Drugs for Dissolving Gallstones A

Following its secretion from liver into bile, water-insoluble cholesterol is held in solution in the form of micellar complexes with bile acids and phospholipids. When more cholesterol is secreted than can be emulsified, it precipitates and forms gallstones (cholelithiasis). Precipitated cholesterol can be reincorporated into micelles, provided the cholesterol concentration in bile is below saturation. Thus, cholesterol-containing stones can be dissolved slowly. This effect can be achieved by long-term oral administration of chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA). Both are physiologically occurring, stereoisomeric bile acids (position of the 7-hydroxy group being p in UCDA and a in CDCA). Normally, they represent a small proportion of the total amount of bile acid present in the body (circle diagram in A); however, this increases considerably with chronic administration because of enterohepatic cycling, p. 38). Bile acids undergo almost complete reabsorption in the ileum. Small losses via the feces are made up by de novo synthesis in the liver, keeping the total amount of bile acids constant (3-5 g). Exogenous supply removes the need for de novo synthesis of bile acids. The particular acid being supplied gains an increasingly larger share of the total store.

The altered composition of bile increases the capacity for cholesterol uptake. Thus, gallstones can be dissolved in the course of a 1- to 2 y treatment, provided that cholesterol stones are pure and not too large (<15 mm), gall bladder function is normal, liver disease is absent, and patients are of normal body weight. UCDA is more effective (daily dose, 8-10 mg) and better tolerated than is CDCA (15 mg/d; frequent diarrhea, elevation of liver enzymes in plasma). Stone formation may recur after cessation of successful therapy.

Compared with surgical treatment, drug therapy plays a subordinate role.

UCDA may also be useful in primary biliary cirrhosis.

Choleretics are supposed to stimulate production and secretion of dilute bile fluid. This principle has little therapeutic significance.

Cholekinetics stimulate the gallbladder to contract and empty, e.g., egg yolk, the osmotic laxative MgSO4, the cholecystokinin-related ceruletide (given parenterally). Cholekinetics are employed to test gallbladder function for diagnostic purposes.

Pancreatic enzymes (B) from slaughtered animals are used to relieve excretory insufficiency of the pancreas (^ disrupted digestion of fats; steator-rhea, inter alia). Normally, secretion of pancreatic enzymes is activated by cholecystokinin/pancreozymin, the en-terohormone that is released into blood from the duodenal mucosa upon contact with chyme. With oral administration of pancreatic enzymes, allowance must be made for their partial inactiva-tion by gastric acid (the lipases, particularly). Therefore, they are administered in acid-resistant dosage forms.

Antiflatulents (carminatives) serve to alleviate meteorism (excessive accumulation of gas in the gastrointestinal tract). Aborad propulsion of intestinal contents is impeded when the latter are mixed with gas bubbles. Defoaming agents, such as dimethicone (dimethyl-polysiloxane) and simethicone, in combination with charcoal, are given orally to promote separation of gaseous and semisolid contents.

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Get Rid of Gallstones Naturally

Get Rid of Gallstones Naturally

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