(18) Acid-related drugs I: antacids & H2 receptor antagonists

Acid-related disorders - overview

• GERD

• Dyspepsia

• PUD

Acid-related disorders - GERD

Stomach acid flows back into esophagus → heartburn + regurgitation

Acid-related disorders - Dyspepsia

Upper abdominal discomfort/pain without a structural lesion on endoscopy.

Acid-related disorders - PUD

Break in stomach/duodenal lining

Drug classes

1. Antacids

2. H2-receptor antagonists

Antacids

topic overview

• Mechanism

• acting type

Antacids

Mechanism

Antacid = weak base that directly neutralizes stomach acid

Antacid + HCl
→ salt + water ± CO₂
→ ↓ stomach acidity

Antacids

acting type

• FAST but SHORT

• That is their main advantage/limitation

The 4 antacids

Drug	Main thing to remember
NaHCO₃	Na⁺ + CO₂
CaCO₃	Milk-alkali syndrome
Mg(OH)₂	Diarrhea
Al(OH)₃	Constipation

Sodium bicarbonate — NaHCO₃

• Produces CO₂

  • → gastric distention

  • → belching

• Also gives Na⁺ load

  • → fluid retention

• Be careful in:

  • Heart failure

  • Hypertension

  • Renal insufficiency

  • Can cause metabolic alkalosis.

Calcium carbonate — CaCO₃

• an also produce CO₂ → belching

• Major association - Milk-alkali syndrome

• Excess CaCO₃

  • → hypercalcemia + renal insufficiency + metabolic alkalosis

Magnesium hydroxide — Mg(OH)₂

• Mg = Makes you GO → DIARRHEA

• Mg is cleared by kidneys → accumulation risk with renal insufficiency.

Aluminum hydroxide — Al(OH)₃

• Easy memory - Al = Arrests the bowel → CONSTIPATION

• Also renally cleared → accumulation risk in renal insufficiency.

Mg + Al together

• Mg → diarrhea

• Al → constipation

• Together → effects can balance each other.

Antacid DDIs

Two ways antacids interfere with drugs:

1. Chelation/binding

• Antacid binds drug

  • → drug absorption ↓

2. Changes stomach pH

• Antacid ↑ pH

  • → changes how another drug dissolves

  • → absorption changes.

3. Separate interacting drugs from antacids by ≥2 HOURS

• Important examples:

  • Tetracyclines

  • Fluoroquinolones

  • Itraconazole

  • Iron

H2-receptor antagonists

Important drugs:

• Famotidine = Pepcid

• Cimetidine = Tagamet

• Nizatidine

• Ranitidine

H2 blocker mechanism

• Histamine normally:

  • Histamine
    → H2 receptor on parietal cell
    → ↑ gastric acid

• H2 blocker:

  • Drug blocks H2
    → histamine cannot activate it
    → ↓ gastric acid

• But acid does NOT go to zero

  • other pathways still stimulate acid:

    • Gastrin

    • ACh

• So:

  • Block H2 → acid decreases, but other acid pathways still exist.

H2 blockers → strongest effect on…

NOCTURNAL acid

• Why?

  • Nighttime acid secretion is more histamine-dependent.

  • Meals activate several pathways:

    • Histamine + gastrin + ACh → blocking only histamine has a smaller effect.

Which acid drug is used when?

Situation	Main lecture choice
Occasional/intermittent symptoms	Antacid PRN
Infrequent heartburn/GERD	OTC H2 blocker
Frequent non-erosive GERD	Scheduled H2 blocker
Erosive esophagitis	PPI preferred
Acute PUD	PPI preferred

Acid Drug

Easy comparison

Antacid = fastest + shortest

H2 blocker = longer relief/prevention

PPI = stronger acid suppression

infrequent heartburn as <3 times/week

H2-receptor antagonist facts

topic overview

• Renal impairment

• Cimetidine

• Creatinine

• Alcohol interaction

H2 blockers + kidneys

• H2 blockers are eliminated through the kidneys.

• Renal function ↓

  • → H2 blocker clearance ↓

  • → drug can accumulate

• Therefore: Renal impairment → reduce/adjust H2-blocker dose

CIMETIDINE

• Cimetidine = Gynecomastia + CYP INHIBITION

  • Gynecomastia = breast tissue development in males

  • Cimetidine inhibits multiple CYP enzymes
    → other drugs are metabolized more slowly
    → ↑ drug levels/half-life
    → many DDIs

H2 blockers and creatinine

H2 blocker and creatinine

• → compete for tubular secretion

• → less creatinine gets secreted

• → blood creatinine can increase

• KEY POINT

  • Creatinine ↑ does NOT automatically mean kidney damage here.

• The drug is competing with creatinine for the same route of excretion.

H2 blockers + alcohol

Most H2 blockers, except famotidine, can increase alcohol exposure/effects