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Drug Therapy For Peptic Ulcer Disease and Gastroesophageal Reflux Disease

Terms in this set (68)

• Characterized by ulcer formation in the esophagus, stomach, or duodenum—areas of the GI mucosa that are exposed to gastric acid & pepsin.
• Gastric & duodenal ulcers are more common than esophageal ulcers.
• Infection w/ H. pylori & use of NSAIDs are common causes. H. pylori is a gram-negative bacterium found in the gastric mucosa of most patients with chronic gastritis (inflammation of gastric mucosa).
• Spread mainly by the fecal oral route. However, iatrogenic spread by contaminated endoscopes, biopsy forceps, & nasogastric tubes has also occurred.
• Stress can cause ulcer formation. Gastric ulcers more likely to occur in older adults, especially in the sixth & seventh decades, & to be chronic in nature.
• Duodenal ulcers occur at any age, & manifested by abdominal pain, & are usually chronic. Also associated w/ cigarette smoking. Compared w/ nonsmokers, smokers are more likely to develop duodenal ulcers; ulcers heal more slowly w/ treatment, & ulcers recur more rapidly.
• Peptic ulcers result from imbalance between cell-destructive & cell-protective effects (i.e., presence of increased destructive mechanisms or presence of decreased protective mechanisms).
• Cell-destructive effects include those of gastric acid (hydrochloric acid), pepsin, H. pylori infection, & NSAID ingestion. Gastric acid (can digest the stomach wall), secreted by parietal cells in the mucosa of the stomach antrum, near the pylorus. The parietal cells contain receptors for acetylcholine, gastrin, & histamine, substances that stimulate gastric acid production. The enzyme H+, K+-ATPase catalyzes the production of gastric acid & acts as a gastric acid (proton) pump to move gastric acid from parietal cells in the mucosal lining of the stomach into the stomach lumen.
• Pepsin, a proteolytic enzyme, helps digest protein foods & can digest the stomach wall. Pepsinogen is converted to pepsin only in a highly acidic environment (i.e., when the pH of gastric juices is 3 or less).
• After H. pylori moves into the body, the bacterium colonizes the mucus-secreting epithelial cells of the stomach mucosa and is thought to produce gastritis and ulceration by impairing mucosal function. Eradication of the microorganism accelerates ulcer healing and significantly decreases the rate of ulcer recurrence.
• Cell-protective effects (e.g., secretion of mucus and bicarbonate, dilution of gastric acid by food and secretions, prevention of diffusion of hydrochloric acid from the stomach lumen back into the gastric mucosal lining, the presence of prostaglandin E, alkalinization of gastric secretions by pancreatic juices and bile, perhaps other mechanisms) normally prevent autodigestion of stomach and duodenal tissues and ulcer formation.
• A gastric or duodenal ulcer may penetrate only the mucosal surface or it may extend into the smooth muscle layers. When superficial lesions heal, no defects remain. When smooth muscle heals, however, scar tissue remains and the mucosa that regenerates to cover the scarred muscle tissue may be defective. These defects contribute to repeated episodes of ulceration.
o Act in the stomach, & take them to prevent/treat peptic ulcer disease, GERD, esophagitis, heartburn, gastritis, GI bleeding, & stress ulcers.
o When pain relief is the goal of treatment, taking them on an as-needed basis is usually sufficient. However, it is important not to take them in high doses or for prolonged periods because of potential adverse effects.

o Use in children: ambulatory children may take Mylanta in doses of 5 to 15 mL every 3 to 6 hours, or after meals, & at bedtime. For prevention of GI bleeding in critically ill children, infants may receive 2 to 5 mL and children may receive 5 to 15 mL every 1 to 2 hours.
o Use in older adults: may use all of the antiulcer, anti-heartburn drugs. W/ Mylanta & the other antacids, smaller doses may be effective because older adults usually secrete less gastric acid than younger adults. W/ decreased renal function, older adults are more likely to have adverse effects, many physicians recommend calcium carbonate antacids (e.g., Tums) as a calcium supplement in older women to prevent or treat osteoporosis.

o Use in Renal Impairment: (creatinine clearance < 30 mL/min) should not take magnesium-based antacids such as because magnesium may be absorbed & accumulate to cause hypermagnesemia. Patients w/ chronic renal failure & hyperphosphatemia may take aluminum-based antacids to decrease absorption of phosphates in food. (Aluminum binds with phosphate in the GI tract, preventing phosphate absorption) However, aluminum may accumulate in patients w/ renal failure, leading to encephalopathy, erythropoietin-resistant anemia, & osteomalacia. Antacids containing calcium carbonate are currently recommended for the purpose of controlling phosphate levels in patients with end-stage renal failure. Antacids w/ calcium carbonate can cause alkalosis & raise urine pH, and chronic use may cause renal stones & hypercalcemia.

o Use in Critical Illness: to prevent stress ulcers in critically ill patients & to treat acute GI bleeding, continuous neutralization of gastric acid is desirable. Dose/frequency of administration must be sufficient to neutralize the gastric acid: a continuous intragastric drip through a nasogastric tube is effective. For patients w/ a nasogastric tube in place, antacid dosage may be titrated by aspirating stomach contents, determining pH, & then basing the dose on the pH. (Most gastric acid is neutralized & most pepsin activity is eliminated at a pH above 3.5.)
o Prevention/treatment of peptic ulcer disease, GERD, esophagitis, GI bleeding due to acute stress ulcers, & Zollinger-Ellison syndrome. W/ gastric or duodenal ulcers, healing occurs w/in 6 to 8 weeks; w/ esophagitis, in 12 weeks. FDA has approved OTC preparations for heartburn.
o Use in Older Adults: More likely to experience adverse effects, especially confusion, agitation, & disorientation.
o Use Renal Impairment: Use in impaired renal function requires caution. Necessary to reduce dosage because the drugs are eliminated through kidneys. Cimetidine may cause mental confusion in patients with renal impairment. It also blocks secretion of creatinine in renal tubules, thereby decreasing creatinine clearance & increasing serum creatinine level. Any dosage increase should be cautious, with close monitoring of renal function.
o QSEN: For patients on hemodialysis, cimetidine adminis-tration should occur at the end of dialysis.
o Use in Hepatic Impairment: Partial metabolism occurs in liver, which means that drug levels are higher than anticipated in patients w/ impaired liver function. Cimetidine inhibits the hepatic metabolism of many other drugs; this is a major concern.
o Use in Critical Illness: commonly used in critically ill to prevent stress-induced gastric ulceration. Usually administered by intermittent IV infusion. Information about the pharmacokinetics of these drugs in critically ill patients is limited. In patients who are critically ill, H2RAs have longer half-life & lower clearance rate than in people who are healthy.
• Antacids decrease absorption of cimetidine; should not be given at the same time.
• QSEN: However, cimetidine contributes to multiple-drug interactions, because it is a known inhibitor of many isozymes of the cytochrome P450 drug-metabolizing system in the liver and therefore interferes with the hepatic metabolism of other drugs. Consequently, the clearance of affected drugs from the body is slower; the increased serum levels means that the drugs are more likely to cause adverse effects and toxicity unless dosage is reduced.
• Drugs that are affected by cimetidine: antidysrhythmics (lidocaine, propafenone, quinidine), warfarin, anticonvulsants (carbamazepine, phenytoin), benzodiazepine antianxiety or hypnotic agents (alprazolam, diazepam, flurazepam, triazolam), beta blockers (labetalol, metoprolol, propranolol), the bronchodilator theophylline, calcium channel blocking agents (e.g., verapamil), tricyclic antidepressants (e.g., amitriptyline), & sulfonylurea antidiabetic drugs.
• May increase serum levels (e.g., fluorouracil, procainamide & its active metabolite) & pharmacologic effects of other drugs (e.g., respiratory depression with opioid analgesics) by unidentified mechanisms.
• May decrease effects of several drugs that require an acidic environment for absorption (e.g., iron salts, indomethacin, fluconazole, tetracyclines) & misc. drugs (e.g., digoxin, tocainide) by unknown mechanisms.
• The accumulation of the antihistamines, terfenadine and astemizole, may result in a prolongation of the QT interval and could lead to the development of ventricular dysrhythmias such as torsades de pointes.
• May decrease the effects of drugs that require an acidic environment for absorption (e.g., iron salts, indomethacin, fluconazole, tetracyclines) & misc. drugs (e.g., digoxin, tocainide) by unknown mechanisms.
o Usually drug class of choice for treatment of peptic ulcer disease; GERD w/ erosive esophagitis; & Zollinger-Ellison syndrome. W/ duodenal and gastric ulcers, healing may occur after 2 weeks compared to 4 weeks using H2RAs. W/ GERD, PPIs usually eliminate symptoms w/in 1 to 2 weeks & heal esophagitis w/in 8 weeks. Lower doses can prevent recurrence of esophagitis, maintain symptom relief, & heal esophagitis. Higher doses or longer therapy may be needed for severe GERD.
o In patients with H. pylori-associated ulcers, eradication of the bacterium w/ antimicrobial drugs is preferable to long-term maintenance therapy with antisecretory drugs. Therapy w/ a PPI & two antimicrobial drugs is most effective regimen.
o Use in Children: gained popularity in children & infants for management of peptic ulcers & GERD & eradication of H. pylori. These drugs are acid labile, & oral formulations consist of capsules that contain enteric-coated granules. A chewable & liquid formulation are available.
o Use in Older Adults: drug of choice for symptomatic GERD because evidence suggests that patients 60+ years require stronger antisecretory effects. However, long-term use (1+ year) is associated w/ increased risk of hip fractures in older than 50 years of age; risk of fractures increases the longer the medications are taken & is greater in people who take higher dosages. Increased risk of fractures is due to decreased calcium absorption due to achlorhydria (low/absent production of gastric acid) from PPI therapy.
o Use in Hepatic Impairment: bioavailability is increased because of decreased first-pass metabolism & plasma half-life is increased. Metabolism occurs in liver, & use may cause transient elevations in liver function tests. Dosage adjustments are not recommended.
o Use in Critical Illness: The PPIs are the strongest gastric acid suppressants used in patients who are critically ill. They usually tolerate the drugs well. IV administration, if necessary, is an option.
• Commonly used prevent/treat peptic ulcers & heartburn. Peptic ulcers usually form in the stomach or first part of small bowel (duodenum), where tissues are exposed to stomach acid. 2 common causes: stomach infection w/ H. pylori & taking NSAIDs. Heartburn (GERD) is caused by stomach acid splashing back onto esophagus.
• Peptic ulcer disease & heartburn are chronic conditions usually managed on outpatient basis. Complications like bleeding require hospitalization. Conditions range from mild to serious.
• W/ heartburn, minimize acid reflux by elevating head of bed; avoid stomach distention (eating small meals); not lying down for 1 to 2 hours after eating; minimizing intake of fats, chocolate, citric juices, coffee, & alcohol; avoiding smoking (stimulates gastric acid production); & avoiding obesity, constipation, or other conditions that increase intra-abdominal pressure. Also, take tablets/capsules w/ 8 ounce water & do not take medications at bedtime unless instructed.
• Most medications decrease stomach acid. An exception is the antibiotics used to treat ulcers caused by H. pylori. Strongest acid reducers: omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix), & rabeprazole (AcipHex). These are prescription drugs, except for omeprazole. Histamine-blocking drugs such as cimetidine (Tagamet), famotidine (Pep-cid), & others are available as prescription & OTC. OTC products are indicated for heartburn, & smaller doses are taken than for peptic ulcer disease. Should not be taken longer than 2 weeks w/out the advice of HCP. (A 2-week treatment w/ Prilosec OTC can be repeated every 4 months if needed.) Concern is OTC drugs delay diagnosis/treatment of serious illness. Also, cimetidine can increase toxic effects of many drugs & be avoided.
• Misoprostol (Cytotec) given to prevent ulcers from NSAIDs. Should be taken only while taking NSAID. Celecoxib (Celebrex) less likely to cause peptic ulcers. Do not take misoprostol if pregnant. Can cause abdominal cramps & miscarriage.
• Numerous antacid preparations are available, but they are not equally safe in all people and should be selected carefully. For example, products that contain magnesium have a laxative effect & may cause diarrhea; those that contain aluminum or calcium may cause constipation. (e.g., the antacid Titralac [Tums] contains calcium). Some commonly used antacids (e.g., Maalox, Mylanta) are a mixture of magnesium & aluminum, attempt to avoid constipation & diarrhea. People w/ kidney disease should not take products that contain magnesium because magnesium can accumulate in the body & cause serious adverse effects. Important to read product labels &, if you have a chronic illness or take other medications, ask HCP to help select an antacid.
• All H2 receptor antagonists (e.g., cimetidine, famoti-dine) are available by prescription & OTC. When obtained w/ prescription, avoid concomitant use of OTC versions of the same or similar drugs.
• Take drugs as directed. For acute peptic ulcer disease or esophagitis, drugs are given in high doses for 4 to 8 weeks to promote healing. For long-term maintenance therapy, dosage is reduced.
• W/ Prilosec, AcipHex, Nexium, & Protonix, do not open, chew, or crush. W/ Prevacid, capsule can be opened & the granules sprinkled on applesauce. Also, the granules are available in a packet for preparing a liquid suspension; should not be crushed or chewed.
• Take cimetidine w/ meals or at bedtime. Take famotidine, nizatidine, & ranitidine with or without food. Do not take an antacid for 1 hour before or after taking one of these drugs.
• Take sucralfate on empty stomach at least 1 hour before meals & bedtime. Do not take an antacid for 1 hour before or after taking sucralfate. Take misoprostol w/ food.
• For treatment of peptic ulcer disease, take antacids 1 & 3 hours after meals & at bedtime (4-7 doses daily), 1 to 2 hours before or after other medications. Antacids decrease absorption of many medications if taken at the same time. Chew chewable tablets thoroughly before swallowing, then drink a glass of water; allow effervescent tablets to dissolve com-pletely & almost stop bubbling before drinking (this increases the surface area of drug available to neutralize gastric acid); & shake liquids well before measuring the dose. A high-fiber diet, adequate fluid intake (2000-3000 mL daily), & exercise may help prevent constipation if it occurs w/ Mylanta therapy.
• W/ Pepcid RPD orally disintegrating tablets, open the blister package with dry hands immediately before use, place the tablet on the tongue, and allow the tablet to dissolve with saliva. Taking with liquids is not necessary.