Mechanism of Action
Ursodeoxycholic acid features a multifaceted mechanism aimed at reducing biliary cholesterol saturation. Its action occurs at three primary levels:
- In the intestine: The drug inhibits cholesterol absorption, decreasing its entry into the bloodstream.
- In the liver: It suppresses cholesterol synthesis by inhibiting the rate-limiting enzyme—3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase).
- In the gallbladder: Directly within the bile, the acid interacts with cholesterol to form liquid crystals (unlike chenodeoxycholic acid, which forms a micellar solution).
Pharmacological Effects
The described mechanism yields the following clinically significant effects:
- Reduced cholesterol secretion into bile.
- Prevention of new gallstone formation.
- Dissolution of preexisting cholesterol gallstones (litholytic effect).
Note: Compared to chenodeoxycholic acid, Ursodesoxycholic acid demonstrates higher efficacy and a superior safety profile.
Indications and Administration
The primary indication is medical dissolution of gallstones (litholytic therapy).
Dosing Regimen: Administered orally at 0.01 g/kg of body weight. The entire daily dose is taken once daily at bedtime. This regimen is strictly justified by the physiological peak of biliary cholesterol secretion that occurs during the night.
Duration of Treatment: Therapy is prolonged, typically ranging from 3 months to 2 years.
Side Effects
Although the drug has a favorable safety profile and fewer side effects than older alternatives, typical adverse reactions associated with litholytics include:
- Gastrointestinal: Diarrhea, nausea, epigastric discomfort.
- Laboratory findings: Transient elevations in serum transaminases.
Clinical Course: These adverse reactions generally do not require drug discontinuation and resolve spontaneously 2–3 weeks after starting therapy.
Contraindications for Litholysis
Medical gallstone dissolution is strictly contraindicated in several conditions:
- Gallbladder and biliary tract pathology: Acute inflammatory processes, a non-functioning ("non-visualizing") gallbladder, and large stones (diameter greater than 2 cm).
- Concomitant GI diseases: Liver disease, peptic ulcer disease, chronic pancreatitis, acute inflammatory bowel disease.
- Systemic states: Diabetes mellitus, pregnancy.
Prescription Writing Guidelines
The drug is available in 0.25 g capsules. Dosage is calculated individually based on the patient's body weight.
Rp.: Caps. Acidi ursodesoxycholici 0.25 D.t.d. N. 50 S. Oral, at a dose of 0.01 g/kg of body weight once daily at night.