HISTAMINE2 RECEPTOR ANTAGONISTS (H2RAs)

🧠 WHAT ARE H2RAs?

• These drugs block H2 receptors on parietal cells in the stomach.

• H2 receptors are normally activated by histamine (released by vagal stimulation), causing gastric acid secretion.

• H2RAs decrease both basal and stimulated gastric acid production (stimulated by histamine, gastrin, and acetylcholine).

• H1 blockers (like diphenhydramine) do NOT affect acid production—only H2 blockers do.

💊 PROTOTYPE: CIMETIDINE (Tagamet HB)

🔬 PHARMACOKINETICS

• Liver metabolism (partial)

• Excreted in urine (unchanged)

• Dosage must be adjusted in kidney or liver impairment

⚙ ACTION

• Blocks H2 receptors on parietal cells → ↓ secretion of:

  • Hydrochloric acid

  • Pepsin content

  • Acidity of gastric juices

• IV form → rapid action, useful in acute GI bleeding

• Oral dose → often taken at bedtime, or with meals + bedtime if multiple doses

🩺 USES

• Peptic ulcer disease (PUD)

• GERD

• Esophagitis

• GI bleeding due to stress ulcers

• Zollinger-Ellison syndrome (gastrin-secreting tumor)

• OTC: for heartburn

⏱ Healing Times:

• PUD: 6–8 weeks

• Esophagitis: ~12 weeks

👵 SPECIAL POPULATIONS

🧓 Older Adults:

• Risk for CNS effects: confusion, agitation, delirium, disorientation

• Risk ↑ with kidney/liver impairment

🤰 Pregnancy & Lactation:

🧬 Renal & Liver Impairment

• ↓ Creatinine clearance = reduce dose (otherwise ↑ risk for toxicity)

• Cimetidine blocks tubular secretion of creatinine → ↑ serum creatinine (false elevation)

• Metabolism slowed in liver disease = drug levels can get too high

🏥 CRITICALLY ILL PATIENTS

• Longer half-life, slower clearance due to ↓ perfusion + kidney function

• H2 blockers may be used to prevent stress ulcers

😵‍💫 ADVERSE EFFECTS

Common:

• Diarrhea

• Headache

• Dizziness, drowsiness

• Muscle aches

• Fatigue

Less Common but Important:

• Mental confusion, delirium, coma (esp. elderly/kidney disease)

• Gynecomastia (men)

• Galactorrhea (women)

• Decreased sperm count (long-term)

⛔ These are mostly associated with Cimetidine. Famotidine and Nizatidine are better tolerated.

⚠ CONTRAINDICATIONS

• Hypersensitivity

• Caution in kidney/liver disease

• Avoid Cimetidine if on many other drugs (major interactions!)

🚫 DRUG INTERACTIONS (💣 VERY TESTABLE)

🔺 Cimetidine inhibits CYP450 enzymes → ↑ serum levels of many drugs!

🔼 Cimetidine Increases Effects of:

• Warfarin (↑ bleeding risk!)

• Phenytoin, carbamazepine (toxicity)

• Theophylline

• Benzodiazepines (↑ sedation)

• Propranolol, metoprolol

• Tricyclic antidepressants

• Opioids (↑ respiratory depression risk)

🔽 Cimetidine Decreases Effects of:

• Iron

• Digoxin

• Tetracyclines

• Fluconazole

• Indomethacin

PEARL: Use Famotidine or Nizatidine instead in patients taking lots of meds—they don’t inhibit CYP450.

💉 ADMINISTRATION

📏 Always use a marked cup or syringe for oral liquid.

🧪 ASSESSMENT — THERAPEUTIC EFFECTS

• ↓ epigastric pain, heartburn

• Ulcer healing within 6–8 weeks

• Reassess for:

  • Ongoing symptoms

  • GI bleeding

  • Need for endoscopy/radiology follow-up

⚠ ASSESSMENT — ADVERSE EFFECTS

• CNS (confusion, hallucinations)

• GI (diarrhea or constipation)

• Neuro (fatigue, dizziness)

• Reproductive (gynecomastia, ↓ sperm)

• Skin rash, fever, depression

📚 PATIENT TEACHING – Box 37.1 Highlights (Specific to H2RAs)

• Take cimetidine with meals or at bedtime

• Take famotidine/nizatidine with or without food

• Do NOT take antacids 1 hour before or after H2RA (except Pepcid Complete)

• Avoid OTC cimetidine/famotidine if prescribed version is being taken

• Don't use OTC versions longer than 2 weeks without provider advice

• Educate on lifestyle changes to reduce reflux (see below)

🧠 TEACHING: Lifestyle to Reduce Reflux (KNOW THIS!)

✅ Patient understands teaching if they say:

• ⬆ “Elevate the head of the bed”

• 🚭 “Avoid smoking”

• 🚫 “Avoid fats, chocolate, caffeine, alcohol, and citrus”

• 🛏 “Don’t lie down 1–2 hours after eating”

• 💩 “Avoid constipation”

⛔ Wrong choice: "Take medication with no more than 2 oz of water"
➡ You need 8 oz of water to help the med go down and absorb properly unless otherwise specified (e.g., Pepcid AC orally disintegrating tablets).

✅ NCLEX SUCCESS QUESTIONS (From the Text)

❓1. Cimetidine + Warfarin = ?

Correct answer:
✅ Warfarin effects would be increased

❓2. Which patient statement shows proper understanding of minimizing reflux? (Select all that apply)

✅ Correct answers:

• Elevate the head of the bed

• Avoid smoking

• Minimize intake of fats, chocolate, citric juices, coffee, and alcohol

• Avoid lying down for 1 to 2 hours after eating

• Avoid constipation

🚫 Incorrect answer: “Take with no more than 2 oz of water”

✅ KEY TAKEAWAYS: H2RAs

• Cimetidine = prototype, but famotidine/nizatidine are safer for drug interactions.

• Block H2 receptors on parietal cells → ↓ gastric acid & pepsin

• Used for PUD, GERD, esophagitis, stress ulcers

• Caution in elderly, renal, and hepatic impairment

• Cimetidine = many drug interactions via CYP450 inhibition

• Side effects: confusion, gynecomastia, galactorrhea

• Administer with meals or bedtime

• Avoid taking with antacids

• Effective in 6–12 hours, therapy lasts 4–8 weeks

• Do not overuse OTC versions—can mask serious disease!