Drugs for Gastrointestinal Tract Disorders PDF

Group 4 Gastrointestinal Drugs  OVERVIEW GASTROINTESTINAL SYSTEM  OVERVIEW GASTROINTESTINAL SYSTEM 1. Oral Cavity 2. Esophagus 3. Stomach 4. Small Intestine 7. Anus 6. Rectum 5. Large Intestine ...

Group 4 Gastrointestinal Drugs  OVERVIEW GASTROINTESTINAL SYSTEM  OVERVIEW GASTROINTESTINAL SYSTEM 1. Oral Cavity 2. Esophagus 3. Stomach 4. Small Intestine 7. Anus 6. Rectum 5. Large Intestine  OVERVIEW GASTROINTESTINAL SYSTEM The Gastrointestinal (GI) system, or GI tract begins The small intestine runs from the stomach's pyloric at the oral cavity and ends at the anus. sphincter to the cecum's ileocecal valve. Most drug absorption occurs in the duodenum, while lipid-soluble The oral cavity or mouth processes by breaking up drugs and alcohol are absorbed in the stomach. The food in smaller pieces adding saliva, and swallowing duodenum releases secretin to reduce gastric acid and occurs in the pharynx(throat). cholecystokinin to stimulate pancreatic enzymes and bile. These, along with bile and enzymes, break down nutrients for absorption. The esophagus is a tube that extends from the pharynx to the stomach, is composed of striated The stomach is a hollow organ that lies between the muscles in its upper portion and smooth muscle in esophagus and the intestine. It can hold 1000 to its lower portion. There are two sphincters, the 2000ml of gastric contents and empties in 2 to 6 superior and the lower esophageal sphincters. hours, depending on gastric content and motility.  OVERVIEW GASTROINTESTINAL SYSTEM The large intestine accepts undigested material from the small intestine from the small intestine, absorbs water, secretes mucus, and with peristaltic contractions moves the remaining intestinal contents to the rectum for elimination. Defecation completes the process through the anus.  DRUGS FOR GASTROINTESTINAL TRACT DISORDERS 01. 02. Nonpharmacologic Nonpharmacologic measures measures Nonprescription antiemetics Travelers’ Diarrhea VOMITING Prescription antiemetics Emetics DIARRHEA Antidiarrheals 03. Nonpharmacologic measures CONSTIPATION Laxatives DRUGS FOR GASTROINTESTINAL TRACT DISORDERS 04.ANTIULCERDRUGS Helicobacter pylori Histamine2 blockers Gastroesophageal reflux disease Proton Pump Inhibitors Tranquilizers Pepsin Inhibitors Anticholinergics Prostaglandin Analogue Antiulcer Antacids Drugs DRUGS RELATED TO GI TRACT PROBLEMS ANTIEMETICS EMETICS ANTIDIARRHEALS LAXATIVES VOMITING GI TRACT DISORDERS  EMESIS It is the involuntary forceful expulsion of gastric contents. Causes: Viral & Motion Food Bacterial Surgery Pregnancy Sickness Intolerance Infection Effects of Disturbances of Nausea Pain Shock the middle ear selected drugs Radiation (antineoplastics, that affect antibiotics) equilibrium DRUGS RELATED TO EMESIS? ANTIEMETICS EMETICS ANTIDIARRHEALS LAXATIVES ANTIEMETICS Effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of other medications. However, these can mask the underlying cause of vomiting if taken without knowing the cause of vomiting. PHYSIOLOGY OF VOMITING 2 Major Cerebral Centers 1. Vomiting center 2.Chemoreceptor Trigger Zone (CTZ) PHYSIOLOGY OF VOMITING Vomiting center PHYSIOLOGY OF VOMITING CTZ (Area Postrema) PHYSIOLOGY OF VOMITING MOTION SICKNESS PHYSIOLOGY OF VOMITING MOTION SICKNESS PHYSIOLOGY OF VOMITING  NONPHARMACOLOGIC MEASURES The nonpharmacologic methods of decreasing nausea and vomiting include these administrations: Clear liquid (water) Weak tea Flat soda Gelatin Gatorade Pedialyte (for use in children) Crackers and dry toast Intravenous (IV) fluids (for severe cases) 2 MAJOR GROUPS OF ANTIEMETIC DRUGS NONPRESCRIPTION ANTIEMETICS PRESCRIPTION ANTIEMETICS NONPRESCRIPTION PRESCRIPTION ANTIEMETICS ANTIEMETICS Can be purchased as over-the-counter These medications should be prescribed by a (OTC) drugs. healthcare provider based on the underlying Frequently used to prevent motion sickness cause of nausea and vomiting, the patient's Minimal effect on controlling severe medical history, and potential drug vomiting, due to: interactions. anticancer agents (antineoplastic) radiation Antihistamine & Anticholinergic Dopamine Antagonist toxins Phenothiazine Antiemetics ANTIHISTAMINE Butyrophenes Dimenhydrinate Benzodiazepines Cyclizine hydrochloride Inhibit Serotonin (5-HT3) receptor antagonist Meclizine hydrochloride vestibular Glucocorticoids (Corticosteroids) Diphenhydramine stimulation in the middle ear Cannabinoids hydrochloride Miscellaneous antiemetics  NONPRESCRIPTION ANTIEMETICS Can be purchased as over-the-counter (OTC) drugs. Frequently used to prevent motion sickness Minimal effect on controlling severe vomiting, due to: anticancer agents (antineoplastic) radiation toxins  NONPRESCRIPTION ANTIEMETICS Mr. Steel plans to travel to Argao by bus and he usually experiences motion sickness. As a nursing student, when is the best time to take an antiemetic drug to relieve what he is feeling?  NONPRESCRIPTION ANTIEMETICS ANSWER: Mr. Steel should take the drug 30 minutes before travel. These drugs are not effective in relieving motion sickness if taken after vomiting.  NONPRESCRIPTION ANTIEMETICS SELECTED ANTIHISTAMINE: Motion Sickness DRUG ROUTE AND DOSAGE USES AND CONSIDERATIONS Indication: For prevention and treatment of nausea, vomiting, dizziness CYCLIZINE A - PO: 50 mg tablet; every 4-6hrs; 30 min before Contraindication: Avoid concurrent alcohol use HYDROCHLORIDE travel; max: 200mg/d Side Effect: Drowsiness, blurred vision. fatigue, dry mouth, anorexia, constipation, nasal dryness Indication: To prevent and treat motion sickness, A - PO: 50 mg 30-60 min before travel or activity; dizziness, nausea, and vomiting maintenance: 50-100mg every 4-6hr PRN; max: DIMENYHDRINATE Side Effect: Drowsiness, Dizziness, Headache, 400mg/d Restlessness, Blurred vision, anorexia, dry mouth, A - IM/IV: 50-100mg q4hr PRN, max: 400mg/d insomnia, tachycardia Motion Sickness: Indication: For prevention and treatment of nausea, A - PO: 25-50mg 1 hr before travel; may repeat every vomiting, and dizziness due to motion sickness and MECLIZINE 24hr PRN; max: 50mg/d vertigo associated with vestibular disorder HYDROCHLORIDE Side Effect: Drowsiness, headache. ataxia, fatigue, Vertigo: blurred vision, anorexia, and dry mouth A- PO: 35-100mg/d in divided doses; max: 100mg/d  NONPRESCRIPTION ANTIEMETICS DIPHENHYDRAMINE Upper Respiratory Disorder GI Tract Disorder MOA: acts on peripheral MOA: blocks histamine H1 tissues like the skin, nasal receptors in the brain, passages, and respiratory particularly in areas like the tract. vestibular system and the vomiting center in the medulla oblongata.  NONPRESCRIPTION ANTIEMETICS BISMUTH SUBSALICYLATE Indication: To prevent nausea, diarrhea, indigestion, heartburn, gas A - PO: 525mg PO every 30-60min or 1050mg PO every 60min PRN for up to 2 days; max: 4200mg/24hr MOA: Acts directly on the gastric mucosa to suppress vomiting  NONPRESCRIPTION ANTIEMETICS PHOSPHORATED CARBOHYDRATE (Emetrol) A hyperosmolar carbohydrate, meaning it has a high concentration of solutes compared to bodily fluids. Indication: Mild nausea from gastrointestinal upset, Motion sickness, Morning sickness during pregnancy (with physician approval), Non-severe nausea caused by overindulgence in food or drink MOA: Gastric muscle relaxation, Reduction of gastric irritation, delayed gastric emptying A - PO: 15-30mL every 15 minutes until symptoms subside Contraindication: Diabetes Mellitus due to high sugar content, Ineffective for severe nausea and vomiting or vomiting due to more serious underlying conditions. PRESCRIPTION ANTIEMETIC DRUGS a. Antihistamine & Anticholinergic b. Dopamine Antagonist b1. Phenothiazine Antiemetics b2. Butyrophenones b3. Benzodiazepines c. Serotonin (5-HT3) receptor antagonist d. Glucocorticoids (Corticosteroids) e. Cannabinoids f. Miscellaneous antiemetics  PRESCRIPTION ANTIEMETIC DRUGS a1. ANTIHISTAMINE a1. ANTICHOLINERGIC HYDROXYZINE SCOPOLAMINE Indication: Postoperative nausea and vomiting, pruritus, Indication: Nausea and vomiting, motion sickness, and vertigo, anxiety, agitation, sedation induction procedural sedation A: Give deep in large muscle; 25-100mg single dose; max: A: Transdermal patch - 1mg patch; apply to a hairless area 600mg/d behind the ear at least 4 hr before travel and every 3 days MOA: Suppresses activity in certain essential regions of PRN; wash hands after applying; wear no more than 1 patch at the subcortical area of the CNS a time; alternate ears if using for longer than 3 days; t1/2: 8hr Side effects: drowsiness, blurred vision, urinary MOA: inhibits muscarinic actions of acetylcholine on retention, constipation autonomic effectors innervated by post-ganglionic cholinergic Adverse effect: CNS - drowsiness; GI - dry mouth neurons Contraindication: Patient hypersensitive to the drug Side effects: dizziness, drowsiness, fatigue, headache, blurred (cetirizine hydrochloride, levocetirizine hydrochloride, vision, dry conjunctiva, dilated pupils, visual impairment patients with prolonged QTc interval, glaucoma, BPH, Adverse reaction: Orthostatic hypotension, dizziness, urinary structure, asthma, COPD somnolence, agitation, confusion  PRESCRIPTION ANTIEMETIC DRUGS b. DOPAMINE ANTAGONISTS Suppress emesis by blocking Dopamine (D2) receptors in CTZ Common side effects of these drugs are: Extrapyramidal symptoms or Extrapyramidal syndrome (EPS) due to blocking the dopamine receptors and hypotension b1. PHENOTHIAZINE THREE b2. BUTYROPHENONES CATEGORIES b3. BENZODIAZEPINES PRESCRIPTION ANTIEMETIC DRUGS b1. DOPAMINE ANTAGONISTS: PHENOTHIAZINE USES: Treat nausea and vomiting caused by: Surgery Anesthetics Chemotherapy Radiation sickness Act by inhibiting the chemoreceptor trigger zone (CTZ). Cancer patient usage: Administration: Given night before treatment Given during day of treatment Given 24 hours after treatment PRESCRIPTION ANTIEMETIC DRUGS b1. DOPAMINE ANTAGONISTS: PHENOTHIAZINE HISTORY: Chlorpromazine and prochlorperazine edisylate: First phenothiazines used to treat both psychosis and vomiting. Promethazine Introduced in the 1940s as an antihistamine. Also effective for: Sedation Motion sickness Nausea and vomiting management.  PRESCRIPTION ANTIEMETIC DRUGS b1. DOPAMINE ANTAGONISTS: PHENOTHIAZINE PHARMACOKINETICS: DRUG AND LABORATORY INTERACTIONS: Increases CNS depression when combined with: Absorbed in the GI tract. a. alcohol Protein-binding: 80%-93% capacity b. narcotics, Metabolism: Liver. c. sedative-hypnotics Excretion: Urine and feces. d. general anesthetics. Increases anticholinergic effects with: PHARMACODYNAMICS: a. antihistamines b. atropine Blocks H1-receptor sites c. other phenothiazines. Impedes histamine-mediated responses. May interfere with urinary pregnancy tests, causing false results. Onset of action: SIDE EFFECTS: Oral: 15–60 minutes. Moderate sedation, hypotension, CNS effects (restlessness, IM: 20 minutes. weakness, agitation). IV: 3–5 minutes. Mild anticholinergic symptoms (dry mouth, urinary retention, Duration of action: 4–6 hours. constipation). Lower antiemetic doses reduce side effect severity. Extrapyramidal symptoms are rare at antiemetic doses.  b1. DOPAMINE ANTAGONISTS: PHENOTHIAZINE PROMETHAZINE HYDROCHLORIDE DOSAGE: SIDE EFFECTS CONTRAINDICATIONS A: PO/PR/IM/IV: 12.5-25 mg q4-6h PRN; max: Drowsiness, dizziness, confusion, Hypersensitivity, asthma, coma 100 mg/d agitation, insomnia, dry mouth, Caution: Glaucoma, Gl obstruction, bone constipation, blurred vision, excitability, marrow depression, hepatic disease, COPD, PHARMACOKINETICS: photosensitivity, fatigue, urinary dehydration, diabetes mellitus, bradycardia, Absorption: PO: Easily absorbed from GI retention, injection site reaction, skin hypocalcemia, hypokalemia, hypomagnesemia, tract hyperpigmentation, erectile/ejaculation older adults, breastfeeding Distribution: PB: 80%-93% dysfunction Metabolism: t½2: 10-14 h DRUG-LAB-FOOD INTERACTIONS DRUG: Excretion: In urine and feces ADVERSE REACTION Increases CNS depression and anticholinergic Extrapyramidal syndrome, seizures, effects when taken with alcohol and other CNS PHARMACODYNAMICS dyspnea, hypo/hypertension depressants; lowers seizure threshold with PO: Onset: 15-60 min Life-threatening: Agranulocytosis, phenytoin and tramadol Peak: duration: 4-6 h leukopenia, thrombocytopenia, NMS, Lab: False pregnancy test IM: Onset: 20 min respiratory depression Peak: UK; duration: 4-6 h IV: Onset: 3-5 min THERAPEUTIC EFFECTS/USES: Peak: UK; duration: 4-6 h To treat and prevent motion sickness, nausea, vomiting, and sedation induction PR: Onset: 15-60 min Mechanism of Action: Blocks H, receptor sites and inhibits CTZ. Peak: UK; duration: 4-6 h  PHENOTHIAZINE ROUTE AND DRUG USES AND CONSIDERATIONS DOSAGE A - PO/IM/IV: 5-10mg 3/4 Indication: For nausea, vomiting, schizophrenia, times a day PRN (give and anxiety deep in the muscle) max: Contraindication: Avoid concurrent alcohol use PROCHLORPERAZINE 40mg/d Side Effect: Drowsiness, dizziness, headache, MALEATE SR: 10-15mg every 12hr insomnia, blurred vision, dry mouth, EPS, PR: 25mg bid; max: erectile/ejaculatory dysfunction, constipation 50mg/d PB: 91%-99%; t1/2: 6-22hr Indication: For nausea and vomiting, hiccups, A - PO: 10-25mg every 4- and schizophrenia 6hr PRN Side effects: Drowsiness, dizziness, weight gain, CHLORPROMAZINE A - IM: initially 25mg then, dry mouth, photosensitivity, constipation, and if tolerated, may give 25- skin hyperpigmentation 30mg every 3-4hr PRN PB: 90-99%; t1/2: 2-30hr PRESCRIPTION ANTIEMETIC DRUGS b2. DOPAMINE ANTAGONISTS: BUTYROPHENONES DROPERIDOL (a butyrophenone derivative) Blocks D2 receptors in the CTZ, similar to phenothiazines. USED TO TREAT: Postoperative nausea and vomiting. Emesis from toxins, chemotherapy, and radiation therapy. SIDE EFFECTS: Risk of extrapyramidal symptoms (a group of involuntary movement disorders that can be a side effect of certain drugs) with prolonged use. May cause hypotension; blood pressure monitoring is required. PRESCRIPTION ANTIEMETIC DRUGS ROUTE AND DRUG USES AND CONSIDERATIONS DOSAGE Postoperative nausea and For prevention and treatment of vomiting: postoperative nausea and vomiting A - IM/IV: Initially and sedation induction. DROPERIDOL 0.625-2.5 mg, may May cause hypo/hypertension, then give 1.25 mg if tachycardia, dizziness, drowsiness, needed; max: 2.5 anxiety, restlessness, dysrhythmias, mg/initial dose and EPS. PB: 85%-90%: t½: 2 h  PRESCRIPTION ANTIEMETIC DRUGS b3. DOPAMINE ANTAGONISTS: BENZODIAZEPINES USES: Indirectly control nausea and vomiting associated with cancer chemotherapy. Often used in combination with a glucocorticoid and a serotonin (5-HT3)-receptor antagonist. DRUG OF CHOICE: Lorazepam Provides: Sedation Anxiety reduction Amnesia (patients may temporarily struggle to form new memories after taking the drug) Diazepam (previous drug of choice) Previously preferred benzodiazepine for this purpose but replaced by lorazepam due to its greater effectiveness for emesis control, sedation, anxiety reduction, and amnesia PRESCRIPTION ANTIEMETIC DRUGS ROUTE AND DRUG USES AND CONSIDERATIONS DOSAGE For prevention of chemo-induced nausea and vomiting and for anxiety, Chemo-induced insomnia, procedural sedation, and nausea/vomiting: status epilepticus. May cause LORAZEPAM A - IV: 0.025 mg/kg dizziness, drowsiness, ataxia, 45 min before confusion, injection site reaction, chemo constipation, weakness, hypotension, restlessness, headache, and erythema. PB: 85%; t½: 12-14 h  PRESCRIPTION ANTIEMETIC DRUGS b3. DOPAMINE ANTAGONISTS: LORAZEPAM Indication: Prevention of chemo-induced nausea and vomiting and for anxiety, insomnia, procedural sedation, and status epilepticus A: IV - 0.025mg/kg 45 min before chemo MOA: potentiates effects of GABA (Gamma-aminobutyric acid), depresses CNS, and suppresses the spread of seizure Side effects: dizziness, drowsiness, ataxia, confusion, injection site reaction, constipation, weakness, hypotension, restlessness, headache, and erythema PRESCRIPTION ANTIEMETIC DRUGS b4 DOPAMINE ANTAGONISTS: BENZAMIDE ROUTE AND DRUG USES AND CONSIDERATIONS DOSAGE For postoperative nausea and A: IV: 10 mg in single vomiting. May cause chills, AMISULPRIDE dose over 1-2 min; drowsiness, injection site reaction, max: 10 mg/dose hypotension, and hypokalemia. PB: 25%-30%; t½: 4-5 h PRESCRIPTION ANTIEMETIC DRUGS c. SEROTONIN-RECEPOTORS ANTAGONISTS Suppress nausea and vomiting by blocking 5-HT3 receptors in the CTZ and vagal nerve terminals in the upper GI tract. DRUGS: Ondansetron do not block the dopamine receptors; therefore they do Granisetron not cause extrapyramidal symptoms in contrast to Dolasetron phenothiazine antiemetics. Palonosetron EFFECTIVENESS: Most effective antiemetics for chemotherapy-induced nausea and vomiting. Prevent nausea/vomiting before and after surgery. KEY ADVANTAGES: Do not block dopamine receptors, so they avoid extrapyramidal symptoms. Administered orally or intravenously. COMMON SIDE EFFECTS: Headache, dizziness, hypotension, palpitations, constipation, edema, and fatigue. SEROTONIN (5-HT3) RECEPTOR ANTAGONIST DRUG ROUTE AND DOSAGE USES AND CONSIDERATIONS Chemotherapy-induced nausea/vomiting: A: PO: 1 mg bid (1 h before and 12 h after Indication: or prevention and treatment of radiation- chemo); max: 2 mg/d and chemo-induced nausea and vomiting. A: IV: 10 mcg/kg 30 min before chemo; Side Effect: dizziness, headache, weakness, GRANISETRON max: 40 mcg/kg hematoma, fatigue, anorexia, dyspepsia, nausea, A: Transdermal patch: Apply 1 patch (3.1 vomiting, abdominal pain, diarrhea, constipation, mg/24 h) at least 24-48 h before chemo; leukopenia, and injection site reaction remove patch no sooner than 24 h after. PB: 65%; t/: 6.23 h PO, 5-7.7 h IV chemo completion A: PO: 8 mg 30 min before chemo; may Indication: For postoperative and chemo- and repeat in 8 h, then q12h for 1-2 d after radiation-induced nausea and vomiting ONDANSETRON chemo; max: 24 mg/d Side effects: dizziness, drowsiness, agitation, HYDROCHLORIDE A: IV: 0.15 mg/kg (150 mcg/kg) 30 min headache, fatigue, malaise, diarrhea, hypotension, before chemo, infused over 15 min, then urinary retention, fever, and constipation. q4h x 2 PB: 70%-76%. t: 3.1-5.8 SEROTONIN (5-HT3) RECEPTOR ANTAGONIST USES AND DRUG ROUTE AND DOSAGE CONSIDERATIONS Indication: To prevent postoperative and chemo-induced nausea and Postoperative nausea/vomiting: vomiting. PALONOSETRON Side Effect: headache, dizziness, A: IV: 0,075 mg over 10 s before induction hypotension, flatulence, constipation, as a single dose; max: 0.25 mg/single dose diarrhea, and urinary retention. PB: 62%; t/2: 40 h Indication: For nausea and vomiting. A: PO: 100 mg within 1 h before chemo Side effects: headache, dizziness, DOLASETRON hypotension, diarrhea, fatigue, and A: IV: 12.5 mg as single dose. fever. PB: 69%-77%, t/2: