Vliv jaterní cirhózy na farmakokinetiku a farmakodynamiku léčiv
[Effect of liver cirrhosis on pharmacokinetics and pharmacodynamics of drugs]
Language Czech Country Czech Republic Media print
Document type Journal Article, Review
PubMed
23909263
PII: 41152
- MeSH
- Analgesics pharmacokinetics MeSH
- Anesthetics, Local pharmacokinetics MeSH
- Anti-Arrhythmia Agents pharmacokinetics MeSH
- Antihypertensive Agents pharmacokinetics MeSH
- Liver Cirrhosis metabolism MeSH
- Hepatic Insufficiency metabolism MeSH
- Liver metabolism MeSH
- Humans MeSH
- Lidocaine pharmacokinetics MeSH
- Metoprolol pharmacokinetics MeSH
- Propranolol pharmacokinetics MeSH
- Risk MeSH
- Verapamil pharmacokinetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Analgesics MeSH
- Anesthetics, Local MeSH
- Anti-Arrhythmia Agents MeSH
- Antihypertensive Agents MeSH
- Lidocaine MeSH
- Metoprolol MeSH
- Propranolol MeSH
- Verapamil MeSH
Metabolic liver functions are significantly involved in the total clearance of a number of drugs. In liver cirrhosis the reduced drug elimination is a result of the blood flow through the liver, hepatocytes function and volume of hepatic tissue. Pharmacokinetic and pharmacodynamic changes depend on the nature and degree of hepatic impairment and on the characteristics of the dosed drug. Hepatocytes have a different extraction ability with respect to the individual drugs. The following are examples of drugs with high hepatic extraction: anodyne, propranolol, metoprolol, verapamil and lidocaine. These drugs are significantly dependent on the first passage through the liver. Intrahepatic and extrahepatic collateral blood flows significantly increase their bio-logical availability and reduce the clearance. The reduction in hepatic clearance of drugs with low extraction coefficient, such as chlordiazepoxide, diazepam or furosemide, is a result of its own limited functional capacity to eliminate the drug. Predicting a hepatic metabolic disorder based on a common bio-chemical assessment of enzyme activities is not sufficient. In advanced liver cirrhosis a higher risk is demonstrated for drugs with a narrow therapeutic width. It is always necessary to take into account whether the pharmacotherapy is necessary, use small doses and cautiously monitor the patient.