Glomerular Filtration and determinants of glomerular filtration .pptx
Drugs used in diarrhoea 2020
1. Drugs used in Diarrhoea
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical
Pharmacology
Maharajgunj Medical Campus, Kathmandu
25 June 2020 (11 Asar 2077), Thursday
2. By the end of this discussion, BSN 1st
year students will be able to:
List the mechanisms of diarrhoea
List the therapeutic options for the management of
diarrhoea
Explain the basis of use of oral rehydration salts in
management of diarrhoea
Explain the role of antibiotics in diarrhoea
List other drugs used in the management of diarrhoea
3. Diarrhoea
3 or more loose or watery stools in a 24 hour period
Occurs due to:
Decreased electrolyte and water absorption
Increased secretion by intestinal mucosa
Increased luminal osmotic load
Inflammation of mucosa and exudation into lumen
4. Absorption Mechanism of Water and
Electrolytes in Intestines
• Different segments absorb electrolytes and water by
different mechanisms
• Can be absorbed primarily
• Na+ absorption in ileum using Na+-K+ ATPase
• Can be absorbed secondarily
• Na+ absorption secondary to absorption of
nutrients (glucose) in multiple segments
• Water mainly follows iso-osmotically
• Non-absorbable solutes in lumen increases water
content of stool
5. Management: Principles
Treatment of fluid depletion, shock and acidosis
Oral Rehydration Solution; Intravenous Fluids
Zinc
Maintenance of Nutrition
Drug Therapy
Specific antimicrobial drugs
Probiotics
Drugs of Inflammatory Bowel Disease
Nonspecific anti-diarrhoeal drugs
6. Treating fluid depletion, shock and
acidosis
Oral Rehydration:
Mild (5-7%) or Moderate (5-7.5%) fluid loss
Based on integrity of “glucose coupled Na+
absorption”
Composition:
o Isotonic/hypotonic to the fluid lost
o Ratio of glucose and Na+
o Amount of K+ and HCO3-
7. Oral Rehydrating Solution
Components WHO Recommended NEW Formulation
Na+ 75 mM
K+ 20 mM
Cl- 65 mM
Citrate 10 mM
Glucose 75 mM
Total Osmolarity 245 mOsm/L
Remarks Risk of Hyponatremia in adults with
cholera
8. Treating fluid depletion, shock and
acidosis
Intravenous fluids: crystalloids (Dhaka Fluid, Ringer’s
Lactate)
Indicated only in cases of severe dehydration
o >10% body weight or losing @ >10ml/kg/hr
10% Body weight over 2-4 hrs
o Titrated with rate of fluid loss
9. Zinc Supplementation
Reduces the duration and severity of diarrhoea in
children
Continued supplementation for 10-14 days following
episode of diarrhoea reduces recurrences for next 2-3
months
Probably acts by:
Reducing fluid secretion from intestinal cells
Strengthen immune response
Helps regeneration of intestinal epithelium
10. Antimicrobials in Diarrhoea
Specific Antimicrobial Drugs
Are of NO VALUE in:
o Irritable Bowel Syndrome (IBS)
o Coeliac Disease
o Pancreatic Enzyme Deficiency
o Tropical Sprue
o Thyrotoxicosis
11. Antimicrobials in Diarrhoea
Specific Antimicrobial Drugs
Useful in severe diseases due to:
o Traveller’s Diarrhoea (Rifaximin)
o EPEC, Shigella infections
o Nontyphoid Salmonella
o Yersinia enterolytica
o Salmonella infection
13. Drug Therapy in Diarrhoea
Probiotics in Diarrhoea:
Microbial cell preparation
o Lactobacillus sp., Bifidobacterium, Strept.
faecalis, Enterococcous sp., Saccharomyces
boulardii
Live cultures or lypophilised powder
Restore and maintain healthy gut flora
Useful in certain diarrhoeas
Can very rarely cause infection (immunocompromised
individuals), acidosis
14. Nonspecific Anti-diarrhoeal Drugs: Anti-
motility Drugs
Opioids
Increases small intestine tone and segmenting
activity, reduces propulsive movements, diminishes
intestinal secretion, enhances absorption
Symptomatic relief in diarrhoea
Action mediated by μ receptor located in enteric
neuronal network
Examples: Loperamide, Codeine, Diphenoxylate
15. Nonspecific Anti-diarrhoeal Drugs
Absorbants
Isaphgula, methyl cellulose, carboxymethyl cellulose
Absorb water and swell Modifies consistency and
frequency of stool; apparent improvement
Used in diarrhoeal phase of IBS, Colostomy patients
Non fermentable products preferred
16. Drug Therapy in Diarrhoea
Drugs for Inflammatory Bowel Disease (IBD):
5-amino salicylic acid (5-ASA)
o Sulfasalazine, Mesalazine
Corticosteroids
o Prednisolone
Immunosuppressants
o Azathiaprine, Cyclosporine
o Methotrexate
TNF α inhibitors
o Infliximab
17. Conclusion
Diarrhoea can be due four different mechanisms
Replacement of lost fluid is the mainstay of treatment
of diarrhoea
Rehydration solution should be chosen in such a way
that its composition is similar to the fluid lost in
diarrhoea
Antibiotics have a limited role in the treatment of
diarrhoea
Non-specific drugs can have adjuvant role in treatment
of diarrhoea
Jejunum: Freely permeable to salt and water
Absorbed secondary to nutrient
Ileum and Colon: Active Na+-K+ATPase mediated salt absorption
Mature cells lining the villous tip
Water follows iso-osmotically
Diarrhoea due to Rota virus: inhibition of Na+K+ATPase and structural damage to mucosa cell
Glucose facilitated Na+ absorption in ileum
Diarrhoea due to Rota virus: inhibition of Na+K+ATPase and structural damage to mucosa cell
Rifaximin: also used in diarrhoeal phase of IBS, prophylaxis before and after gut surgery
C. difficile: pseudomembranous enterocolitis
Useful in certain diarrhoeas: antibiotic associated, ulcerative colitis (reduces bloating and flatulence),
Use limited to non-infective diarrhoea, mild traveller’s diarrhoea, exhausting diarrhoea, idiopathic diarrhoea in AIDS
Induce constipation: after anal surgery, ileostomy and colostomy patients
Contraindication: acute infective diarrhoea,
Codeine:
Prominent constipating action, 60 mg TDS; primarily via peripheral action on small intestine and colon; central actions present but low depence producing liability
S/E: nausea, vomiting, dizziness; abuse potential
Diphenoxylate:
Synthetic opioid
Absorbed systematically, crosses Blood Brain Barrier CNS effects
Atropine added to decrease abuse potential
S/E: respiratory depression, paralytic ileus, toxic megacolon in children; Contraindicated below 6 years age.
Racecadotril: rapidly converts to thiorphan (enkephalinase inhibitor) inhibits encephalin degradation (δ opioid receptor agonists) decreased intestinal hypersecretion by lowering mucosal cAMP; used for short term treatment of secretory diarrhoea, can be used in children
Bismuth subsalicylate: decreases PG synthesis reducing Cl- secretion; prophylactic value in Travellor’s diarrhoea
Anticholinergics: reduced bowel motility and secretion; may benefit in nervous/drug (neostigmine, metoclopramide) induced diarrhoea, symptomatic relief in dysentries, diverticulitis
Octreotide: somatostatin analogue; potent antisecretory/antimotility action on intestine; used to control diarrhoea in carcinoid and vasoactive intestinal peptide (VIP) secreting tumors, refractory diarrhoea in AIDS; administered s.c.
Opioids(Loperamide): anti-motility and anti-secretory action
Racecadotril: rapidly converts to thiorphan (enkephalinase inhibitor) inhibits encephalin degradation (δ opioid receptor agonists) decreased intestinal hypersecretion by lowering mucosal cAMP; used for short term treatment of secretory diarrhoea, can be used in children
Bismuth subsalicylate: decreases PG synthesis reducing Cl- secretion; prophylactic value in Travellor’s diarrhoea
Anticholinergics: reduced bowel motility and secretion; may benefit in nervous/drug (neostigmine, metoclopramide) induced diarrhoea, symptomatic relief in dysentries, diverticulitis
Octreotide: somatostatin analogue; potent antisecretory/antimotility action on intestine; used to control diarrhoea in carcinoid and vasoactive intestinal peptide (VIP) secreting tumors, refractory diarrhoea in AIDS; administered s.c.
Opioids(Loperamide): anti-motility and anti-secretory action
5-ASA compound
Low, solubility, poorly absorbed from ileum
Split by colonic bacteria into:
5-ASA – local anti-inflammatory effect (?M/A: inhibits COX and LOX Decreased PG, LT: minor role, Cytokine, PAF, TNF α, and nuclear transcription factors generation: major role)
Sulfapyridine – gets absorbed side effects (rashes, fever, joint pain, hemolysis,…; Oligozoospermia and male infertility)
Induces remission when given during active phase of disease, relapse common; low dose used as maintainance therapy
Folic Acid Supplementation required
5-ASA – local anti-inflammatory effect (?M/A: inhibits COX and LOX Decreased PG, LT: minor role, Cytokine, PAF, TNF α, and nuclear transcription factors generation: major role)
Sulfapyridine – gets absorbed side effects (rashes, fever, joint pain, hemolysis,…; Oligozoospermia and male infertility)
Indication: Maintain remission in Ulcerative Colitis, Rheumatoid arthritis
Given orally, i.v. in case of severe disease with extraintestinal manifestations and rapid relief therapy, enema/foam for topical therapy
Thiopurine methyl transferase
Azathioprine cannot be used in population with genetic defect fot TPMT enzyme