GI Study Guide

Serotonin antagonists (5HT3 receptor antagonists)

-Ondansetron [Zofran] -Granisetron [Kytril HCl]- [Sancuso transdermal] -Dolasetron [Anzemet] -Palonosetron [Aloxi] Uses: Chemotherapy induced nausea/vomiting (CINV) N/V associated with radiation therapy N/V associated w/ viral gastritis (off label) Pregnancy related N/V (off label) Post anesthesia N/V These agents selectively block the serotonin receptors (5HT3) found in vagal nerve terminals and centrally in the CTZ that trigger nausea and vomiting. 5HT3 receptors are also found in the GI tract. They have little or no affinity for other serotonin, autonomic, dopamine, histamine, or opioid receptors. 5HT3 receptor antagonists are the most effective drugs available for suppressing nausea and vomiting caused by cisplatin & other emetogenic anticancer drugs. indicated orally, IV or IM for the prophylaxis of nausea and vomiting caused by cancer chemotherapy as well as prevention of postoperative nausea or vomiting or that associated with radiotherapy. given 30 min before and 2 & 8 h after chemotherapy Selective serotonin antagonists inhibit the action of serotonin at the 5-hydroxytryptamine3 (5-HT3) receptor in the small bowel, vagus nerve, and chemoreceptor trigger zone. So, blocks serotonin receptors on vagal afferents and in the CTZ Adverse Effects Common -Headache -Diarrhea -Dizziness Potentially life-threatening -Prolonged QT interval -> inc risk of torsades de pointes Implications Do not give the drug in the following situations: Patients w/ prolonged QT interval syndrome Use cautiously in the following situations: Patients w/ bradycardia Patients w/ heart failure Patients w/ electrolyte abnormalities Ondansetron (Zofran) Usually combined w/ glucocorticoid dexamethasone for inc. efficacy Given oral or parenterally Pharmacodynamics -Antihistamines have strong anticholinergic effects as well as histamine1-blocking effects. -Phenothiazines block dopamine receptors in the chemoreceptor trigger zone. -Cannabinoids work in the CNS to prevent nausea and vomiting associated with cancer chemotherapy. -5-HT3 receptor antagonists block serotonin on vagal nerve terminals and in the chemoreceptor trigger zone. It is first necessary for the practitioner to assess the etiology of the nausea and vomiting. Most OTC antiemetics or motion sickness drugs are antihistamines. Most cause a sedative effect and have anticholinergic actions, all of which add to the action of other CNS depressants or drugs with anticholinergic effect. Their central anticholinergic effect is believed responsible, at least in part, for their antiemetic effect. It is recommended that a dose be administered 30 to 60 minutes before the event and repeated at regular intervals several times a day. Dronabinol (Marinol) is approved for management of chemotherapy-associated nausea and vomiting. Precautions and contraindications -Antihistamines have anticholinergic properties. -Phenothiazines Produce extrapyramidal symptoms (EPS) Contraindicated in Parkinson's disease -Dronabinol Use with caution in patients with seizure disorders. -5-HT3 receptor antagonists may mask progressive ileus. Antihistamines: Cyclizine [Marezine], meclizine [Antivert;], buclizine [Bucladin-S] and dimenhydrinate [Dramamine] are indicated for "prevention and treatment of nausea, vomiting, dizziness of motion sickness. Dimenhydrinate and meclizine may be useful in treating vertigo of motion sickness or vertigo of vestibular origin. Hydroxyzine (#40) (Vistaril) is an antihistamine often used as an anxiolytic, and occasionally for pre- or post-operative nausea. Phenothiazines: Dopamine receptors are found in the chemoreceptor trigger zone. Stimulation of dopamine receptors cause nausea and vomiting by increasing impulses to the NTS and the dorsal vagal complex. Although all phenothiazines, by virtue of their ability to block central dopamine receptors, have antiemetic action, prochlorperazine (Compazine; oral, rectal; IM) and promethazine (Phenergan [suppositories]) are the two used most commonly for nausea and vomiting, particularly in pre- and post-operative patients. Dronabinol (Marinol) is the principal psychoactive substance in marijuana. It is a Tetrahydrocannabinol (Marijuana) Derivative (Schedule III controlled substances) It is highly abusable. It may cause mood changes, decrements in cognitive performance, and decreased ability to control impulses. Approved for management of nauN/V assoc. with cancer chemotherapy & the treatment of anorexia associated with weight loss in patients with AIDS. A meta-analysis of 15 trials showed the cannabinoids to be safe and modestly effective in the treatment of neuropathic pain, fibromyalgia, and rheumatoid arthritis. No serious side effects were reported ADRs -Antihistamines Drowsiness Anticholinergic effects of dry mouth, blurred vision, and urinary retention -Phenothiazines Drowsiness EPS such as dystonia, akathisia, and tardive dyskinesia Promethazine: fatal respiratory depression in children younger than 2 years of age -Cannabinoid dronabinol Euphoria, depression, dizziness, paranoid thoughts, somnolence, and abnormal thoughts Cardiac effects: palpitations, tachycardia, and hypotension Seizure and seizure-like activity have been reported. -Serotonin Receptor Antagonists Constipation, headache, fatigue, dizziness, and diarrhea Rare cases of tachycardia, bradycardia, hypotension, and heart rate-corrected QT interval prolongation Phenothiazines carry side effects of drowsiness, anticholinergic actions, orthostatic hypotension, and parkinsonian movements, the latter especially in children. Parkinsonian movements, also called extrapyramidal symptoms (EPS), include dyskinesia, dystonia & akathisia. Use cautiously in patients taking other CNS depressants. Antihistamines: Adverse effects limit the use of anticholinergics-antihistamines due to sedation, drowsiness or confusion. The anticholinergic effects include blurred vision, dry mouth, urinary retention, and tachycardia. Caution when used in patients with narrow-angle glaucoma, prostatic hypertrophy, and asthma. Chewing gum or sucking on ice chips or hard candy may refresh dry mouth. A high-fiber diet and adequate daily fluid consumption may curb constipation. Cannabinoid dronabinol: Adverse effects occurring more than 1% of patients include palpitations & tachycardia, nausea & vomiting (3-10%), euphoria (3-24%), tinnitus, and sweating. Because of their psychotomimetic effects and abuse potential the cannabinoids are considered 2nd line drugs as antiemetics. 5-HT3 receptor antagonists: Adverse effects mild to moderate headache (25% of patients), diarrhea (6 to 16%), extrapyramidal syndrome (6%) Since ondansetron does not block dopamine receptors, it does not cause EPS (Lehne, 2013), arrhythmias, hypotension, "wound problems" (28%), shivers (5%), anemia (4%). Do not give the drug in the following situations: Patients w/ prolonged QT interval syndrome Use cautiously in the following situations: Patients w/ bradycardia Patients w/ heart failure Patients w/ electrolyte abnormalities Drug interactions -Additive CNS depression when combined with CNS depressants -Additive anticholinergic effects -Phenothiazines and lithium may increase EPS. -Phenothiazines + lithium may mask lithium toxicity. Clinical use -Nausea and vomiting due to drugs or gastroenteritis 5-HT3 receptor antagonists Phenothiazines (not in children) Dronabinol is only for use in chemotherapy-associated nausea and vomiting, and appetite stimulation. -Motion sickness Antihistamines Dimenhydrinate and meclizine -Vomiting due to gastroparesis Prokinetic drugs Monitoring -Short-term use requires minimal monitoring. -Long-term use of promethazine requires complete blood count to monitor for bone marrow depression and blood dyscrasias (week 4 and week 10 of therapy). Patient education -Administration Take 1 to 2 hours before departure to treat motion sickness. -ADRs Drowsiness, dry mouth, dry eyes, constipation, and urinary retention Dronabinol (Marinol) may cause euphoria and behavior changes. -Lifestyle Hydration Electrolyte replacement solutions * Before using any centrally acting antiemetic, assess the patient for contraindications, especially for anticholinergic drugs. Monitor patients for side effects (anticholinergic or CNS depressant). Warn the patient about driving or use of alcohol or other CNS depressants *If vomiting is severe and prolonged, parenteral fluids may be needed to prevent hypovolemia and electrolyte imbalances *Nausea and vomiting is common during pregnancy (morning sickness). Nondrug measures (e.g., crackers, eating small meal in morning) are recommended.

Antacid precautions and contraindications

Abdominal pain of unknown cause Calcium-based antacids contraindicated if patient is hypercalcemic or has renal calculi. Magnesium-based antacids contraindicated in patients with renal failure or renal insufficiency. Aluminum-based antacids should not be used in patients with renal failure on dialysis. Sodium content may affect patients with hypertension, congestive heart failure, or renal failure. The major side effect of antacids is altered gut motility. Aluminum & calcium salts produce constipation; magnesium salts produce diarrhea. Many commercial preparations are mixtures to balance effect on GI motility. Serum electrolytes & acid-base balance may be affected, particularly by systemic antacids (sodium bicarbonate), sodium-containing drugs, and magnesium in patients with renal insufficiency. There is usually no problem in pregnant and breast-feeding women. (Pregnancy Category A) Elderly people with impaired renal function must use magnesium products carefully. Those with cardiovascular problems may need to avoid antacids containing sodium (e.g., Rolaids).

Antidiarrheals

Absorbent preparations -Kaolin and pectin -Bismuth subsalicylate Opiates -Diphenoxylate with atropine (Lomotil) -Diphenoxin with atropine (Motofen) -Loperamide (Imodium) Anticholinergics -Atropine Absorbents like Kaolin and pectin act locally to bind noxious substances that stimulate the gut (e.g., foods, drugs, toxins). They are generally safe but have not been clearly demonstrated to be efficacious. Absorbents are usually administered after every loose stool.

PUD Treatment Outcome

After treating for H. pylori, continue PPI for 8 to 12 weeks to promote healing. If patient is low risk, no further treatment. If patient is high risk, consider chronic acid suppression therapy. If symptoms do not resolve refer the patient. Most people are cured after finishing one to two weeks of medicine. Some people need to take another two weeks of medicine. It is important to finish all of the medicine to ensure that the bacteria are killed. After completing H. pylori treatment, repeat testing is usually performed to ensure that the infection has resolved. This is typically done with a breath or stool test. Blood tests are not recommended for follow up testing; the antibody detected by the blood test often remains in the blood for four or more months after treatment, even after the infection is eliminated.

Inflammatory Bowel Disease Treatment

Aminosalicylates (sulfasalazine, mesalamine, olsalazine and balsalazide) Antibiotics (metronidazole and ciprofloxacin) Corticosteroids (prednisone, prednisolone, or methylprednisolone) Immunomodulators ( azathioprine, cyclosporine, 6-mercaptopurine, and methotrexate) Biologic Therapies (anti-TNF agents [adalimumumab, certolizumab pegol, golimumab, infliximab, and infliximab-dyyb] & anti-integrins [natalizumab and vedolizumab]) Control the inflammation of IBD by delivering a compound containing 5-aminosalicylic acid (5-ASA) to the bowel. Examples of aminosalicylates are sulfasalazine, mesalamine, olsalazine and balsalazide. These medications are used for both ulcerative colitis and Crohn's disease; however, they are much more effective for ulcerative colitis and are being used less often for Crohn's disease. Effective in treating mild-to-moderate episodes of ulcerative colitis and Crohn's disease; Effective in preventing relapses and maintaining remission; Available in rectal preparations, which may allow for more targeted administration into specific areas of the bowel; Affordable for many patients. ABX: Given orally or intravenously, antibiotics are used selectively in patients with Crohn's disease and in patients with IBD who develop infection with Clostridium difficile. Examples of antibiotics are metronidazole and ciprofloxacin. Effective in treating fistulas and fissures in Crohn's disease; Metronidazole has been shown to reduce recurrence of Crohn's disease for the first 3 months after ileum resection surgery. Corticosteroids (prednisone, prednisolone, or methylprednisolone) used to treat acute (sudden onset and/or short duration) flare-ups Immunomodulators work by quieting down the immune system, helping to reduce inflammation. They can be given orally or by injection. Examples of immunomodulators are azathioprine, cyclosporine, 6-mercaptopurine, and methotrexate (for Crohn's disease). Biologic Therapies-help to reduce inflammation by blocking specific proteins that play a role in inflammation. Two main classes of biologics: The anti-TNF agents, block the protein tumor necrosis factor alpha (examples include adalimumumab, certolizumab pegol, golimumab, infliximab, and infliximab-dyyb). The second, anti-integrins, block integrins, which are proteins used by white blood cells to travel to areas of active inflammation, such as the intestine (examples include natalizumab and vedolizumab). Currently, adalimumab, golimumab, infliximab and vedolizumab are the only biologic therapies that are FDA approved to treat ulcerative colitis. Adalimumab, certolizumab pegol, infliximab, natalizumab and vedolizumab are the only biologic therapies that are FDA approved to treat Crohn's disease. Newest treatment for moderate-to-severe IBD, targeting the source of inflammation; Can be effective in achieving and maintaining remission without the use of steroids; Works fairly quickly (within weeks) as opposed to immunomodulators (which may take a few months)

PPIs MOA, pharmacodynamics, clinical use and dosing, precautions and contraindications, ADRs, & drug interactions

Anti-secretory drugs used to treat gastric conditions characterized by hyperacidity. MOA: irreversible inhibition of the H+, K+-ATPase (proton pump), an enzyme that generates gastric production. Because irreversible, effects persist until more enzyme made; partial recovery 3-5 days after stopping a PPI drug Pharmacodynamics Reduce H+ secretion by inhibition of the H+/K+/ATPase enzyme system at the secretory surface of the parietal cell Decrease in acid secretion lasts for up to 72 hours after each dose Proton pump inhibitors are first-line agents that have antisecretory effects and rapidly relieve symptoms. Pharmacokinetics: given orally in enteric coating or capsule to bypass stomach because they are highly unstable in acid. Dissolve in small intestine Proton pump inhibitors are more effective in preventing complications than H2 blockers. PPIs suppress gastric acid secretion (both fasting and meal-stimulated) by specific irreversible inhibition of the H+/K+ ATPase enzyme system (termed proton pump inhibitors) at the secretory surface of the gastric parietal cell. This is the final phase in acid secretion. The PPIs are the most effective drugs we have for suppressing gastric acid secretion. Clinical use and dosing Duodenal and gastric ulcers -PPIs are combined with antibiotics to treat H. pylori. GERD -Used for 8 weeks then weaned off -May need to double dose for 4 weeks then decrease dose for another 4 weeks PPIs may mask the symptoms of gastric cancers. Weaning: Decrease from twice/day to q day, then every other day with an H2RA used for symptoms, then wean off. Short-term treatment of active gastric ulcers Active duodenal ulcers Erosive esophagitis Symptomatic GERD that isn't responding to other therapies Active peptic ulcers w/ H. pylori infection Long-term treatment of hypersecretory states such as Zollinger-Ellison syndrome The proton pump inhibitors are indicated in gastroesophageal reflux disease (GERD) (1st line therapy) and pathological hypersecretory conditions (e.g., Z-E syndrome) as well as in the treatment of duodenal ulcers, and, with clarithromycin, in eradication of H. pylori. Because they inhibit the final step in gastric acid formation, they inhibit gastric secretion regardless of the stimulus Discontinuation of PPIs may result in acid rebound. A randomized double-blind-placebo-controlled study reported acid-related symptoms 1-3 weeks after discontinuation of the PPI (esomeprazole) Precautions and contraindications -Extensively metabolized in the liver; use cautiously in patients with hepatic dysfunction and the elderly -Pregnancy category B or C -Congenital anomalies have been reported -Use with caution. Children -Esomeprazole, omeprazole, and lansoprazole approved for short-term use in children as young as 1 year -Pantoprazole and rabeprazole not approved in children less than 12 years ADRs -Risk for significant nutrient deficiencies: iron, vitamin B12, and calcium -Long-term PPI use increases risk for osteoporosis and increased hip fractures. -Long-term PPI therapy increases risk of Clostridium difficile, salmonella, and campylobacter infections. -Increased risk of pneumonia -Questionable gastric cancer risk Adverse effects: Abdominal pain Diarrhea Nausea & vomiting Inc risk of pneumonia Long term use - inc. risk of fractures due to dec calcium absorption Rebound hypersecretion hypomagnesemia Long-term suppression of acid may allow bacteria overgrowth in the gut including Clostridium difficile. The use of acid suppressant therapy, especially PPIs, is associated with increased risk of community-acquired C. difficile infections The use of gastric acid-suppressive therapy is associated with an increased risk of community-acquired pneumonia (4-fold increase); Studies suggest PPIs increase the risk of osteoporosis. Studies indicate B12 status declines during prolonged PPI use in older adults, but not with prolonged H2 blocker use. Drug interactions -Decrease effectiveness of atazanavir, indinavir, and nelfinavir -Interfere with absorption of drugs and depend on an acidic gastric pH to be effective -Increased monitoring of INR if taking with warfarin -Clopidogrel (Plavix) has a Black Box warning regarding interactions with omeprazole. Omeprazole inhibits hepatic enzymes and has increased drug blood levels in patients taking diazepam, flurazepam, triazolam, phenytoin, and warfarin. Recent studies showed that omeprazole decreased calcium absorption by decreasing gastric acidity (O'Connell MB et al. Am J Med 2005;118:778). Patients who used PPIs plus clopidogrel had a 64% higher risk of rehospitalization for an MI or coronary stent It also decreased tacrolimus serum concentrations about 15%. This occurred when renal transplant recipients were converted from cimetidine to omeprazole for ulcer prophylaxis. This was attributed to increased CYP3A4 intestinal activity (but not hepatic 3A4 activity)

Scopolamine

Anticholinergic Drug MOA: muscarinic antagonist; suppresses nerve impulses from the vestibular apparatus of the inner ear to the vomiting center (VC) Uses: Motion sickness Adverse effects: Most common are dry mouth, blurred vision, drowsiness Most severe but less common: constipation, urinary retention, disorientation Route of administration Oral, subcutaneous, transdermal patch Transdermal patch - teach patient to apply behind the ear

Antiemetics and drug classes

Antiemetics may be used to provide -Symptom relief for nausea and vomiting -Prevention of fluid and electrolyte disturbances Drug classes -Antihistamines -Phenothiazines -Sedative hypnotics -Cannabinoids -5-HT3 receptor antagonists (Serotonin Antagonist) Multiple neurotransmitters in both the GI tract and CNS seem to be involved in the pathophysiology of chemotherapy-induced nausea and vomiting (CINV). The emetic center (in the lateral reticular formation of the medulla) may be stimulated by afferent impulses from the vestibular apparatus (neurotransmitters acetylcholine & histamine), the chemoreceptor trigger zone (CTZ) (neurotransmitters serotonin, dopamine & substance P), and vagal fibers in the upper GI tract (neurotransmitters serotonin [5HT3] & substance P). The action of substance P at neurokinin-1 (NK-1) receptors in the CNS is among the final common pathways in emetic response. Aprepitant is a selective antagonist of NK-1 receptors. NK-1 and 5HT3 receptors are found in both the chemoreceptor trigger zone and in the gastrointestinal viscera.

meclizine (Antivert) & cyclizine (Marezine)

Antihistamine agents MOA: block receptors for acetylcholine in addition to receptors for histamine. Management of motion sickness: Blocking histamine1 receptors Muscarinic (cholinergic) receptors blocked along the neuronal pathway between inner ear and VC Uses: motion sickness Adverse effects: Sedation from H1 blockade Anticholinergic effects - dry mouth, blurred vision, urinary retention, constipation Less effective than scopolamine for motion sickness

Antidiarrheals: Rational Drug Selection

Any antidiarrheal can be used for acute diarrhea in adults. Bismuth subsalicylate and loperamide are used for traveler's diarrhea. Cost: inexpensive

Acute Gastroenteritis

Appropriate fluids & electrolytes; Then treat for specific indications: -Cholera, shigella: TMP/SMX -Giardia, amebiasis: metronidazole -Clostridia: vancomycin, metronidazole, fidaxomicin Traveler's diarrhea: Colistin sulfate [Coly-Mycin S]) for children/travelers with diarrhea caused by E coli or shigella. Doxycycline, azithromycin or ciprofloxacin used to reduce the incidence of traveler's diarrhea. Rifaximin [Xifaxan] a rifampin derivative treats traveler's diarrhea caused by E. coli. Acute infectious gastroenteritis: Characterized by vomiting and diarrhea due to microorganisms. Acute Gastroenteritis Treatment: Appropriate fluids & electrolytes Then treat for specific indications: cholera, shigella: TMP/SMX giardia, amebiasis: metronidazole clostridia: vancomycin, metronidazole, fidaxomicin Traveler's diarrhea: colistin sulfate [Coly-Mycin S]) may be used in children and travelers with diarrhea caused by E coli or shigella. Colistin, also known as polymyxin E, is an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. Colistin is a mixture of the cyclic polypeptides colistin A and B and belongs to the class of polypeptide antibiotics known as polymyxins. Colistin is effective against most Gram-negative bacilli. Traveler's diarrhea: doxycycline (100 mg/d), azithromycin (1000 mg once or 500 mg once/d x 3 d) or ciprofloxacin (500 mg bid x 3d) are also used to reduce the incidence of traveler's diarrhea. Resistance is reported to doxycycline. Can also treat with Rifaximin [Xifaxan] is a rifampin derivative but is not absorbed from the GI tract. It has been approved as 200 mg tid x 3 d for the treatment of traveler's diarrhea caused by E. coli. It is about as effective as ciprofloxacin

Crofelemer (Fulyzaq)

Approved to treat diarrhea in patients with HIV/AIDS who are taking antiretrovirals 125 mg twice a day without regard for food delayed-release tablets 125 mg (Rx) are indicated for the treatment of HIV-related diarrhea. The drug inhibits calcium-activated chloride channels. The drug is minimally absorbed

Antidiarrheals: Clinical Use

Bowel disease Loperamide QID may be used as adjunct therapy. Chronic infantile diarrhea Bismuth subsalicylate - Must weigh risk/benefit due to potential for Reye Syndrome. Probiotic use is safer than Bismuth Traveler's diarrhea -Bismuth subsalicylate with each meal and at bedtime to prevent traveler's diarrhea -If diarrhea develops -Bismuth subsalicylate every 30 minutes (maximum 8 doses) for up to 48 hours -Loperamide 4 mg then 2 mg after every stool (maximum 8 mg/day) Acute diarrhea -Treat the source of diarrhea. -Absorbents (kaolin-pectin or bismuth subsalicylate) used after each loose stool -Maintain hydration. Electrolyte solution in infants and young children Flat soda or water in adults -Opioids dosed 3 or 4 times/day or after each stool Imodium / Loperamide is an opioid receptor agonist, meaning that it binds to and stimulates opioid receptors. The drug primarily works on receptors in the myenteric plexus of the large intestine, where it decreases activity of the smooth muscle of the intestine. National Reye Syndrome Foundation: "Children should not take medication with bismuth subsalicylate because epidemiologic evidence points to an association between the use of salicylate-containing products during viral infections and the onset of Reye's Syndrome." Some of the best proof that probiotics work comes from studies of diarrhea in children, especially when it's caused by rotavirus. Probiotics might cut bouts of infectious diarrhea by half a day to about 2 days.- Severe diarrhea with fever and dysentery should be treated with antibiotic alone; antimotility agents are contraindicated. If the diarrhea continues, a stool sample should be obtained for pathogen identification. Metronidazole has been shown to be effective in most of these cases.

Methylcellulose Polycarbophil Psyllium hydrophilic mucilloid

Bulk forming Laxatives MOA: The polysaccharides in these drugs are converted into osmotically active metabolites that draw water into intestines. Increases stool mass & water content. Promotes peristalsis. Excreted in feces. Uses: Simple cases of constipation esp. when due to low-fiber or low-fluid diet Aid patients recovering from acute MI or cerebral aneurysms who need to avoid Valsalva's maneuver Can also be used to treat diarrhea ADRs: Cramping, bloating, flatus. Important to increase water intake. Flatulence A sensation of abdominal fullness Intestinal obstruction Fecal impaction Esophageal obstruction Drug-drug interactions: Decreased absorption of digoxin, warfarin, & salicylates if taken within 2 hours of fiber or bulk forming laxatives

Meds to Treat Constipation

Bulk-producing laxatives: fibers; e.g. psyllium, methylcellulose, and polycarbophil. best and least expensive medication for long-term treatment. Rapidly acting Lubricant: mineral oil. (Acute or subacute constipation management) Surfactant / Emollient (Stool Softener): docusate compounds - docusate sodium [Colace]. Optimal for short-term prophylaxis (eg, postop, post natal, hemorrhoids) Osmotics: magnesium citrate, Milk of Magnesia (MOM), sodium phosphate [Fleet Phospho-soda], polyethylene glycol electrolyte solution, and polyethylene glycol (PEG) 3350 [Miralax] Hyperosmolar laxatives: glycerine, lactulose Stimulant Laxatives: cascara, senna, bisacodyl, and castor oil OTC meds not for long-term use Simplified definition of constipation: infrequent or difficult evacuation of stool. Laxatives are defined as drugs that gradually soften, or facilitate passage of, a formed stool. Cathartics are drugs that produce a more prompt, complete & watery evacuation. Laxatives are contraindicated in patients with nausea and vomiting, abdominal pain or tenderness, or obstruction. Hyperosmotic laxatives-glycerin given as a suppository evacuates the colon in 15-60 minutes. Its action is similar to saline products, the local osmotic effect draws water into the rectum, stretching the rectum and stimulating defecation. Osmotics (Bowel evacuants) Polyethylene Glycol (PEG) Electrolyte Solution is considered a hyperosmotic laxative; it's an isosmotic, non-absorbable liquid that should pass through the bowel without net absorption. (GoLytely; Colyte). (Inclusion of electrolytes prevents alteration of systemic fluid or electrolyte status.) When taken as directed (240 mL q 10 min until 4 L are consumed), they induce diarrhea within 30-60 min after initiation of therapy. PEG solutions used prior to GI exams (e.g., colonoscopy). The large volume of fluid and salty taste can cause nausea and sometimes vomiting. Polyethylene Glycol 3350 [Miralax] is listed as a softening, lubricating, bulky, osmotic laxative for the treatment of occasional constipation. Lactulose (Cephulac); Duphalac): Lactulose solution is indicated for the treatment of constipation (Duphalac) or for the prevention and treatment of portal-systemic encephalopathy (Cephulac). It reduces blood ammonia 25%-50%. The drug is given 30-45 ml three or four times a day. It may be administered rectally during impending coma.

Antacids: Clinical Use

Calcium deficiency -Chronic renal failure: 1,000 mg calcium carbonate daily -Osteoporosis prevention -Men and premenopausal women: 1,000 mg daily -Postmenopausal women: 1,500 mg daily -Doses > 2,000 mg/day not recommended Calcium: usually as calcium carbonate (TUMS, Titralac), is prompt-acting and prolonged but can be absorbed and cause hypercalcemia and acid rebound (by stimulating release of gastrin). Calcium salts are also used in treatment of osteoporosis. The most common side effect is constipation. Release of carbon dioxide in the stomach can cause eructation and flatulence. Excessive doses with calcium-containing dairy products can lead to hypercalcemia, renal insufficiency, and metabolic alkalosis ("milk-alkali syndrome" - SX HA, nausea, irritability, weakness).

Issues with Promethazine (Phenergan)

Children Respiratory depression can be severe Local tissue injury Death have occurred -> contraindicated in children under 2 & use cautiously in children > 2 Tissue injury Extravasation of IV form of drug -> abscess formation, tissue necrosis, nerve damage Risk not so great w/ IM form If must give IV - 25mg/ml or less in a large bore IV w/ free flowing fluids Patients frequently complain of burning sensation w/ IV administration

Chronic Constipation

Chronic Idiopathic Constipation -Lubiprostone [Amitiza] - an osmotic agent. Approved for IBS constipation and opioid-induced in adults w/ chronic non-cancer pain -Linaclotide [Linzess] & plecanatide [Trulance]- guanylate cyclase C (GC-C) agonists. Indication: chronic idiopathic constipation & IBS constipation in adults Opioid-induced constipation -Methylnaltrexone [Relistor] - peripherally-acting mu-opioid receptor antagonists. Indication: opioid-induced constipation in adults with chronic noncancer pain and/or for palliative care. (Others in this group - naloxegol, naldemedine) Lubiprostone (Amitiza) treatment of chronic idiopathic constipation (Rx drug - the only other Rx laxative is tegaserod for irritable bowel syndrome) and irritable bowel syndrome with constipation. It has also been approved for treatment of opioid-induced constipation in adults with chronic non-cancer pain. Acts locally in the GI tract by opening chloride channels on the surface of the GI epithelium, stimulating chloride-rich intestinal fluid secretion and accelerating small intestine and colonic transit time. ADR: H/A, nausea & diarrhea Linaclotide [Linzess] for treatment of chronic idiopathic constipation & irritable bowel syndrome with constipation. It acts on the lumen of the intestinal epithelium to cause increased secretion of chloride and bicarbonate into the intestine which results in creased intestinal fluid and accelerated transit. contraindicated in children up to 17 years of age or suspected mechanical GI obstruction. most common ADR is diarrhea Methylnaltrexone [Relistor] is a mu opioid antagonist that binds to mu receptors in the GI tract. It does not cross the blood-brain barrier. It is indicated 8-12 mg SC every other day for opioid-induced constipation. It is NOT a laxative

Histamine2 receptor Antagonists "H2 Blockers" Examples

Cimetidine (Tagamet) - 1st drug. Not used as much because of ADRs Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid)

Antacid: Rational Drug Selection

Combination products have the highest ANC Sodium content Cost -OTC -Inexpensive, but may vary -Generics OK Monitoring -Magnesium level in elderly patients who use magnesium-containing products chronically Magnesium oxide or hydroxide is rapid acting and potent. It can be absorbed but is rapidly eliminated in patients with normal renal function. Magnesium hydroxide (Milk of Magnesia, MOM) is most commonly combined with aluminum hydroxide. The dose as an antacid is often 5-15 mL; the dose as a laxative is often 30-60mL. Signs of magnesium intoxication (usually due to renal insufficiency) include NV, hypotension, lethargy, confusion, and muscle weakness Magnesium has a laxative effect. Excessive use can cause fluid & electrolyte loss.

Antidiarrheals: ADRs

Constipation Bismuth causes black tongue and gray-black stools. Diphenoxylate and difenoxin with atropine have anticholinergic effects. Opioids have central nervous system (CNS) effects Dizziness, drowsiness, sedation, headache Motofen (difenoxin & atropine) is an opioid drug used, often in combination with atropine, to treat diarrhea. It is an antispasmodic It is the principal metabolite of diphenoxylate. Diphenoxylate with atropine is Lomotil. These opioid antidiarrheals contain a sub-therapeutic dose of atropine to produce unpleasant effects if taken in overdose, thus discourages abuse. Side effects include drowsiness, dry mouth, abdominal cramps & dizziness. Euphoria has been reported.

Antacids: Patient Education

Contact provider if using longer than 2 weeks. Symptoms of GI bleed Aluminum- and calcium-based antacids cause constipation. -May need a stool softener Magnesium-based products cause diarrhea. Lifestyle changes -Stop smoking, elevate head while sleeping, avoid spicy foods, alcohol, or foods that affect lower esophageal sphincter tone (fatty food, chocolate, caffeine).

Antacids pharmacokinetics

Different combinations have differing acid neutralizing capacities. -Sodium bicarbonate and calcium carbonate have the highest absolute Acid Neutralizing Capacity(ANC). Pharmacokinetics -Aluminum- and magnesium-based antacids not absorbed with normal use -Chronic use increases absorption -Renally excreted -Calcium-containing antacids require vitamin D for absorption. -Excreted in feces Antacids create a local environment that favors healing rather than stimulating cell growth & tissue repair. Thus, antacids need to be taken until the ulcer heals (usually 6-8 weeks). In addition, antacids must be kept in the stomach, often accomplished by frequent administration, to buffer the constant secretion of acid produced by the stomach. It is important for the practitioner to stress the need to continue antacids as directed even though pain may be relieved. The stomach in a fasting state empties its contents into the duodenum as often as every 30 minutes to one hour, limiting the amount of antacid in the stomach. Acid secretion is greatest in response to a meal and at night. *Sodium Bicarbonate (baking soda) is a systemic antacid and is not recommended for treating peptic ulcer disease. It is very effective and prompt, but may alkalinize stomach and cause acid rebound. It is absorbed, causing systemic alkalosis and high serum concentrations of sodium. Sodium absorption may exacerbate fluid retention in patients with heart failure, hypertension, and renal insufficiency. Sodium bicarbonate forms carbon dioxide in the stomach, causing belching. (Most Alka-Seltzer preparations contain sodium bicarbonate). *Many OTC antacids today are combinations of calcium carbonate and magnesium hydroxide to balance the effect on gut motility. Liquids are more effective than tablets. The tablets must be chewed thoroughly and followed with 4-6 oz water.

Pancreatin and pancrelipase

Digestive Enzymes medications to mimic pancreatic enzymes secreted by the pancreas. -Enzyme replacement therapy for cystic fibrosis -Creon, Pancreaze, and Zenpep -Administer with each meal and snack -Excessive doses may cause nausea, abdominal cramps, or diarrhea. The pancreatic enzymes are lipase, protease, and amylase. Pancrelipase and pancreatin, are commercial mixtures of amylase, lipase and protease. The trade names are Creon, Pancreaze, and Zenpep. They hydrolyze fats to glycerol and fatty acids, change protein into proteases, and convert starch into dextrins and sugars. 2. Enzyme replacement therapy is indicated in patients with deficient exocrine pancreatic secretions including cystic fibrosis. 3. Excessive doses may cause nausea, abdominal cramps, or diarrhea. 4. Only three pancreatic enzyme products have been approved by the FDA (2010), they are Creon, Pancreaze, and Zenpep. Pancreatic enzyme products are rapidly inactivated by gastric acid, thus are available as enteric-coated preparations. They are administered with each meal and snack. Excessive doses may cause diarrhea and abdominal pain.

Phenothiazines

Drugs: Chlorpromazide (thorazine) - not used routinely as an antiemetic Perphenazine - not used routinely as an antiemetic Prochlorperazine (Compazine) Promethazine (Phenergan) Adverse effects Dry mouth Dizziness Low blood pressure w/ reflex tachycardia MOA: suppress emesis by blocking dopamine2 receptors in the CTZ. Uses: Post-operative n/v Cancer chemotherapy Used frequently for most n/v Adverse effects: Extrapyramidal reactions Anticholinergic effects Hypotension Sedation

GERD: Treatment

Dyspepsia or mild GERD -Antacids and lifestyle modification -H2 receptor antagonists for 4 to 8 weeks -If better, continue for 12 weeks then wean off. Moderate to severe GERD -PPIs for 8 weeks -If better, wean off PPIs. -If symptoms not improved, refer. -Symptoms not relieved: Increase PPI to twice daily for 4 to 8 weeks. -If symptom free for 4 weeks, step down to once a day PPI and reassess in 6 to 12 months. -If symptoms not relieved after 8 weeks, refer.

Inflammatory Bowel Diseases

Five basic classes of medications: Aminosalicylates Antibiotics Corticosteroids Immunomodulators Biologic Therapies Crohn's disease and ulcerative colitis are long-term diseases. Ulcerative colitis is a disease that causes inflammation and sores (ulcers) in the lining of the large intestine. It usually affects the lower section (sigmoid colon) and the rectum. But it can affect the entire colon. In general, the more of the colon that's affected, the worse the symptoms will be. The disease can affect people of any age. But most people who have it are diagnosed before the age of 30. Crohn's At the present time, there are five basic classes of medications used in the treatment of inflammatory bowel diseases (IBD):At the present time, there are five basic classes of medications used in the treatment of inflammatory bowel diseases (IBD): Aminosalicylates; Antibiotics; Corticosteroids; Immunomodulators; Biologic Therapies

Pediatric Gastroesophageal Reflux (GER)

GER is very common in infants. -Almost 100% in 3 months old, 4% of 6 month olds, 20% of 12 month olds -Most outgrow by 12 to 18 months -Lifestyle modification is very important to teach and encourage. -Empiric medication treatment without studies is not appropriate in infants. -Medical management reserved for few experiencing -Poor weight gain -Feeding difficulties -Persistent irritability and pain, apnea, and cyanosis

Gastroesophageal Reflux Disease (GERD)

GERD is a common problem in primary care and is listed as the primary diagnosis for 6,859,000 ambulatory care visits annually, a rate of 2,332 per 100,000. Pathophysiology -Lower esophageal sphincter tone -Gastric content regurgitation into the esophagus -Complaints of burning substernal pain that radiates upward -Persistent acid reflux that occurs more than twice a week is considered GERD.

Drugs Used for GERD

Histamine2 (H2) receptor antagonists Proton pump inhibitors (PPIs) Antacids Prokinetics

Antacids: Clinical Use and Dosing

Hyperacidity: antacids used for symptomatic relief of heartburn -May take four times per day (QID) or more -Discuss maximum dosages with patient Peptic ulcer disease -May be used as adjunct to peptic ulcer disease (PUD) triple therapy treatment -Used after meals and at bedtime Gastroesophageal reflux disease (GERD) -Antacids are over-the-counter (OTC) and often used first before patient seeks care. -May be given every 30 to 60 minutes until symptoms subside -Maintenance after meals and bedtime -Histamine2 receptor antagonists or proton pump inhibitors (PPIs) are first-line therapy for GERD. Antacids are used for GERD - symptom relief, but no healing properties. Liquids are more effective than tablets. The tablets must be chewed thoroughly and followed with 4-6 oz water.

Causes of diarrhea in primary care

Infectious Food or drug induced Inflammatory bowel disease Acute vs. chronic Children can become dehydrated quickly from diarrhea. Most diarrhea does not require medication. Diarrhea can be defined as a significant increase in the frequency of defecation compared with normal. Diarrhea usually involves excreta that are very watery and poorly formed. The most common causes of travelers' diarrhea are strains of E. coli, Campylobacter, Shigella, or Salmonella.

Antidiarrheals: Pharmacokinetics

Kaolin and pectin are not absorbed; they are eliminated in stool. Bismuth subsalicylate dissociates into salicylate that is absorbed (similar to aspirin), metabolized in the liver, and excreted in the urine with the bismuth that is not absorbed. The opioid agents are all absorbed and distributed systemically, metabolized in the liver, and eliminated in urine and/or feces. Bismuth subsalicylate has acid secretion suppressing and antimicrobial effects preventing H. Pylori adhesion to epithelial cells. The salicylate component likely adds an anti-inflammatory effect as well.

Description of different antidiarrheals

Kaolin: clay-like powder that attracts and holds onto bacteria Pectin: thickens stool Bismuth subsalicylate: antisecretory and antimicrobial effects Diphenoxylate is an opioid. Atropine causes decreased bowel secretions and slows peristalsis. Loperamide binds to opioid receptors and slows gastric motility. Pepto-Bismol (bismuth subsalicylate) (chewable tablets and liquid) has been demonstrated to be effective for preventing traveler's diarrhea. It acts not only as an adsorbent, but the vehicle may protect the mucosa and the bismuth may have some local antimicrobial action which is why it can be used to treat H-Pylori. Remember, bismuth subsalicylate will likely cause black stool and sometimes a black tongue. Diphenoxylate (opioid) and loperamide (Imodium) are narcotic derivatives that are relatively free of analgesic, euphoric or abuse-promoting effects but have a predominant effect on the gut. They decrease propulsive movements, allowing more time for water to be absorbed from fecal contents. Are generally for management of acute diarrhea of nonspecific origin, or chronic diarrhea caused by inflammatory bowel disease, or traveler's diarrhea. Diphenoxylate with atropine is Lomotil & it contains a sub therapeutic dose of atropine to produce unpleasant effects if taken in overdose, thus discourages abuse. Side effects of Lomotil include drowsiness, dry mouth, abdominal cramps & dizziness. Euphoria has been reported.

Cannabinoids

MOA: Derivative of Cannabis sativa; contains tetrahydrocannabinol (THC), an analogue of endogenous neurotransmitter anandamide; antiemetic mechanism unknown but probably involves inhibition of vomiting center (VC) in medulla oblongata Uses: -CINV (2nd line therapy) -Stimulation of appetite in patients w/ AIDS induced anorexia (only dronabinol) -Schedule III drug -Does not produce some of the "highs" seen w/ marijuana because has slow onset -Have not seen interest in these drugs as "street" drugs Drugs: Dronabinol (Marinol) Nabilone (Cesamet) Adverse effects: Potential unpleasant effects such as temporal disintegration, dissociation, depersonalization, & dysphoria Contraindicated in patients w/ psychiatric disorders Tachycardia & hypotension -> use cautiously in patients with CV history Drowsiness -> do not combine w/ ETOH, sedatives, or CNS depressants

Misoprostol (Cytotec) MOA, Uses, precautions, ADRs, drug interactions, off label, clinical use and dosing, pt education, ADRs

MOA: an analog of prostaglandin E which helps protect the stomach by suppressing secretion of gastric acids, promoting secretion of bicarbonate & cytoprotective mucus, & maintaining submucosal blood flow by promoting vasodilation. Uses: -In US, only approved use is prevention of gastric ulcers caused by long term NSAID use -Other uses: -Cervical ripening in induced pregnancy -Combined w/ RU486 to induce abortion Precautions and contraindications -Misoprostol pregnancy category X (abortifacient) ADRs -diarrhea, menstrual problems Drug interactions -diarrhea with magnesium-containing antacids Off-label Misoprostol is also used for cervical ripening and labor induction, as an abortifacient with Mifepristone (it stimulates uterine contractions), treatment of postpartum hemorrhage, and chronic idiopathic constipation. Be careful not to use in child-bearing age women or pregnant women Clinical use and dosing Ulcers associated with NSAID use -First choice is to stop NSAIDs. -Use misoprostol if patient requires NSAID therapy. -Dose four times per day. -Women of childbearing age need pregnancy test w misoprostol. Misoprostol and enprostil are indicated for prevention of NSAID- (including aspirin) induced gastric ulcers in patients at high risk of complications from a gastric ulcer. For the treatment of NSAID-induced ulcers, misoprostol is given orally 200 mcg four times daily with food. Patient education Administration Misoprostol taken with food ADRs Misoprostol: diarrhea, contact provider if lasts more than 1 week Misoprostol: pregnancy category X Misoprostol is rapidly absorbed, is quickly changed to its free acid (which is active), has a Tmax of 12 minutes and is quickly eliminated in the urine (half-life is 20 to 40 minutes). The main adverse effect is diarrhea. Other common side effects (>1%) are abdominal pain, nausea, flatulence, dyspepsia, vomiting, headache, and constipation. They are contraindicated in pregnant women (Pregnancy Category X) because of their potent abortifacient property.

Antacid MOA

MOA: react w/ gastric acid to produce neutral salts or salts low in acidity to neutralize acids in the gastrointestinal (GI) tract -If pH of stomach rises above 5, then reduce pepsin activity -Also enhance prostaglandin production which protects the gastric mucosa Common metallic cation Aluminum Calcium Magnesium Basic anion Hydroxide Bicarbonate Carbonate Antacids are simple chemicals that "neutralize" gastric acid (i.e., raise pH from 1.5 to 4.5). Four major drugs are aluminum or magnesium hydroxide, calcium carbonate, and sodium bicarbonate. Important properties include neutralizing power, onset and duration of action, effect on gut motility, and effect on electrolyte balance. Antacids reduce ("neutralize") gastric acid and relieve pain. They need to increase gastric pH only slightly (to about pH 4.5) to reduce pepsin activity. Complete neutralization of gastric acid is unnecessary and doing so tends to cause acid rebound. The antacid regimen most often used is 15-30 ml 1 & 3 hours p.c. and h.s.

4 Families of antacids

Magnesium hydroxide -Dangerous when used in patients w/ renal failure; failing kidneys can't excrete Mg++ and become toxic -Drugs: maalox, mylanta, Milk of magnesia Aluminum hydroxide -Can bind with warfarin, digoxin, tetracyclines Sodium bicarbonate -Can exacerbate heart failure, HTN, other cardiac problems; renal failure Calcium carbonate -Can cause kidney stones -Drugs: Tums

Antacid ADRs

Magnesium-based antacids may cause diarrhea. Aluminum- and calcium-based antacids may cause constipation. The major side effect of antacids is altered gut motility. Constipation (aluminum hydroxide, calcium carbonate) diarrhea (magnesium hydroxide) Na+ loading (sodium bicarbonate) Aluminum & calcium salts produce constipation; magnesium salts produce diarrhea. Many commercial preparations are mixtures to balance effect on GI motility. Serum electrolytes & acid-base balance may be affected, particularly by systemic antacids (sodium bicarbonate), sodium-containing drugs, and magnesium in patients with renal insufficiency.

Antacid drug interactions

Many; may affect the absorption of most drugs Separate antacid administration with other drugs by at least 2 hours. Antacids interfere with the absorption of tetracyclines, fluoroquinolones, penicillamine, and ketoconazole. They should NOT be used concurrently with certain enteric-coated preparations (e.g., Dulcolax Laxative). Antacids may cause breakdown of enteric coating in the stomach causing nausea & vomiting. Interference with absorption of other drugs is poorly documented but, because of possible interactions, antacids should be separated from administration of other drugs by at least one hour, optimal is 2 hours. Health care providers must emphasize to the patient or caretaker the need to follow instructions and not take them with other drugs

Constipation

Most common digestive complaint in US Rome III criteria- Pt has at least 2 of following symptoms over past 3 months: -< 3 bowel movements per week -Straining -Lumpy or hard stools -Sensation of anorectal --obstruction -Sensation of incomplete defecation -Manual maneuvering required to defecate Patient may be totally asymptomatic or may complain of 1 or more of following: -Abdominal bloating -Pain on defecation -Rectal bleeding -Spurious diarrhea -Low back pain Symptoms which suggest difficult rectal evacuation: -Feeling of incomplete evacuation -Digital extraction -Tenesmus -Enema retention Diagnostics -Need workup if > 3-6 months failed medical management. -Rectal & perineal examination should already have been performed but should be repeated -Laboratory evaluation does not play large role initially -Imaging studies used to R/O acute processes that may be causing colonic ileus or to evaluate chronic constipation cause -If acute abdominal pain, fever, leukocytosis, or other symptoms suggesting possible systemic or intra-abdominal processes, imaging studies needed to R/O sources of sepsis or intra-abdominal problems -Lower gastrointestinal (GI) endoscopy, colonic transit study, defecography, anorectal manometry, surface anal electromyography (EMG), and balloon expulsion may be used in the evaluation of constipation Laboratory evaluation does not play large role initially, however, if due for labs would check CBC, TSH, CMP & Stool for occult blood When to be Concerned -Rectal bleeding -Abdominal pain (suggestive of possible irritable bowel syndrome [IBS] with constipation [IBS-C]) -Inability to pass flatus -Vomiting

What are cytoprotective agents?

NSAIDs cause gastric mucosal damage and ulcer formation. Cytoprotective agents -Sucralfate (Carafate): selectively binds to ulcer tissue, acting as a barrier -Misprostol (Cytotec): inhibits gastric secretion, has mucosal protective qualities In the stomach, both mucus and epithelial cell-cell tight junctions restrict back diffusion of acid and pepsin. Epithelial bicarbonate secretion establishes a pH gradient within the mucous layer. Blood flow carries bicarbonate and vital nutrients to surface cells. Mucosal prostaglandins appear to be important in stimulating mucus and bicarbonate secretion and mucosal blood flow. Sucralfate is an aluminum salt of a polysaccharide which, in the acidic medium of the stomach, splits off the aluminum leaving a highly polar substance that is non-absorbable and protects against acid, pepsin and bile salts. Sucralfate (Carafate) binds with selectively binds to proteinaceous exudate in the stomach and covers the ulcer with a viscous gel, acting as a barrier and protects from effect of acid and pepsin. Misoprostol is a synthetic prostaglandin E1 that has both antisecretory and mucosal protective properties, so it facilitates regeneration of the mucosa after NSAID-induced injury. It enhances mucous and bicarbonate secretion.

Examples of Proton Pump Inhibitors

Omeprazole [Prilosec {Prilosec OTC}] Lansoprazole [Prevacid];dexlansoprazole [Kapidex] Pantoprazole [Protonix] Rabeprazole [Aciphex] Esomeprazole Magnesium [Nexium (#1)] (Note -prazole as a class name) PPIs at 2 hr reduce peak acid output >80% and at 24 hr there is 50% inhibition. Effects persist up to 72 hr until new H+/K+-ATPase is synthesized. Zegerid powder (a combination of omeprazole and sodium bicarbonate) for oral suspension is an immediate-release formulation of omeprazole. Each 20- or 40-mg packet contains sodium bicarbonate, which protects the drug from gastric acid degradation. The drug is approved for reduction of risk of upper GI bleeding in critically ill patients and may be useful for patients who have nasogastric tubes in place.

Antidiarrheals: Precautions and Contraindications

Opioids decrease intestinal motility and may cause toxic megacolon. Bismuth subsalicylate is contraindicated in children with viral or flu-like illness. Use all cautiously in older adults. Antidiarrheals are contraindicated in the treatment of diarrhea in most children Bismuth may cause harmless blackening of the stool (maybe confused with GI bleeding) or darkening of the tongue. Avoid using bismuth compounds in patients with renal insufficiency. High doses may cause salicylate toxicity. Arcangelo suggests that bismuth subsalicylate, 2 tablets with meals and at bedtime, as chemoprophylaxis for patients who cannot or will not comply with dietary restrictions Opioids (diphenoxylate & loperamide) are used generally for management of acute diarrhea of nonspecific origin, or chronic diarrhea caused by inflammatory bowel disease, or traveler's diarrhea. Dose of d iphenoxylate: 2 tablets stat then 1 after each loose stool. Bismuth subsalicylate is contraindicated in children with viral or flu-like illness because of potential Reye syndrome association.

Acute Diarrhea treatment

Oral electrolyte mixtures American Academy of Pediatrics suggests oral rehydration important in children 1 month to 5 years of age. Rehydration Preparations: Rehydralyte Solution, Ricelyte Oral Solution, Resol Solution, Infalyte, and Pedialyte solution. Sports drinks do not have enough sodium to replace losses from diarrhea. Drinks high in sugar content should be avoided because it may increase the osmotic load and worsen the diarrhea. Pedialyte or other fluid/lyte replacement fluid needed to replace mild to moderate fluid losses when food and liquid intake are discontinued; or to restore fluid and minerals lost in diarrhea and vomiting in infants and children. They generally contain sodium, potassium, chloride, and glucose. Preparations are Rehydralyte Solution, Ricelyte Oral Solution, Resol Solution, Infalyte, and Pedialyte solution. Given every 3-4 h or as frequently and in amounts tolerated The WHO extemporaneous oral rehydration formulation for adults is ½ tsp table salt, ¼ tsp potassium salt, ½ tsp baking soda, and 2 tbsp glucose or 4 tbsp table sugar per liter.

Glycerin; Lactulose Saline compounds including Magnesium salts Sodium bisphosphate Polyethylene glycol (PEG) Sorbitol

Osmotic (Hyperosmolar) laxatives MOA: work by drawing water into the intestine, thereby promoting bowel distention & peristalsis. -Works fastest for constipation Uses: -Glycerin helpful for bowel retraining -Lactulose used to treat constipation & help reduce ammonia production & absorption from the intestines in liver disease -Saline compounds used when prompt & complete bowel evacuation is required Hyperosmolar laxatives produce a bowel movement by drawing water into the intestine. Fluid accumulation distends the bowel & promotes peristalsis & a bowel movement. Adverse Effects: Glycerin: Weakness, fatigue Lactulose: Abdominal distention, gas, & abdominal cramps n/v Diarrhea Hypokalemia Hypovolemia Increased glucose levels Saline compounds Weakness, lethargy Dehydration, hypernatremia, hypermagnesemia, hyperphosphatemia, hypocalcemia Cardiac arrhythmias PEG Nausea, abdominal fullness, explosive diarrhea, bloating

Peptic Ulcer Disease (PUD)

PUD has a lifetime incidence of 12% in men and 10% in women. Pathophysiology -Increased acid and pepsin secretion -Impaired mucosal cytoprotection -Use of NSAIDs, H. pylori -Gastric: antral stomach region erosion, raised gastrin -Duodenal: H. pylori releases toxins, phospholipase enzymes promoting inflammation and erosion Pepsin is stored in the body as inactive pepsinogen. Acid activates pepsinogen to form pepsin, which digests protein foods as well as the layers of the stomach & intestines if the cytoprotective layer is absent (due to H. pylori or NSAIDs). This leads to ulcer formation. The normal gastric mucosa is protected from ulceration by several mechanisms. Mucus and bicarbonate act as a barrier to hydrogen ion back-diffusion and keep the pH almost neutral at the surface of the mucosa. If damaged, mucosal epithelial cells regenerate rapidly. Certain prostaglandins (PGE) stimulate mucus and bicarbonate secretion and increase blood flow. Good blood flow is necessary for healing. NSAIDs, which block prostaglandins, are a common cause of gastric ulcers Infection with H. pylori is the most common cause of peptic ulcers. There is growing evidence that Helicobacter pylori is somehow involved in the pathogenesis of active chronic gastritis, gastric ulcer, duodenitis, duodenal ulcer, and gastric carcinoma. The prevalence of H. pylori infection increases with increasing age and decreasing socioeconomic status. H pylori bacteria appear to produce GI mucosal damage. Helicobacter pylori is a gram-negative organism found in the narrow interface between the gastric epithelial cell surface and the overlying mucus gel layer. H. Pylori is a common gastric infection, affecting >50% of the world's population. Although it plays an important role in ulcer disease, the majority of H pylori-infected patients do not develop peptic ulcers. However, the presence of H. pylori doubles the risk of GI bleeding in patients taking. Eradication of H. pylori facilitates ulcer healing, eliminated the need for maintenance therapy, and markedly reduces the risk of ulcer recurrence. Less common forms of peptic ulcer disease: a. Zollinger-Ellison (ZE) syndrome b. Acute stress ulcers (Curling's ulcer) Zollinger-Ellison (ZE) syndrome, pancreatic tumors, or other tumors often are accompanied by secretion of massive amounts of gastric acid. In these hypersecretory states, ulcers may be large and numerous and develop in both the stomach and duodenum. Acute stress ulcers (Curling's ulcer) are those that develop rapidly in response to severe physical insults (e.g., burns, trauma). The causes are not known, but may involve decreased mucosal blood flow (sympathetic stimulation) and release of corticosteroids (that inhibit formation of prostaglandins). Morbidity & mortality are very high with stress ulcers. The incidence of nosocomial pneumonia was 22-27% in patients in intensive care treated with H-2 antagonists for prophylaxis of stress ulcer Goals for treating NSAID-induced PUD are to relieve ulcer pain and heal existing ulcers. An additional consideration is identifying an alternative to the NSAID for pain management. Prophylaxis could include switching to acetaminophen or changing to an enteric-coated NSAID, adding misoprostol to the therapeutic regimen, or switching to an NSAID with COX-2 selectivity if NSAID therapy must be continued. Patients with duodenal ulcers secrete excessive amounts of gastric acid that fails to be neutralized by alkaline pancreatic secretions, hence gastric acid reaches the duodenum. These patients usually require higher doses of antiulcer drugs.

Antidiarrheals: Patient Education

Patient Education Rebound constipation Bismuth turning tongue and stool black Products with atropine may cause dry mouth and anticholinergic effects. Opioids may cause CNS effects. Lifestyle management Adequate hydration

Histamine2 Receptor Antagonists (H2RAs) Pharmacodynamics

Pharmacodynamics -H2RAs are reversible competitive blockers of histamine at histamine2 receptors located on the parietal cells of the stomach. -Highly selective; Reduce H+ concentration -Reduce gastric acid secretion by 35% to 50% Potency in controlling gastric acid secretion -Ranitidine is 5 to 12 times more potent than cimetidine. -Famotidine is 30 to 60 times more potent than cimetidine Histamine, acting on histamine-2 receptors in the stomach wall, is believed to be the final common mediator of acid secretion released by a variety of chemical stimuli. However, H2 antagonists only partially block gastric acid secretion stimulated by acetylcholine and gastrin. They predominantly inhibit basal acid secretion, which accounts for their efficacy in suppressing nocturnal acid secretion. Histamine-2 blockers are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells, causing a dose-dependent inhibition of gastric acid secretion. They are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. They are effective in alleviating symptoms and in preventing complications of peptic ulcer disease. They have, for the most part, similar adverse reaction profiles. Cimetidine [Tagamet] is the prototype

General laxative precautions and contraindications, ADRs, clinical use and dosing, pt education

Precautions and contraindications -All are contraindicated in in the presence of nausea, vomiting, or undiagnosed abdominal pain or if bowel obstruction is suspected or diagnosed -Magnesium hydroxide contraindicated in renal dysfunction ADRs -Excessive bowel activity, cramping, flatulence, and bloating Clinical use and dosing -Dependent on class of drug -Rapid response and short-term use Stimulants are the drug of choice. Osmotic laxatives also work well (magnesium hydroxide, PEG 3350). Surfactants: docusate -Slower response and long-term use Bulk-forming laxatives -Pregnancy Bulk-forming laxatives are safest. PEG (Miralax) or docusate may be used. Patient education Administration -Rapid-acting laxatives are best taken in the morning; slower-acting ones are best taken at bedtime. ADRs -Cramping, flatulence, and bloating Lifestyle management -Prevention is the key. -Laxatives are temporary fixes. -Misconceptions about bowel function should be corrected. The key to treating most patients with constipation is correction of dietary deficiencies, which generally involves increasing intake of fiber and fluid and decreasing the use of constipating agents (eg, milk products, coffee, tea, alcohol).

Traveler's Diarrhea

Prevention: Travelers should be advised to avoid raw vegetables, fruit they have not peeled themselves, unpasteurized dairy products, cooked food not served steaming hot, and tap water (including ice). Common causes: E. coli, Campylobacter, Shigella, or Salmonella. Mild diarrhea: loperamide (Imodium) 4 mg loading dose then 2 mg orally after each loose stool is well tolerated. Moderate to severe diarrhea: Lasting > 3 days or with fever, treat with a fluoroquinolone for 1-3 days. Rifaximin is similar in efficacy to ciprofloxacin with fewer ADRs but should not be used in infections caused by Campylobacter. Rifaximin is teratogenic in animals. The most common causes of travelers' diarrhea are strains of E. coli, Campylobacter, Shigella, or Salmonella. For mild diarrhea, loperamide 4 mg loading dose then 2 mg orally after each loose stool is well tolerated. If diarrhea is moderate to severe, persists > 3 days or with fever, treatment is a fluoroquinolone for 1-3 days. Fluoroquinolones are not recommended for use in children or pregnant women in which case azithromycin should be considered. Rifaximin is similar in efficacy to ciprofloxacin with fewer adverse effects but should not be used in infections caused by Campylobacter. Rifaximin is teratogenic in animals. Travelers should be advised to avoid raw vegetables, fruit they have not peeled themselves, unpasteurized dairy products, cooked food not served steaming hot, and tap water (including ice).

Metoclopramide

Prokinetic drug Stimulate the motility of the GI tract without stimulating gastric, biliary, or pancreatic secretions Pharmacodynamics Metoclopramide stimulates motility in the upper GI tract. Metoclopramide also has some actions similar to the phenothiazines and dopamine antagonists. Uses: N/V (IV) Diabetic gastroparesis (oral) Suppression of GERD (oral) Facilitation of small bowel intubation and examination (IV) Hiccups (off label) Metoclopramide is termed a "prokinetic" or "promotility" drug, which increases lower esophageal sphincter pressure and improves esophageal peristalsis. It stimulates motility of the upper GI tract without increasing secretions from the pancreas or having an effect on gall bladder motility. It may provide symptomatic relief but the effect in healing esophageal lesions is marginal and not consistent. it appears to block dopamine (D2) receptors in the GI tract and sensitize tissues to the action of acetylcholine. It increases the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and duodenal bulb, and increases peristalsis. Metoclopramide also blocks dopamine receptors in the CNS, hence produces sedation, antiemetic effect, and may rarely produce extrapyramidal reactions. Nevertheless, e Metoclopramide (reglan) MOA: increase upper GI motility by enhancing action of ACh. Precautions and Contraindications -Metoclopramide has a Black Box warning due to risk of developing tardive dyskinesia. -Contraindicated in GI hemorrhage, mechanical obstruction, new surgery on the GI tract, or perforation -Use cautiously in patients with a history of depression. -Depression may occur, including suicidal ideation. Warnings: May produce depression & extrapyramidal symptoms. Metoclopramide has been reported to cause tardive dyskinesia. Warning against using with MAO inhibitors. Investigational uses of metoclopramide include improve lactation, N&V due to various causes, improve response to ergotamine, analgesics & sedatives when used to treat migraine, atonic bladder, and esophageal variceal bleeding. Pregnancy Category B ADRs Tardive dyskinesia Depression, dizziness Diarrhea Hypoglycemia in patients with diabetes Rare: galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia Extrapyramidal effects and drowsiness limits the value of this medication in GERD. Drug Interactions Additive CNS depression occurs with other CNS depressants. Increased risk of EPS occurs with other drugs that have the potential for EPS. Drugs with anticholinergic effects reverse the action of metoclopramide. -Warning against using with MAO inhibitors. Metoclopramide also blocks dopamine receptors in the CNS, hence produces sedation, antiemetic effect, and may rarely produce extrapyramidal reactions. Clinical use and dosing -GERD Adults: 10 mg 30 minutes before meals -Diabetic gastroparesis 10 mg 30 minutes before meals and at bedtime for 2 to 8 weeks -Patients with continuous complete remission below 40 mL/minute should have their therapy initiated at approximately half the recommended dosage. Metoclopramide is indicated for the treatment of diabetic gastroparesis, symptomatic gastroesophageal reflux, and nausea & vomiting associated with emetogenic cancer chemotherapy. Neonatal: Metoclopramide is recognized in Neofax to facilitate gastric emptying and GI motility and states its use in GE reflux is controversial Monitoring Renal function New onset movement disorder Depression or suicidal ideation Patient education -Administration Take 30 minutes before meals. Do not double doses. -ADRs Drowsiness Additive CNS depression with CNS depressants (alcohol) Report any involuntary movements. -Lifestyle management GERD lifestyle changes

PUD: Treatment

Step 1 -Lifestyle modifications and over-the-counter antacids or H2 blockers Step 2 -H. pylori testing -Treatment with PPIs Step 3 -Treatment for H. pylori Peptic Ulcer Disease Therapeutic plan: Relieve pain, enhance healing, prevent complications, & prevent recurrence Stop smoking; avoid alcohol (both impair healing) Avoid ulcerogenic drugs, caffeine & foods or beverages that aggravate Avoid eating after dinner (stimulates acid secretion at night) Stress management. H. Pylori testing: Can test serum & stool for H Pylori or take samples from stomach during an EGD, or perform a Urea breath test. Urea breath test: Pt drinks a liquid that contains urea. Pt. breathes into a bag, which is sent to a lab for testing. If H. pylori positive, the bacteria will change the urea into CO2, and lab tests will show that breath has higher than normal levels of the CO2. A number of drugs can be used for effective management of PUD. Relapses are common and can be prevented only by eradicating H. pylori. All regimens include a PPI plus antibiotics to treat H. pylori. Triple therapy: PPI plus -Clarithromycin: 500 mg twice daily, or -Metronidazole: 500 mg twice daily -Amoxicillin: 1 gm twice daily -Treat for 10 to 14 days. Quadruple therapy: PPI plus -Metronidazole: 250 mg four times/day -Tetracycline: 500 mg four times/day -Bismuth subsalicylate: 525 mg four times/day -Treat for 14 days. -Usually used as second-line therapy in patients who fail first-line therapy. The proton pump inhibitors are indicated during the eradication of H. pylori. The treatment involves taking 14 or more pills per day for a few weeks. First-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Levofloxacin-based triple therapy -PPI: twice daily -Levofloxacin: 250 to 500 mg twice daily -Amoxicillin: 1 gm twice daily -Treat for 10 to 14 days. -Second-line or rescue therapy -First-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Common ADRs: ●Treatment regimens using metronidazole (Flagyl) or clarithromycin (Biaxin) cause a metallic taste in the mouth. ●Alcoholic beverages (eg, beer, wine) should be avoided while taking metronidazole; the combination can cause skin flushing, headache, nausea, vomiting, sweating, and a rapid heart rate. ●Bismuth causes the stool to become black and may cause constipation. ●Many of the regimens cause diarrhea and stomach cramps

Bisacodyl (Dulcolax) Cascara sagrada Castor oil Senna

Stimulant laxatives MOA: stimulate peristalsis & produce a bowel movement by irritating the intestinal mucosa or stimulating the nerve endings of the intestinal smooth muscle. **Almost instantaneous relief of constipation. Uses: DOC for emptying bowels prior to surgery Colonoscopy or sigmoidoscopy prep Tx constipation from prolonged bedrest Neurological dysfunction of colon Treat opioid induced constipation. Adverse effects: Weakness Nausea Abdominal cramps Mild inflammation of rectum & anus Urine discoloration (cascara or senna)

docusate sodium [Colace; Dulcolax Stool Softener] docusate calcium [Surfak]; DOSS {for dioctyl sodium sulfosuccinate}

Stool Softeners Stool softeners are "surfactants." They reduce surface tension of the stool and help form an emulsion between fats and water, which penetrate the hard, dry stool, making it soft. They are supplied as capsules, tablets, and oral liquids. Docusate is often an ingredient in many laxative preparations. (DOSS was the surfactant used to disperse the oil from the BP oil spill in the Gulf). Stool softeners are used to ease painful passage of hard stools or to avoid straining, such as in patients with hemorrhoids or post CVAs. They may be used during pregnancy, if necessary. In that they do not stimulate production of a stool, they are not truly laxatives. The Dulcolax Stool Softener advertisement says it "doesn't make you go, it makes it easier to go."

Sodium, potassium, or calcium docusate Trade name - Colace

Surfactant laxatives AKA emollient laxatives MOA: emulsify the fat & water components of feces in the small & large intestines. Reduces the surface tension of the interfacing liquid contents of the bowel promoting incorporation of additional liquid into stool, thus forming softer mass -Detergent action allows water & fat to penetrate the stool, making it softer & easier to eliminate -Also stimulate electrolyte & fluid secretion from intestinal mucosal cells -Does not stimulate intestinal peristaltic movement Uses: -Recent MI or surgery -Disease of the anus or rectum (i.e., hemorrhoids) -Increase intracranial pressure hernias Adverse effects -> over all well tolerated: Bitter taste Diarrhea Throat irritation Mild, transient abdominal cramping

Overview of GI system and disorders

The gastrointestinal tract extends from the mouth to the anus. Enzymes, hormones, electrolytes, and fluids are secreted to aid in the digestion of nutrients, to move the intestinal contents along the tract, and eventually to eliminate those substances not absorbed. Digestive diseases afflict 12% of Americans and cause 16% of all absences from work. Acute diarrheal illness is the second most common illness reported (common cold is first). Drug-induced GI disorders include erosive gastritis and ulcers (caused by potassium chloride, corticosteroids, aspirin, NSAIDs), diarrhea, and constipation.

Antacids: Administration

Usually taken 1 to 3 hours after meals and at bedtime Chewable tablets must be chewed. Antacids affect absorption of other drugs. -Separate by 2 hours. -Do not use antacids without consulting with provider. Calcium-based antacid absorption is decreased by oxalic acid and phytic acid and increased by acidic fruit juice.

H2 Blockers uses, clinical use and dosing, precautions and contraindications, ADRs, drug interactions, monitoring, pt education,

Uses: Gastric & duodenal ulcers -Gastric ulcers require 8-12 weeks to heal -Duodenal ulcers require 4-6 weeks Gastroesophageal reflux disease (GERD) Zollinger-Ellison Syndrome - (hypersecretion of gastric acid -> peptic ulcers) Aspiration pneumonitis R/T gastric aspiration during anesthesia intubation Heartburn, acid indigestion, sour stomach Clinical use and dosing GERD -Twice daily dosing -No empiric treatment of infants with GERD with H2RAs PUD -Not used as frequently. PPI is drug of choice Heartburn, acid Indigestion, and "sour stomach" -Use OTC dosing. Decrease dosing for renal dysfunction. Precautions and contraindications -Cautious use in renal impairment -Hepatocellular injury may occur with nizatidine. -Occasional reversible hepatitis or hepatocellular disorders have occurred with ranitidine. -Pregnancy category B -Ranitidine and famotidine use approved in children nizatidine (Axid) watch for hepatocellular damage with long term use Cimetidine (Tagamet) contains a warning of interactions with theophylline, warfarin, and phenytoin; not used much. large doses of cimetidine given to patients unable to eliminate the drug may develop central effects such as severe agitation, slurred speech, confusion, & delirium. This is especially applicable to the elderly or subjects with renal impairment. This CNS effect is generally not seen with the other H2 antagonists ADRs *Antiandrogenic reactions Gynecomastia and impotence-especially with cimetidine *CNS adverse reactions Mental confusion, agitation, psychosis, depression, and disorientation *Elevating gastric pH increases risk of pneumonia *Agranulocytosis, granulocytopenia, thrombocytopenia, and aplastic anemia Administration: The histamine-2 antagonists can be given as divided daily doses or as a single dose, usually at bedtime By decreasing gastric acid the H2 antagonists (all) may interfere with the absorption of certain azole antifungals (e.g., ketoconazole) which require acid for solubilizing. There are ongoing studies trying to link H2 blockers (and PPIs) and pneumonia. Drug interactions -Cimetidine uses several isoenzymes (CYP 1A2, CYP 2C9, and CYP 2D6). Monitoring -Monitor liver function if high-dose or long-term use. Problems with cimetidine: Not the DOC for H2 blockers Adverse effects: Antiandrogen effects - the drug binds w/ androgen receptors. Gynecomastia, dec. libido, impotency CNS effects - esp in elderly w/ renal or hepatic impairment. Confusion, hallucinations, depression or restlessness Cimetidine inhibits hepatic drug-metabolizing enzymes & inc. levels of other drugs including warfarin & phenytoin Patient education Administration -Take with meals. -Separate antacids by 30 minutes to 1 hour. ADRs -May cause drowsiness or dizziness -Cimetadine may cause gynecomastia and impotence in men. Lifestyle -Smoking decreases absorption of H2RAs. -Alcohol increases gastric irritation.

Orlistat (Xenical and as Alli) Diethylpropion and phentermine Phentermine with topiramate (Qnexa) Topiramate and zonisamide [Zonegran]

obesity Orlistat is a reversible (Lehne says irreversible) lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. Undigested triglycerides are not absorbed, resulting in a caloric deficit that may have a positive effect on weight control. Orlistat is not absorbed (Pregnancy Category B). The drug may be taken with each main meal or up to 1 hour after the meal. "minimally effective as a weight loss agent." Adverse reactions were primarily a manifestation of the mechanism of action with oily evacuation, flatus, fecal urgency, and fecal incontinence (in >20% of patients). Post marketing reports reveal cases of hypothyroidism in patients taking orlistat and levothyroxine. Diethylpropion and phentermine are nonamphetamines but CNS stimulants that suppress appetite by increasing the availability of NE in the brain. Indicated only for short term (3 months or less) use. Tolerance can develop; abuse may occur, and the drugs cause increased alertness, decreased fatigue, nervousness & insomnia. Peripheral effects are tachycardia, angina pain & hypertension. Phentermine with topiramate (Qnexa) as an antiobesity drug. PHEN/TPM is a once-daily, controlled-release, combination weight-loss product approved as an adjunct to diet and exercise for chronic weight management of obese or overweight patients with weight-related comorbidities. PHEN/TPM is modestly effective and a viable option for patients interested in losing weight, although long-term safety data are lacking. Side effects that were reported in >5% of patients included paresthesias, dizziness, dysgeusia, insomnia, constipation, and dry mouth. topiramate and zonisamide [Zonegran] for weight reduction. There was a high incidence of adverse effects; most common were altered taste, constipation, diarrhea, dry mouth, headache, fatigue, N/V, somnolence, speech problems, impaired attention, memory problems, anxiety, and depression

Sucralfate (Carafate): MOA, Uses, precautions, ADRs, drug interactions, off label, clinical use and dosing, pt education, ADRs

selectively binds to ulcer tissue, acting as a barrier ADRs Sucralfate: constipation Drug interactions Sucralfate: decreases absorption of other drugs Clinical use and dosing -Ulcers associated with NSAID use First choice is to stop NSAIDs. Use misoprostol if patient requires NSAID therapy. Dose four times per day. Women of childbearing age need pregnancy test w misoprostol. -Duodenal ulcers from other causes Sucralfate for up to 8 weeks to heal ulcer Give four times per day, 1 hour before meals. Sucralfate is indicated for short-term treatment and maintenance therapy for duodenal ulcers. It is given 1 g qid 1 hour before meals and at bedtime but not within a half an hour of antacids. Sucralfate may be used for prevention of stress-related bleeding because of concerns that acid inhibitory therapies may increase the risk of nosocomial pneumonia. Sucralfate: Constipation is the most common side effect. The drug interferes with the absorption of digoxin, beta-blockers, warfarin, phenytoin, some antiarrhythmics, and fluoroquinolones. Pregnancy category B. Patient education Administration Sucralfate taken on empty stomach