Lecture 13 Gastrointestinal Disorders Nausea and Vomiting University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY II PHCY 410 Lecture 13 Gastrointestinal Disorders Nausea and Vomiting Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

Course Outcomes Upon completion of this lecture the students will be able to Describe etiology, clinical manifestations and diagnosis of vomiting, diarrhea and constipation. Develop skills for monitoring drug therapy and patient education in patients with vomiting, diarrhea and constipation. Explain drug related problems and develop pharmaceutical care plan in patients with vomiting, diarrhea and constipation.

DEFINITION Nausea is usually defined as the inclination to vomit or as a feeling in the throat or epigastric region alerting an individual that vomiting is imminent. Vomiting is defined as the ejection or expulsion of gastric contents through the mouth, often requiring a forceful event. CAUSES Gastrointestinal Mechanisms Mechanical gastric outlet obstruction    Peptic ulcer disease    Gastric carcinoma    Pancreatic disease Cardiovascular Diseases    Acute myocardial infarction    Congestive heart failure    Shock and circulatory collapse

Neurologic Processes Midline cerebellar hemorrhage, Increased intracranial pressure Migraine headache, Vestibular disorders, Head trauma Metabolic Disorders Diabetes mellitus (diabetic ketoacidosis), Renal disease (uremia), Addison’s disease Psychiatric causes Psychogenic vomiting, Anxiety disorders, Anorexia nervosa Therapy-induced Causes Cytotoxic chemotherapy, Radiation therapy ,Opiates, Antibiotics, Theophylline preparations , Digitalis preparations, Anticonvulsant preparations Drug withdrawal Opiates, Benzodiazepines Miscellaneous causes Pregnancy Noxious odors Operative procedures

PATHOPHYSIOLOGY The three consecutive phases of emesis include nausea, retching, and vomiting. Nausea, the imminent need to vomit, is associated with gastric stasis. Retching is the labored movement of abdominal and thoracic muscles before vomiting. Vomiting, the forceful expulsion of gastric contents due to gastrointestinal (GI) retroperistalsis. Vomiting is triggered by afferent impulses to the vomiting center, a nucleus of cells in the medulla.

Impulses are received from sensory centers, such as the chemoreceptor trigger zone (CTZ), cerebral cortex, and visceral afferents from the pharynx and GI tract. When excited, afferent impulses are integrated by the vomiting center, resulting in efferent impulses to the salivation center, respiratory center, and the pharyngeal, GI, and abdominal muscles, leading to vomiting. The CTZ, located in the area postrema of the fourth ventricle of the brain, is a major chemosensory organ for emesis and is usually associated with chemically induced vomiting.

NONPHARMACOLOGIC MANAGEMENT For patients with simple complaints, perhaps related to food or beverage consumption, avoidance or moderation of dietary intake may be preferable. Nonpharmacologic interventions are classified as behavioral interventions and include relaxation, biofeedback, self-hypnosis, cognitive distraction, guided imagery, and systematic desensitization. Psychogenic vomiting may benefit from psychological interventions.

PHARMACOLOGIC MANAGEMENT Antiemetic drugs (over-the-counter [OTC] and prescription) are most often recommended to treat nausea and vomiting. Certain patients, oral medications may be inappropriate because of their inability to retain any appreciable oral ingestion. In these patients, the rectal or injectable route of administration might be preferred. For most conditions, a single-agent antiemetic is preferred. For those patients not responding to such therapy and those receiving highly emetogenic chemotherapy, multiple-agent regimens are usually required.

Antacids Single or combination OTC antacid products, especially those containing magnesium hydroxide, aluminum hydroxide, and/or calcium carbonate, may provide sufficient relief from simple nausea or vomiting, primarily through gastric acid neutralization. Antihistamines, Anticholinergics Histamine2 antagonists (cimetidine, famotidine, nizatidine, ranitidine) may be used in low doses to manage simple nausea and vomiting associated with heartburn. Antiemetic drugs from the antihistaminic-anticholinergic category may be appropriate in treatment of simple symptomology. Adverse reactions include drowsiness or confusion, blurred vision, dry mouth, urinary retention, and possibly tachycardia, particularly in elderly patients.

Phenothiazines (Promethazine, Prochlorperazine) Phenothiazines are most useful in patients with simple nausea and vomiting or in those receiving mildly emetogenic doses of chemotherapy. Rectal administration is most preferred when parenteral administration is impractical or oral medications cannot be retained. In many patients, low doses of phenothiazine drugs may not be effective, while larger doses may produce unacceptable risks. Corticosteroids Dexamethasone have been used successfully in the management of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV) with few problems. It is used either as a single agent or in combination with selective serotonin reuptake inhibitors (SSRIs).

Metoclopramide Metoclopramide increases lower esophageal sphincter tone, aids gastric emptying, and accelerates transit through the small bowel, possibly through the release of acetylcholine. Because the adverse reactions to metoclopramide include extrapyramidal effects, IV diphenhydramine, 25 to 50 mg, should be administered prophylactically or provided on-call for its anticipated need. Benzodiazepines Benzodiazepines (particularly lorazepam) represent the best of the therapeutic alternatives in the treatment of anticipatory nausea and vomiting.

Substance P/Neurokinin 1 Receptor Antagonists Aprepitant is indicated as part of a multiple drug regimen for prophylaxis of nausea and vomiting associated with high-dose cisplatin-based chemotherapy. Selective Serotonin Receptor Inhibitors (Ondansetron, Granisetron, Dolasetron, and Palonosetron) SSRIs (dolasetron, granisetron, ondansetron, and palonosetron) act by blocking presynaptic serotonin receptors on sensory vagal fibers in the gut wall.

CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING Prophylaxis of Chemotherapy-Induced Nausea and Vomiting Patients receiving chemotherapy that is classified as being of high emetic risk should receive a combination antiemetic regimen containing three drugs on the day of chemotherapy administration (day 1)—an SSRI plus dexamethasone plus aprepitant. Moderate emetic risk should receive a combination antiemetic regimen containing an SSRI plus dexamethasone on day 1. Dexamethasone alone in for low emetic risk.

Treatment of Chemotherapy-Induced Nausea and Vomiting Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. Aprepitant and dexamethasone can be used on the 2 days following administration of high emetic risk chemotherapy.

POSTOPERATIVE NAUSEA AND VOMITING (PONV) Selective serotonin antagonists are very effective in the prevention of postoperative nausea and vomiting but are much more expensive than alternative agents. SSRIs in doses of dolasetron 12.5 mg, granisetron 0.1 mg, ondansetron 1 mg, or tropisetron 0.5 mg are recommended in patients who experience PONV despite prophylactic dexamethasone. RADIATION-INDUCED NAUSEA AND VOMITING (RINV) Patients receiving total or hemibody irradiation or single-exposure, high-dose radiation therapy to the upper abdomen should receive prophylactic doses of granisetron 2 mg or ondansetron 8 mg. Preventive therapy with an SSRI and dexamethasone is recommended in patients receiving total-body irradiation.

DISORDERS OF BALANCE Antihistaminic–anticholinergic agents. Scopolamine is commonly used to prevent nausea or vomiting caused by motion. ANTIEMETIC USE DURING PREGNANCY Initial management of nausea and vomiting of pregnancy often involves dietary changes and/or lifestyle modifications. Pyridoxine (10 to 25 mg one to four times daily) is recommended as first line therapy. If symptoms persist, addition of a histamine-1 receptor antagonist, such as dimenhydrinate, diphenhydramine, or meclizine, is recommended.

ANTIEMETIC USE IN CHILDREN For children receiving chemotherapy of high or moderate risk, a corticosteroid plus SSRI should be administered. The best doses or dosing strategy has not been determined. For nausea and vomiting associated with pediatric gastroenteritis, there is greater emphasis on rehydration measures than on pharmacologic intervention.