GI DRUGS. ANTIDIARRHEALS LAXATIVES ANTIEMETICS DRUGS FOR INFLAMMATORY BOWEL DISEASE. TREATMENT OF IRRITABLE BOWEL SYNDROME. GI MOTILITY AND SECRETION. Colonic function is subject to complex sets of regulatory influences. NEURAL PATHWAYS.
GI DRUGS • ANTIDIARRHEALS • LAXATIVES • ANTIEMETICS • DRUGS FOR INFLAMMATORY BOWEL DISEASE. • TREATMENT OF IRRITABLE BOWEL SYNDROME
GI MOTILITY AND SECRETION • Colonic function is subject to complex sets of regulatory influences.
NEURAL PATHWAYS • CNS -both sympathetic and parasympathetic innervation. • Myenteric nervous system.
OTHER PATHWAYS • Hormonal –somatostatin, opioids, ADH, prostaglandins, VIP. • Immunological.
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.
GI MOTILITY • Neurohumoral mechanisms, pathogens and drugs can alter uptake and secretory processes.
GI MOTILITY • Altered GI motility contributes to diarrhea or constipation. • Drugs can stimulate or reduce intestinal motility.
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.
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.
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.
TREATMENT OF DIARRHEA • The aim is to enhance intestinal absorption of water or decreasing intestinal motility. • Treatment is generally nonspecific.
NONDRUG APPROACHES • Patience
TREATMENT OF DIARRHEA • Supportive therapy and oral rehydration therapy.
PHARMACOTHERAPY • Reserved for patients with significant or persistent symptoms.
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.
ANTIBIOTICS • Usually not required. • Infectious agent must be matched with the appropriate antibiotic. • Improper use encourages resistance.
OPIOIDS • Mainstay of nonspecific drug therapy. • Agonists for myenteric opiate receptors. • Anti-secretory and anti-motility properties. • Effective vs. moderate to severe diarrhea.
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.
OPIOIDS • Diphenoxylate has some abuse potential (atropine added)(Lomotil) . • Loperamide (Immodium) is highly specific for intestinal opiate receptors.
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.
OPIOIDS-ADVERSE EFFECTS • With excessive use or overdose. • CNS depression, constipation, inflammatory conditions of the colon and megacolon.
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.
ADVERSE REACTIONS • Staining of oral and anal tissues. • Tinnitus.
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.
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.
BULK-FORMING AND HYGROSCOPIC AGENTS • For mild diarrhea. • Hydrophilic colloids (psyllium, polycarbophil and CMC). • Kaolin and other clays.
BILE ACID SEQUESTRANTS • Used in bile salt-induced diarrhea, as in patients with resection of the distal ileum.
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.
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.
AIM OF THERAPY • To increase the water content of the feces and to increase intestinal motility.
TYPES OF THERAPY • NonDrug Approaches • Laxatives • Enemas
NONDRUG APPROACHES • Increasing water and fiber content of the diet, appropriate bowel habits and by exercise and bowel training.
LAXATIVES • Promote passage of the stools. • Overused by the public due to misconception of what is normal.
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.
CONTRAINDICATIONS • Obstruction • Megacolon and megarectum
ENEMAS AND SUPPOSITORIES • Adjuncts to bowel preparation regimens. • Glycerin suppositories (acts as hygroscopic agent and lubricant)
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.
BULK FORMING LAXATIVES • Increase fecal mass and stimulate colonic stretch receptors. • Promote fluid retention in feces. • Natural or semisynthetic polysaccharides and cellulose derivatives.
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++
Dietary fiber, psyllium and methylcellulose Poorly digested fibers or digested by colonic bacteria.
CALCIUM POLYCARBOPHIL • Synthetic resin that absorbs large amounts of water.
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.
SALINE LAXATIVES • (MgSo4, Mg(OH)2, MgCitrate, Na Phosphate). • Poorly absorbed ions that favor osmotic movement of water into the lumen.
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.
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.
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.