Dual Mechanism of Action on Cholesterol Metabolism
To successfully dissolve cholesterol gallstones, it is necessary to sharply reduce the influx of cholesterol into bile. Cholelitholytic agents achieve this through a potent dual mechanism of action targeting two key points of lipid metabolism:
- At the intestinal level: the drugs specifically disrupt cholesterol absorption from the gastrointestinal lumen. Thus, exogenous cholesterol does not enter the systemic circulation.
- At the hepatic level: there is direct suppression of endogenous cholesterol synthesis. This is achieved through the pharmacological inhibition of a specific enzyme — 3-hydroxy-3-methylglutaryl-CoA reductase (commonly abbreviated as HMG-CoA reductase).
The result of this dual hit is a marked decrease in cholesterol concentration in bile. Bile loses its lithogenic properties, halting the growth of old stones and the formation of new ones. Concurrently, the drugs interact with the cholesterol already present in the calculi, forming liquid crystals or micellar solutions, which leads to the gradual dissolution of the stones.
Characteristics of Main Drugs
In modern clinical practice, preparations based on two bile acids are used for medical litholysis. A common rule for both is the timing of administration: the drugs are prescribed before bedtime. This is strictly justified by physiology, as nighttime hours show a peak rise in cholesterol content in bile.
- Chenodeoxycholic acid (trade name — Chenofalk). The main dissolution mechanism involves the drug forming a micellar solution with cholesterol.
- Ursodeoxycholic acid (trade name — Ursofalk). Unlike the previous agent, it forms liquid crystals with cholesterol. It is taken once daily before bedtime. When comparing the two drugs, ursodeoxycholic acid demonstrates higher clinical efficacy. Furthermore, it has a better safety profile, as adverse effects during its use are significantly less pronounced.
Principles of Therapy and Strict Contraindications
Medical dissolution of gallstones requires patient discipline, as therapy is very prolonged. Depending on the clinical picture, treatment ranges from 3 months to 2 years of continuous drug administration.
At the same time, litholytic therapy has a number of strict contraindications. The drugs must not be prescribed in the following conditions:
- Pathologies of the gallbladder and ducts: presence of stones exceeding 2 cm in diameter, acute inflammatory processes in the biliary tract, and the «excluded» (completely non-functioning) gallbladder syndrome.
- Concomitant GI diseases: any liver diseases, peptic ulcer disease, chronic pancreatitis, and acute intestinal inflammation.
- Systemic body conditions: pregnancy and diabetes mellitus.
Adverse Effects and Management Strategy
Despite general safety, undesirable reactions may develop during treatment with cholelitholytic agents (particularly characteristic of chenodeoxycholic acid).
Main clinical manifestations include digestive system disorders: diarrhea, nausea, and epigastric pain. Laboratory blood tests may reveal a transient increase in liver transaminases.
It is important to understand the dynamics of these conditions: as a rule, these adverse reactions do not require specific treatment or drug discontinuation. They resolve completely on their own 2–3 weeks after the start of litholytic therapy.