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Drugs for Diarrhoea

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Drugs for Diarrhoea DRUGS FOR DIARRHOEA COMPOSITION OF NEW FORMULA WHO-ORS High sodium content ORS is use for adult diarrhea For children and infants, low sodium glucose-based formulation is preferred because losses of sodium are less Can be used in cholera May cause hyponatremia in adults with cholera The composition of new 245mmol/L formula: Contents Concentrations Sodium chloride – 2.6 g Na+ – 75 mM Potassium chloride – 1.5 g K+ – 20 Mm Sodium citrate – 2.9 g Cl- – 65 mM Glucose – 13.5 g Citrate – 10 Mm Water – 1.0 L Glucose – 75 mM Total osmolarity = 245 mmol/L IMPORTANCE OF EACH INGREDIENT IN ORS 1) Potassium: Important constituent; to replace substantial loss of K+ during acute diarrhoea 2) Base (citrate, lactate, bicarbonate): To correct acidosis which developed due to loss of alkali in stools. May independently promote sodium and water absorption 3) Glucose: To capitalize on the intactness of glucose coupled Na+ absorption 4) Na+: Increase Na+ level will facilitate water retention to counter dehydration NON-DIARRHOEAL USES OF ORAL REHYDRATION THERAPY Post-surgical, post-burn and post-trauma maintenance of dehydration and nutrition (in place of I.V. infusion) Heat stroke During changeover from intravenous to enteral alimentation SUPER ORS ORS replaces the fluid or electrolytes what the body has lost due to diarrhoea Glucose-based ORS can easily be made at home as per WHO standard formula: Higher sodium preparation Low sodium preparation Sodium chloride 3.5 g Sodium chloride 2.6 g Potassium chloride 1.5 g Potassium chloride 1.5 g Sodium citrate 2.9 g Sodium citrate 2.9 g Glucose 20.0 g Glucose 13.5 g Water 1.0 L Water 1.0 L Total osmolarity : 311 mmol/L Total osmolarity : 245 mmol/L Preparation available: Preparation available: 1. RELYTE: one sachet dissolve in 1. ELECTRAL MULTIDOSE, 200 ml water PUNARJAL, ELECTROKIND: one 2. PEDITRAL & GENLYTE: one sachet dissolve in 1.0 L water sachet dissolve in 100 ml water Cereal-based ORS (Super ORS) Has advantage of controlling diarrhoea much more effectively than the glucose-based ORS Undigested starch is fermented in the colon to short chain fatty acid stimulate sodium & water absorption back from the colon Rice powder also has protein which on hydrolysis, yields amino acid-stimulate colonic salt & water absorption Commonly used cereal-based ORS formula: Super ORS Pre-cooked rice flour 10.15 g Sodium chloride 0.94 g Sodium citrate 0.20 g Potassium citrate 0.44 g Water 200 ml Total osmolarity : 311 mmol/L Preparation available: 1. CERELYTE, RICETRAL: one sachet dissolve in 200 ml water NON-SPECIFIC ANTI-DIARRHOEAL AGENTS Anti-motility & anti secretory agents: 1) Opiod agonists: Acts by stimulating peripheral µ and δ receptors on small intestine and large intestine. µ receptors decrease motility, while δ receptors decrease intestinal secretions Loperamide Diphenoxylate Difenoxin Racecadotril 2) Anti-cholinergic: Decrease bowel motility Hyosyamine Dicyclomine 3) α₂-adrenergic receptor agonists: Facilitates absorption, inhibits secretions of fluids and electrolytes & increase intestinal transit time Clonidine 4) Octreotide: Action is similar to somatostatins. Inhibit the release of 5-HT3, gastrin, secretin, CCK, motilin, pancreatic polypeptide. Reduce GIT motility, intestinal fluids & electrolytes secretions, pancreatic secretion, gall bladder contraction DRUGS USED IN INFLAMMATORY BOWEL DISEASE Ulcerative Colitis Crohn’s Disease 1. Aminosalicylates: 1. Anti-TNFα Drugs : Sulfasalazine Infliximab Olsalazine Adalimumab Balsalazine Certolizumab 2. Immunosupressant: 2. Methotrexate Glucocorticoids: Prednisone 3. Antibiotics: & Prednisolone Metronidazole Cyclosporine Ciprofloxacin Azathioprine & 6- 4. Anti-Integrin Monoclonal antibody : Mercaptopurine Natalizumab Role Of Sulfalazine In Inflammatory Bowel Disease Is a prodrug An aminosalicylate Commonly used in ulcerative colitis Composed of sulfapyridine & 5-aminosalicylic acid (5-ASA) On oral administration, sulfasalazine reach colon Broken down by colonic bacteria (azoreductase enzyme) to sulfapyridine & 5-ASA 5-ASA acts locally by inhibiting the production of inflammatory mediators: Inhibits the synthesis of prostaglandins (by inhibiting cyclo-oxygenase Inhibit the production of cytokinins Inhibit the activity of nuclear factor-kB Suppress the generation of superoxide free radicals While sulfapyridine get absorbed and causes side effects: nausea, vomiting, headache Advantages Of Mesalazine Over Sulfalazine Also 5-ASA Well absorbed in the upper GIT, therefore has to be given as special formulations (delayed release capsule or pH-dependent tablets) Have a lower incidence of side effects and more efficacious compared to sulfasalazine Rational For Combining Diphenoxylate With Atropine In The Treatment Of Diarrhoea Most popular formulation – LOMOTIL contains diphenoxylate (2.5 mg) with small doses of atropine (0.025 mg) to discourage abuse potential Atropine, besides providing antispasmodic effects, prevents the possible abuse of diphenoxylate Undesirable effects of atropine would appear prior to the pleasurable effects of the opioid, if the dose is increased for abuse MECHANISM OF ACTION OF ANTI-MOTILITY & ANTI-SECRETORY DRUGS 1) Opiod agonists Drugs: Loperamide, Diphenoxylate, Difenoxine (an active metabolite of diphenoxylate), Racecadotril Mechanism of action: Stimulate peripheral µ as well as δ receptors present on small and large intestine Effects: Activation of µ receptor decreases motility, while activation of δ receptor decreases intestinal secretion Racecadotril (enkephalinase inhibitor) increases local concentration of enkephalins in intestinal mucosa which then stimulate µ and δ receptors 2) Anticholinergics Drugs: Hyoscyamine, Dicyclomine Effects: decrease bowel motility which results in an increase of fluid absorption, back from the intestinal tract, and a decrease in abdominal cramps 3) α2 adrenergic receptor agonists Drug: Clonidine Effects: facilitate absorption, inhibits secretion of fluids and electrolytes as well as increases the intestinal transit time 4) Octreotide Actions are similar to somatostatin Mechanism of action: Inhibition of the release of 5-HT, gastrin, secretin, CCK, motilin and pancreatic polypeptide Effects: It reduces GIT motility, intestinal fluid and electrolyte secretion, pancreatic secretion and gall bladder contractions Lactase digests lactose and prevents drawing of water into the GIT Advantage Of Loperamide Over Codeine As An Anti-Diarrhoeal Agent CNS effects and dependence liability of codeine limit its usefulness Loperamide does not cross BBB and has neither analgesic effects nor any addiction liability ADVERSE EFFECTS AND CONTRAINDICATIONS 1) Opiod agonists Adverse effects: abdominal discomfort and dry mouth Contraindications: patients with colitis, acute bacterial diarrhoea associated with high fever or blood in stool, and also for children below 2 years of age 2) Anti-cholinergics Adverse effects: usual anti-cholinergic effects 3) α2 adrenergic receptor agonists Adverse effects: blood pressure lowering effect 4) Octreotide Short term adverse effects: nausea, abdominal discomfort, pain at the site of injection Long term adverse effects: gall stone formation, hypothyroidism .
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