Anti-Diarrheal Agents: Pathophysiology, Drugs & Treatment

ANTI-DIARRHEAL AGENTS Pathophysiology 1. Increased Secretion: Excessive fluid and electrolyte secretion into the intestinal lumen (e.g., cholera). 2. Decreased Absorption: Impaired absorption of fluids and nutrients (e.g., viral gastroenteritis). 3. Increased Motility: Rapid intestinal transit that...

ANTI-DIARRHEAL AGENTS Pathophysiology 1. Increased Secretion: Excessive fluid and electrolyte secretion into the intestinal lumen (e.g., cholera). 2. Decreased Absorption: Impaired absorption of fluids and nutrients (e.g., viral gastroenteritis). 3. Increased Motility: Rapid intestinal transit that reduces fluid absorption (e.g., IBS). Complications 1. Dehydration: The most serious complication, leading to electrolyte imbalance and shock. 2. Malnutrition: Common in children with persistent or recurrent diarrhea. 3. Systemic Infections: Especially in severe bacterial or parasitic infections. 4. Electrolyte Imbalance: Hypokalemia,  Principles in management of diarrhoeas In diarrhoea there is increase in motility and secretions in the gut with ↓ absorption of water and electrolytes. Approaches involved include 1. Replacement of fluid and electrolytes. Non specific treatment: ORS and IV fluids in severity of the dehydration. Adequate nutrition: To prevent malnutrition, maintain normal turnover of gastric mucosal cells, maintain normal enzymatic activity. Specific treatment Administration of anti-diarrhoeal agents Classes of Antidiarrhoeals : Non antimicrobial anti-diarrhoeal agents I. Antimotility agents: diphenoxylate, loperamide, codeine. II. Anticholinergic agents: atropine, scopolamine III. Anti-inflammatory agents: sulfasalazine, mesalazine Specific anti-diarrhoeal agents  Anti-motility drugs 1.Diphenoxylate 2. Codeine 3. Loperamide Common Properties ¨ Opioid in nature. MOA; they act by modulating intestinal contraction and reducing the frequency of bowl movements Actions are mediated through µ, (mu) and Delta opioid receptors present in enteric neuronals and direct action on intestinal 1.Pharmacological Properties Mu receptors ↓ propulsive movements ↑ absorption Increase small bowel tone. Diminish intestinal secretions. Delta receptors Modulate pain and inflammation, promote absorption and inhibit secretion. Overall they increase the luminal transit time CODEINE Opioid alkaloid ¨Peripheral action on intestine and colon → constipation ¨No central action (in low doses) ¨Less dependence liability ¨Side effects: nausea, vomiting, dizziness Contraindication; Caution in children who have undergone tonsillectomy and/or adenoidectomy for sleep apnea syndrome due to increased risk of developing serious and life- threatening adverse reactions such as loss of consciousness and respiratory arrest Diphenoxylate ¨ Synthetic opioid.  Action similar to codeine causing constipation.  Most marked antidiarrhoeal effect. ¨ Crosses BBB → CNS effects. ¨ Paralytic ileus, toxic megacolon in children. ¨ It causes respiratory depression. Loperamide ¨ opiate analogue.  peripheral µ opioid with weak anticholinergic activity. ¨ It inhibits secretion by directly interacting with calmodulin. ¨ More potent than codeine in causing constipation ¨ CNS effects are rare. ¨ Very little absorbed from intestine ¨ No abuse liability Adverse effects: Abdominal cramps Rashes paralytic ileus toxic megacolon abdominal distension. Contraindicated in children