A. There are three strategies for treating ulcers: treat the infection, decrease stomach acid, and protect the stomach mucosa.
Deficiency Common Causes of Deficiency Toxicity Water-Soluble Vitamins
Thiamine (B1) Beriberi Polished rice diet None
Wernicke-Korsakoff Alcoholism syndrome
Riboflavin (B2) Infrequent N/A None
Niacin Pellagra (3Ds: dermatitis, Low protein diet Lower serum triglycerides
(nicotinic acid, B3) diarrhea, dementia) and cholesterol
Flushing and GI distress
Pantothenic acid (B5) Infrequent N/A None
Pyridoxine (B6) Peripheral neuropathy Infrequent–ISONIAZID Peripheral neuropathy
Microcytic anemia Lower anticonvulsant
and L-dopa effects Cyanocobalamin (B12) Pernicious anemia Gastrectomy (no intrinsic None
(megaloblastic, factor),
macrocytic) Autoimmune destruction Neurological symptoms of gastric parietal cells
Folic acid (B9) Megaloblastic, macrocytic Alcoholism, None
anemia Anticonvulsants,
Neural tube birth defects Pregnancy
Ascorbic acid (C) Scurvy Dietary None
Biotin Infrequent Raw egg whites None
Fat-Soluble Vitamins
Vitamin A Decreased dark Dietary Dry, scaly skin
adaptation Night blindness Xerophthalmia
Vitamin D Rickets (kids) Lack of sunlight Hypercalcemia
Osteomalacia (adults) Dietary
Vitamin E Infrequent hemolytic Premature infants Least toxic
anemia fat-soluble vitamin
Vitamin K Decreased blood Warfarin, Jaundice in newborn
coagulation Otherwise rare in adults Decreased effect of oral anticoagulants DEFICIENCY AND TOXIC STATES FOR VITAMINS
TABLE7-2
XI
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1. Triple therapy including two antibiotics and a proton pump inhibitor (e.g., amoxicillin, clarithromycin, omeprazole) will kill the Helicobacter pylori that causes most ulcers.
a. A permanent cure can be produced in many patients.
b. Antibiotic therapy is inappropriate for salicylate-induced and nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers.
c. Metronidazole can be used in patients who are allergic to penicillins.
2. Neutralization or decreased production of stomach acid helps allow ulcers to heal by preventing further damage to the stomach mucosa.
a. H2-Antihistamines, such as cimetidine (Tagamet), ranitidine (Zantac), and famotidine (Pepcid) are competitive antagonists at H2-receptors in the intestinal tract. They are used less commonly now vs. proton pump inhibitors.
i. Acid and pepsin secretion are reduced. Proton release due to gastrin or histamine binding is completely inhibited, whereas proton release due to acetylcholine binding is partially inhibited.
ii. The release of intrinsic factor is unchanged.
iii. There are no effects at H1-receptors.
iv. Cimetidine has several side effects:
(a) Impotence and swelling of the breasts due to antiandrogen activity (b) Increased prolactin release, which can cause galactorrhea
(c) Inhibition of cytochrome P450 enzymes, which can slow the metabolism of many drugs (e.g., warfarin, propranolol) and enhance their effects
v. Ranitidine and famotidine have fewer side effects and longer durations of action.
vi. H2 blockers compete with other basic drugs (e.g., pramipexole, pro-cainamide) for secretion by the renal organic cation transporter.
b. Omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium) are proton pump inhibitors.
i. They irreversibly inhibit the H⫹⫹/K⫹⫹ATPase, which blocks the final step in acid secretion.
ii. These drugs are very effective, especially for gastroesophageal reflux (heartburn) and are generally well tolerated. Thus, they are often the first-line class of drugs used to treat ulcers.
c. Antacids directly neutralize stomach acid; however their duration of action is limited by stomach-emptying time.
i. Sodium bicarbonate is a systemic antacid.
(a) It is readily absorbed into the body.
(b) Side effects are common, including metabolic alkalosis, hyperna-tremia, fluid retention, and acid rebound, due to high gastric pH.
ii. Nonsystemic antacids are poorly absorbed into the body.
(a) Magnesium hydroxide induces the side effect of diarrhea, whereas aluminum hydroxide induces constipation. Thus, magnesium hydroxide and aluminum hydroxide are combined to create an antacid preparation with little effect on GI motility.
(b) Calcium carbonate (Tums) has more side effects, including hypercal-cemia (e.g., milk alkali syndrome), acid rebound, and constipation.
3. Physical protection of the gastric mucosa can be an effective strategy.
a. Sucralfate (Carafate) adheres to the ulcerated mucosal wall of the stomach and provides a barrier to acid and pepsin. It should not be coadministered with H2 antagonists or antacids because acid is required for the sucralfate to work.
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101 AUTACOIDS, DRUGS FOR INFLAMMATORY AND GASTROINTESTINAL DISORDERS, AND VITAMINS
b. Misoprostol (Cytotec), a prostaglandin E1 analog, enhances the mucosal bar-rier by stimulating mucus and bicarbonate secretion. It is used for NSAID-induced ulcers.
4. Metoclopramide (Octamide, Reglan) is an antidopaminergic drug that increases lower esophageal sphincter tone.
a. Gastroesophageal reflux is decreased.
b. It also has antiemetic actions due to blocking D2receptors in the medulla.
B. ANTIDIARRHEAL DRUGS are useful to reduce the loss of fluid and electrolytes that occurs with diarrhea. These drugs should not be used for treating diarrhea that is caused by a toxin, an infection, or chronic ulcerative colitis.
1. Opiates act by increasing the tone and reducing the motility of the GI tract.
a. Diphenoxylate, which is insoluble and poorly absorbed, is combined with atropine (Lomotil).
b. Loperamide (Imodium) has no systemic side effects.
2. Bismuth salicylate (Pepto-Bismol) decreases fluid secretion in the bowel.
3. Attapulgite, a hydrophilic substance, absorbs water and reduces the looseness of the feces. Kaolin/pectin (Kaopectate) is another adsorbent agent.
C. LAXATIVE CATHARTICS add bulk and water to the feces, thereby stimulating peri-stalsis and relieving constipation. They should never be used for undiagnosed abdominal pain or when there is possible intestinal obstruction.
1. Bulk laxatives (e.g., psyllium and methylcellulose) are fiber, which increases the volume of the GI contents and thereby enhances peristalsis.
2. Osmotic (bulk) cathartics are also called saline laxatives.
a. Magnesium sulfate (milk of magnesia) and polyethylene glycol (MiraLAX, GoLytely) cause osmotic retention of large amounts of water in the gut.
b. The increased bulk markedly enhances peristalsis.
3. Castor oil and bisacodyl (Dulcolax) are contact laxatives.
a. The active metabolite of castor oil is ricinoleic acid.
b. Irritation of nerve endings increases peristaltic contractions.
c. Prolonged use can lead to irritable bowel syndrome.
4. Docusate (Colace, Doxinate) and mineral oil are fecal softeners that make the passage of stools easier.
D. ANTIEMETICS ANTAGONIZE D2 and 5HT3 RECEPTORS in the chemoreceptor trigger zone of the brain to prevent vomiting. These chemoreceptors sense chemical stimuli, whereas the actual act of vomiting is controlled by the medulla.
1. Anticholinergic drugs (scopolamine) and H1-antagonists (meclizine [Antivert], dimenhydrinate [Dramamine]) prevent motion sickness but do not prevent stim-ulation of the chemoreceptor trigger zone.
2. Several drugs are used to control chemotherapy-induced nausea and vomiting:
a. D2 dopamine receptor antagonists include prochlorperazine (Compazine), metoclopramide (Reglan), and droperidol (Inapsine). Use of droperidol is associated with prolonged QT and torsades de pointes.
b. Odansetron (Zofran) is a 5HT3serotonin receptor antagonist.
c. Cannabinoids like dronabinol (Marinol) work by an unknown mechanism and are not commonly used.
d. Aprepitant (Emend) blocks neurokinin receptors in the chemoreceptor trigger zone.
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