Drug Treatment of

Diarrhoea

Dr. Jatin Dhanani

Principles of Mx

¨ Treatment of Dehydration ¨ Maintenance of nutrition¨ Drug therapy

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

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

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

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

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.

Drug Therapy

¨ Specific antimicrobial agents ¨ Probiotics¨ Drug for Inflammatory Bowel Diseases(IBD)¨ Nonspecific antidiarrhoeal drugs

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

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

Nonspecific antidiarrhieal dugs

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

Antisecretory drugs¨ Racecadotril (thiorphan)

– Enkephalinase inhibitor – prevent hypersecretion by blocking δ receptor

– Use in ac. secretory diarrhoea¨ Others

5-ASA comp.Bismuth SubsalicylateAtropineOctreotideRacecadrotril

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

¨ 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

¨ 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

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

– 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

¨ 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

¨ 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.

Thank You