Nausea & Vomiting Notes & Objectives PDF

Nausea & Vomiting Therapeutic Principles of Self-Care Leticia Shea, PharmD, BCACP Objective Explain why antihistamines may provide some benefit in minimizing or preventing nausea & vomiting based on how N/V originates from the brainstem. ...

Nausea & Vomiting Therapeutic Principles of Self-Care Leticia Shea, PharmD, BCACP Objective Explain why antihistamines may provide some benefit in minimizing or preventing nausea & vomiting based on how N/V originates from the brainstem.  Anticipation, Central Nervous Motion sickness Fear, Pain, System Smell… Cortex Hypothalamus Meninges Thalamus Vestibular apparatus ❑ H1 ❑ M1 Gastrointestinal Tract ❑ Chemoreceptors Vomiting Center ❑ 5HT3 Chemoreceptors ❑ Mechanoreceptors ❑ H1 ❑ M1 Chemoreceptor ❑ 5HT3 Trigger Zone (CTZ) ❑ NK1 CTZ ❑ Chemoreceptors ❑ D2 ❑ 5HT3 Vomiting center ❑ NK1 Parasympathetic and motor efferent activity Objective Identify the receptors that 1st generation antihistamines interact that support the inhibition and/or prevention of N/V. Objective Identify the types of nausea and vomiting that may be managed with what is available OTC. N/V OTC ◦ Prevention of motion sickness ◦ Treatment of motion sickness In concert with OBGYN recommendations ◦ N/V associated with pregnancy* and awareness Drugs Objective Explain why 2 generation nd antihistamines are not likely provide any mechanism towards inhibiting or minimizing N/V. Objective Identify the 1 generation st antihistamines indicated for managing or preventing N/V. Objective Differentiate between the 1st generation antihistamines. Objective Identify when you would select one [1st generation antihistamine] over the other for the management and/or prevention of N/V.  OTC Antihistamines in review… Second generation First generation (Sedating) ◦ fexofenadine (60–120 mg) (Allegra®) ◦ Diphenhydramine ◦ levocetirizine (5 mg) (Xyzal®) ◦ Doxylamine ◦ loratadine (10 mg) (Claritin®) ◦ cetirizine (10 mg) (Zyrtec) ◦ Dimenhydrinate ◦ Brompheniramine Sedation Comparison KEY Highly sedating ◦ Dexbrompheniramine Moderately sedating Mildly sedating ◦ Chlorpheniramine Sedation possible ◦ Meclizine Sedation unlikely No sedation  OTC Antihistamines in review… First generation (Sedating) Approved for prevention of motion sickness ◦ Diphenhydramine (Benadryl®) Approved for N/V associated with pregnancy when given with pyridoxine- ◦ Doxylamine (Unisom®) Vitamin B6 ◦ Dimenhydrinate (Dramamine®) Treatment and prevention of N/V associated with motion sickness ◦ Brompheniramine ◦ Dexbrompheniramine ◦ Chlorpheniramine Treatment and prevention of N/V associated with motion sickness ◦ Meclizine (Dramamine “Less Drowsy”®)  Anticipation, Central Nervous Motion sickness Fear, Pain, System Smell… Cortex 1st generation Hypothalamus antihistamines Meninges Thalamus Vestibular apparatus antiemetic ❑ H1 mechanisms ❑ M1 ◦ H1 receptors are located in the vomiting center and Gastrointestinal vestibular apparatus Tract ◦ 1st gen antihistamines also ❑ Chemoreceptors Vomiting Center Chemoreceptors ❑ 5HT exhibit 3 antimuscarinic ❑ H1 ❑ Mechanoreceptors activity at the same sites. ❑ M1 Chemoreceptor ❑ 5HT3 ◦ Antihistamines must cross Trigger Zone (CTZ) ❑ NK1 the blood-brain barrier to CTZ ❑ Chemoreceptors ❑ D2 affect the central nervous ❑ 5HT3 system ❑ NK1 Vomiting center Parasympathetic and motor efferent activity Objective Create recommendations for the successful execution of a prevention of motion sickness action plan, including when a patient should initiate the therapy, which therapy they should select, and how often they may re- administer. Motion Sickness ◦ Dimenhydrinate (Dramamine®): for treatment of N/V; for prophylaxis of N/V ◦ Diphenhydramine (Benadryl®) FDA-approved for N/V prevention ◦ Doxylamine (Unisom®) ◦ Off-label use for the treatment of nausea ◦ Meclizine (“Non-drowsy Dramamine®”) ONLY for those > 12 years of age. Take 30-60 minutes prior to travel and continue as needed for time of motion (q 6-8 hours) ◦ Children 2-5 years of age: 12.5mg-25mg 30 to 60 minutes prior to travel. Then take 12.5- 25mg every 6-8 hours as needed. (Max 75mg/day) ◦ Children 6-12 years of age: Take 25-50mg 30 to 60 minutes prior to travel. Then take 25-50mg every 6 hours as needed. (Max 150mg/day) ◦ Children & Adults > 12 years: Take 50mg 30 to 60 minutes prior to travel. Then take 50mg- 100mg every 6 hours as needed. (Max 400mg/day)  DRAMAMINE FOR KIDS® Children 2-5 years of age: 12.5mg-25mg 30 to 60 minutes prior to travel. Then take 12.5- 25mg every 6-8 hours as needed. (Max 75mg/day) Children 6-12 years of age: Take 25-50mg 30 to 60 minutes prior to travel. Then take 25-50mg every 6 hours as needed. (Max 150mg/day) Dimenhydr inate 25mg tablets Age-appropriate antihistamines for N/V > 12 years Dimenhydrinate 6-12 years Diphenhydramine Dimenhydrinate Meclizine 2-6 years Diphenhydramine Dimenhydrinate  Diphenydramine Appropriate Dosing ◦ Ages 6-12 years: 12.5 to 25mg every 4-6 hours (Max 150mg/day) ◦ Liquid Benadryl® and (liquid generics) come in 12.5mg/5mL ◦ Chewable tablets come in 12.5mg tablets There is currently also an adult chewable tablet that comes as a 25mg tablet, so be careful in ensuring you are selecting a chewable tablet for the right age. Meclizine “less drowsy” ❑ 25 to 50 mg PO 1 hour before travel. ❑ May repeat dose every 24 hours as needed. ❑ Start at the lowest dosage for older adults as they may be more sensitive to anticholinergic effects  Antihistamines No brain penetration Non/Less Sedating Sedating Loratidine High sedation Desloratidine Milder sedation Dimenhydrinate Fexofenadine Cetirizine Meclizine Diphenhydramine Levocetirizine Doxylamine Objective Explain the difference in tablet strengths for Dramamine (dimenhydrinate) original and Dramamine for kids. Objective Explain the appropriate dosing of Benadryl (diphenhydramine) for children vs. Adults in the setting of preventing or managing N/V. Objective Identify when [1st gen] antihistamines are age- appropriate, meaning at what can each 1st gen indicated for N/V be used? Objective Counsel on methods to manage/prevent side effects associated with 1 generation st antihistamines. Objective Explain the reason why 1 st generation antihistamines should not be utilized in individuals with BPH. Objective Identify populations at higher risk of adverse events with the use of 1st generation antihistamines. Side effects/Precautions with 1st gen antihistamines First Generation Antihistamines Precautions ◦ Dimenhydrinate ◦ Because of anticholinergic effects (dry eyes, dry mouth…) these may thicken bronchial secretions and should be used ◦ Diphenhydramine with caution in patients with asthma, COPD and emphysema ◦ Doxylamine ◦ Mydriatic effects (pupil dilation) can exacerbate angle closure ◦ Brompheniramine glaucoma ◦ Urinary retention, a common side effect exhibited with ◦ Dexbrompheniramine drugs that have anticholinergic activity, may ◦ Chlorpheniramine exacerbate/worsen benign prostatic hypertrophy (BPH) ◦ Anticholinergic = drowsiness, constipation, dizziness, fall risk ◦ Meclizine (elderly), dry mouth, dry eyes, confusion (elderly) Understanding BPH ◦ Why are 1st generation antihistamines a concern in BPH? ◦ In BPH the prostate enlarges which may result in difficulty urinating, with the term “Lower urinary tract symptoms” used to accommodate several symptoms presenting with this condition: ◦ A hesitation before urine flow starts despite the urgency to urinate ◦ Straining when urinating ◦ Weak or intermittent urinary stream ◦ A sense that the bladder has not emptied completely ◦ Dribbling at the end of urination or leakage afterward ◦ Antihistamines (1st generation) and other anticholinergics prevent the bladder muscle from contracting, thus resulting in urinary retention. Objective Explain the relationship between diphenhydramine (Benadryl®) and the CYP2D6. Objective Describe the proposed mechanism for Emetrol®.  Diphenhydramine CYP 2D6 ◦ CYP2D6 inhibitor ◦ Caution with use of other drugs metabolized through CYP2D6 ◦ (Approximately ~25% of medications on the market)! ◦ Psychiatric medications examples: fluoxetine (Prozac®), paroxetine (Paxil®), bupropion, duloxetine (Cymbalta®), venlafaxine (Effexor®) ◦ Opiates examples: codeine, hydrocodone, oxycodone ◦ Beta-blockers: carvedilol, metoprolol ◦ Other OTCs: chlorpheniramine, dextromethorphan ◦ Others: tramadol, trazadone THE OTHER “DRUG” Phosphorated Carbohydrate Solution (PCS) ◦ > 12 years/Adult dosing 15–30 mL every 15 minutes until distress subsides. Taking more than 5 doses in 1 hour is not recommended. ◦ Children 2–12 years can take 5–10 mL every 15 minutes. Dosing should not be diluted, and other fluids should be avoided immediately before or after taking PCS. ◦ Possible adverse effects of PCS are stomach pain and diarrhea. ◦ Each 5 mL of PCS contains 3.74 g of total sugar Phosphorated Carbohydrate Solution (PCS) ◦ This solution is a mixture of dextrose (glucose), levulose (fructose), and phosphoric acid. ◦ The hyperosmolar solution is believed to relieve N/V by direct local action on the GI tract wall that may decrease smooth muscle contraction and delay gastric emptying time. ◦ Last studied: 1953 ◦ Efficacy: remains to be determined ◦ Safety: Likely safe for most, however caution should be instituted for those with diabetes and avoided in those unable to metabolize fructose (hereditary fructose intolerance) ◦ Instructions for use: don’t dilute Alternative options Objective Counsel a patient on how they can perform acupressure for the prevention or management of N/V as described in the video. Objective Explain how acupuncture is utilized for the management of nausea and vomiting. Acupuncture, Acupressure Acupressure Video ◦ https://www.youtube.com/watch?v=8dhvkGGTnHU Acupuncture Video ◦ https://www.youtube.com/watch?v=XWdDMrS8WlA Objective List the “active” components found in ginger, list their suspected receptor activity, and explain how it may be considered in the management of N/V. Ginger ❖ Gingerol ❖ Shogaol ❖ Zingerone ❖ 5HT3 ❖ NK1 ❖ may provide benefit in the delay in nausea onset and decreasing the severity This P hoto by Unknown Author is license d under CC BY-NC-ND Nonpharmacological Objective Explain the “doses” recommended for children exhibiting dehydration. Oral Rehydration Solution(ORS) ◦ Minimal Dehydration ◦ Children weighing less than 10kg: 60-120mL after each vomiting episode ◦ Children weighing 10 kg or more should be given 120–240 mL per episode ◦ Mild to moderate dehydration ◦ 50-100mL/kg over 3-4 hours ◦ Severe dehydration ◦ Referred to ER for IV rehydration Objective Review the symptoms associated with mild, moderate, and severe dehydration. Review the video link at the bottom of the page so that you can explain why these symptoms exist in the setting of dehydration.  P resentation Mild (3-5% ) Moderate (6-9% ) Severe (>10% ) Pulse Ful, normal rate Rapid* Rapid* and weak or absent Systolic pressure Normal Normal to low Low Deep, tachypnea or decreased Respirations Normal Deep, rate may be increased to absent Buccal mucosa Tacky or slightly dry Dry Parched Anterior fontanelle Normal Sunken Markedly sunken Eyes Normal Sunken Markedly sunken Tears (in infants) Present Decreased Absent Skin turgor Normal Reduced Tenting Skin temperature and Normal Cool Cool, mottled, acrocyanosis appearance Urine output Normal or mildly reduced Markedly reduced Anuria Systemic signs Increased thirst Listlessness, irritability Grunting, lethargy, coma * Tachycardia may be the first sign of hypovolemic shock in infants https://www.youtube.com/watch?v=3vVivQMLCGA Shane AL, et al. Clin Infect Dis. 2017 Nov 29;65(12):e45-e80. Oral Rehydration Solution (ORS) ◦ ORSs should be offered 10 minutes after the last episode of vomiting and provided in small increments. ◦ In general, 5 mL (1 teaspoon) of ORS may be given to children every 5 minutes, and 15 mL may be given to older children and adults every 5 minutes Complications Objective Review the complications presented associated with N/V. Possible acute complications of vomiting ◦ Esophageal tears (Mallory-Weiss syndrome) ◦ Aspiration ◦ Malnutrition ◦ Electrolyte and/or acid base abnormalities  Mallory-Weiss Syndrome ◦ Mallory-Weiss syndrome is one of the common causes of acute upper gastrointestinal bleeding, characterized by the presence of longitudinal superficial mucosal lacerations (Mallory-Weiss tears). ◦ These tears occur primarily at the gastroesophageal junction; they may extend proximally to involve the lower or even mid esophagus and at times extend distally to involve the proximal portion of the stomach. ◦ Heavy alcohol ingestion is one of the most prevalent predisposing factors; it was initially described in those with alcohol use disorder, but it can occur in anyone who This Photo by Unknown Author is licensed under CC BY-SA vomits forcefully.  Aspiration ◦Aspiration occurs when a person accidentally inhales particles into their airway ◦Aspiration is a major medical concern because it may lead to pneumonia, This P hoto by Unknown Author is license d under CC BY-SA-NC infection, pulmonary edema or other issues Objective Explain the processes that may take place in the setting of N/V that may result in metabolic alkalosis. Metabolic Alkalosis Acid Base Electrolyte Imbalance ◦ Repetitive vomiting may cause: ◦ Hypovolemia ◦ Hypokalemia K+ ◦ Hypochloremia Cl- ◦ Metabolic alkalosis Cl- H+ ◦ Gastric stomach fluid contains potassium and HCl, so excessive vomiting can lead to the loss of these electrolytes References 1. Heckroth M, Luckett RT, Moser C, Parajuli D, Abell TL. Nausea and Vomiting in 2021: A Comprehensive Update. J Clin Gastroenterol. 2021 Apr 1;55(4):279-299. 2. Zhong W, Shahbaz O, Teskey G, Beever A, Kachour N, Venketaraman V, Darmani NA. Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems. Int J Mol Sci. 2021 May 28;22(11):5797. doi: 10.3390/ijms22115797. PMID: 34071460; PMCID: PMC8198651. 3. Jin Z, Lee G, Kim S, Park CS, Park YS, Jin YH. Ginger and its pungent constituents non-competitively inhibit serotonin currents on visceral afferent neurons. Korean J Physiol Pharmacol. 2014 Apr;18(2):149-53. doi: 10.4196/kjpp.2014.18.2.149. Epub 2014 Apr 3. PMID: 24757377; PMCID: PMC3994302. 4. Qian QH, Yue W, Chen WH, Yang ZH, Liu ZT, Wang YX. Effect of gingerol on substance P and NK1 receptor expression in a vomiting model of mink. Chin Med J (Engl). 2010 Feb 20;123(4):478-84. PMID: 20193490. 5. Streitberger K, Ezzo J, Schneider A. Acupuncture for nausea and vomiting: an update of clinical and experimental studies. Auton Neurosci. 2006 Oct 30;129(1-2):107-17. doi: 10.1016/j.autneu.2006.07.015. Epub 2006 Sep 1. PMID: 16950659. 6. Li, QW., Yu, MW., Wang, XM. et al. Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single- blind, randomized, sham-controlled clinical research. Chin Med 15, 57 (2020). https://doi.org/10.1186/s13020-020-00333-x 7. Ongel E, Erdag E, Adiyeke E, et al. Acupressure versus ondansetron usage for postoperative nausea