Cholesterol (CH) remains dissolved in bile with the help of bile salts (salts of cholic acid and chenodeoxycholic acid conjugated with glycine and taurine) because bile salts are highly amphiphilic.
GALLSTONE DISSOLVING
DRUGS
Cholesterol (CH)
remains dissolved in bile with the help of bile salts (salts of cholic acid and
chenodeoxycholic acid conjugated with glycine and taurine) because bile salts
are highly amphiphilic. A high CH : bile salt ratio favours crystallization of
CH in bile; these crystals act as nidi for stone formation. Chenodeoxycholic acid (Chenodiol)
and Ursodeoxycholic acid (Ursodiol)
decrease CH content of bile, enabling solubilization of CH from stone surface.
These two bile acids act differently.
Chenodiol
In a dose of 10–15
mg/kg/day it has been found to partially or
completely dissolve CH gallstones in about 40% patients over 1/2 to 2 years.
However, only 1/3 of these had complete dissolution. Pigment stones and calcified
stones (15–20% cases) are not affected.
Side Effects:
Diarrhoea occurs in nearly half of the patients. It is dose-related and generally
mild.
Raised aminotransferase level is also common and dose-related,
but overt liver damage occurs in only 3% patients. It is reversible.
Gastric and esophageal mucosal resistance to acid is impaired
favouring ulceration.
Ursodiol
It is a hydroxy epimer of chenodiol, is more effective and needs to be used at lower doses
(7–10 mg/ kg/day). Complete dissolution of CH stones has been achieved in upto
50% cases. It is also much better tolerated. Diarrhoea and hyper-transaminaemia
are infrequent, but effect on mucosal resistance is similar to chenodiol. Calcification
of some gall stones may be induced.
Dose:
450–600 mg daily in 2–3 divided doses after meals; UDCA, UDIHEP 150 mg
tab.
Dissolution of
gallstones is a very slow process: patient compliance is often poor. However,
medical treatment is now possible in selected patients:
· Only CH stones (radiolucent, generally multiple
stones that float on oral cholecystography) are amenable.
· Smaller stones respond better; therapy is not
indicated if stone is > 15 mm in diameter.
·
Gallbladder should be functional. If bile is
not entering gallbladder, it will not be able to solubilize the stones.
· Contraindicated in pregnant women and those
likely to conceive (foetal damage possible).
Efficacy of these
drugs is enhanced by a single daily bedtime dose and by low CH diet. Concurrent
lithotripsy speeds dissolution rate. Because chenodiol and ursodiol act
differently, their combination at 1/2 of the individual doses is more effective
and attended with fewer adverse effects. However, ursodiol alone is the
preferred drug.
Another method of achieving
quick dissolution is direct instillation of liquid ether, methyl-terbutyl ether
into the gallbladder through a percutaneous pigtail catheter.
Once treatment is
discontinued after stone dissolution, recurrences are common, because bile
returns to its CH supersaturated state. Repeat courses may have to be given.
Because of these problems the pros and cons of medical therapy must be weighed
against cholecystectomy.
Other uses: Bile salts and bile
acids have been used as replacement therapy in
cholestasis, biliary fistula and liver disease. They are a constituent of many
combination formulations. Ursodiol, because it is not hepatotoxic, may be
useful in cirrhosis and some other hepatic disorders.
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