DRUGS AFFECTING THE GASTROINTESTINAL SYSTEM

By: Maam Marites Godoy *parietal cells- produce HCl* Cells of the Gastric Gland Parietal o Produce and secrete HCl o Primary site of action for many acid-controller drugs Chief cells o Secrete pepsinogen, a proenzyme o Pepsinogen becomes pepsin when activated by exposure to acid o Pepsin breaks down proteins (proteolytic) Mucous cells o Mucus-secreting cells (surface epithelial cells) o Provide a protective mucus coat o Protect against self-digestion by HCl Hydrochloric Acid Secreted by the parietal cells when stimulated by food Maintains stomach at pH of 1 to 4 Secretion also stimulated by: o Caffeine, chocolate o Large fatty meals* o Excessive amounts of alcohol* o Emotional stress* *causes hyperproduction of HCl* Acid-related Diseases Caused by imbalance of the three cells of the gastric gland and their secretions Most harmful: hypersecretion o Includes: PUD, esophageal cancer Most common impairment: hyperacididty Lay terms for overproduction of HCl by the parietal cells o Indigestion, sour stomach, heartburn, acid stomach PUD: peptic ulcer disease o Duodenal ulcer (DU) o Gastric Ulcer (GU) GERD: gastroesophageal reflux disease Helicobacter pylori (H. pylori) o Bacterium found in the GI tract of 90% of patients with duodenal ulcers, and 70% of those with gastric ulcers o Can be detected by serum antibody testers o Antibiotics are use to eradicate H. pylori

Types of Acid- Controlling Drugs Antacids H2 antagonists Proton pump inhibitors 3 receptor sites for Acetylcholine (via vagus nerve) Histamine (H2) via mast cells Gastrin (via circulation) Adenylate Cyclase Converts to ATP > Converts to CAMP > CAMP transports Hydrogen ions into cells > HCl is produced Proton Pump Inhibitors halt ATP mediated conversion into CAMP, therefore stopping the production of HCl Antacids: Mechanism of Action Neutralizes stomach acid = NEUTRALIZERS Principal anti-ulcer treatment Also contains anti-flatulent drug Promote gastric mucosal defense mechanisms Antacids DO NO prevent the overproduction of acid Antacids DO neutralize the acid once it is in the stomach Drug Effects Reduction of pain associated with acid-related disorders o Raising gastric pH from 1.3 to 1.6 neutralizes 50% of the gastric acid o Raising the pH 1 point (1.3 to 2.3) neutralizes 90% of the gastric acid o Reducing acidity reduces the pain Antacids OTC formulations available as o Capsules and tablets o Powders o Chewable tablets o Suspensions o Effervescent granules and tablets Used alone or in combination o Aluminum salts (adverse effect: constipation) o Magnesium salts (adverse effect: diarrhea) o Calcium salts o Sodium bicarbonate Should be taken at least 2 hours before regular medications o Medications need an acidic environment to absorb Should be taken 30 minutes before meals Antacids: Aluminum Salts

Have constipating effects Often used with magnesium to counteract constipation Often recommended for patients with renal disease (more easily excreted) Examples o Gaviscon, Maalox, Mylanta, Di-Gel o Aluminum carbonate: Basaljel o Hydroxide salt: Alterna GEL

Antacids: Magnesium Salts Commonly cause Diarrhea; usually used with other drugs to counteract this effect Dangerous when used with renal failure- the failing kidney cannot excrete extra magnesium, resulting in accumulation Examples o Hydroxide salt: magnesium hydroxide (MOM) o Carbonate salt: Gaviscon (also a combination product) o Combination products such as Maalox, Mylanta (aluminum and magnesium) Antacids: Calcium Salts Forms: many, but carbonate is most common May cause Constipation, kidney stones Also not recommended for patients with renal disease- may accumulate to toxic levels Long duration of acid action may cause increased gastric acid secretion (hyperacidity rebound) Often advertised as an extra source of dietary calcium Example o Tums (calcium carbonate) Antacids: Sodium Bicarbonate Highly soluble Buffers the acidic properties of HCl Quick onset, but short duration May cause metabolic alkalosis Sodium content may cause problems in patients with HF, hypertension, or renal insufficiency Antacids and Antiflatulents Antiflatulents; used to relieve the painful symptoms associated with gas Several drugs are used to bind or alter intestinal gas and are often added to antacid combination products OTC antiflatulents o Activated charcoal o Simethicone Alters elasticity of mucus-coated bubbles, causing them to break Adverse effects o Minimal, and depend on the compound used Aluminum and calcium Constipation Magnesium Diarrhea

Calcium carbonate Produces gas and belching; often combined with simethicone To prevent constipation and diarrhea = combine magnesium and aluminum (Maalox, Mylanta)

Nursing Implications Assess for allergies and preexisting conditions that may restrict the use of antacids, such as: o Fluid imbalances o Pregnancy o Renal disease o HF Patients with HF of hypertension should not use antacids with high sodium content Be sure that chewable tablets are chewed thoroughly, and liquid forms are shaken well before giving Administer with at least 8 ounces of water to enhance absorption (except for the rapid dissolve forms) Monitor for adverse effects o Nausea, vomiting, abdominal pain, diarrhea o With calcium-containing products do not take it at mealtime; slows gastric emptying time

HISTAMINE TYPE 2 (H2) ANTAGONISTS (BLOCKERS)

reduce acid secretion/most popular all available OTC in lower dosage forms most popular drugs for treatment of acid-related disorders o cimetidine (Tagment) 1975 o ranitidine (Zantac) 1983 o famotidine (Pepcid) 1986 o nizatidine (Axid) 1988

Mechanism of Action block histamine at the (H2) receptors of acid-producing parietal cells production of hydrogen ions is reduced, resulting in decreased production of HCl DOES NOT abolish acid secretion Adverse Effects Overall, very few adverse effects May see o Headaches, lethargy, confusion, diarrhea, urticaria, sweating, flushing especially in elderly patients Nursing Implications Assess for allergies or impaired renal or liver function Use with caution in patients who are confused, disoriented, or elderly Take 1 hour before or after antacids (may decrease its effectiveness) SMOKING has been shown to decrease the effectiveness of H2 blockers

PROTON PUMP INHIBITORS

The parietal cells release positive hydrogen ions (protons) during HCl production This process is called the proton pump (H2 blockers and antihistamines do not stop the action of this pump) Blocks the final step in the acid production More powerful than H2 blockers Given 30 minutes before meals

Mechanism of Action Irreversibly binds to H+/K+ ATPase enzyme This bond prevents the movement of hydrogen ions form the parietal cell into the stomach Halts Achlorhydria cells Drug Effect Total inhibition (over 90%) of gastric acid secretion o Lansoprazole (Prevacid) o Omeprazole (Prilosec; the first in this new class of drugs; 1st marketed) o Rabeprazole (Aciphex) o Pantoprazole (Protonix; IV form available) o Esomeprazole (Nexium; newest PPI) Indications GERD maintenance therapy Erosive Esophagitis (1st line therapy) Short-term treatment of active duodenal and benign gastric ulcers Treatment of H. pylori-induced ulcers Nursing Implications Prolonged use may increase the risk of cancer PPIs often work best when taken 30 to 50 minutes before meals