Drugs for diarrhoea

Antidiarrhoeals

1. Drugs for Diarrhoea

2. Introduction Diarrhoea - it is an abnormal increase in the frequency and the liquidity of stool. Important Factors in causation of diarrhoea . Increased motility of GIT Decrease ability of intestine to absorb water from stool.

3. Types of Diarrhoea Osmotic Diarrhoea . Secretory Diarrhoea . Motility Diarrhoea .

4. Osmotic Diarrhoea Occurs when due to any factor , there is an osmotic drive of water into intestinal tract. Thus ingestion of some specific type of meal Use of some osmotic substances, glycerine , lactulose , magnesium containing antacids Lactase enzyme deficiency leads diarrhoea .

5. Secretory diarrhoea Occurs when Intestinal wall loses its functional integrity or gets damaged resulting in an increased secretion of electrolytes into intestinal tract. This occurs due to Bacterial infection, V iral infection, P rotozoal infection, underlying pathology or due to side effects of drug .

6. Motility disorder diarrhoea Increased motility reduces the contact period of faecal mass with the intestinal wall so that lesser amount of water is absorbed from faeces . Causes- IBD, scleroderma Drugs- Metoclopramide, B ethanecol , Digitalis, Quinidine, Ampicillin Anxiety Hyperthyroidism

7. Principles of management T/t of fluid depletion, shock, acidosis Maintenance of nutrition Drug therapy

8. For rehydration - ORS NaCl - 2.6gm (60mM) vs 75mM KCl - 1.5gm (20mM) Trisodium citrate/Sodium bicarbonate- 2.9 gm (30mM) Glucose - 13.5 gm (75mM) vs 110mM Total molarity – 245mM ( vs 310 mM ) New formula of ORS contains low sodium and glucose K+ imp constituent of ORS as K+ loss is substaintial in acute diarrhoea . The base bicarbonate, citrate, lactate is added to convert acidosis due to alkali loss in stool. It indirectly promote Na and water absorption.

9. Super ORS Addition of certain actively transported amino acid alanine , glycine . Boiled rice powder 40-50g/l is an efficient substitute for glucose

10. Non – diarrhoeal uses of ORS Post –surgical, post burn, post trauma, Maintenance of hydration and nutrition during changeover from parenteral to oral Heat stroke

11. Drugs 1. Absorbants – Ispaghula Psyllium Methyl cellulose 2 . Antisecretory S ulfasalazine Mesalazine Cortico s teroids Bismuth s ubsalicylate Anticholinergics Octreotide Racecadotril Immuno s upressants 3. Antimotility Codeine Diphenoxylate atropine Loperamide 4. Antimicobial Nalidixic acid tetracycline Cotrimoxazole Norfloxacin Erythromycin metronidazole 5 . Probiotics Lactobacillus spp Bifidobacterium bifidium Strep. faecalis

12. Probiotics Live microorganisms that confer a health benefit on the host when administered in adequate amounts. Prebiotic These are non digestible food ingredients which confer benefits on host by selective stimulation of growth or activity of one bacterium or group of bacteria in the colon and thus improve the health of host. .

13. Antisecretory drugs Sulfasalazine – ( Salicyl azo sulfapyridine ) 5 – Amimnosalicylic acid (ASA) and sulfapyridine Poor absorption from ileum, low solubility The azo bond is split by colonic bacteria to release 5-ASA and Sulfapyridine . The 5-ASA produces local antiinflammatory effect, MOA – not clear Less effective than corticosteroids in IBD. 3-4 g/day, Maintenance therapy 1.5-2g/day Sulfapyridine only serves to carry 5-ASA to colon. Part of the released sulfapyridine is absorbed in the colon causing adverse effects like fever,pain,rashes, haemolysis ., Nausea,vomiting,headache,anaemia . Sulfasalazine interfere with folate absorption ; folic acid supplementation should be given. Absorbed sulfapyridine has been found to be useful in Rheumatoid arthritis as a DMARD.

14. Racecadotril Prodrug An enkephalinase inhibitor Prevents degradation of endogenous enkephalins – delta receptor agonist. Use Short term treatment of acute secretory diarrhoea Not contraindicated in children. s/e Nausea,vomiting,drowsiness,flatulence .

15. Uses of antisecretory drugs Ulcerative colitis IBS Travellers diarrhoea Nervous drug induced diarrhoea Carcinoid , Diarrhoea in AIDS Acute secretory diarrhoea

16. Antimotility drugs Uses Non- infective diarrhoea Idiopathic diarrhoea in AIDs After anal surgery Antimotility drugs are opioid drugs which increase small bowel tone and segmenting activity, reduce propulsive movement, Diminish intestinal secretion, Enhance absorption Most opioids are strong agonist at µ receptors Morphine(Prototype) acts as agonist at both µ and k receptors.

17. Major action is mediated through µ opioid receptor present on enteric neuronal network. Direct action on intenstinal smooth muscle & secretory / absorptive epithelium µ receptors – Analgesia/Respiratory depression/ Euphoria / Miosis /Sedation / Physical dependence / reduced gastrointestinal motility  receptors – Analgesia/Respiratory depression / Feeding/Inhibition of dopamine release/Increased release of GH. k receptors – Analgesia/ Miosis / Sedation / Respiratory depression / Dysphoria / Physical dependence / Hallucinations .

18. 1.CODIENE Methyl morphine Partial agonist of µ opioid receptor with low ceiling effect Constipating action- 60 mg 8 hrs interval T1/2 – 4-6 hrs Action primarily on smooth muscle of intenstine & colon Other action - CNS (analgesics) - Antitussive action Side effects – Nausea, vomittin , dizziness Use – short periods only

19. 2. DIPHENOXYLATE Synthetic opioid related to Pethidine Action similar to codiene Partial agonist of µ opioid receptor. Can cross BBB Atropine is added in subpharmacological doses to discourage abuse Diphenoxylate 2.5 mg + Atropine 0.025 mg (LOMOTIL) Overdose produce atropinic side effects Side effect - paralytic ileus, toxic megacolon & respiratory depression Dose 5-10 mg followed by 2.5 – 5.0 mg 6 hrly Contraindication - < 6 years

20. 3. LOPERAMIDE Imodium Derivative of haloperidol Major action on µ receptor Doesn’t cross BBB No abuse liability T ½ - 12 hrs

21. Directly inhibit secretion:- by interacting with calmodulin Improves faecal continence Adverse effect – abdominal cramps, rashes, paralytic ileus, toxic megacolon Contraindication < 4 yrs Dose & prepration - imodium , lopestal , diarlop 4 mg followed by 2 mg on each motion; 2 mg BD in chronic diarrhoea

22. Uses Non infective diarrhoea , mild traveller’s diarrhoea Idiopathic diarrhoea in AIDS pt To delibrate short term constipation. Eg after anal surgery , reduce volume fluidity & bag cleaning frequency in colostomy pt CONTRAINDICATIONS Acute infective diarrhoea IBS, ulcerative colitis, diverticulosis

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