Introduction • Diarrhea is generally defined by an increased

frequency of bowel movements ( >3 in 24 hrs) & decreased stool consistency & increased stool weight.

• Diarrhea caused due to the use of drugs/medication is called drug induced diarrhea.

• It accounts for 7% of all adverse drug effects and over 700 drugs have been implicated in causing diarrhea.

Drugs & their mechanismOf causing diarrhoea

S.NO DRUGS MECHANISM

1 Laxatives Osmotic diarrhea

2 Antibiotics Bacterial proliferation

3 Anticancer drugs

Exudative diarrhea

4 NSAIDS Lymphocytic colitis

5 ἀ Glucosidaseinhibitors

Osmotic diarrhea

6 Lipase inhibitors Malabsorption of fat

7 Antacids Osmotic diarrhea

8 Misoprostol (used to dissolve cholesterol gallstones)

impair fluid absorption by activating adenylate

cyclase which increases the level of cyclic

AMP,secretion of Cl− & HCO3

−,efflux of Na+, K+ and water and inhibition of

Na+ and Cl− into the enterocyte

9 Neomycin and Colchicine Mucosal damage of the small and large bowel

Antibiotic associated diarrhea (AAD)

• Can be defined as unexplained onset of diarrhea that occurs with the administration of any antibiotic.

• Usually relieved with fasting

• Responsible for 25% of drug induced diarrhea.

• The disease spectrum from benign diarrhea to pseudomembranous colitis.

• Most commonly caused by Penicillin, clindamycin, tetracyclines, erythromycin, cephalosporins etc.

• Normally, the gut is filled with many different bacteria. They keep each other in balance. Antibiotics destroy some of the bacteria in the gut.

• This allows other bacteria to grow too much. In some cases, antibiotics can allow a type of bacteria called Clostridium difficile to grow too much.

• This can lead to severe, watery, and often bloody diarrhea called pseudomembranous colitis.

Clinical presentations • Mild diarrhoea to pseudomembranous colitis,

characterized by a watery diarrhoea• Fever• Leucocytosis• presence of pseudomembranes on endoscopic

examination

Severe complications include -• Toxic megacolon• Perforation• Shock

Risk factors

Drug factors –

1. Antibiotics with large spectrum

2. Duration of antibiotics therapy – prolonged treatment

– repeated treatment

3. Combination therapies

4. Antibiotics with high billiary excretion

Host factors-

1. Extreme ages of life （＜6 years ,＞65 years).

2. Underlying pathologic cause-• previous AAD • severe underlying disease• chronic disease of the digestive tract• Immunosuppression

3. Hospitalization• length of hospital stay• gastric – intestinal surgery

Treatment of AAD

• Rehydration

• Drug therapy

• Probiotics

Rehydration

• Can be done orally or i.v.

• i.v rehydration is needed only when fluid loss is severe i.e. > 10% body weight or patient is losing > 10 ml/kg/hr or is unable to take enough oral fluids due to weakness and vomiting.

• Oral rehydration therapy can be started from beginning when fluid loss is mild or moderate.

Replacement of appropriate antibiotics- drug with lower AAD risk can be effective.

• Quinolones• Co-trimoxazole• Aminoglycosides

Drug therapy

For C.difficile diarrhoea

• Antibiotic treatment, with glycopeptides(vancomycin) or metronidazole.

• Oral metronidazole (250 mg 4 times daily) or oral vancomycin (125 mg 4 times daily)

• Diarrhoea usually resolves in 2 or 3 days. • Metronidazole is the first line of treatment to

prevent the emergence of vancomycin resistant organism.

• Vancomycin should be reserved for those with severe illness, intolerance to metronidazole, failure to respond to metronidazole, or pregnancy.

Probiotics are non-pathogenic living organisms, capable of re-establishing the bacterial equilibrium of the intestine.

• Lactobacillus acidophilus, & Enterococcus faecium.

• Saccharomyces boulardii yeast has been shown to be a safe and effective therapy in relapses of C. difficile colitis.

Probiotics

Prevention of AAD

• Taking supplements containing healthy bacteria (probiotics)

• Limit antibiotic use

• In the case of C difficile related diarrhoea hygiene measures-

• use of gloves

• Handwashing etc.