Drugs of the gastrointestinal system

Histamine (H2) blockers: H2 blockers (H2 antagonists) reduce gastric acid production by blocking the H2 histamine receptor. Histamine is a chemical mediator produced in the body that increases stomach acid by stimulating H2 receptors. Current examples include famotidine (Pepcid) and cimetidine (Tagamet). Ranitidine (Zantac) is also an example of the class, but it was withdrawn from the US market in April 2020 at the FDA’s request due to unacceptable levels of the probable carcinogen NDMA; the product now sold as Zantac 360 contains famotidine, not ranitidine.

Adverse effects include diarrhea, constipation, headache, and fatigue. In patients with kidney or liver disease, more serious effects such as hallucinations, slurred speech, and confusion may occur. Cimetidine is associated with potentially life-threatening drug interactions because it inhibits cytochrome P450 liver enzymes and can interfere with the metabolism of drugs such as warfarin and SSRIs.

Antidiarrheals: Antidiarrheals decrease the frequency of loose stools. Some work by decreasing gastrointestinal motility, such as loperamide (Imodium A-D) and atropine plus diphenoxylate (Lomotil).

Probiotics may decrease the duration of diarrhea by introducing beneficial microorganisms that help protect against 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 used to treat constipation. They are classified by mechanism of action as follows:

• Osmotic laxatives - They pull water into the colon to soften the stool. Examples include polyethylene glycol (MiraLAX) and magnesium hydroxide (Milk of Magnesia).
• Stool softeners - They soften stool by increasing the fat and water content of the stool. An example is docusate (Colace).
• Bulk forming laxatives - They increase stool bulk by adding soluble fiber, which attracts water and helps soften stool. Examples include psyllium (Metamucil), methylcellulose (Citrucel), and wheat dextrin (Benefiber).
• Stimulant laxatives - They stimulate the bowel and increase intestinal contractions. Examples include bisacodyl (Dulcolax) and senna (Fletcher’s Laxative, Senokot).

Miscellaneous: The following drugs are used to treat common gastrointestinal symptoms.

Sucralfate: Sucralfate is an aluminum-containing drug used to treat peptic ulcers. It helps ulcers heal by forming a protective barrier over the ulcer, shielding it from gastric acid. It can decrease the absorption of many drugs, including quinolones, digoxin, and levothyroxine. Sucralfate is sold under the brand name Carafate.

Simethicone: Simethicone reduces bloating and flatulence by decreasing the surface tension of gas bubbles in the gastrointestinal tract. Common brands include Gas-X and Mylicon. It’s also available in combination with other medications (such as aluminum and magnesium hydroxide or calcium carbonate) for treating heartburn and peptic ulcers.

Misoprostol: Misoprostol is a synthetic version of prostaglandin E1. It decreases gastric acid production and increases protective mucus production. It’s used to prevent peptic ulcers in patients taking NSAIDs. Other uses include medical termination of pregnancy and control of bleeding associated with childbirth. Adverse effects include diarrhea, abdominal pain, fever, and chills. It’s marketed as Cytotec.

Ondansetron: Ondansetron is an antiemetic used to prevent and treat nausea and vomiting. It blocks a serotonin receptor called 5-HT3. It’s available as Zofran and Zuplenz. Adverse effects include dizziness, confusion, and irregular heartbeat. It’s contraindicated with apomorphine because the combination may cause low blood pressure and loss of consciousness.

Metoclopramide: Metoclopramide is a dopamine antagonist used as an antiemetic and to treat GERD and gastroparesis (slow gut motility). It’s sold under the brand names Reglan, Maxolon, and Metozolv ODT.

Common adverse effects include drowsiness, tiredness, weakness, headache, diarrhea, missed menstrual periods, impotence, and urinary incontinence. Serious adverse effects include extrapyramidal symptoms, which can cause severe muscle spasms and abnormal muscle tone (such as laryngospasm, dystonia, Parkinson-like symptoms, and tardive dyskinesia).

The FDA has issued a black box warning for metoclopramide due to the risk of tardive dyskinesia. Tardive dyskinesia presents as unusual, uncontrollable movements such as lip smacking, mouth puckering, chewing motions, eyelid blinking, sticking the tongue out, and shaking of the arms or legs. Risk increases with longer duration of use and is higher in people with diabetes and in older adults.

Metoclopramide may rarely cause a life-threatening adverse effect called neuroleptic malignant syndrome, which can present as high fever, rigidity, and serious cardiovascular disturbances. Risk is higher when metoclopramide is taken with antipsychotic drugs.

Metoclopramide also inhibits cytochrome P450 enzymes, which can slow the metabolism of concurrently administered drugs and increase their levels.