1.4.6 Drugs of the gastrointestinal system
Gastrointestinal drugs are used to treat conditions like peptic ulcers, acid reflux, diarrhea, constipation and vomiting. Peptic ulcers are breaks in the lining of the stomach and/or duodenum that form when there is a loss of the protective mucus layer from inflammation or hyperacidity. Antacids, proton pump inhibitors and H2 blockers are used in the treatment of peptic ulcers and GERD or gastroesophageal reflux disease.
Antacids: Antacids neutralize gastric acid by binding to HCl or hydrochloric acid in the stomach. Examples include aluminum hydroxide (Amphojel), magnesium hydroxide (Milk of Magnesia), calcium carbonate (Tums, Rolaids), and bismuth subsalicylate (Pepto-Bismol). Many formulations are combinations of antacids, such as calcium carbonate with magnesium hydroxide (Mylanta Supreme) and aluminum hydroxide with magnesium hydroxide (Alamag, Maalox). Gelusil, Alka Seltzer, and Gas-X have multiple formulations of antacids with other gastrointestinal drugs. Adverse effects include diarrhea or constipation, kidney stones, bloating, aluminum toxicity, and electrolyte disturbances. Antacids may interfere with the absorption of and excretion of other drugs like digoxin, phenytoin, pseudoephedrine, tetracyclines, iron, and bisphosphonates.
Proton pump inhibitors: Also called PPIs, they decrease the production of gastric acid by blocking proton pumps or H+/K+ATPase pumps. Examples include omeprazole (Prilosec), pantoprazole (Protonix), esomeprazole (Nexium) and lansoprazole (Prevacid). Adverse effects include flatulence, nausea, abdominal pain, constipation or diarrhea, magnesium or Vitamin B12 deficiency, and taste disturbances. Long-term use of PPIs is associated with kidney failure, Clostridium difficile diarrhea, and osteoporosis.
Histamine (H2) blockers: H2 blockers, also known as H2 antagonists reduce gastric acid production by blocking the histamine receptor H2. Histamine is a chemical mediator produced in the body that increases acid production in the stomach by stimulating a specific type of histamine receptor called H2. Examples include ranitidine (Zantac), famotidine (Pepcid), and cimetidine (Tagamet). Adverse effects include diarrhea, constipation, headache, and fatigue. In patients with kidney or liver diseases, adverse effects like hallucinations, slurred speech, and confusion may occur. Cimetidine is associated with life-threatening drug interactions as it inhibits cytochrome P450 liver enzymes and interferes with the metabolism of drugs like warfarin and SSRIs.
Antidiarrheals: Antidiarrheals decrease the frequency of loose stools or diarrhea. Some of them work by decreasing gastrointestinal motility, e.g., loperamide (Imodium A-D ) and atropine plus diphenoxylate (Lomotil). Probiotics may decrease the duration of diarrhea by introducing gut-friendly microorganisms which protect against the disease-causing bacteria. Examples include Lactobacillus acidophilus (Florajen, Acidophilus) and Saccharomyces boulardii (Florastor). Bismuth subsalicylate (Pepto-Bismol, Bismarex, Bismatrol, Kaopectate) kills diarrhea causing bacteria.
Laxatives: Laxatives are drugs that are used to treat constipation. They are classified according to their mechanism of action as follows:
Miscellaneous: The following drugs are used to treat common gastrointestinal symptoms.
Sucralfate: Sucralfate is an aluminum containing drug that is used in the treatment of peptic ulcers. It helps ulcers to heal and forms a barrier that protects the ulcer from gastric acid. It can decrease the absorption of many drugs like quinolones, digoxin and levothyroxine. Sucralfate is sold under the brand name Carafate.
Simethicone: Simethicone is used to reduce bloating and flatulence by decreasing the surface tension of gas bubbles in the gastrointestinal tract. Common brands include Gas-X and Mylicon. It is also available in combination with other medications, such as aluminum and magnesium hydroxide or calcium carbonate, for the treatment of heartburn and peptic ulcers.
Misoprostol: Misoprostol is a synthetic version of prostaglandin E1. It decreases gastric acid production and increases protective mucus production. It is used to prevent the development of peptic ulcers in patients taking NSAIDs. Other uses include the medical termination of pregnancy and control of bleeding associated with childbirth. Adverse effects include diarrhea, abdominal pain, fever, and chills. It is marketed as Cytotec.
Ondansetron: Ondansetron is an antiemetic drug used to prevent and treat nausea and vomiting. It blocks a serotonin receptor called 5-HT3. It is available as Zofran and Zuplenz. Adverse effects include dizziness, confusion, and irregular heartbeat. It is contraindicated with apomorphine as it may cause low blood pressure and loss of consciousness.
Metoclopramide: Sold under the brand name Reglan, Maxolon, and Metozolv ODT, metoclopramide is a dopamine antagonist that is used as an antiemetic and to treat GERD and gastroparesis or slow gut motility. Adverse effects include drowsiness, tiredness, weakness, headache, diarrhea, missed menstrual periods, impotence, and urinary incontinence. Serious adverse effects include extrapyramidal symptoms causing severe muscle spasms and tone issues like laryngospasm, dystonia, Parkinson-like issues, and tardive dyskinesia. FDA had issued a black box warning for metoclopramide for a serious adverse effect known as tardive dyskinesia, which presents as unusual, uncontrollable movements of the mouth, face-like lip smacking, mouth puckering, chewing, eyelid blinking, sticking tongue out, shaking arms or legs, etc. The risk is higher the longer the medication is taken in diabetics and the elderly. It may rarely cause a life-threatening adverse effect called neuroleptic malignant syndrome, presenting as high fever, rigidity, and serious cardiovascular disturbances. The risk is higher when metoclopramide is taken along with antipsychotic drugs. Metoclopramide also inhibits cytochrome P450 resulting in the slowing down of metabolism of concurrently administered drugs. This may increase drug levels.