PHARM 345 Nausea and Vomiting Lecture Notes 2025 PDF

PHARM 345 Nausea and Vomiting Dr. Rene Breault Winter 2025 Slides adapted with permission from Dr. Tara Leslie and Dr. Nese Yuksel 1 Reminder: Review Course Orientation Video...

PHARM 345 Nausea and Vomiting Dr. Rene Breault Winter 2025 Slides adapted with permission from Dr. Tara Leslie and Dr. Nese Yuksel 1 Reminder: Review Course Orientation Video 2 Learning Objectives By the end of the two lectures, students will be able to: 1. Describe the etiology and pathophysiology of nausea and vomiting (NV). 2. Compare and contrast the non-pharmacologic and pharmacologic options for NV. 3. Assess patients presenting with symptoms of nausea or vomiting (or both) and carry out the therapeutic approach to management of NV. 4. Identify when it is appropriate to refer patients with NV to an alternate health care provider/setting. 5. With consideration of etiology, patient factors, co-morbidities, and potential drug interactions, provide an appropriate recommendation (pharm and/or non-pharm), develop a suitable monitoring plan (parameters for efficacy/safety and timelines), and provide appropriate education for patients with motion sickness, NV of pregnancy, postoperative NV (PONV), antineoplastic-induced 3 NV, NV in children. Resources Chapter 53: Nausea and vomiting. DiPiro JT ed. 12th edition Pharmacotherapy: A pathophysiologic approach Chapter: Nausea and vomiting. CPhA, Therapeutic Choices CPS (formerly RxTx) Chapter 6: Nausea and vomiting. Mahmoud ed. Patient Assessment in Clinical Pharmacy 4  Case Natalie Natalie is a 32-year old woman (she/her) who is 10 weeks pregnant. Natalie comes to your pharmacy with a 4-week history of nausea. She has no dizziness or light-headedness and reports no diarrhea. Natalie has had a weight loss of around 1 kg in recent weeks. She reports that symptoms are somewhat resolved by eating salty foods. Natalie would like help for the nausea. How would you assess Natalie? 5 What is nausea and vomiting? Definition Nausea Subjective feeling of “impending vomiting” or “need to vomit” Retching Spasmodic contractions of the diaphragm and intercostal muscles (“respiratory muscles”) with epiglottis closed Vomiting (emesis) Forceful oral expulsion of gastric contents ○ GI retroperistalsis ○ often associated with pallor, tachycardia, diaphoresis DIFFERENT than regurgitation (contents rise to the pharynx but not associated with forceful ejection) 6  How does vomiting happen? Vomiting is triggered by afferent impulses to the VOMITING CENTER (VC) (aka emetic center (EC)) Vomiting occurs: Contraction of diaphragm + abdominal muscle. Relaxation of lower esophageal sphincter. Peristalsis reverses direction: ○ pushes stomach contents out of mouth. Soft palate is raised to prevent GI contents going into nasopharynx. Epiglottis closed to prevent pulmonary aspiration. https://sites.google.com/a/mtlstudents.net/homepage/home/pharynx-and-esophagus 7 Afferent Impulses (Stimuli) Chemical signals: Drugs, toxins, or metabolic disturbances (e.g., hypercalcemia, uremia) stimulate the chemoreceptor trigger zone (CTZ), located in the area postrema of the brainstem. Visceral signals: Irritation or distension of the gastrointestinal (GI) tract sends signals via the vagus nerve and splanchnic nerves to the vomiting center. Vestibular input: Motion sickness or inner ear disturbances stimulate the vestibular nuclei (mediated by histamine H1 and acetylcholine M1 receptors). Cortical input: Psychological factors such as anxiety, fear, or disgust, as well as sensory inputs like bad smells or sights, can activate the vomiting reflex. 8  Pathophysiology Key Organ Location Summary Emetic Center / Medulla Oblongata The VC (or EC) receives afferent impulses from the locations listed below. In Vomiting Center (EC or response, the VC (or EC) sends efferent impulses to salivation center, VC) respiratory center, pharyngeal, GI, and abdominal muscles to cause vomiting. Chemoreceptor trigger Area postrema of 4th Chemosensory organ sensitive to chemicals and toxins in blood or CSF zone (CTZ) ventricle of the brain (near When stimulated by chemicals in blood or CSF (such as some medications, connection of brain stem hormones, toxins, noxious substances) the CTZ will send afferent impulses to VC and CSF)- partially outside the BBB and close to VC Central nervous system Cerebral Cortex Cognitive stimulation of the cerebral cortex due to emotions, smells, taste, sight Thalamus can send afferent impulses to VC. Hypothalamus Meninges Vestibular apparatus Ear labyrinth stimulation of the vestibular cochlear nerve (cranial nerve VIII) will stimulate the vestibular nuclei in brain stem, sending afferent messages to VC Visceral Afferents many organs (examples: in response to visceral stimuli (such as medications, trauma, infection), afferent GIT, pharynx, heart) impulses can be sent leading to stimulation of the VC 9  Pathophysiology Emetic reflex involves multiple receptors: Receptor for *Serotonin (5-HT3) *Dopamine (D2) *Acetylcholine (Ach, muscarinic, M1) *Histamine (H1) *Neurokinin-1 (NK-1) – substance P Cannabinoid (CB1) Opioid *neurotransmitter s 10 Pathophysiology of Nausea / Vomiting 11  Neural Pathways that mediate vomiting Malagelada JR et al. Chapter 14: Nausea and Vomiting. In Feldman, Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 9th edition. 12 Etiology 13  Etiology - Causes of Nausea and Vomiting Motion sickness NV of pregnancy (NVP) Postoperative nausea/vomiting (PONV) Medications Antineoplastic Induced Nausea Vomiting (AINV) Radiation Therapy Disease ○ Infections (gastroenteritis) ○ Cardiac ○ Gastrointestinal ○ Metabolic/endocrine causes ○ Central Nervous System ○ Psychiatric Leslie T. Chapter 6. Leslie T. Chapter 6. Patient Assessment in Clinical Pharmacy p8014 Patient Assessment in Clinical Pharmacy p80 Complications of Vomiting Fluid, electrolyte and metabolic alterations. ○ Dehydration, hypotension, hemoconcentration, oliguria, muscle weakness, electrolyte abnormalities, cardiac arrhythmias Aspiration pneumonia Prolonged vomiting: ○ Nutritional deficiencies - malnutrition ○ Esophagitis (inflammation of esophagus) ○ Lacerations at the gastroesophageal junction* ○ Multiple purpuric lesions ○ Dental caries/erosions 15 Approach to NV Three Step Approach 1. Recognize and correct any consequences of the vomiting e.g. dehydration, electrolyte abnormalities 2. Identify underlying cause for NV. 3. Treat/manage underlying cause. If no etiology can be determined use empiric therapy to treat symptoms. Goals of Therapy: 1. Prevent/halt nausea and/or vomiting 2. Prevent complications such as dehydration 3. Improve quality of life 4. Additional goals depending on etiology (eg AINV goal – maintain anticancer therapy schedule) 16 Patient Assessment of NV Assess signs and symptoms: ○ SCHOLAR Gather additional patient information (recent events and long-standing issues) ○ Medical history (acute and chronic) ○ Medication history (new and ongoing) prescription, non-prescription, herbal ○ Social history (including recent experiences) ○ Allergies (food and drug) Physical Exam? Rule out Red Flags (or refer if present) ○ refer if complications present (signs/symptoms of significant dehydration) ○ refer if etiology (cause) requires medical attention 17  SCHOLAR – Symptom-Assessment Mnemonic Questions What specific questions would you ask for NV? Symptom What are the main symptoms? Characteristic What are the symptoms like? History What has happened in the past? What has been done so far? Onset When did it start? Location Where is the problem? Aggravating Factors What made it worse? Remitting Factors What makes it better? 18  Assessment of NV S Symptoms Ask the patient to describe their symptoms Are you experiencing N, V or both? Do you feel any associated sx. Such as abdominal pain, dizziness, fever or diarrhea? Have you noticed any changes in appetite or weight? C Characteristics characteristics such as vomitus appearance, symptom severity, frequency, and timing can help determine cause and identify red flags (blood, or bile) H History Has this happened before? Has anything unusual happened recently? Could you be pregnant? Consider unusual food/drink intake, new or recent medications, travel history, sick contacts, trauma to help determine cause and identify red flags O Onset When did the symptoms begin? Gradual vs sudden? If ongoing, timing? consider implications for timing in relation to exposure to medications, food/drink, illness, travel, last menses consider risk of complications like dehydration if a lot of time has passed L Location n/a A Aggravating What makes the NV start or worsen? Factors triggers such as medications, odors, activities can help identify cause and the type of NV R Remitting Factors Have you tried anything in the past? Additional Information can be found: Chapter 6, Nausea and Vomiting - Patient Assessment in Clinical Pharmacy 19 Algorithm, Figure 3 in Chapter Therapeutic Choices, Nausea and Vomiting, CPS (formerly RxTx) Assessment of NV Types of physical examination: ○ Signs of dehydration dry mucous membranes, increased thirst, reduced urination, weak/dizzy/lightheaded in children - few or no tears when crying, less wet diapers, sunken eyes, skin turgor ○ Abdominal examination abdominal pain/tenderness, abdominal extension ○ Neurologic examination head trauma/concussions, drug overdose, migraines ○ Signs of psychiatric cause anxiety, panic, depression General examination/diagnostic tests to explore or rule out potential causes and/or complications ○ home pregnancy test? 20  Prompt Evaluation Required: Red Flags Altered mental status, neurologic Symptoms of dehydration symptoms, disorientation ○ may need aggressive rehydration with IV fluids ○ intracranial disorder, stroke, or Persistent vomiting complication of dehydration? ○ may be a worrisome infectious Recent head trauma cause and high risk of complications ○ concussion? brain injury? Blood or “coffee-grounds” in vomitus ○ ulcer or other bleeding? Blood in stools (black or tarry) ○ GI bleed? cancer? Severe pain ○ abdominal - appendicitis? pancreatitis? cholecystitis? serious infection? ○ chest - myocardial infarction? ○ pelvis - pelvic inflammatory disease? 21 Other Considerations for Referral Difficulty swallowing Age > 55 Weight loss (unintended) ○ nutritional deficiency? Signs/symptoms of prolonged vomiting 22  Case Natalie What are the treatment options? 23 Approach to Treatment 1. What is the cause? 2. How severe are the symptoms? 3. If pharmacotherapy is indicated, can the patient swallow oral formulations? 4. What has already been tried with what success? 24 Non-pharmacologic Therapy for NV 25 Non-Pharmacologic Therapy General Approaches: Adequate hydration Avoid noxious odors/foods that cause nausea Eat frequent, small meals Decrease physical activity Gear approach to cause/etiology of NV ○ If labyrinth changes produced by motion then assume stable physical position 26 Non-Pharmacologic Therapy Maintain fluid intake: ○ Depends on amount of vomiting ○ Normal amounts - adults need 1-3 L of total water intake Amount required will depend on amount lost with vomiting (and/or diarrhea) ○ Moderate or severe vomiting may require electrolyte replacement: E.g. oral rehydration solution (ORS) - will be discussed in diarrhea lecture 27  Youtube video to perform acupressure for N/V by MD Non-pharmacologic Therapy Anderson Cancer Center: https://www.youtube.com/watch?v=8dhvkGGTnHU Acupressure ○ Sixth point along the pericardial meridian (P6) ○ Nei Guan (“inner guard”) ○ approximately three finger breadths below the wrist on the inner forearm between the two tendons ○ 3 - 5 minutes of pressure every 4 hours ○ NVP, motion sickness, AINV, PONV Acupuncture 28 http://www.sea-band.com/why-seaba Non-pharmacological Therapy Acupressure Wristbands: ○ Seabands®, others ○ Have not been shown to be effective in motion sickness Less effective than manual pressure 29 Antiemetics Overview 30 Remember Pharmacology … For mechanism/pharmacology of antiemetics please refer to your pharmacology. This lecture will build on concepts and focus on therapeutics of antiemetics (role, doses, side Rang & Dale’s Pharmacology 8th edition 31 effects, etc)  Histamine (H1)-Receptor Antagonists Role: management of motion sickness, vertigo, mild gastroenteritis Agents in Canada Available Route Adult Dose dimenhydrinate (GravolTM,, OTC (Schedule III) Oral, IM, Rectal 50 – 100 mg q4 – 6h generics) Schedule II (po, rectal, im) prn (injectable) 100 mg long acting q8-12h diphenhydramine OTC Oral 25 – 50 mg q6 -8h prn (BenadrylTM, generics) hydroxyzine (generics) Prescription Oral 25 – 100 mg bid – tid prn 32 Histamine (H1)-Receptor Antagonists Side effects: Note: blocks H1 receptors, but also has anticholinergic effects ○ Drowsiness ○ Confusion ○ Dry mouth ○ Blurred vision ○ Urinary retention ○ Constipation Elderly are increased risk of anticholinergic side effects 33 Muscarinic Receptor Antagonists (anticholinergics) Scopoloamine (Transderm-V®) - Schedule III - D/C Role: motion sickness Side effects: sedation, confusion, dry mouth, blurred vision, constipation, rash, urinary retention Do not use in children ( 2 risk factors or history of PONV Moderate risk (2 risk factors) – consider 1 – 2 anti-emetics Severe risk (>3-4 risk factors) – 2 anti-emetics before surgery PONV Prophylaxis therapies: 5-HT3 RA (granisetron, ondansetron) Dexamethasone Dimenhydrinate Phenothiazines (promethazine) NK1 RA (aprepitant, fosaprepitant) https://gas.careteamapp.com/Apfel 67 Postoperative NV (PONV) Factors to consider in selection of therapy for PONV: ○ Timing of administration ○ Consider goal of prevention vs treatment of PONV ○ Consider side effect profile ○ Cost and formulary issues Examples: ○ 5HT3 RA (eg ondansetron) – administered at the end of the surgical procedure to PREVENT PONV, but is often order prn after surgery as well to treat PONV. Remember that 5HT3 antagonists can cause constipation (and so can opiates) ○ Aprepitant has good efficacy for prevention when administered within 3 hours of anesthesia. However, it is quite costly and may access may be restricted (hospital formularies) ○ Dexamethasone – administered after induction of anesthesia for prevention, but may be a less favourable choice after surgery (treatment) due to side effect profile (hyperglycemia, infection risk, sleep disturbances) ○ Antidopaminergic drugs – consider risk of QT prolongation – is this an important factor for PMH and type of surgery? 68 Antineoplastic Induced Nausea and Vomiting 69 Antineoplastic Induced NV (AINV) - Classifications Acute AINV ○ Occurs within the first 24 hours after exposure to antineoplastic agents ○ Onset within a few minutes to several hours after drug administration ○ Intensity peaks after 5-6 hours ○ Resolves in approximately 24 hours Delayed AINV ○ Onset is 24 hours or more after chemo administration ○ Common with Cisplatin and Cyclophosphamide with Doxorubicin (AC combination) ○ Maximal intensity at 48-72 hours post chemo and can last 6-7 days ○ More common than acute (approximately 68% vs 34%) 70 AINV - Classifications Anticipatory AINV ○ Occurs before patients receive their next chemotherapy treatment ○ Considered a conditioned response Breakthrough AINV ○ Nausea or vomiting that occurs despite prophylactic treatment and/or requires rescue with antiemetic agents Refractory AINV ○ Nausea and/or vomiting that occurs during subsequent treatment cycles when antiemetic prophylaxis and/or rescue have failed in earlier cycles 71 Emetic Risk of Antineoplastic Agent/Regimen Antineoplastic agents are categorized by “Emetic Risk” The emetic risk is the risk to cause vomiting in patients that don’t receive prophylaxis. High (>90%), moderate(30-90%), low (10-30%), minimal 1500mg/m2 (HEC) Anthracycline + Cyclophosphamide (AC combo) Carboplatin or Oxaliplatin Moderate Emetic Risk 30-90% Cyclophosphamide < 1500mg/m2 (MEC) Anthracyclines (Doxorubicin, Epirubicin) Docetaxel or Paclitaxel Low Emetic Risk 10-30% Fluorouracil Minimal Emetic Risk < 10% Vincristine, Vinorelbine 73 Other factors affecting risk of AINV Biological Sex - women at higher risk than men Past alcohol consumption - high alcohol consumption (past or present alcoholism) is associated with less nausea History of motion sickness/NVP - Positive history of motion sickness and/or NVP is associated with higher risk for CINV Age - younger age (2 years (note: