Anti-Secretory Agents Group Drugs H2 Blockers Cimetidine Ranitidine Famotidine Nizatidine

Mode of Action Competitive antagonist of H2 receptors.

Proton Pump Inhibitors

Oral: Omeprazole Lansoprazole Rabeprazole IV Pantoprazole

Irreversibly binds to the sulfhydryl groups (cysteine residues of proton pumps).

Side Effects Most associated w/ cimetidine Inhibits cytochrome P-450 (Prolongs t warfarin/ phenytoin) Anti-androgenic (High Doses) [Libido loss, gynecomastia & impotence in men, galactorrhea b/c prolactin in women] CNS disturbances Hematologic effects (All 4) Nausea, diarrhea, myalgia, rashes, & itching. Nausea, diarrhea, cramps 3% Headache, dizziness, rashes, somnolence Hypergastrinema Nocturnal Acid Breakthrough Bacterial Overgrowth in GI Inhibits cytochrome P-450 (in vitro) (rare)

Random Potency: Famotidine (40mg) > Ranitidine & Nizatidine (300mg) > Cimetidine (800mg) Tablets (One @ bedtime) & IV. Single bedtime dose as effective as multiple day doses. dose used for maintenance. Efficacy: 80-90% in 4-6 weeks

Substituted Benzimidazoles (weak bases) Prodrugs, only active at acidic pH (<5). Prodrug absorbed in intestine, transported back to stomach epithelium & conc. in parietal cell canaliculi. Omeprazole 20mg/d for dose Maintenance or full dose Acid secretion restarts only when new pumps are synthesized. MOST POTENT INHIBITORS. Higher efficacy & rates than H2 blocks: 90-95% in 4 weeks. Also used in anti-H-pylori therapy. Approved short-term treatment = 4-8 weeks. Effective long term in reducing secretion in gastric hypersecretory states (Zollinger-Ellison syndrome)

Antacids Drug Mode of Action Antacids Neutralize/Buffer Acids May Prostaglandins & mucus

Side Effects Mg-based: Diarrhea (laxative) Al-based: Constipation (adsorbent) Ca-based: Hypercalcemia & milk-alkali syndrome (w/ high doses) Risk of rebound secretion of acid, due to gastrin triggered by acidity (High in Mg/Al, Low in Ca)

Random Generally consist of MgOH, AlOH, CaCO3 & NaHCO3. Cost the same as H2 blockers & sucralfate Dosage: 4 doses of 140 meq of an antacid with high neutralizing capacity (3 post-meal & 1 bedtime); post-meal doses taken 1-3 hours after each meal. *Requires proper doing & compliance* Ca2+ stimulates gastrin & HCl release.

Cytoprotective Agents Drug Mode of Action Prostaglandins Cytoprotective: release of gastroduodenal mucus & bicarb. Antisecretory: Reduces cAMP levels, inhibiting histamine-stimulated acid release by parietal cells. Sucralfate - Acid turns it into sticky slurry that binds to hemoglobin & pepsin & acts as a barrier against further acid-pepsin damage. - tissue levels of prostaglandins & mucus. Bismuth Compounds - Binds to ulcer crater & protects it from damage - May stimulate mucus production & prostaglandin synthesis - Anti-H. pylori activity.

Side Effects Abortifacient Ab. Cramping Diarrhea (dose-dependent/self limited) Constipation Dry Mouth Reduces bioavailability of tetracycline, phenytoin, digoxin, cimetidine Black stool, dark tongue. Risk of bismuth & subsalicylate toxicity. ie. encephalopathy

Random Ex.: Misoprostol Synthetic PGE1 analog - Prevents NSAID-induced gastric ulcers - Protective, BUT at doses that acid release Non-absorbable Al salt of octasucrose. No acid neutralizing capacity. Dose: 4g a day (Usually 1g 4x a day) Same healing rate as H2-blockers & antacids. Limited use due to efficacy of other agents. Used in ICU to prevent stress-induced GI bleeds. Pepto-Bismol Bismuth subsalicylate & bismuth subcitrate.

Antimicrobials (Anti-H. pylori therapy) Therapy Triple Therapy Random PPI PPI agents may have some antimicrobial actions. 90% cure rate 2 week regimen First-line therapy Lower ulcer reoccurrence rate than H2 or PPI (10%vs90%) Quadruple Triple Therapy +Tinizadole 90% duodenal ulcers (But requires good patient Therapy Tetracycline + Metronidazole + Bismuth + H2-antagonist (or PPI) compliance) 2 week regimen & cheap Other Combos Ranitidine bismuth citrate Amoxicillin (Tritec) Metronidazole Clarithromycin Tetracycline (2 of these) Omeprazole + Amoxicillin + Levofloxacin There are metronidazole & clarithromycin-resistant H. pylori. Antibiotic Amoxicillin Metronidazole Clarithromycin Tetracycline (2 of these)

Treats Constipation Group Mode of Action Bulk-forming -Absorbs water agents (Dietary - growth of intestinal bacteria Fiber) -fermentation by bacterial action produces metabolites that alter colonic handling of fluid and electrolytes. -Digestion by bacterial action to metabolites that increase stool osmolality Pulls water & ions into GI Saline (Osmotic) -Poorly absorbed, osmotically active Laxatives salts which increase water in colon Stimulant Laxatives Lubricants (Stool Softeners) Group - secretion of H2O & electrolytes into GI - colonic motility - Acts as lubricants - Emulsified in stool & softens it.

Side Effects Minimal - Intestinal Gas

Random Safest/Least expensive Plant Cell walls Patient should drink lots of water to prevent impaction. Expect increased initially. - Bran, Rice & psyllium (Metamucil)

Very NON-toxic Fluid Loss Abuse can lead to cathartic colon

Onset: 3-4 hours Often used in prep for surgeries Mg Salts, Lactulose, Sorbitol, Osmotic lavage fluids Rectal Onset 1-2 hr. Oral Onset 6-12 hr. Ex. Castor Oil, Bisacodyl, Senna Ex. Docusate sodium (Detergent), Mineral Oil ( fat soluble vitamin absorption) & Glycerin (suppository). Side Effects Random Less effective than other diarrheals Bismuth subsalicylate (Pepto-bismol) Relieves mild diarrhea Mainstay drug

Treat Diarrhea Drugs Bulk Forming Agents Kaopectate: kaolin (Al) & pectin (fruit) Donnagel: attapulgite (= kaolin) Bismuth Compounds

Adsorbents/ Demulcents

Mode of Action - Water absorption ( bowel fluidity & bulk) Bind intestinal bacteria & toxins

Adsorbent to bacteria, toxins, Abuse & viruses Anti Microbial Act via and opiate receptors Slow GI motility ( ACh release). Ab. pain, emesis, constipation, fatigue, drowsiness.

Opiates

Loperimide: Poor CNS penetration Diphenoxylate w/ atropine Difenoxin w/ atropine: active metabolite of diphenoxylate

Antiemetic Group Drug Mode of Action Dopamine Prochlorperazine -Blocks dopamine receptors in Antagonist CTZ & GI Metoclopramide -Blocks dopamine receptors in CTZ and GI -GI motility and emptying: prokinetic (via cholinomimetic action) act centrally (CTZ) & peripherally (vestibular apparatus) Blocks H1 receptors

Side Effects Dystonias Dystonias, Parkinsonism, somnolence, nervousness, galactorrhea ( prolactin); diarrhea. Sedation and dry mouth (therapeutic doses) 4 Confusion and memory loss

Random Phenothiazine Not effective against motion sickness, or patients achieving chemo Benzamide

Anticholinergic Scopolamine Antihistamines (H1 Blockers) Cyclizine Meclizine Dimenhydrinate Promethazine

Serotonin Antagonists

Ondansetron Dolasetron Granisetron

Blocks 5-HT3 receptors in CTZ & Vagal terminals

Constipation Diarrhea Headache

Prevents motion sickness. Given orally, by injection, or transdermal patch Promethazine Most effective, but sedating Prevents motion sickness (Also is anticholinergic) Control Post-Op Emesis Little Potency against chemo-induced emesis Available by injection or tablet General Anti-emetic NOT effective against motion sickness Originally used against cisplatin effects. Approved in 2003 Used as adjunct to standard antiemetics to control emesis from highly emetogenic chemo.

Substance P (Neurokinin 1) Antagonists

Aprepitant

Blocks NK-1 receptor in emesis center

Generally well tolerated, but: Fatigue (most common), anorexia, constipation, diarrhea. Aprepitant is metabolized by P-450; potential drug interactions

Benzamides

Metoclopramide Cisapride (No longer available) Cisapride (No longer available)

Mode of Action Cholinomimetics ACh release from enteric neurons & response to Ach

Side Effects Extrapyramidal effects

Cardiotoxic effects (Ik block) when coadministered with drugs/foods which metabolism: - QT interval - arrhythmias - cardiac arrest

Random Used to increase gastric motility and emptying Treats GERD dopamine-blocking effect may contribute to prokinetic effect NO dopamine blockage NO extrapyramidal effects Prolongs action potentials May contribute to use as heartburn drug by enhancing contractions of esophageal sphincter