Pharmacology - Gastrointestinal

Cimetidine, ranitidine, famotidine, nizatidineTake H2 before you dine. Mechanism: Reversible block of histamine H2-receptors → ↓ H+ secretion by parietal cells Clinical use: Peptic ulcers, gastritis, mild esophageal reflux Adverse effects: - Cimetidine is a potent inhibitor of cytochrome P-450 and has antiandrogenic effects (prolactin release, impotence, ↓ libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta.- Cimetidine and ranitidine ↓ renal excretion of creatinine.

Preparations that neutralize gastric acid. - Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. - All can cause hypokalemia. - Aluminium hydroxide- Calcium carbonate- Magnesium hydroxide

Mechanism: Bind to ulcer base, providing physical protection and allowing HCO3- secretion to reestablish pH gradient in the mucous layer. Require acidic environment; usually not given with PPIs/H2 blockers. Clinical use: ↑ ulcer healing, travelers' diarrhea (bismuth)

PGE1 analog. ↑ production and secretion of gastric mucous barrier, ↓ acid production. Clinical use: Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production).- Also used off-label for induction of labor (ripens cervix). Adverse effects: - Diarrhea- Contraindicated in women of childbearing potential (abortifacient).

Long-acting somatostatin analog; inhibits secretion of various splanchnic vasodilatory hormones. Clinical use: - Acute variceal bleeds- Acromegaly- VIPoma- Carcinoid tumors Adverse effects:- Nausea, cramps, steatorrhea- ↑ risk of cholelithiasis due to CCK inhibition

- Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose Mechanism: Provide osmotic load to draw water into the GI lumen Clinical use: Constipation- Lactulose also treats hepatic encephalopathy since gut flora degrate it into metabolites that promote nitrogen excretion as NH4+. Adverse effects: - Diarrhea, dehydration, may be abused by bulimics

Combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory).- Activated by colonic bacteria (effect restricted to colon). Clinical use: Ulcerative colitis, Crohn disease (colitis component) Adverse effects: - Hepatotoxicity- Stomatitis- Hemolytic anemia- Malaise, nausea- Sulfonamide toxicity- Reversible oligospermia

Agonist at µ-opioid receptors; slows gut motility. - Poor CNS penetration (low addictive potential). Clinical use: Diarrhea Adverse effects: Constipation, nausea.

5-HT3 antagonist; ↓ vagal stimulation. Central-acting antiemetic. Clinical use: Control vomiting postoperatively and in patients undergoing cancer chemotherapy. Adverse effects: QT interval prolongation, headache, constipation, serotonin syndrome.

D2 receptor antagonist. ↑ resting tone, contractility, LES tone, motility, promotes gastric emptying. - Does not influence colon transport time. Clinical use: Diabetic and postsurgery gastroparesis, antiemetic, persistent GERD. Adverse effects: ↑ parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea.- Drug interaction with digoxin and diabetic agents. - Contraindicated in patients with small bowel obstruction or Parkinson disease.

Inhibits gastric and pancreatic lipase → ↓ breakdown and absorption of dietary fats. Clinical use: Weight loss Adverse effects: Steatorrhea, ↓ absorption of fat-soluble vitamins, abdominal pain, flatulence, bowel urgency/frequent bowel movements

- Nontoxic bile acid. ↑ bile secretion, ↓ cholesterol secretion and reabsorption Clinical use: Primary biliary cirrhosis, gallstone prevention or dissolution

- polymerizes on gastrointestinal luminal surface to form a protective gel-like coating of ulcer beds - requires acid pH (antacids may interfere) - ↑ healing- ↓ ulcer recurrence

Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole Irreversibly inhibit H+/K+ ATPase in stomach parietal cells. Clinical use: Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome- Component of therapy for H pylori, stress ulcer prophylaxis Adverse effects: - ↑ risk of C difficile infection, pneumonia, acute interstitial nephritis- ↓ Mg2+ with long-term use- ↓ serum Mg2+ and ↓ Ca2+ absorption (potentially leading to increased fracture risk in elderly)

Indicated for constipation or patients on opiates requiring a bowel regimen Bulk-forming laxatives: Psyllium, methylcelluloseOsmotic laxatives: Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactuloseStimulants: SennaEmollients: Docusate

Substance P antagonist. Blocks NK1 (neurokinin-1) receptors in brain. Clinical use: Antiemetic for chemotherapy-induced nausea and vomiting.

Histamine-2 blocker Adverse effects:- Potent inhibitor of cytochrome P-450 (multiple drug interactions)- Antiandrogenic effects (prolactin release, gynecomastia, impotence,?libido in males)- Can cross blood-brain barrier (confusion, dizziness, headaches) and placenta. - Renal failure- Pancytopenia- Vitamin B12 deficiency (long-term use)

Histamine-2 blocker

Histamine-2 blocker

Histamine-2 blocker

Antacid Adverse effects:- Constipation - Hypophosphatemia- Proximal muscle weakness- Osteodystrophy- Seizures

Antacid Adverse effects:- Hypercalcemia (milk-alkali syndrome)- Rebound acid ↑- Can chelate and ↓ effectiveness of other drugs (eg, tetracycline)

Antacid Adverse effects:- Diarrhea- Hyporeflexia- Hypotension- Cardiac arrest

Psyllium, methylcellulose Mechanism: Soluble fibers draw water into gut lumen, forming a viscous liquid that promotes peristalsis. Adverse effects: Bloating

Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose Mechanism: Provides osmotic load to draw water into GI lumen Adverse effects:- Diarrhea, dehydration; may be abused by bulimics - Magnesium hydroxide is also used as an antacid; may cause hyporeflexia, hypotonia, cardiac arrest.- Lactulose also treats hepatic encephalopathy: gut flora degrade lactulose into metabolites (lactic acid, acetic acid) that promote nitrogen excretion as NH4+.

Stimulants: Senna Mechanism: Enteric nerve stimulation → colonic contraction Adverse effects: Melanosis coli

Docusate Mechanism: Promotes incorporation of water and fat into stool.

Emmolient laxative

Stimulant laxative

Osmotic laxative

Osmotic laxative

Osmotic laxative

Bulk-forming laxative

Bulk-forming laxative

A metal-chelating agent that facilitates the renal excretion of heavy metals by forming water-soluble compounds. - Used in the treatment of copper, lead, and mercury poisoning. - Also used as an antifibrotic in patients with systemic sclerosis. - Rarely used to treat rheumatoid arthritis in patients who do not respond to other therapies. Adverse effects:- Membranous nephropathy (nephrotic syndrome)- Goodpasture's syndrome- Bone marrow toxicity including thrombocytopenia or total aplasia- Myasthenia gravis- Polymyositis- Hepatotoxicity