drug treatment of diarrhoea
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treatment of diarrhoeaTRANSCRIPT
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Drug Treatment of
Diarrhoea
Dr. Jatin Dhanani
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Principles of Mx
¨ Treatment of Dehydration ¨ Maintenance of nutrition¨ Drug therapy
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Rehydration
Intravenous
¨ Fluid loss > 10% of BW¨ Dhaka fluid - Recommended
NaCl - 85mM = 5 gm
KCl - 13mM = 1 gm
NaHCO3- 48mM = 4 gm
(Na – 133mM, K – 13mM, Cl – 98mM, HCO3 – 48mM)¨ Ringer Lactate: Na – 130 mM, K – 4 mM, Cl – 109mM¨ Initial volume equal to 10% BW – in 2-4 hrs
Oral
In 1 L of water or 5D
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Oral rehydration¨ Mild (5-7%BW) to moderate (7.5-10%BW)
fluid loss¨ Bases of oral rehydration…….
Intactness of Glucose-Na+ co-transporter ¨ General principle
– Should be iso-/hypotonic (200-310mOsm/L)– Glucose Molar ratio should be slight high(but
not >110mM)– K+ and bicarbonate/citrate should be enough
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Oral Rehydration Sol.
¨ Na+ – 90 mM¨ K + – 20 mM¨ Cl- – 80 mM¨ Citrate – 10 mM¨ Glucose – 110 mM¨ Total osmolarity –
310 mOsm/L
New ORS
¨ Na – 75 mM¨ K – 20 mM¨ Cl – 65 mM¨ Citrate – 10 mM¨ Glucose – 75 mM¨ Total osmolarity –
245 mOsm/L
NaCl – 2.6 gmKCl -1.5 gmTrisod. Citrate – 2.9 gmGlucose – 13.5 gm
Home based ORSSuper ORS
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Zinc in pediatric
¨ Non diarrheal use:– Postsurgical, postburn, post-trauma maintence
of hydration and nutrition – Heat stroke– From IV to enteral nutrition change over
¨ Reduce duration and severity of ac. Diarrhoea
¨ Continue Zn for 10-14 days prevent diarrhoea for next 2-4 months
¨ Zn – ORS are available
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Maintenance of Nutrition
¨ Never fasting ¨ Feeding during dirrhoea increase digestive
enz. and cell proliferation in mucosa¨ Give simple food – breast milk, half buffalo
milk, boiled potato, rice, chicken soup, banana, sago, etc.
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Drug Therapy
¨ Specific antimicrobial agents ¨ Probiotics¨ Drug for Inflammatory Bowel Diseases(IBD)¨ Nonspecific antidiarrhoeal drugs
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Antimicrobial Agents
¨ Antimicrobials of no value in – – Irritable Bowel
Syndrome (IBS)– Coeliac disease– Tropical sprue – Pancreatic enz def.– Thyrotoxicosis– Viral inf. (rotavirus)– Some bacterial inf. (S.
enterobacterius, ETEC)
¨ Antimicrobials useful in severe cases only – – Travellers’ diarrhoea– EPEC– Shigella enteritis– Nontyphoid salmonella– Y. enterocolitica
¨ Routinely used – irrational
¨ Antimicrobials regularly used in– – Cholera– C. jejuni– C. defficile– Amoebiasis/giardiasis
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Role of Probiotics in Diarrhoea¨ Live culture or lyophillised powder ¨ Bases of use: restore and maintain the
normal gut flora ¨ Organism commonly used –
– Lactobacillus sp., Bifidobacterium, S. faecalis, Enterococcus sp., yeast Saccharomyces boulardii
¨ Widely used in travellers’ diarrhoea, acute Infective diarrhoea, antibiotic associated diarrhoea
¨ Efficacy evidence is lacking
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Nonspecific antidiarrhieal dugs
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Absorbants and adsorbants
¨ Colloidal bulk forming agents – ispaghulla, carboxy methyl cellulose – absorbants – Absorb the water and swell – modify
consistency and frequency of stool¨ Adsorbants - Kaolin, pectin, attapulgite –
believed to adsorb the bacterial toxins and protect the gut mucosa
Adsorbants are banned in India
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Antisecretory drugs¨ Racecadotril (thiorphan)
– Enkephalinase inhibitor – prevent hypersecretion by blocking δ receptor
– Use in ac. secretory diarrhoea¨ Others
5-ASA comp.Bismuth SubsalicylateAtropineOctreotideRacecadrotril
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Anti motility drugs
¨ Opioid analogue¨ Acts through μ and δ receptors –
– prevent propulsive movement, increase absorption and decrease secretion: increase resistance to luminal transit and allow more time for absorption
¨ Codeine – Primary action peripheral in intestine and colon– Not use widely
CodeineDiphenoxylateLoperamide
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¨ Diphenoxylate (2.5mg) + atropine (0.025mg)
– Similar to pethidine– Cross BBB – abuse liability (atropine prevents) – A/E – respiratory depression, paralytic ileus
and toxic megacolon in children – C/I in <6yr¨ Loperamide
– Major peripheral action – very less absorbed and can’t cross BBB – no abuse liability
– Inhibits secretion – direct acts on calmodulin– A/E – rashes, abd. pain, toxic megacolon and
paralytic ileus – C/I in < 4yrs– Dose: 4mg f/b 2 mg at each motion
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¨ Role of antimotility drugs– Utility limited to
• Noninfective diarrhoea• Mild travellers’ diarrhoea• Idiopathic diarrhoea in AIDS• Chronic diarrhoea of IBS• Very mild IBD with urgency interfering with daily
work
Never use antimotility drugs in acute infective diarrhoea
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Drug for Inflammatory Bowel Diseases
¨ 5-ASA compounds – Sulfasalazine, mesalazine, olsalazine,
balsalazine– M/A: 5-ASA have local antiinflammatory
action by inhibition of production of cytokine, PAF, TNFα, NFKB
– Also inhibits COX and LOX
Sulfasalazine = sulfapyridine + 5-ASA– Use for mild to moderate disease– Dose: Acute condi. – 3-4 gm/d and for
maintainance – 1.5-2 gm/d
5-ASA compounds CorticosteroidsImmunosuressants TNF α inhibitors
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– A/E: • b/c of sulfapyridine – rashes, joint pain, fever,
hemolysis, blood dyscrasias• Others: headache, malaise, anemia, oligozoospermia,
infertility, folic acid def.
Mesalazine (mesalamine): a delayed release prep.– Less side effect – fever, leucopenia, headache,
nephrotoxicity– Dose: 2.5 gm
Olsalazine: two 5-ASA compound
Balsalazine: 5-ASA linked to 4-aminobenzoyl-B-alanine
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¨ Corticosteroid– For moderately sever to very severe condition– For acute exacerbation of disease– Prednisolone (40-60mg/d) – effect starts
within 3-7 days and remission in 2-3 week – Hydrocortisone and methyl prednisolone for
IV inj in very severe condi. with extraintestinal symptoms
– Hydrocortisone enema for proctitis– Steroid use for short term therapy only– If not controlled – immunosupressants
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¨ Immunosupressant – Azathioprine(6-MP), methotrexate, cyclosporine– Use in steroid dependent, steroid resistant,
relatively severe cases – Adverse effect should be weighed to the efficacy
¨ TNFα inhibitor– Infliximab, adalimumab– Use in severe and refractory cases.
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Thank You