2. Diarrhea
• Comes from (Greek and Latin: dia, “through,” and rheein, “to flow or run”)
• Defined as
excessive fluid weight, with 200 g per day (upper limit of normal stool
water weight for healthy adults in the Western world)
• Stool weight is largely determined by stool water
• Appreciation and knowledge of the underlying causative processes in
diarrhea facilitates effective treatment
3. caused by
❖Increased osmotic load within the intestine (resulting in retention of
water within the lumen)
❖excessive secretion of electrolytes & water into the intestinal lumen
❖exudation of protein & fluid from the mucosa
❖Altered intestinal motility resulting in rapid transit (and decreased
fluid absorption)
❖Acute diarrhea Usually due to infection with bacteria, viruses, or
protozoa
4.
5. Management of diarrhea
• Many patients with sudden onset of diarrhea have a benign, self-
limited illness requiring no Tx or evaluation.
• In more severe cases of diarrhea and in infants and small children,
dehydration and electrolyte imbalances are the principal risk.
• Oral rehydration therapy therefore is a cornerstone for patients
with acute illnesses resulting in significant diarrhea.
• Pharmacotherapy of diarrhea in adults should be reserved for
patients with significant or persistent symptoms
6.
7.
8. Uses
• Used to control chronic diarrhea caused by
-Irritable bowel syndrome
-Inflammatory bowel disease
9. Specific treatment
• The first-line therapy for acute (most commonly, traveler’s) diarrhea in adults is
Oral fluoroquinolone antibiotics
Ciprofloxacin (500 mg twice daily for up to 3 days), norfloxacin (400 mg twice daily for up to 3 days),
ofloxacin (200 mg twice daily for up to 3 days), or levofloxacin (500 mg daily for up to 3 days)
Alternatives
Azithromycin (500 mg per day for 1–3 days, or a maximum of 1000-mg single dose) and rifaximin
• (200 mg three times per day for up to 3 days)
• Trimethoprim/sulfamethoxazole -1 double-strength tab [160/8000 mg) twice daily for 5 days
• In children (traveler’s diarrhea) –Azithromycin (10 mg/kg to a maximum of 500-mg single dose) is
preferred
10.
11.
12.
13. Classification of Antidiarrheals
• Include
1. Opiod agonist:-Loperamide & Diphenoxylate
2. Colloidal bismuth compounds
3. Bile salt-binding resins (E.g cholestyramine, colestipol or
colesevelam)-may decrease diarrhea caused by excessive fecal
bile acids
4. Somatostatin analog (Octreotide)
14. Octreotide
• Octapeptide analogue of SST
• Effective in inhibiting the severe secretory diarrhea brought about
by hormone-secreting tumors of the pancreas and the GI tract
• Inhibits secretion of 5HT and various GI peptides.
• Greatly utilised in “dumping syndrome” seen in some patients
after gastric surgery and pyloroplasty
15. • Alpha 2 Adrenergic Receptor Agonists eg clonidine
MOA:-can interact with specific receptors on enteric neurons and
enterocytes, thereby stimulating absorption and inhibiting secretion
of fluid and electrolytes and increasing intestinal transit time.
May have a role for use by diabetics with chronic diarrhea
16. Bile Acid Sequestrants
effectively bind bile acids and some bacterial toxins
• Cholestyramine is useful in the treatment of bile salt–induced diarrhea, as in
patients with resection of the distal ileum or after cholecystectomy
Bulk-Forming and Hydroscopic Agents
• Absorb water and increase stool bulk (calcium polycarbophil absorbs 60 times
its weight in water).
• used for constipation but are sometimes useful in acute episodic diarrhea and
in mild chronic diarrhea in patients with IBS.
• Also may bind bacterial toxins and bile salts.
17. Crofelemer
• Purified oligomeric proanthocyanidin from “dragon’s blood,” the reddish
latex-like sap of a South American euphorbia.
• used for the treatment of diarrhea associated with antiretroviral therapy for
HIV/AIDS
MOA:-works by inhibiting the cyclic AMP–stimulated CFTR Cl- channel and
Ca2+-activated chloride ion channels on the luminal aspect of the enterocyte,
thereby reducing the water loss associated with chloride secretion into the
lumen
18. • Telotristat Ethyl----Reduces diarrhea associated with carcinoid
tumors by inhibiting tryptophan hydroxylase, the rate-limiting
enzyme of 5HT biosynthesis.
5HT secretion stimulates fluid secretion and motility in the GI tract.
