Gastroenterology: Nausea and Vomiting - PowerPoint Presentation

1. Gastroenterology:Nausea and VomitingCourses in Therapeutics and Disease State Management

2. Learning Objectives (Slide 1 of 2)Describe the various etiologies of N/VDiscuss the pathophysiology of N/VCompare and contrast simple and complex N/VDiscuss the various pharmacologic approaches to the treatment of N/VExplain the mechanisms of action of the antiemetics and how they are used in the prophylaxis/treatment of N/V

3. Learning Objectives (Slide 2 of 2)Given a patient case, evaluate the patient’s risk of PONV, recommend appropriate prophylaxis/treatment (both pharmacologic and nonpharmacologic), and explain the rationale behind your decisionGiven a patient case, recommend appropriate prophylaxis/treatment (both pharmacologic and nonpharmacologic) for N/V and explain the rationale behind your decisionDiscuss the antiemetic drugs’ adverse effects and monitoring parameters

4. Required ReadingGravatt L, Donohoe KL, DiPiro CV. Nausea and Vomiting. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; 2017.

5. OverviewNauseaUnpleasant, painless sensation that one may vomitVomitingAn organized, autonomic response that results in the forceful expulsion of gastric contents through the mouthNausea and vomiting have a significant negative impact on quality of life

6. EtiologyNausea and/or vomiting may be associated with a number of conditions including gastrointestinal, cardiovascular, infectious, neurologic, metabolic, psychogenic processes, or pregnancyNausea and/or vomiting is also associated with numerous medications and noxious agents

7. Iatrogenic, Toxic, and Infectious CausesAlmost any medication can cause N/V with chemotherapeutic agents being the most well knownOverdoses of alcohol, illicit drugs, and other toxins may cause acute N/VInfectious causes usually result in acute onset N/VViral gastroenteritis is very commonBacteria and their toxins may also be the cause

8. Gastrointestinal Disorders (Slide 1 of 2)Acute N/V typically the result of an inflammatory processAppendicitis, cholecystitis, pancreatitisObstructions can cause acute or chronic symptomsGastric outlet obstructions tend to cause intermittent N/VIntestinal obstructions tend to acute N/V and severe pain

9. Gastrointestinal Disorders (Slide 2 of 2)Motility disordersGastroparesis produces N/V from the inability to move food through the GI tractThe following GI disorders may have N/V associated with them, but these are not the primary symptomsDyspepsia, GERD, PUD, and IBS

10. CNS and Psychiatric ConditionsConditions that increase intracranial pressure can cause N/VTumor, infarct, infectionConditions that affect the labryinthus often cause vertigo that can be accompanied by N/VInfections, Meniere’s disease, tumorsMigraine headaches often cause N/VPatients may also experience N/V from emotional or physical stressorsN/V can also be associated with anorexia nervosa, bulimia nervosa, depression, and anxiety

11. Other ConditionsPregnancy is the most common endocrinologic cause of N/VMetabolic causes of N/V include the following:Acidosis, uremia, hyperthyroidism, adrenal disorders, parathyroid disorders

12. EtiologyLink: list of specific etiologies of nausea and vomiting

13. Pathophysiology (Slide 1 of 3)3 phases of emesis include:NauseaThe need to vomitRetchingLabored movement of the abdominal and thoracic muscles before vomitingVomitingForceful expulsion of gastric contents through the mouth caused by GI retoperistalsis

14. Pathophysiology (Slide 2 of 3)Areas involved in nausea and vomitingVomiting centerIntegrates afferent impulses from sensory centers to efferent impulses to different areas including the salivation and respiratory centers and to pharyngeal, GI, and abdominal muscles leading to vomiting Chemoreceptor trigger zone (CTZ)Located in the brain and is the major chemosensory organ for emesisAssociated with chemically-induced vomitingGI tract

15. Pathophysiology (Slide 3 of 3)Neurotransmitter receptors are located in the vomiting center, CTZ, and GI tractThese include cholinergic, histaminic, dopaminergic, opiate serotonergic, neurokinin, and benzodiazepine receptorsLink: Figure of pharmacologist’s view of emetic stimuliMedications, disease states, and various circumstances can cause stimulation of these receptors to cause N/VLink: list of specific etiologies of nausea and vomitingThere are antiemetic drugs that block these receptors

16. 3 Step Initial EvaluationAttempt to recognize and correct any consequences of the N/V such as dehydration or electrolyte disturbancesTry to identify the underlying cause and provide specific therapiesIf the etiology can’t be determined, use empiric therapy to treat the symptoms

17. Clinical PresentationNausea and vomiting are common in a variety of different circumstancesThe presentation of nausea and vomiting is often described as simple or complex depending on the amount of distress the patient is experiencing

18. Simple Nausea and VomitingSymptomsSelf-limitingResolves spontaneouslyRequires only symptomatic therapySignsComplaints of queasiness and discomfortLaboratory TestsNone

19. Complex Nausea and VomitingSymptomsNot relieved after administration of antiemeticsProgressive deterioration of patient secondary to fluid-electrolyte imbalancesUsually associated with noxious agents (e.g. oncology/chemotherapy agents) or psychogenic eventsSignsWeight lossFeverAbdominal painLaboratory TestsSerum electrolyte concentrationsUpper/lower GI evaluation

20. Simple and Complex Nausea and VomitingOther information to consider when evaluating simple or complex nausea and vomiting include:Fluid input and outputMedication historyRecent history of behavioral or visual changes, headache, pain, or stressFamily history positive for psychogenic vomitingLink: Table on Clinical Presentation of Nausea and Vomiting

21. TreatmentIn this module, we will cover the treatment of the following types of nausea/vomitingSimple nausea and vomitingPostoperative nausea and vomiting (PONV)Nausea and vomiting associated with disorders in balanceNausea and vomiting and antiemetic medication use in pregnancyTherefore, we will focus on the medications and treatment for nausea and vomiting that is NOT associated with chemotherapy agents (CINV)

22. Nonpharmacologic TherapyModalities utilized depends on the etiology of the nausea/vomitingAvoid food/beverages that may be problematic and avoid overindulgenceIf the N/V is part of the symptomatology of an illness, the N/V will subside as the illness resolvesIf the N/V are from labyrinthine changes produced by motion, the N/V will improve by adapting a stable physical positionOther behavioral nonpharmacologic interventions include relaxation, biofeedback, self-hypnosis, cognitive distraction, guided imagery, acupuncture, and systematic desensitization

23. Pharmacologic Therapy (Slide 1 of 2)Various antiemetic medications are available in both the nonprescription and prescription categoriesSimple nausea and vomiting is often managed by the patient using nonprescription agents (self-care)If the patient’s condition does not improve or gets worse, prescription medication(s) are usually warrantedComplex nausea and vomiting (e.g. from anesthesia, chemotherapy agents, etc.) requires prescription medications and often involves combination therapy

24. Pharmacologic Therapy (Slide 2 of 2)Antiemetic medications have different mechanisms of action and are also available in different dosage formsFactors to consider when choosing a medicationEtiology of the N/VFrequency, duration, and severity of the N/VAbility of the patient to use oral, rectal, injectable, or transdermal productsSuccess of previously used antiemetic therapies

25. Antiemetic Medication ClassesAntacidsAntihistamines-AnticholinergicsButyrophenonesH2-receptor antagonists5-hydroxytryptamine-3 receptor antagonists (5-HT3 RA)PhenothiazinesCorticosteroidsNeurokinin 1 receptor antagonists

26. Antacids (Slide 1 of 2)Can be used to help relieve simple nausea and vomitingWork primarily through gastric acid neutralizationMOANeutralize hydrochloric acid in the stomach, which results in an increase in gastric pHAgentsMagnesium hydroxideAluminum hydroxideCalcium carbonateAdverse effectsDiarrhea (magnesium hydroxide)Constipation (aluminum hydroxide and calcium carbonate)Alterations in mineral metabolismAcid-base disturbances

27. Antacids (Slide 2 of 2)MonitoringPeriodic calcium and phosphate levels if on chronic antacid therapyPatient counselingAntacids can decrease the levels of numerous other drugs including tetracyclines, digoxin, iron supplements, fluroquinolones, and ketoconazole. Patients should separate antacids and other medications by at least 2 hoursPatients with renal impairment should not use aluminum or magnesium containing antacids unless directed by their physician

28. Antihistamine-Anticholinergic Drugs(Slide 1 of 2)Used for simple N/V especially when it is associate with motion sicknessMOAInterrupt visceral afferent pathways that stimulate N/VSuppresses vestibular end-organ receptors and inhibits activation of central cholinergic pathwaysAgentsDimenhydrinate (Dramanine)Diphenhydramine (Benadryl)Hydroxyzine (Vistaril, Atarax)Meclizine (Bonine, Antivert)Scopolamine (Transderm Scop)Trimethobenzamide (Tigan)

29. Antihistamine-Anticholinergic Drugs(Slide 2 of 2)Adverse effectsDrowsiness, confusion, blurred vision, dry mouth, urinary retentionMonitoring Improvement in N/VPatient counselingEspecially problematic in the elderly Increased risk of complications in those with BPH, narrow angle glaucoma, or asthmaAvoid activities that require mental alertness until the the effects of the medication is realizedAvoid alcohol and other CNS depressants as an additive effect may occur

30. Butyrophenones (Slide 1 of 2)Used in palliative care and postoperative nausea and vomiting (PONV)Not recommended as first-line therapyMOABlock dopaminergic stimulation of the CTZAgentsHaloperidol (Haldol)Droperidol (Inapsine)

31. Butyrophenones (Slide 2 of 2)Adverse effectsSedation, constipation, hypotension, QT prolongation/torsade de pointesMonitoringEKG prior to administration followed by cardiac monitoring 2 to 3 hours after administration

32. H2-Receptor Antagonists (Slide 1 of 2)Used to manage simple nausea and vomiting associated with increased gastric acid secretion, pyrosis, or gastroesophageal reflux disease (GERD)MOACompetitive inhibition of histamine at H2 receptors of gastric parietal cells which inhibits gastric acid secretionAgentsCimetidine (Tagamet)Famotidine (Pepcid)Nizatidine (Axid)Ranitidine (Zantac)

33. H2-Receptor Antagonists (Slide 2 of 2)Adverse effectsHeadache, somnolence, fatigue, dizziness, constipation, diarrheaMonitoringMonitor for CNS effects (rare) in those over 50 years old or in those with renal or hepatic impairmentPatient counselingOnset of relief is 30 to 45 minutes and duration of relief is 4 to 10 hours

34. 5-hydroxytryptamine-3 Receptor Antagonists(Slide 1 of 2)Useful as single agent or combination therapy for prophylaxis of CINV and PONVMOABlock presynaptic serotonin receptors in sensory vagal fibers in the gut wallAgentsDolasetron (Anzemet)Ondansetron (Zofran)Granisetron (Kytril)Palonosetron (Aloxi)

35. 5-hydroxytryptamine-3 Receptor Antagonists(Slide 2 of 2)Adverse effectsAsthenia, constipation, headacheMonitoringEffectiveness in preventing N/V Patient counselingCounsel patients regarding adverse effects and to report any signs/symptoms of cardiac arrhythmias

36. Phenothiazines (Slide 1 of 2)Useful in simple N/V and for breakthrough CINVMOABlock dopamine receptors in the CTZ (chlorpromazine and prochlorperazine)Competitively blocks histamine-1 receptors (promethazine)AgentsChlorpromazine (Thorazine)Prochlorperazine (Compazine)Promethazine (Phenergan)

37. Phenothiazines (Slide 2 of 2)Adverse effectsConstipation, dizziness, sedation, tachycardia, tardive dyskinesia, prolonged QT intervalMonitoring Improvement of N/VPatient counselingMay cause photosensitivity (use sunblock and avoid prolonged exposure to sunlight)Avoid activities that require mental alertness until the the effects of the medication is realizedAvoid alcohol

38. Corticosteroids (Slide 1 of 2)Used as monotherapy or in combination therapy for prophylaxis of CINV and PONVMOAExact mechanism of action for nausea/vomiting prophylaxis is unknownAgentsDexamethasoneMost commonly used corticosteroid for N/VMethylprednisolone (Medrol)

39. Corticosteroids (Slide 2 of 2)Adverse effectsInsomnia, GI symptoms, agitation, appetite stimulationMonitoring Effectiveness in preventing N/VPatient CounselingIf on long-term therapy advise to avoid live or live, attenuated vaccinesReport signs/symptoms of infection or hyperglycemiaDiabetic patients may need to closely monitor their blood glucose

40. NK-1 Receptor Antagonists (Slide 1 of 2)Used for both CINV and PONVCan be used alone or in combination (particularly with 5-HT3 receptor antagonists and corticosteroids)MOAPrevents acute and delayed vomiting by inhibiting substance P/neurokinin 1 (NK1) receptorAgentsAprepitant (Emend)

41. NK-1 Receptor Antagonists (Slide 2 of 2)Adverse effectsConstipation, diarrhea, headache, hiccupsMonitoring Improvement in N/VPatient counselingEducate on adverse effects

42. Common Antiemetic MedicationsLink: Table on Common Antiemetic Preparations and Adult Dosage RegimensLink: Table on Receptor Specificity of Anti-emetic Agents

43. Simple Nausea and VomitingTreatment often involves self-care with nonprescription (OTC) agentsIf OTC medications do not help or if the patient’s symptoms worsen, prescription agents are often employed

44. Nausea and VomitingFor both simple and complex nausea and vomiting, an attempt should be made to identify the etiology so that targeted therapy can be utilizedIf the etiology is unknown and OTC medications are not working:It is reasonable to begin prescription therapy with a trial of a phenothiazine, such as prochlorperazine5-HT3RA’s like ondansetron are also effective and may be better tolerated then phenothiazines, but their high cost is a concern particularly if being used long-term

45. Overview of Postoperative Nausea and Vomiting (PONV)PONV is common and distressing to patientsGeneral incidence of vomiting is 30%General incidence of nausea is 50%High-risk patients can have a PONV rate of 80%General approach taken is to assess a patient’s PONV risk, reduce baseline risks, and provide appropriate PONV prophylaxis

46. Risk Factors for PONV (Slide 1 of 3)Risk factors with positive overall evidence:Female sexHistory of PONV or motion sicknessNonsmokingYounger age (< 50 years old)General vs. regional anesthesiaUse of volatile anesthetics and nitrous oxidePostoperative opioidsDuration of anesthesiaType of surgery Higher incidence with cholecystectomy, laparoscopic, gynecological)

47. Risk Factors of PONV (Slide 2 of 3)Risk factors with conflicting evidencePhysical statusMenstrual cycleLevel of anesthetist’s experienceMuscle relaxant antagonistsFactors that have been disproven or have limited clinical relevanceBMIAnxietyNasogastric tubeSupplemental oxygenPerioperative fastingMigraine

48. Risk Factors for PONV (Slide 3 of 3)Link: Table covering Risk Factors for Postoperative Nausea and Vomiting (PONV)

49. Apfel Simplified Risk Score (Slide 1 of 3)Predicts a patient’s risk of PONV based on presence of 4 risk factorsRisk FactorsPointsFemale Gender1Non-smoker1History of PONV1Postoperative Opioids1Sum 0 to 4

50. Apfel Simplified Risk Score (Slide 2 of 3)When 0 risk factors are present, risk of PONV is about 10%When 1 risk factor is present, risk of PONV is about 20%When 2 risk factors are present, risk of PONV is about 40%When 3 risk factors are present, risk of PONV is about 60%When 4 risk factors are present, risk of PONV is about 80%

51. Apfel Simplified Risk Score (Slide 3 of 3)If 0 – 1 risk factors, categorized as “low” riskIf 2 to 3 risk factors, categorized as “medium” riskIf 4 risk factors, categorized as “high” risk

52. Strategies to Reduce Baseline RiskReducing baseline risk factors can significantly decrease the incidence of PONVStrategies recommended to reduce baseline risk include:Avoidance of general anesthesia by the use of regional anesthesiaPreferential use of propofol infusionsAvoidance of nitrous oxideAvoidance of volatile anestheticsMinimization of peri-operative opioidsAdequate hydration

53. PONV ProphylaxisWho should receive PONV prophylaxis and the number of interventions used depends on riskLow riskProphylaxis not recommendedUse a wait and see approachMedium riskUse 1 or 2 interventionsHigh riskUse more than 2 interventions (a multimodal approach)

54. Monotherapy (Slide 1 of 2)5-HT3 receptor antagonistsOndansetron is the “gold standard” antiemeticGranisetronRamosetronThe 5HT3 receptor antagonists are most effective for prophylaxis when given at the end of surgeryNK-1 receptor antagonistsAprepitantSimilar to ondansetron in achieving complete response 24 hours after surgerySignificantly more effective than ondansetron for preventing vomiting at 24 and 48 hours after surgery and reducing nausea 48 hours after surgeryGiven within 3 hours of the induction of anesthesia

55. Monotherapy (Slide 2 of 2)CorticosteroidsDexamethasoneSimilar efficacy to ondansetron and droperidolGiven at induction of anesthesiaButyrophenonesDroperidolSimilar efficacy to ondansetronGiven at the end of surgeryLow doses used for PONV and hence unlikely to be associated with significant cardiovascular events

56. Two Drug Combination TherapyCombination therapy for PONV is preferable to using a single drug aloneAdults at moderate or high risk for PONV should receive combination therapy with drugs from different classesThe following combinations are frequently used5-HT3 RA plus droperidol5-HT3 RA plus dexamethasoneDroperidol plus dexamethasone

57. PONV Prophylaxis for High Risk PatientsPatients who are considered high risk for PONV should receive combination therapy or a multimodal approach that includes 2 or more interventionsUse combination therapy and eliminate any modifiable risk factorModifiable risk factors were previously discussed

58. Recommended Doses for Antiemetics for PONV Prophylaxis DrugAdult DosePediatric Dose (IV)Timing of DoseaAprepitantb40 mg orallyNot labeled for use in pediatricsWithin 3 hours prior to inductionDexamethasone4–5 mg IV150 mcg/kg up to 5 mgAt inductionDimenhydrinate1 mg/kg IV0.5 mg/kg up to 25 mgNot specifiedDolasetron12.5 mg IV350 mcg/kg up to 12.5 mgAt end of surgeryDroperidolc0.625–1.25 mg IV10–15 mcg/kg up to 1.25 mgAt end of surgeryGranisetron0.35–1.5 mg IV40 mcg/kg up to 0.6 mgAt end of surgeryHaloperidol0.5–2 mg (IM or IV)dNot specifiedOndansetron4 mg IV50–100 mcg/kg up to 4 mgAt end of surgeryPalonosetronb0.075 mg IVNot labeled for patients <18 yearsAt inductionProchlorperazine5–10 mg IM or IVdAt end of surgeryPromethazinec6.25–25 mg IVdAt inductionScopolamineTransdermal patchdPrior evening or 4 hours before surgeryTropisetron2 mg IV0.1 mg/kg up to 2 mgAt end of surgeryaBased on recommendations from consensus guidelines; may differ from manufacturer’s recommendations.bLabeled for use in PONV but not included in consensus guidelines.cSee FDA “black box” warning.dPediatric dosing not included in consensus guidelines.

59. Treatment of PONVWhen N/V occur postoperatively, treatment should be administered with an antiemetic from a pharmacologic class that is different from the prophylactic drug(s) givenIf no prophylactic drug(s) were given, the recommended treatment is a low-dose 5-HT3 receptor antagonistDoses of 5-HT3 RA are lower for treatment than for prophylaxisOndansetron 1mg, Granisetron 0.1mg

60. Treatment of N/V in Disorders of BalanceDisorders of balance include vertigo, dizziness, and motion sicknessThe antihistamine-anticholinergic antiemetics appear to be the most beneficial in this groupThey are thought to act as vestibular depressants and hence can help decrease vertigo in addition to nausea and vomiting

61. Overview: Antiemetic Use During pregnancyUp to 75% of pregnant woman nausea and vomiting to some degree during the first trimesterSymptoms are self-limiting for most women but 1% to 3% develop hyperemesis gravidarumHyperemesis gravidarum is marked by severe N/V and complications requiring hospitalization

62. Prevention and Treatment (Mild N/V in Pregnancy)Taking prenatal vitamins for 3 months prior to conception may reduce the incidence and severity of N/V in pregnancyFirst-line therapy for treatmentPyridoxine (vitamin B6) alone or in combination therapy with doxylamine (an antihistamine)Doxylamine 12.5 to 20mg one to four times a dayPyridoxine 10 to 25mg one to four times a dayCan acquire each separately OTC or the combination by prescriptionTreatment with ginger has shown benefit in reducing nausea and can be considered a nonpharmacologic option

63. Treatment of Severe N/V in Pregnancy or Hyperemesis GravidarumIf dehydrated, the patient should receive IV fluid replacement with thiamineOndansetron 2 to 8mg every 8 hours orally or IV may help to alleviate symptomsFor refractory cases, can treat with methylprednisolone 16mg every 8 hours orally or IV for 3 days followed by a 2 week taper

64. References (Slide 1 of 3)Gravatt L, Donohoe KL, DiPiro CV. Nausea and Vomiting. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; 2017.Sharkey KA, Wallace JL. Treatment of Disorders of Bowel Motility and Water Flux; Anti-Emetics; Agents Used in Biliary and Pancreatic Disease. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e. New York, NY: McGraw-Hill; 2011.

65. References (Slide 2 of 3)Gan TJ, Diemunsch P, Habibi AS, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2014; 118: 85-113.Scorza K, Williams A, Phillips JD, et al. Evaluation of nausea and vomiting. Am Fam Physician 2007; 76: 76-84.Practice Bulletin Summary No. 153: Nausea and Vomiting of Pregnancy. Obstet Gynecol. 2015; 126: 687-688.

66. References (Slide 3 of 3)Micromedex Solutions.  Truven Health Analytics, Inc. Ann Arbor, MI.  Accessed November 6, 2016.Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc. Accessed November 6, 2016.