(From Lippincott’s Pharm and lecture, 7 Feb 2001, by Brian Buschman)
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Gastric acid is stimulated by a number of things. It may be produced by parietal cells or by H. pylori. Stimulation of parietal cells may be local or via the vagus nerve.
Since the vagus stimulates parietal cells muscarinic antagonists can be used to decrease H+ secretion. Atropine can definitely be used but with it’s many adverse affects. The same goes for scopolamine or which ever one you choose. The M1 selective antagonist pirenzepine is being evaluated. It looks like low doses solve the problem.
Antimuscarinic therapy is usually only used with patients that are resistant to H2-antagonist drugs.
Antacids neutralize acid in the stomach. They include aluminum hydroxide, calcium carbonate, magnesium hydroxide and sodium bicarbonate. Sodium bicarbonate is a systemic antacid while the rest are intestinal. If the intestinal pH is raised above 2 than pepsinogen is cleaved to release pepsin to stimulate H+ secretion. As you approach a pH of 4 pepsinogen cleavage is decreased and is irreversible inhibited at pH 5.
The Al3+ and Mg2+ both help the healing of gastric ulcers.
Adverse effects vary per drug:
Drug-drug interactions include problems with absorption of PO drugs. If you alter the gastric pH you mess with drug ionization. The ions of Mg2+ and Al3+ can bind many drugs.
H2-antagonists bock cAMP production thereby lowering HCl release. They include cimetidine, ranitidine, famotidine and nizatidine. They both reduce HCl secretion and reduce intrinsic factor production.
H2-antagonists are used for peptic ulcer treatment, Zollinger-Ellison syndromes, acute stress ulcers and GERD (heartburn). With peptic ulcer disease you also need to treat the H. pylori infection or else it will come back after you end treatment. Zollinger-Ellison syndrome is a gastrin-secreting tumor. H2-blockers work well. H2-blockers are now available OTC for GERD but when you have heartburn it’s better to use antacids first. The antacids take effect immediately to neutralize the acid where H2-blockers will take at least 45 min before they have a significant effect.
Omeprazole and lonsoprazole are prodrugs that block the parietal cell proton pump. They are used for all discussed acid problems (GERD, GUD, Zollinger-Ellison, etc.)
PgE2 and PgI2 are found to decrease HCl secretion. Misoprostol is an analogue of PgE2 that is approved for use in GUD. It is most used as treatment for ulcers resulting from NSAID use.
Sucralfate forms a cross-linked gel on the mucosal surface of the stomach. It blocks damage to the mucosa. It also stimulates prostaglandin release thereby reducing the acid in the stomach.
Bismuth salts also help heal peptic ulcers. Bismuth also has a level of anti-H. pylori action.
H. pylori is a nasty gram-negative rod because it easily develops antibiotic resistance. IT should be treated with two or three drugs to prevent that from happening. A good combination includes:
1) Metronidazol
2) Bismuth salts
3) Amoxacillin or a tetracycline
Emesis is triggered through a center located below the 4th ventricle which happens to be outside the blood-brain barrier. This center can be triggered by D2 and 5-HT3 agonists. Many chemotherapeutic agents do just that. Muscarine and H1 receptors also play a role in some emesis.
Ondansetron blocks both central and peripheral 5-HT3 receptors thereby reducing emesis.
Prochlorperazine is a central D2 antagonist that works well but has hypotension as a possible adverse affect.
Antimuscarinics like benzatropine and scopolamine are most often used in prevention of motion sickness. They have antimuscarinic adverse affects (like atropine).
H1-antagonists are meclizine and diphenhydramine.
Cannabinoids (THC derivatives) work as antiemetics. Synthetic cannabinoids like dronabinol have no psychotropic activity but work as antiemetics and increase appetite.
Diabetics and others with neuropathy need prokinetics to get things moving on the inside. The benzamides like metoclopramide and cisapride work to increase cholinergic activity which increases motility. They also block D2 receptors in the emetic trigger zone.
Domperidone blocks D2 receptors and inhibits receptive relaxation. That increases gastric emptying.
Laxatives work by one of three mechanisms:
1) Increasing intestinal motility.
2) Decreasing absorption of H2O.
3) Increasing fluid retention due to osmotic properties.
Bulk forming laxatives form gels with large amounts of water. They decrease transit time and may also bind bile acids. The two of importance are methylcellulose and psyllium.
Saline laxatives add salts to the stool thereby altering the osmotic properties.
Lactulose causes decreased transit time ad alters the osmotic balance to allow it to reabsorb more water.
Bisacodyl is a stimulant of intestinal activity.
The two commonly used antidiarrheal agents are diphenoxaylate and loperamide. Both are synthetic opiate agonists acting on m-receptors to decrease motility and d-receptors to decrease secretion.
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