopami ne, 5 HT Neurokini n 1 2/5/2021 43 NAUSEA & VOMITING 2020
- 44. Haloperidol 1.5 mg to 2.5 mg od – bd Metoclopramide 10 mg tid Trial of another opioid if troublesome Drugs... 2/5/2021 44 NAUSEA & VOMITING 2020
- 45. Scenario 7 Increased pain over right upper abdomen, continuous pain, increased on deep inspiration and loss of appetite 56 year old male with carcinoma colon has persistent vomiting
- 46. Scenario 8 History of heart disease on Aspirin 325mg/day with symptoms of epigastria pain 56 year old male with carcinoma colon has persistent vomiting
- 47. Scenario 9 History of fever and diarrhea 56 year old male with carcinoma colon has persistent vomiting
- 48. Scenario 10 Sore mouth, loss of taste and anorexia 56 year old male with carcinoma colon has persistent vomiting
- 49. Summary • Identify the likely cause(s) of nausea and/or vomiting. • Identify the pathway by which each cause triggers the • vomiting reflex. • Identify the neurotransmitter receptor involved in the • identified pathway. • Choose the most potent antagonist to the receptor identified— • the binding affinity of a particular antagonist predicts its • antiemetic efficacy. • Choose a route of administration that ensures that the drug • reaches its site of action—this often excludes the oral route.
- 50. • Titrate the dose carefully, review the patient frequently. • Give the antiemetic regularly. • If symptoms persist, review the likely cause(s): additional treatment may be required for an overlooked cause, or alternative treatment may be suggested by a different cause becoming apparent. • If combining antiemetics, potential drug interactions need to be considered. For example, an antihistamine may counteract the effects of a prokinetic agent.
- 51. Thank you