Gastrointestinal: Major Drugs

The major classes of drugs include antacids (purchased otc, including Tums, Maalox, Mylantin, etc.), anti-diarrheal drugs, histamine H2 receptor antagonists, laxatives, prokinetic agents, proton pump inhibitors (PPIs), protectants, antiemetic agents, and anticholinergic agents.


When we talk about peptic ulcers, the saying used to be “no acid, no ulcer” and that is still so, but we need to consider the role of Helicobacter pylori infection. We can eradicate H. pylori and cure ulcers, not just manage the symptoms. This is very important, most pts who present to an MD with dyspepsia or chronic heartburn will be worked up to test for the presence of these bacteria as a causative agent.


The prokinetic drugs are usually used for the treatment of GERD (Gastro Esophageal Reflux Disorder). Pts with untreated GERD will regurgitate acid contents into the oral cavity, usually at night, and that will cause erosion of teeth. The prokinetic drugs in combination with the PPIs can manage GERD very effectively.


Laxatives are used as treatment for constipation. Many drugs that we five pts cause constipation or diarrhea (esp. the antibiotics cause mild diarrhea).


There is a significant vagal component within the gut. This is the rationale for using anticholinergic drugs for hyperactive smooth muscle in the stomach and intestine – we use anti-spasmodics. They are almost always anti-muscarinic, the atropine class. In the past, bilateral vagotomies were used to treat peptic ulcers or excessive motility (before H2 blockers and other alternates were discovered).


We look at the gastric Parietal cell, which produces HCl secreted into the gastric lumen, there are acetylcholine receptors, histamine H2 receptors, gastrin receptors, and probably other receptors that respond to a variety of stimuli. You’ll notice the muscarinic M3 receptor, easily blocked with any atropine or atropine derivative. Regardless of the receptor activation, there tends to be a common pathway probably through cAMP, in which there is a Hydrogen-Potassium ATPase (proton pump). Certain drugs inhibit this pathway (PPIs).


The H2 receptor antagonists were discovered in the late ‘60s and revolutionized the way we treat hyperacidic syndromes and ulcers. The prototype is Cimetidine (Tagamet), which is closely related to histamine. There is also famotidine (Pepcid), ranitidine (Zantac), and Nizatidine (Axid). These drugs are available otc now. The H2 receptor blockers are used for treating heartburn and dyspepsia, and ultimately have a role in the treatment of peptic and duodenal ulcers (no acid, no ulcer). The H2 antagonists were basically bumped aside by the PPIs, which are more potent. Cimetidine (Tagamet) is a notorious p450 inhibitor.


The simple antacids that contain magnesium or MgCl2 act locally to neutralize acid, whereas an H2 blocker acts systemically. Propantheline (Pro-Banthine) is an atropine derivative used not only for management of peptic ulcers, but for hyper-salivation (many pharmacists don’t carry this anymore because its obsolete for tx of peptic ulcers, but its still an effective way to get anticholinergic induced xerostomia without affecting the heart).

Misoprostol is a prostaglandin derivative that is very closely guarded in its prescription because it’s a very powerful uterotropic prostaglandin; never use in pregnancy because it can cause abortion of the fetus.

Sucralfate (Carafate) is a locally acting agent that coats the stomach lining and is a mucosal barrier protectant that allows mucosa to heal in an ulcer pt.

Omeprazole (Prilosec) is the prototype of the PPIs and markedly inhibits HCl (90-95%!!). The efficacy is so pronounced that it is used either alone in the treatment of GERD or as an adjunct for the management of H. pylori induced ulcers.

Clarithromycin, an antibiotic, is very effective in treating H. pylori induced ulcers. Although its not really considered a GI drug, clarithromycin is the antibiotic of choice when fighting H. pylori ulcers.


Any drug ending in “-prazole” is a proton pump inhibitor (PPI). There are many of them competing for the multi-billion dollar market. They all basically work the same, but have different potencies and durations.


The antacids contain aluminum, magnesium, calcium, etc. and react with the acid in the stomach, as a result neutralizing the acid. So if you prescribe an antibiotic with chelating properties, it will form an irreversible complex with the antacid and effectively inactivates the antibiotic. Many women are told by their MDs to take Tums, not because they have ulcers, but because it is a good source of calcium. Sucralfate (Carafate) is also an aluminum-containing product, so its mucosal protection relates to this aluminum hydroxyl complex. It is a non-systemic drug!!!

Category: Pharmacology Notes