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GI DRUGS

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  1. GI DRUGS • ANTIDIARRHEALS • LAXATIVES • ANTIEMETICS • DRUGS FOR INFLAMMATORY BOWEL DISEASE. • TREATMENT OF IRRITABLE BOWEL SYNDROME

  2. GI MOTILITY AND SECRETION • Colonic function is subject to complex sets of regulatory influences.

  3. NEURAL PATHWAYS • CNS -both sympathetic and parasympathetic innervation. • Myenteric nervous system.

  4. OTHER PATHWAYS • Hormonal –somatostatin, opioids, ADH, prostaglandins, VIP. • Immunological.

  5. GI MOTILITY • Proper movement of nutrients, wastes, electrolytes and water thru the intestine depends on a balance of absorption and secretion of water and electrolytes by the intestinal epithelium.

  6. GI MOTILITY • Neurohumoral mechanisms, pathogens and drugs can alter uptake and secretory processes.

  7. GI MOTILITY • Altered GI motility contributes to diarrhea or constipation. • Drugs can stimulate or reduce intestinal motility.

  8. GI MOTILITY • GI motility is also an important component of vomiting. • During nausea and vomiting there is inhibition of gastric motility • Enhanced gastric emptying is a significant aspect of the actions of some antiemetics.

  9. TREATMENT OF DIARRHEA

  10. PATHOBIOLOGY • Excessive fecal loss of fluid and electrolytes. • Due to a combination of increased motility, decreased fluid absorption and increased fluid secretion. • Dehydration and electrolyte imbalances occur.

  11. CAUSES • Infections. • Malabsorption-e.g. lactose, sorbitol, olestra. • Allergy/inflammation. • Intoxication and drug reactions (preformed enterotoxins, alcohol, some antibiotics, antacids and laxatives). • Hormone secreting tumors.

  12. TREATMENT OF DIARRHEA • The aim is to enhance intestinal absorption of water or decreasing intestinal motility. • Treatment is generally nonspecific.

  13. NONDRUG APPROACHES • Patience

  14. TREATMENT OF DIARRHEA • Supportive therapy and oral rehydration therapy.

  15. PHARMACOTHERAPY • Reserved for patients with significant or persistent symptoms.

  16. TREATMENT OF DRUG CAUSED DIARRHEA • Adjustment of dosage or change in medication is preferred to the use of an antidiarrheal agent especially on a long term basis.

  17. ANTIBIOTICS • Usually not required. • Infectious agent must be matched with the appropriate antibiotic. • Improper use encourages resistance.

  18. OPIOIDS • Mainstay of nonspecific drug therapy. • Agonists for myenteric opiate receptors. • Anti-secretory and anti-motility properties. • Effective vs. moderate to severe diarrhea.

  19. OPIOIDS • Codeine and paregoric are effective but have a high abuse potential. • Synthetic opioids are preferred because they penetrate poorly into the CNS and produce antidiarrheal effects at doses that produce few central effects.

  20. OPIOIDS • Diphenoxylate has some abuse potential (atropine added)(Lomotil) . • Loperamide (Immodium) is highly specific for intestinal opiate receptors.

  21. TRAVELERS DIARRHEA • The combination of loperamide and an antimicrobial drug is probably the best treatment for most patients with travelers diarrhea (effective alone also). • Ciprofloxacin (or another quinolone) is usually the DOC.

  22. OPIOIDS-ADVERSE EFFECTS • With excessive use or overdose. • CNS depression, constipation, inflammatory conditions of the colon and megacolon.

  23. BISMUTH SUBSALICYLATE AND SUBCITRATE • Some anti-secretory and anti-inflammatory properties but also antibacterial activity. • Nausea and abdominal cramps also are relieved. • Prophylaxis and treatment of travelers diarrhea.

  24. ADVERSE REACTIONS • Staining of oral and anal tissues. • Tinnitus.

  25. SOMATOSTATIN ON THE GI TRACT • Multiple actions. • Inhibition of gastric acid and pepsin secretion. • Inhibition of endocrine secretions. • Inhibition of intestinal fluid and bicarbonate secretion. • Decrease of smooth muscle contractility. • Half-life is too short to be useful as a drug.

  26. OCTREOTIDE • Peptide analog of somatostatin. • Effective for the diarrhea associated with some hypersecretory tumors and AIDS -related diarrhea. • Short-term therapy may produce nausea and GI upset.

  27. BULK-FORMING AND HYGROSCOPIC AGENTS • For mild diarrhea. • Hydrophilic colloids (psyllium, polycarbophil and CMC). • Kaolin and other clays.

  28. BILE ACID SEQUESTRANTS • Used in bile salt-induced diarrhea, as in patients with resection of the distal ileum.

  29. CONSTIPATION-PATHOPHYSIOLOGY • Decreased intestinal and colonic motility and excessive fluid uptake. • It is not a disease but a symptom that may result from a broad variety of underlying causes.

  30. CAUSES • Congenital. • Inadequate dietary fiber and fluid ingestion. • Ignoring defecatory urge. • Drugs and toxins. • Neurogenic, metabolic and endocrine conditions. • Structural abnormalities in the GI tract.

  31. AIM OF THERAPY • To increase the water content of the feces and to increase intestinal motility.

  32. TYPES OF THERAPY • NonDrug Approaches • Laxatives • Enemas

  33. NONDRUG APPROACHES • Increasing water and fiber content of the diet, appropriate bowel habits and by exercise and bowel training.

  34. LAXATIVES • Promote passage of the stools. • Overused by the public due to misconception of what is normal.

  35. LAXATIVES • Constipation. • Used prior to surgical, radiological and endoscopic procedures where an empty colon is desirable. • To help maintain soft stools in patients with anorectal disorders such as hemorrhoids and in patients with irritable bowel syndrome and diverticulitis.

  36. CONTRAINDICATIONS • Obstruction • Megacolon and megarectum

  37. ENEMAS AND SUPPOSITORIES • Adjuncts to bowel preparation regimens. • Glycerin suppositories (acts as hygroscopic agent and lubricant)

  38. LAXATIVES • Precise mechanism of action of many laxatives remains unknown. • Three or four common groups can be described. • Bulk forming laxatives, saline and osmotic laxatives, stimulant laxatives and stoolsofteners.

  39. BULK FORMING LAXATIVES • Increase fecal mass and stimulate colonic stretch receptors. • Promote fluid retention in feces. • Natural or semisynthetic polysaccharides and cellulose derivatives.

  40. ADVERSE EFFECTS • Relatively safe and rarely abused. • Allergic reactions. • Flatulence occurs occasionally (as well as bloating and abdominal pain). • Intestinal obstruction and impaction may occur. • Some preps may release Ca++

  41. Dietary fiber, psyllium and methylcellulose Poorly digested fibers or digested by colonic bacteria.

  42. CALCIUM POLYCARBOPHIL • Synthetic resin that absorbs large amounts of water.

  43. SALINE AND OSMOTIC LAXATIVES • Poorly and slowly absorbed, act by their osmotic properties in the luminal fluid. • Increase fluid retention in stools or increase luminal fluid contents. This stimulates peristalsis. • May produce inflammatory mediators.

  44. SALINE LAXATIVES • (MgSo4, Mg(OH)2, MgCitrate, Na Phosphate). • Poorly absorbed ions that favor osmotic movement of water into the lumen.

  45. SALINE LAXATIVES • Use caution or avoid in patients with congestive heart failure and renal impairment and in the elderly. • Some have bitter taste. • Excessive evacuation of intestinal contents is possible.

  46. NONDIGESTABLE SUGARS AND ALCOHOLS • Glycerin,lactulose, sorbitol, mannitol. • Poorly absorbed carbohydrates that favor osmotic movement of water into the intestinal lumen. • Resistant to digestion. • Relatively safe.

  47. LACTULOSE, SORBITOL AND MANNITOL • Nonabsorbable sugars that are hydrolyzed in the intestine to organic acids which acidify the luminal contents and osmotically draw water into the lumen, stimulating motility.