UNIT-3- Drugs acting on G.I system

Introduction to Drugs Acting on the Gastrointestinal (G.I.) System

The gastrointestinal (G.I.) system plays a crucial role in digestion, absorption of nutrients, and elimination of waste. Various disorders, such as acid-peptic diseases, gastroesophageal reflux disease (GERD), constipation, diarrhea, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), require pharmacological interventions.

Drugs acting on the G.I. system help regulate gastric acid secretion, motility, digestion, and absorption while addressing common disorders like nausea, vomiting, and infections.

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1. Classification of Drugs Acting on the G.I. System

A. Drugs for Acid-Peptic Diseases

1. Antacids – Neutralize gastric acid (e.g., Magnesium hydroxide, Aluminum hydroxide).
2. H2-Receptor Antagonists (H2 Blockers) – Reduce acid secretion (e.g., Ranitidine, Famotidine).
3. Proton Pump Inhibitors (PPIs) – Block acid production (e.g., Omeprazole, Pantoprazole).
4. Mucosal Protective Agents – Enhance mucosal defense (e.g., Sucralfate, Misoprostol).

B. Drugs Affecting G.I. Motility

1. Prokinetic Agents – Increase motility (e.g., Metoclopramide, Domperidone).
2. Laxatives – Promote bowel movement (e.g., Bisacodyl, Lactulose, Psyllium).
3. Antidiarrheal Agents – Reduce stool frequency (e.g., Loperamide, Diphenoxylate).

C. Drugs for Nausea and Vomiting (Antiemetics)

1. 5-HT3 Receptor Antagonists – Block serotonin (e.g., Ondansetron, Granisetron).
2. Dopamine Antagonists – Reduce nausea (e.g., Metoclopramide, Domperidone).
3. Antihistamines – Block H1 receptors (e.g., Promethazine, Meclizine).
4. Neurokinin-1 (NK1) Receptor Antagonists – Used in chemotherapy-induced nausea (e.g., Aprepitant).

D. Drugs for Inflammatory Bowel Disease (IBD)

1. Aminosalicylates – Reduce inflammation (e.g., Mesalazine, Sulfasalazine).
2. Immunosuppressants – Suppress immune response (e.g., Azathioprine, Methotrexate).
3. Biologics (TNF-α inhibitors) – Target inflammatory mediators (e.g., Infliximab, Adalimumab).

E. Drugs for Irritable Bowel Syndrome (IBS)

1. Antispasmodics – Relieve abdominal cramps (e.g., Dicyclomine, Hyoscine).
2. Serotonin Modulators – Regulate gut motility (e.g., Alosetron, Tegaserod).

F. Drugs for Hepatic and Biliary Disorders

1. Hepatoprotective Agents – Protect liver cells (e.g., Silymarin, Ursodeoxycholic acid).
2. Choleretics and Cholagogues – Stimulate bile flow (e.g., Ursodiol).

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2. Importance of G.I. Drugs in Clinical Practice

• Acid suppression therapy is essential for GERD and ulcers.
• Laxatives and antidiarrheals help regulate bowel function.
• Antiemetics provide relief from nausea and vomiting, especially in chemotherapy.
• IBD and IBS medications improve the quality of life in chronic gut disorders.

Proper selection and rational use of G.I. drugs ensure effective treatment with minimal side effects.

Pharmacology of Commonly Used Emetics and Antiemetics

Introduction

Emetics and antiemetics are drugs that affect the vomiting reflex, which is controlled by the vomiting center (VC) in the medulla and the chemoreceptor trigger zone (CTZ).

• Emetics induce vomiting and are used in poisoning cases (except for corrosives, hydrocarbons, and unconscious patients).
• Antiemetics prevent or treat nausea and vomiting caused by motion sickness, pregnancy, chemotherapy, and gastrointestinal disorders.

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1. Emetics (Drugs That Induce Vomiting)

A. Classification of Emetics

1. Peripheral Acting Emetics – Act on the stomach lining.
   • Examples: Warm salt water, Copper sulfate, Mustard water
2. Central Acting Emetics – Stimulate the Chemoreceptor Trigger Zone (CTZ).
   • Examples: Apomorphine, Ipecac syrup

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B. Commonly Used Emetics

1. Apomorphine

Composition

• A derivative of morphine but lacks analgesic properties.

Action

• Stimulates dopamine (D2) receptors in the Chemoreceptor Trigger Zone (CTZ), leading to vomiting.

Dosage and Route

• Dose: 5-10 mg subcutaneously.
• Route: Given subcutaneously (SC).

Indications

• Induced vomiting in poisoning (only under medical supervision).

Contraindications

• Unconscious patients.
• Ingestion of corrosive poisons (e.g., acids, alkalis).
• Respiratory depression (may worsen condition).

Drug Interactions

• CNS depressants (opioids, sedatives): Increase risk of respiratory depression.

Side Effects

• Nausea, excessive salivation, dizziness.

Adverse Effects

• Severe respiratory depression.
• Hypotension.

Toxicity

• Can cause prolonged vomiting and dehydration.
• Treatment: IV fluids, antiemetics (if needed).

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2. Ipecac Syrup

Composition

• Contains emetine and cephaeline, which irritate the stomach lining.

Action

• Acts both centrally (stimulates CTZ) and peripherally (irritates gastric mucosa) to induce vomiting.

Dosage and Route

• Dose: 15-30 mL orally, followed by 200-300 mL of water.

Indications

• Induction of vomiting in poisoning (rarely used now).

Contraindications

• Corrosive poison ingestion.
• Petroleum poisoning (risk of aspiration).

Drug Interactions

• CNS depressants: Increase sedation.

Side Effects

• Nausea, drowsiness, diarrhea.

Adverse Effects

• Myopathy, cardiotoxicity (with prolonged use).

Toxicity

• Large doses cause muscle weakness and cardiac toxicity.

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2. Antiemetics (Drugs That Prevent or Control Vomiting)

A. Classification of Antiemetics

1. Serotonin (5-HT3) Receptor Antagonists
   • Examples: Ondansetron, Granisetron
   • Used in chemotherapy-induced nausea and vomiting (CINV), post-operative nausea and vomiting (PONV).
2. Dopamine (D2) Receptor Antagonists
   • Examples: Metoclopramide, Domperidone, Prochlorperazine
   • Used for nausea due to gastroesophageal reflux disease (GERD) and gastric stasis.
3. Antihistamines (H1 Receptor Antagonists)
   • Examples: Promethazine, Meclizine, Diphenhydramine
   • Used for motion sickness, vertigo, and pregnancy-induced nausea.
4. Neurokinin-1 (NK1) Receptor Antagonists
   • Examples: Aprepitant, Fosaprepitant
   • Used in chemotherapy-induced nausea and vomiting (CINV).
5. Cannabinoids
   • Examples: Dronabinol, Nabilone
   • Used in chemotherapy-induced nausea, especially in cancer patients.
6. Anticholinergics (Muscarinic M1 Receptor Antagonists)
   • Examples: Scopolamine (Hyoscine)
   • Used for motion sickness and post-operative nausea.

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B. Commonly Used Antiemetics

1. Ondansetron (5-HT3 Receptor Antagonist)

Composition

• Available as tablets, injections (IV/IM), and oral disintegrating tablets.

Action

• Blocks 5-HT3 receptors in the CTZ and gut, preventing vomiting.

Dosage and Route

• Dose: 4-8 mg orally or IV every 8 hours.
• Route: Oral, IV, IM.

Indications

• Chemotherapy-induced nausea and vomiting (CINV).
• Post-operative nausea and vomiting (PONV).
• Radiation therapy-induced nausea.

Contraindications

• Hypersensitivity to ondansetron.
• QT prolongation (may worsen arrhythmias).

Drug Interactions

• QT-prolonging drugs (e.g., Amiodarone, Fluoroquinolones) increase cardiac risk.
• CYP3A4 inhibitors (e.g., Ketoconazole, Ritonavir) increase plasma levels.

Side Effects

• Headache, constipation, dizziness.

Adverse Effects

• QT prolongation, arrhythmias.
• Serotonin syndrome if combined with SSRIs.

Toxicity

• Overdose may cause severe arrhythmias and hypotension.

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2. Metoclopramide (D2 Receptor Antagonist, Prokinetic)

Composition

• Available as tablets, IV/IM injection.

Action

• Blocks D2 receptors in the CTZ and enhances gastric motility.

Dosage and Route

• Dose: 10 mg orally or IV every 6-8 hours.

Indications

• GERD-related nausea.
• Post-operative nausea and vomiting (PONV).
• Delayed gastric emptying (gastroparesis).

Contraindications

• Parkinson’s disease (worsens symptoms).
• Bowel obstruction.

Drug Interactions

• CNS depressants (Benzodiazepines, Alcohol) enhance sedation.
• Anticholinergics (Atropine, Hyoscine) reduce effectiveness.

Side Effects

• Drowsiness, diarrhea.

Adverse Effects

• Extrapyramidal symptoms (EPS) like dystonia, tardive dyskinesia.
• Neuroleptic malignant syndrome (NMS).

Toxicity

• Overdose may cause severe EPS, seizures.

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3. Scopolamine (Anticholinergic)

Composition

• Available as patches, tablets, and injections.

Action

• Blocks muscarinic receptors (M1) in the vomiting center.

Dosage and Route

• Dose: 1 mg patch applied behind the ear every 72 hours.

Indications

• Motion sickness.
• Post-operative nausea.

Contraindications

• Glaucoma (increases intraocular pressure).
• Prostatic hypertrophy.

Drug Interactions

• Antihistamines and benzodiazepines increase sedation.

Side Effects

• Dry mouth, blurred vision, dizziness.

Adverse Effects

• Confusion, hallucinations (especially in elderly patients).

Toxicity

• Overdose causes delirium, tachycardia, and seizures.

Pharmacology of Laxatives and Purgatives

Introduction

Laxatives and purgatives are drugs used to relieve constipation by facilitating bowel movements. While both promote defecation, laxatives produce a mild effect, whereas purgatives (cathartics) cause forceful evacuation of stool.

These drugs are essential in treating chronic constipation, bowel preparation before surgery or colonoscopy, and conditions requiring soft stools (e.g., hemorrhoids, post-operative recovery).

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1. Classification of Laxatives and Purgatives

A. Bulk-Forming Laxatives (Natural and Synthetic Fibers)

• Examples: Psyllium husk (Isabgol), Methylcellulose, Bran
• Mechanism: Absorb water, increase stool bulk, and stimulate peristalsis.
• Onset of Action: 12-24 hours.
• Indications: Chronic constipation, Irritable Bowel Syndrome (IBS).
• Side Effects: Bloating, flatulence.

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B. Stool Softeners (Emollient Laxatives)

• Examples: Docusate sodium, Liquid paraffin
• Mechanism: Increase water content in stool, making it soft.
• Onset of Action: 12-72 hours.
• Indications: Post-operative patients, pregnant women, hemorrhoids.
• Side Effects: Diarrhea, nausea, lipid pneumonia (with prolonged use of liquid paraffin).

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C. Osmotic Laxatives (Saline and Hyperosmotic Agents)

• Examples:
  • Saline Laxatives: Magnesium sulfate (Epsom salt), Sodium phosphate.
  • Hyperosmotic Laxatives: Lactulose, Polyethylene glycol (PEG), Sorbitol.
• Mechanism: Draw water into the bowel via osmosis, softening stool and increasing peristalsis.
• Onset of Action:
  • Saline Laxatives: 1-3 hours.
  • Lactulose/PEG: 24-48 hours.
• Indications: Chronic constipation, hepatic encephalopathy (lactulose), bowel preparation for colonoscopy.
• Side Effects: Abdominal cramps, bloating, electrolyte imbalance (saline laxatives).

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D. Stimulant Laxatives (Irritant Purgatives)

• Examples: Bisacodyl, Senna, Castor oil
• Mechanism:
  • Stimulate intestinal motility by irritating the intestinal mucosa.
  • Increase secretion of water and electrolytes in the colon.
• Onset of Action:
  • Bisacodyl (oral): 6-8 hours.
  • Bisacodyl (rectal suppository): 15-60 minutes.
  • Senna: 6-12 hours.
  • Castor oil: 1-3 hours.
• Indications: Acute constipation, preoperative bowel clearance.
• Side Effects: Abdominal cramps, diarrhea, dependence with long-term use.

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E. Lubricant Laxatives

• Examples: Mineral oil, Glycerin suppositories
• Mechanism: Coats stool and intestinal wall, reducing water absorption, easing stool passage.
• Onset of Action: 6-8 hours.
• Indications: Temporary relief of constipation, post-operative cases.
• Side Effects: Fat-soluble vitamin malabsorption (A, D, E, K), aspiration risk (if ingested in excess).

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F. Enema (Rectal Laxatives)

• Examples: Phosphate enema, Soap suds enema, Glycerin enema
• Mechanism: Stimulates rectal contraction and softens stool.
• Onset of Action: 5-15 minutes.
• Indications: Fecal impaction, rapid bowel clearance.
• Side Effects: Rectal irritation, electrolyte imbalance (phosphate enema).

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2. Comparison of Laxatives and Purgatives

Type	Laxatives (Mild Action)	Purgatives (Strong Action)
Effect	Gentle bowel movement	Forceful evacuation
Use	Chronic constipation	Acute constipation, preoperative bowel clearance
Examples	Psyllium, Lactulose, Docusate	Bisacodyl, Senna, Castor oil
Onset of Action	Slow (6-72 hours)	Rapid (1-6 hours)
Dependency Risk	Low	High (with prolonged use)

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3. Pharmacology of Commonly Used Laxatives and Purgatives

1. Lactulose (Osmotic Laxative)

Composition

• A synthetic disaccharide (galactose + fructose).

Action

• Draws water into the colon, softening stool.
• Lowers ammonia levels in hepatic encephalopathy.

Dosage and Route

• Dose for constipation: 10-20 mL orally, 1-2 times daily.
• Dose for hepatic encephalopathy: 30-60 mL orally, 3-4 times daily.

Indications

• Chronic constipation.
• Hepatic encephalopathy (reduces blood ammonia levels).

Contraindications

• Galactosemia (contains galactose).
• Diabetes mellitus (can increase blood sugar).

Drug Interactions

• Antibiotics (Neomycin, Metronidazole): Reduce lactulose effectiveness.

Side Effects

• Bloating, flatulence, diarrhea.

Adverse Effects

• Electrolyte imbalance (with prolonged use).

Toxicity

• Overdose causes severe diarrhea, dehydration, and hypokalemia.

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2. Bisacodyl (Stimulant Laxative)

Composition

• Available as tablets (5 mg, 10 mg) and suppositories (10 mg).

Action

• Stimulates enteric nerves, increasing peristalsis and stool secretion.

Dosage and Route

• Oral: 5-10 mg at bedtime.
• Rectal Suppository: 10 mg for rapid action.

Indications

• Acute constipation.
• Bowel preparation for diagnostic procedures.

Contraindications

• Intestinal obstruction.
• Inflammatory bowel disease (IBD).

Drug Interactions

• Antacids, Milk: Reduce drug effectiveness if taken together.

Side Effects

• Abdominal cramps, rectal irritation.

Adverse Effects

• Electrolyte imbalance, dehydration.
• Dependence (if used chronically).

Toxicity

• High doses lead to severe diarrhea, hypokalemia, dehydration.

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3. Senna (Natural Stimulant Laxative)

Composition

• Contains sennosides, derived from Senna plant leaves.

Action

• Stimulates colonic motility by irritating the intestinal mucosa.

Dosage and Route

• Dose: 15-30 mg orally at bedtime.

Indications

• Occasional constipation.

Contraindications

• Pregnancy (risk of uterine contraction).
• Intestinal obstruction.

Drug Interactions

• Diuretics, corticosteroids: Increase risk of hypokalemia.

Side Effects

• Abdominal cramps, nausea.

Adverse Effects

• Melanosis coli (chronic use causes black pigmentation of colon).

Toxicity

• Prolonged use can cause dependence, dehydration, and electrolyte imbalance.

Pharmacology of Antacids and Antipeptic Ulcer Drugs

Introduction

Antacids and antipeptic ulcer drugs are used to treat acid-related disorders like gastritis, gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and Zollinger-Ellison syndrome.

• Antacids: Neutralize stomach acid and provide symptomatic relief.
• Antipeptic ulcer drugs: Reduce acid secretion, protect the gastric mucosa, and promote ulcer healing.

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1. Classification of Antacids and Antipeptic Ulcer Drugs

A. Antacids (Acid Neutralizers)

1. Systemic Antacids
   • Sodium bicarbonate (NaHCO₃)
2. Non-Systemic Antacids
   • Magnesium hydroxide (Milk of Magnesia)
   • Aluminum hydroxide
   • Calcium carbonate

B. Antipeptic Ulcer Drugs

1. H2-Receptor Antagonists (H2 Blockers)
   • Examples: Ranitidine, Famotidine, Cimetidine
2. Proton Pump Inhibitors (PPIs)
   • Examples: Omeprazole, Pantoprazole, Esomeprazole
3. Mucosal Protective Agents
   • Examples: Sucralfate, Bismuth subsalicylate, Misoprostol
4. Antibiotics (For H. pylori Eradication)
   • Examples: Amoxicillin, Clarithromycin, Metronidazole

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2. Pharmacology of Common Antacids and Antipeptic Ulcer Drugs

1. Sodium Bicarbonate (Systemic Antacid)

Composition

• Sodium bicarbonate (NaHCO₃)

Action

• Neutralizes gastric acid by forming sodium chloride, water, and carbon dioxide (CO₂).

Dosage and Route

• Oral: 500 mg–1 g every 4–6 hours as needed.

Indications

• Immediate relief of acid indigestion and heartburn.

Contraindications

• Hypertension and heart failure (due to sodium load).
• Chronic kidney disease (risk of alkalosis).

Drug Interactions

• Reduces absorption of tetracyclines, fluoroquinolones, and iron supplements.

Side Effects

• Bloating, belching due to CO₂ release.

Adverse Effects

• Metabolic alkalosis with prolonged use.

Toxicity

• Overdose symptoms: Hypernatremia, muscle twitching, confusion.
• Management: IV fluids, correction of electrolyte imbalance.

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2. Magnesium Hydroxide (Milk of Magnesia, Non-Systemic Antacid)

Composition

• Magnesium hydroxide (Mg(OH)₂)

Action

• Neutralizes acid and acts as an osmotic laxative.

Dosage and Route

• Oral: 5–15 mL (400–1200 mg) up to 4 times daily.

Indications

• Peptic ulcer disease (PUD).
• Acid indigestion and heartburn.

Contraindications

• Renal failure (risk of hypermagnesemia).

Drug Interactions

• Decreases absorption of iron, fluoroquinolones, and tetracyclines.

Side Effects

• Diarrhea (due to osmotic effect).

Adverse Effects

• Hypermagnesemia (lethargy, hypotension, respiratory depression).

Toxicity

• Overdose symptoms: Weakness, cardiac arrhythmias.
• Management: IV calcium gluconate, hemodialysis if needed.

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3. Aluminum Hydroxide (Non-Systemic Antacid)

Composition

• Aluminum hydroxide (Al(OH)₃)

Action

• Neutralizes acid and binds bile acids, providing mucosal protection.

Dosage and Route

• Oral: 500 mg–1 g every 6 hours.

Indications

• Peptic ulcers, GERD.

Contraindications

• Chronic kidney disease (risk of aluminum toxicity).

Drug Interactions

• Reduces absorption of warfarin, digoxin, and tetracyclines.

Side Effects

• Constipation, hypophosphatemia.

Adverse Effects

• Aluminum toxicity (osteomalacia, encephalopathy).

Toxicity

• Overdose symptoms: Bone pain, confusion.
• Management: Chelation therapy (deferoxamine).

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4. Ranitidine (H2-Receptor Antagonist)

Composition

• Ranitidine hydrochloride

Action

• Blocks histamine H2-receptors, reducing gastric acid secretion.

Dosage and Route

• Oral: 150 mg twice daily or 300 mg at bedtime.
• IV: 50 mg every 6–8 hours.

Indications

• Peptic ulcers, GERD, Zollinger-Ellison syndrome.

Contraindications

• Severe liver disease.

Drug Interactions

• Inhibits metabolism of warfarin, phenytoin (increases toxicity).

Side Effects

• Headache, dizziness.

Adverse Effects

• Rare: Confusion, gynecomastia (Cimetidine-related).

Toxicity

• Overdose symptoms: Bradycardia, hypotension.
• Management: Supportive care.

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5. Omeprazole (Proton Pump Inhibitor – PPI)

Composition

• Omeprazole sodium

Action

• Irreversibly inhibits H+/K+ ATPase (proton pump), reducing acid secretion.

Dosage and Route

• Oral: 20–40 mg once daily.
• IV: 40 mg once daily.

Indications

• Peptic ulcers, GERD, Zollinger-Ellison syndrome.

Contraindications

• Osteoporosis (increased fracture risk).

Drug Interactions

• Increases warfarin, diazepam levels (risk of bleeding, sedation).

Side Effects

• Headache, nausea.

Adverse Effects

• Long-term use: Vitamin B12 deficiency, osteoporosis, increased infection risk.

Toxicity

• Overdose symptoms: Seizures, metabolic alkalosis.
• Management: Symptomatic treatment.

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6. Sucralfate (Mucosal Protective Agent)

Composition

• Aluminum sucrose sulfate

Action

• Forms a protective gel over ulcers, shielding them from acid and pepsin.

Dosage and Route

• Oral: 1 g, 4 times daily before meals.

Indications

• Peptic ulcer disease (PUD).

Contraindications

• Chronic kidney disease (CKD) (risk of aluminum toxicity).

Drug Interactions

• Reduces absorption of fluoroquinolones, digoxin, phenytoin.

Side Effects

• Constipation.

Adverse Effects

• Aluminum toxicity in CKD patients.

Toxicity

• Overdose symptoms: Confusion, bone pain.
• Management: Chelation therapy.

Pharmacology of Antidiarrheal Drugs

Introduction

Diarrhea is defined as an increase in the frequency, fluidity, or volume of bowel movements. It may result from infections, malabsorption, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or medication-induced effects.

Antidiarrheal drugs are used to reduce stool frequency, improve stool consistency, and prevent dehydration. However, they should be used cautiously, especially in infectious diarrhea, as they may prolong the illness.

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1. Classification of Antidiarrheal Drugs

A. Adsorbents and Bulk-Forming Agents

• Examples: Kaolin, Pectin, Activated Charcoal
• Mechanism: Absorb toxins and bacteria, provide stool bulk.
• Uses: Mild diarrhea, toxin-induced diarrhea.

B. Opioid Agonists (Motility Inhibitors)

• Examples: Loperamide, Diphenoxylate + Atropine
• Mechanism: Reduce intestinal motility, prolong stool transit time.
• Uses: Non-infectious diarrhea, traveler’s diarrhea.

C. Antisecretory Agents

• Examples: Bismuth subsalicylate, Octreotide
• Mechanism: Reduce secretion of fluids into the intestine.
• Uses: Traveler’s diarrhea, secretory diarrhea (e.g., carcinoid syndrome).

D. Probiotics

• Examples: Lactobacillus, Saccharomyces boulardii
• Mechanism: Restore normal gut flora, suppress pathogenic bacteria.
• Uses: Antibiotic-associated diarrhea, mild infectious diarrhea.

E. Anti-inflammatory and Immunosuppressive Agents

• Examples: Sulfasalazine, Mesalazine
• Mechanism: Reduce gut inflammation.
• Uses: Inflammatory bowel disease (IBD).

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2. Pharmacology of Common Antidiarrheal Drugs

1. Loperamide (Opioid Agonist)

Composition

• Loperamide hydrochloride

Action

• Acts on opioid receptors in the gut, slowing intestinal motility.
• Increases absorption of water and electrolytes.

Dosage and Route

• Oral: 4 mg initially, then 2 mg after each loose stool (max: 16 mg/day).

Indications

• Non-infectious diarrhea.
• Traveler’s diarrhea.
• Chronic diarrhea in IBS.

Contraindications

• Bacterial or C. difficile-associated diarrhea (may worsen infection).
• Children <2 years (risk of paralytic ileus).

Drug Interactions

• CNS depressants (alcohol, opioids) enhance sedation.
• Ritonavir, Macrolides increase toxicity risk.

Side Effects

• Constipation, dry mouth, drowsiness.

Adverse Effects

• Paralytic ileus, toxic megacolon (with overdose).

Toxicity

• Overdose symptoms: Severe constipation, CNS depression.
• Management: Naloxone (opioid antidote), supportive care.

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2. Diphenoxylate + Atropine (Opioid Agonist)

Composition

• Diphenoxylate hydrochloride + Atropine sulfate

Action

• Diphenoxylate: Reduces intestinal motility by acting on opioid receptors.
• Atropine: Prevents abuse by causing unpleasant effects in high doses.

Dosage and Route

• Oral: 2.5 mg (diphenoxylate) + 0.025 mg (atropine) 3–4 times daily.

Indications

• Moderate-to-severe non-infectious diarrhea.

Contraindications

• Infectious diarrhea, severe hepatic disease.

Drug Interactions

• CNS depressants (benzodiazepines, opioids) enhance sedation.

Side Effects

• Dry mouth, dizziness, drowsiness.

Adverse Effects

• Paralytic ileus, respiratory depression (high doses).

Toxicity

• Overdose symptoms: Confusion, difficulty breathing.
• Management: Naloxone for opioid toxicity, supportive care.

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3. Bismuth Subsalicylate (Antisecretory Agent)

Composition

• Bismuth subsalicylate

Action

• Coats ulcers and the gut, reducing irritation.
• Inhibits bacterial growth, reducing secretory diarrhea.

Dosage and Route

• Oral: 524 mg every 30–60 minutes as needed (max: 8 doses/day).

Indications

• Traveler’s diarrhea.
• Mild bacterial diarrhea.
• Peptic ulcer disease (H. pylori eradication).

Contraindications

• Salicylate allergy (aspirin-sensitive patients).
• Children <12 years (risk of Reye’s syndrome).

Drug Interactions

• Aspirin, anticoagulants (increased bleeding risk).

Side Effects

• Dark stool, black tongue.

Adverse Effects

• Salicylate toxicity (tinnitus, metabolic acidosis).

Toxicity

• Overdose symptoms: Nausea, vomiting, confusion.
• Management: Activated charcoal, IV fluids.

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4. Octreotide (Somatostatin Analog)

Composition

• Synthetic octapeptide somatostatin analog.

Action

• Inhibits secretion of gut hormones, reducing diarrhea.

Dosage and Route

• Subcutaneous (SC): 100–500 mcg three times daily.
• IV infusion: 25–50 mcg/hour for severe cases.

Indications

• Secretory diarrhea (e.g., carcinoid tumors, VIPoma).
• Severe chemo-induced diarrhea.

Contraindications

• Gallbladder disease (risk of gallstones).

Drug Interactions

• Insulin, antidiabetic drugs (may cause hypoglycemia).

Side Effects

• Nausea, bloating, abdominal pain.

Adverse Effects

• Gallstones, steatorrhea, hyperglycemia.

Toxicity

• Overdose symptoms: Severe bradycardia, hypotension.
• Management: Supportive care.

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5. Probiotics (Lactobacillus, Saccharomyces boulardii)

Composition

• Beneficial bacterial strains (Lactobacillus, Bifidobacterium).

Action

• Restore normal gut flora, suppress pathogenic bacteria.

Dosage and Route

• Oral: 1–2 capsules daily.

Indications

• Antibiotic-associated diarrhea.
• Mild infectious diarrhea.

Contraindications

• Severely immunocompromised patients (risk of sepsis).

Drug Interactions

• Antibiotics reduce probiotic effectiveness (should be spaced apart).

Side Effects

• Bloating, flatulence.

Adverse Effects

• Rare: Fungal/bacterial sepsis in immunocompromised patients.

Toxicity

• Minimal risk of overdose.

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3. Summary Table of Common Antidiarrheals

Drug	Mechanism	Indications	Side Effects	Serious Adverse Effects
Loperamide	Opioid agonist	Non-infectious diarrhea	Constipation, drowsiness	Paralytic ileus, toxic megacolon
Diphenoxylate	Opioid agonist	Moderate diarrhea	Dry mouth, dizziness	Respiratory depression
Bismuth Subsalicylate	Antisecretory	Traveler’s diarrhea	Black tongue, dark stool	Salicylate toxicity
Octreotide	Inhibits gut hormones	Secretory diarrhea	Abdominal pain	Gallstones, hyperglycemia
Probiotics	Restore gut flora	Antibiotic-associated diarrhea	Bloating	Rare: Sepsis in immunocompromised

Pharmacology of Fluid and Electrolyte Therapy

Introduction

Fluid and electrolyte therapy is used to maintain or restore the balance of fluids, electrolytes, and acid-base levels in the body. It is essential in conditions like dehydration, shock, burns, kidney disease, and electrolyte imbalances.

• Crystalloids: Solutions that contain electrolytes and can distribute across body compartments.
• Colloids: Contain large molecules that stay in the vascular space, drawing water from the interstitial compartment.
• Electrolyte Solutions: Restore specific ion deficits such as sodium, potassium, calcium, chloride, bicarbonate, and magnesium.

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1. Classification of Fluid and Electrolyte Therapy

A. Crystalloids (Volume Expanders)

1. Isotonic Solutions – Maintain fluid balance.
   • Examples: 0.9% Normal Saline (NS), Ringer’s Lactate (RL), 5% Dextrose in Water (D5W)
2. Hypotonic Solutions – Used in dehydration.
   • Examples: 0.45% Saline (Half NS), 5% Dextrose in Water (D5W in vivo)
3. Hypertonic Solutions – Used in hyponatremia, cerebral edema.
   • Examples: 3% Saline, 10% Dextrose, 20% Mannitol

B. Colloids (Plasma Expanders)

• Examples: Albumin, Dextran, Hetastarch (HES), Gelatin Solutions

C. Electrolyte Therapy

1. Sodium Replacement – Hypertonic saline (3%), Normal saline (0.9%)
2. Potassium Replacement – Potassium chloride (KCl), Potassium citrate
3. Calcium Replacement – Calcium gluconate, Calcium chloride
4. Magnesium Replacement – Magnesium sulfate (MgSO₄)
5. Bicarbonate Therapy – Sodium bicarbonate (NaHCO₃) in metabolic acidosis

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2. Pharmacology of Common Fluid and Electrolyte Solutions

1. Normal Saline (0.9% Sodium Chloride)

Composition

• 154 mEq/L of Sodium (Na⁺)
• 154 mEq/L of Chloride (Cl⁻)

Action

• Expands intravascular volume, restores sodium levels.

Dosage and Route

• IV Infusion: 500–1000 mL at a controlled rate.

Indications

• Dehydration, hypotension, hypovolemia, shock.
• Fluid loss due to vomiting, diarrhea, burns.
• Dilution of IV medications.

Contraindications

• Heart failure, kidney disease (risk of fluid overload).

Drug Interactions

• Potassium supplements: May increase hyperkalemia risk.

Side Effects

• Fluid overload, edema, mild hypernatremia.

Adverse Effects

• Pulmonary edema, hypertension, metabolic acidosis (if overused).

Toxicity

• Overdose symptoms: Hypertension, difficulty breathing.
• Management: Diuretics, oxygen therapy.

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2. Ringer’s Lactate (RL)

Composition

• Sodium (130 mEq/L), Potassium (4 mEq/L), Calcium (3 mEq/L), Chloride (109 mEq/L), Lactate (28 mEq/L).

Action

• Expands plasma volume, provides electrolytes, corrects mild metabolic acidosis.

Dosage and Route

• IV Infusion: 500–1000 mL as needed.

Indications

• Burns, trauma, surgery, hypovolemia.
• Metabolic acidosis correction.

Contraindications

• Severe liver disease (lactate metabolism impairment).
• Hyperkalemia, renal failure (risk of high potassium levels).

Drug Interactions

• Calcium-containing drugs (e.g., ceftriaxone) cause precipitation.

Side Effects

• Mild fluid overload, transient alkalosis.

Adverse Effects

• Hyperkalemia, metabolic alkalosis (excessive lactate metabolism).

Toxicity

• Overdose symptoms: Respiratory distress, severe alkalosis.
• Management: Stop infusion, monitor electrolytes.

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3. Dextrose 5% in Water (D5W)

Composition

• 5% glucose (50 g/L), no electrolytes.

Action

• Provides calories and free water, shifts fluid into cells.

Dosage and Route

• IV Infusion: 500–1000 mL at controlled rate.

Indications

• Dehydration, hypoglycemia, diabetic ketoacidosis (adjunct therapy).

Contraindications

• Hyperglycemia, intracranial pressure (risk of cerebral edema).

Drug Interactions

• Insulin: Increases glucose uptake.

Side Effects

• Hyperglycemia, hyponatremia (due to dilution).

Adverse Effects

• Cerebral edema, osmotic diuresis in diabetics.

Toxicity

• Overdose symptoms: Severe hyperglycemia, dehydration.
• Management: Insulin, IV saline.

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4. 3% Hypertonic Saline

Composition

• 513 mEq/L Sodium (Na⁺), 513 mEq/L Chloride (Cl⁻).

Action

• Increases serum sodium, draws water from cells (treats cerebral edema).

Dosage and Route

• IV Infusion: Slow infusion, not exceeding 50 mL/hour.

Indications

• Severe hyponatremia (<120 mEq/L).
• Cerebral edema, traumatic brain injury.

Contraindications

• Hypertension, heart failure, kidney disease.

Drug Interactions

• Diuretics (may worsen sodium depletion).

Side Effects

• Irritation at infusion site, thirst.

Adverse Effects

• Osmotic demyelination syndrome (if corrected too rapidly).

Toxicity

• Overdose symptoms: Confusion, seizures, muscle weakness.
• Management: Slow correction with hypotonic fluids.

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5. Potassium Chloride (KCl)

Composition

• Potassium chloride (KCl), available in 10–40 mEq per dose.

Action

• Restores potassium balance, essential for muscle and nerve function.

Dosage and Route

• Oral: 10–20 mEq/day.
• IV: 10–20 mEq/hour (diluted in saline or dextrose water, never IV push).

Indications

• Hypokalemia, muscle weakness, cardiac arrhythmias.

Contraindications

• Hyperkalemia, kidney disease.

Drug Interactions

• ACE inhibitors, potassium-sparing diuretics (increase K⁺ levels).

Side Effects

• Nausea, abdominal discomfort.

Adverse Effects

• Severe hyperkalemia, cardiac arrest.

Toxicity

• Overdose symptoms: Irregular heartbeats, muscle weakness.
• Management: IV calcium gluconate, insulin with glucose.

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3. Summary Table of Fluid and Electrolyte Therapy

Solution	Indications	Contraindications	Key Side Effects	Toxicity Management
Normal Saline	Dehydration, shock	Heart failure, CKD	Fluid overload	Diuretics
Ringer’s Lactate	Burns, acidosis	Liver failure	Hyperkalemia	Stop infusion
Dextrose 5%	Dehydration	Hyperglycemia	Hyperglycemia	Insulin therapy
3% Saline	Severe hyponatremia	Hypertension	Osmotic demyelination	Slow correction
Potassium Chloride	Hypokalemia	Hyperkalemia	Cardiac arrhythmias	Calcium gluconate

Pharmacology of Furazolidone, Dicyclomine, and Metronidazole

1. Furazolidone

Composition

• Furazolidone (synthetic nitrofuran derivative)

Action

• Antimicrobial action: Inhibits bacterial and protozoal DNA synthesis.
• Bactericidal against Gram-positive and Gram-negative bacteria.
• Active against Giardia lamblia, Trichomonas vaginalis, and some enteric pathogens.

Dosage and Route

• Oral: 100 mg every 6–8 hours for 5–7 days.

Indications

• Bacterial and protozoal diarrhea (Giardiasis, Cholera, Enteric fever).
• Urinary tract infections (UTIs).
• Helicobacter pylori infection (adjunct therapy).

Contraindications

• Neonates (risk of hemolysis).
• G6PD deficiency (risk of hemolytic anemia).
• Severe hepatic or renal impairment.

Drug Interactions

• Tyramine-rich foods (cheese, wine, fermented products): May cause hypertensive crisis.
• Alcohol: Causes a disulfiram-like reaction (nausea, flushing, palpitations).
• MAO inhibitors: May lead to hypertensive crisis.

Side Effects

• Nausea, vomiting, loss of appetite.

Adverse Effects

• Peripheral neuropathy (long-term use).
• Hemolytic anemia in G6PD-deficient individuals.

Toxicity

• Overdose symptoms: Seizures, hepatic damage.
• Management: Supportive care, IV fluids, activated charcoal.

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2. Dicyclomine

Composition

• Dicyclomine hydrochloride (Anticholinergic/Antispasmodic).

Action

• Blocks muscarinic receptors in the smooth muscles of the gastrointestinal (GI) tract.
• Reduces intestinal spasms and pain.
• Decreases excessive gastric and intestinal secretions.

Dosage and Route

• Oral: 10–20 mg, 3–4 times daily.
• IM Injection: 10–20 mg every 6 hours (used in acute conditions).

Indications

• Irritable bowel syndrome (IBS).
• Colicky abdominal pain, intestinal spasms.
• Dysmenorrhea (menstrual cramps).

Contraindications

• Glaucoma (increases intraocular pressure).
• Urinary retention (e.g., benign prostatic hyperplasia – BPH).
• Myasthenia gravis.
• Severe ulcerative colitis (risk of toxic megacolon).

Drug Interactions

• Increases the effects of tricyclic antidepressants (TCAs) and antihistamines.
• Reduces the effectiveness of antacids.
• Enhances the action of opioids (risk of constipation).

Side Effects

• Dry mouth, dizziness, blurred vision.

Adverse Effects

• Paralytic ileus, urinary retention, tachycardia.

Toxicity

• Overdose symptoms: Hallucinations, delirium, seizures.
• Management: Activated charcoal, benzodiazepines (for seizures), IV fluids.

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3. Metronidazole

Composition

• Metronidazole (Nitroimidazole class antimicrobial).

Action

• Inhibits DNA synthesis in anaerobic bacteria and protozoa.
• Bactericidal and antiprotozoal.
• Works against Helicobacter pylori, Clostridium difficile, Giardia lamblia, Trichomonas vaginalis.

Dosage and Route

• Oral:
  • Bacterial infections: 400–500 mg every 8 hours for 7–10 days.
  • Amoebiasis: 500–750 mg three times daily for 7–10 days.
• IV: 500 mg every 8 hours (for severe infections).
• Topical: 1% gel for rosacea.

Indications

• Amoebiasis, Giardiasis, Trichomoniasis.
• Clostridium difficile-associated diarrhea (CDAD).
• Anaerobic bacterial infections (e.g., Bacterial vaginosis, Pelvic inflammatory disease).
• H. pylori eradication (part of triple therapy).

Contraindications

• Alcohol consumption (causes a disulfiram-like reaction).
• First trimester of pregnancy (teratogenic in animal studies).
• Severe hepatic dysfunction.

Drug Interactions

• Warfarin: Increases risk of bleeding.
• Lithium: Increases lithium toxicity.
• Cimetidine: Prolongs the half-life of metronidazole.
• Phenytoin and Phenobarbital: Reduce metronidazole levels.

Side Effects

• Metallic taste, nausea, dizziness.

Adverse Effects

• Neurotoxicity (seizures, peripheral neuropathy).
• Stevens-Johnson syndrome (rare but serious).

Toxicity

• Overdose symptoms: Vomiting, convulsions, neuropathy.
• Management: Supportive therapy, IV fluids, anti-seizure medications if needed.

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4. Summary Table of Furazolidone, Dicyclomine, and Metronidazole

Drug	Mechanism	Indications	Side Effects	Serious Adverse Effects	Contraindications
Furazolidone	Inhibits bacterial DNA	Bacterial diarrhea, UTIs	Nausea, vomiting	Hemolytic anemia in G6PD deficiency	Neonates, MAO inhibitors
Dicyclomine	Antispasmodic, blocks muscarinic receptors	IBS, colic pain	Dry mouth, dizziness	Paralytic ileus, urinary retention	Glaucoma, BPH, Myasthenia gravis
Metronidazole	Inhibits DNA synthesis in anaerobes	Amoebiasis, H. pylori, C. difficile	Metallic taste, nausea	Neurotoxicity, Stevens-Johnson syndrome	Alcohol use, pregnancy (1st trimester)

Role of Nurse in the Pharmacology of Commonly Used G.I. Drugs

Introduction

Nurses play a critical role in the administration, monitoring, and patient education of gastrointestinal (G.I.) drugs. These medications include antacids, proton pump inhibitors (PPIs), H2-receptor antagonists, antiemetics, laxatives, antidiarrheals, and prokinetic agents. Nurses ensure correct dosage, prevent adverse effects, educate patients on proper use, and assess therapeutic effectiveness.

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1. General Nursing Responsibilities in G.I. Drug Administration

A. Patient Assessment

• Assess patient history for allergies, contraindications, and existing conditions (e.g., kidney disease before giving antacids).
• Monitor symptoms like nausea, vomiting, diarrhea, constipation, and abdominal pain.
• Check vital signs (BP, heart rate, hydration status, bowel sounds).

B. Drug Administration and Monitoring

• Ensure correct dosage, timing, and route of administration.
• Monitor for therapeutic effects (relief of symptoms, improved bowel movements).
• Observe for adverse reactions (allergic reactions, drug toxicity).

C. Patient Education

• Teach about drug interactions (e.g., PPIs should not be taken with calcium supplements due to decreased absorption).
• Advise on dietary modifications (e.g., increase fiber with laxatives).
• Instruct on correct usage (e.g., antacids should not be taken with iron supplements).

D. Documentation and Reporting

• Record drug administration, patient response, and any side effects.
• Report adverse drug reactions and medication errors immediately.

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2. Nursing Role in Specific G.I. Drugs

1. Antacids (e.g., Aluminum Hydroxide, Magnesium Hydroxide, Calcium Carbonate)

Nursing Responsibilities

• Assess renal function before administering magnesium-based antacids.
• Monitor for side effects:
  • Constipation (aluminum-based), diarrhea (magnesium-based).
• Administer 1 hour before or 2 hours after other medications to avoid interactions.
• Educate the patient to avoid excessive calcium-based antacids (risk of kidney stones, metabolic alkalosis).

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2. Proton Pump Inhibitors (PPIs) (e.g., Omeprazole, Pantoprazole, Esomeprazole)

Nursing Responsibilities

• Administer before meals for maximum absorption.
• Monitor for long-term effects:
  • Hypomagnesemia, osteoporosis, increased risk of infections (C. difficile, pneumonia).
• Educate patients:
  • Avoid NSAIDs (increased risk of ulcers).
  • Do not crush enteric-coated tablets.

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3. H2-Receptor Antagonists (e.g., Ranitidine, Famotidine)

Nursing Responsibilities

• Assess for drug interactions (e.g., Cimetidine inhibits metabolism of warfarin and phenytoin).
• Monitor for central nervous system (CNS) effects in elderly patients (confusion, dizziness).
• Educate patients:
  • Take 30–60 minutes before meals for best effect.
  • Avoid alcohol and smoking, which increase acid secretion.

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4. Antiemetics (e.g., Ondansetron, Metoclopramide, Promethazine)

Nursing Responsibilities

• Monitor for side effects:
  • Ondansetron: Risk of QT prolongation (monitor ECG).
  • Metoclopramide: Watch for extrapyramidal symptoms (EPS) (tremors, tardive dyskinesia).
• Administer IV antiemetics slowly to avoid hypotension.
• Educate patients:
  • Avoid alcohol and sedatives, which enhance CNS depression.
  • Report involuntary muscle movements (dystonia, tardive dyskinesia).

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5. Laxatives and Purgatives (e.g., Psyllium, Lactulose, Bisacodyl, Senna)

Nursing Responsibilities

• Assess bowel habits before administration.
• Monitor for dehydration and electrolyte imbalances, especially with osmotic laxatives.
• Educate patients:
  • Increase fluid intake and fiber consumption.
  • Avoid long-term stimulant laxative use (risk of dependency).

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6. Antidiarrheal Agents (e.g., Loperamide, Bismuth Subsalicylate, Diphenoxylate)

Nursing Responsibilities

• Assess for infection before administration (do not give in C. difficile diarrhea).
• Monitor for signs of toxic megacolon in inflammatory bowel disease (severe abdominal distension, fever).
• Educate patients:
  • Avoid self-medication for more than 48 hours.
  • Stay hydrated to prevent electrolyte imbalance.

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7. Prokinetic Agents (e.g., Metoclopramide, Domperidone)

Nursing Responsibilities

• Monitor for CNS side effects:
  • Metoclopramide: Dystonia, tardive dyskinesia (risk in elderly patients).
• Assess bowel sounds before administration (avoid in obstruction).
• Educate patients:
  • Avoid alcohol and sedatives due to CNS depression risk.

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8. Helicobacter pylori Eradication Therapy (Triple Therapy: PPI + Clarithromycin + Amoxicillin/Metronidazole)

Nursing Responsibilities

• Ensure full course adherence (10–14 days) to prevent resistance.
• Monitor for side effects:
  • Diarrhea (due to antibiotics), metallic taste (metronidazole).
• Educate patients:
  • Avoid alcohol with metronidazole (causes a disulfiram-like reaction).
  • Report signs of allergic reactions (rash, difficulty breathing).

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3. Summary Table of Nurse’s Role in Common G.I. Drugs

Drug Class	Examples	Key Nursing Responsibilities	Patient Education
Antacids	Aluminum hydroxide, Magnesium hydroxide	Assess renal function, monitor bowel habits	Take 1 hour before or 2 hours after meals, avoid excessive use
PPIs	Omeprazole, Pantoprazole	Monitor for hypomagnesemia, osteoporosis	Take before meals, avoid NSAIDs
H2-Blockers	Ranitidine, Famotidine	Monitor for CNS effects in elderly	Avoid alcohol, smoking
Antiemetics	Ondansetron, Metoclopramide	Monitor for QT prolongation, EPS	Avoid alcohol, sedatives
Laxatives	Lactulose, Bisacodyl	Assess for dehydration	Increase fluids, fiber
Antidiarrheals	Loperamide, Bismuth subsalicylate	Rule out infection before use	Use for ≤48 hours, stay hydrated
Prokinetics	Metoclopramide, Domperidone	Monitor for extrapyramidal symptoms	Avoid alcohol, CNS depressants
H. pylori Therapy	PPI + Clarithromycin + Amoxicillin/Metronidazole	Ensure full course adherence	Avoid alcohol with metronidazole