Pharmacology of GI Drugs: Gastric Acid Reducers

Pharmacology of GI Drugs 1: Gastric Acid Reducing Drugs

• This presentation covers gastric acid-reducing drugs, specifically antacids, H2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), and mucosal defense-enhancing drugs.

• Learning Objectives: Compare and contrast the therapeutic and adverse effects of different drug classes, identify pharmacokinetic characteristics, and recognize common drug interactions, precautions, and contraindications.

Antacids

• Mechanism of Action (MOA): Physically neutralize gastric acid.
• Agents: Calcium carbonate, magnesium hydroxide, aluminum hydroxide, and sodium bicarbonate (not recommended).

Calcium Carbonate

• Brand Names: Tums®, Rolaids®.
• Neutralizing Ability: Moderate.
• Adverse Effects: Belching, flatulence, nausea, constipation, and potential for rebound acid secretion. Short-term hypercalcemia is possible due to absorption. Should be used with caution in renal disease or kidney stones.
• Dosage: Take 1 hour after meals and at bedtime.

Magnesium Hydroxide

• Neutralizing Ability: Rapid.
• Adverse Effects: Antacid-laxative effect when used alone (Phillips® Milk of Magnesia). Combining with aluminum hydroxide reduces the laxative properties (Maalox®, Mylanta®.) May cause chelation of other GI tract drugs. Cautious use in renal impairment and geriatric patients.
• Use with Caution: Renal impairment, geriatric patients

Aluminum Hydroxide

• Neutralization: Takes time/slow.
• Treatment for: Hyperphosphatemia
• Side Effects: May cause constipation. Caution in renal impairment. Aluminum toxicity, encephalopathy, and chelation of other drugs. Increased bone resorption and osteoporosis with prolonged use.
• Brand name: Amphojel®

Antacids- Considerations For Use

• Dosage: Best results 1 hour after meals and at bedtime. Liquids preferred over tablets. Chew tablets thoroughly and take with water.
• Drug Interactions: Antacids may cause chelation of some drugs (e.g., quinolones, tetracyclines, levothyroxine). Administer antacids 2 hours before or after other medications. Levothyroxine should be administered at least 4 hours before or after antacids. May affect absorption of iron, or certain HIV medications, and some azole antifungals.

H2 Receptor Antagonists (H2RAs)

• Mechanism of Action (MOA): Competitive antagonists of histamine at H2 receptors on parietal cells, inhibiting acid secretion.
• Available Agents: Cimetidine, famotidine, and nizatidine.
• Adverse Effects (Common): Diarrhea, constipation, drowsiness, headache, dizziness.
• Adverse Effects (Rare): Thrombocytopenia, vitamin B12 deficiency, confusion, delirium, hallucinations (CNS effects), and gynecomastia (with cimetidine); IV formulations can be used for elderly patients who need quicker onset.
• Drug Interactions: Some H2RAs, especially cimetidine, inhibit cytochrome P450 enzymes, potentially impacting metabolism of other drugs (e.g., warfarin). Eletriptan should not be administered within 72 hours of cimetidine. Avoiding concomitant use of phenytoin with some H2RAs due to toxicity concerns. Drugs affected by increased gastric pH.

Proton Pump Inhibitors (PPIs)

• Mechanism of Action (MOA): Irreversibly inhibit gastric H+/K+-ATPase (proton pump), reducing acid secretion.

• Prodrugs: Require acid activation.

• Agents: Dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.

• Adverse Effects: Diarrhea, headache, nausea, constipation, flatulence, abdominal pain.

• Drug Interactions: Omeprazole, and esomeprazole inhibit the metabolism of certain drugs through CYP inhibition, including clopidogrel, ketoconazole, warfarin, and diazepam.

Potassium-Competitive Acid Blockers (PCABs)

• Mechanism of Action: Inhibits H+/K+-ATPase in a potassium-dependent manner.
• Agent: Vonoprazan
• Adverse Effects: Nasopharyngitis, diarrhea, constipation, flatulence, abdominal pain, dyspepsia, headache.
• Drug Interactions: CYP3A4 inducers and drugs with pH dependent absorption.

Misoprostol (Cytotec®)

• Mechanism of Action: Prostaglandin E1 analog, acting on gastric mucosa to increase mucus and bicarbonate production, and reduce acid secretion.
• Indication: Usually used to prevent NSAID-induced ulcers.
• Adverse Effects: Multiple daily doses, diarrhea, abdominal cramps, potential exacerbation of inflammatory bowel disease. Must be used with caution, due to pregnancy contraindications.

Sucralfate (Carafate®)

• Mechanism of Action: Forms a protective coating over ulcer areas.
• Adverse Effects: Constipation.
• Avoid in: Severe renal impairment.
• Drug-Interactions: Inhibits absorption of phenytoin, digoxin, fluoroquinolones, and ketoconazole.

Bismuth Subsalicylate

• Mechanism of Action: Direct mucosal protective effect and antimicrobial action against H. pylori.
• Adverse Effects: Black stools, discoloration of oral cavity and tongue, constipation.
• Cautious Use: Salicylate allergy, children under 12(risk of Reye's syndrome), increases bleeding risk

Principles of Therapy

• Basis of Therapy: Neutralize excess acid, reduce gastric acid secretion, enhance gastric mucous defense. Different disease states (GERD, PUD, stress ulcers, Zollinger-Ellison syndrome) drive the need for different therapies.