enalapril and Fatty-Liver

The aim of our study was to analyze drug-induced liver disease over a 3-year period in one gastroenterological department.. International consensus standard definitions and criteria for assessing causality of adverse drug reactions were applied to all patients with abnormal hepatic test results.. Drugs were implicated in hepatic injury in 14 patients (8 females) in whom causal relationship between drug and liver disease was definite or highly probable. The drugs responsible were amoxicillin with clavulanic acid (3 cases), fluvastatin and pravastatin (3 cases), antituberculous drugs (2 cases), estrogens, roxithromycin, asacol, satolol, enalapril and thiamazol. A total of 78.6% (11 cases) were classified as hepatocellular or mixed hepatitis, while cholestatic injury was found in 21.4% (3 cases). There were no lethal or severe (prothrombin < 50%) hepatic drug reactions. In 13 patients the course of liver disease after withdrawal of the offensive drug was either acute or protracted, while in one patient there was chronic cholestasis (>3 years) resulting from injury to interlobular bile ducts by amoxicllin with clavulanic acid.. A thorough history of drug intake should be taken in all patients presenting with abnormal hepatic test results. Amoxicillin & clavulanic acid, cholesterol-lowering and antituberculin drugs were the most frequent hepatotoxic factors in our patients. In a majority of cases the liver injury was not severe, and resolved after prompt withdrawal of the responsible drug.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticholesteremic Agents; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Comorbidity; Enalapril; Estrogens; Fatty Liver; Female; Humans; Liver Diseases; Male; Mesalamine; Middle Aged

It is necessary to take into account presence of concomitant pathology while prescribing hypotensive therapy to patients with arterial hypertension (AH). Hydrophilic angiotensin converting enzyme inhibitors (ACEI) (lisinopril) which are not metabolized in the liver are theoretically safest in liver cirrhosis. We have examined and treated 180 patients with AH and assessed efficacy and tolerability of ACEI lisinopril and enalapril with consideration of their pharmacokinetic peculiarities in patients with various severity of involvement of the liver (steatosis or cirrhosis). Advantage of hypotensive effect of lisinopril (which required no biotransformation in the liver) over enalapril based on its pharmacokinetic properties has been demonstrated.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Enalapril; Fatty Liver; Female; Humans; Hypertension; Lisinopril; Liver Cirrhosis; Male; Middle Aged

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Enalapril; Fatty Liver; Female; Humans; Hypertension; Lisinopril; Liver Cirrhosis; Male; Middle Aged; Peptic Ulcer; Treatment Outcome

The metabolic syndrome is a cluster of risk correlates that can progress to type 2 diabetes. The present study aims to evaluate a novel molecule with a dual action against the metabolic syndrome and type 2 diabetes.. We developed and tested a novel dual modulator, RB394, which acts as a soluble epoxide hydrolase (sEH) inhibitor and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in rat models of the metabolic syndrome-the obese spontaneously hypertensive (SHROB) rat and the obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat. In SHROB rats we studied the ability of RB394 to prevent metabolic syndrome phenotypes, while in ZSF1 obese diabetic rats we compared RB394 with the ACE inhibitor enalapril in the treatment of type 2 diabetes and associated comorbid conditions. RB394 (10 mg/kg daily) and enalapril (10 mg/kg daily) were administered orally for 8 weeks.. RB394 blunted the development of hypertension, insulin resistance, hyperlipidaemia and kidney injury in SHROB rats and reduced fasting blood glucose and HbA. These findings demonstrate that a novel sHE inhibitor/PPAR-γ agonist molecule targets multiple risk factors of the metabolic syndrome and is a glucose-lowering agent with a strong ability to treat diabetic complications.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Enalapril; Enzyme Inhibitors; Epoxide Hydrolases; Fatty Liver; Glucose Tolerance Test; Hypertension; Insulin Resistance; Kidney Glomerulus; Liver Cirrhosis; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; PPAR gamma; Rats; Rats, Zucker

A case of enalapril-induced acute hepatotoxicity with an unusual morphology is described. This morphology was characterized by macro- and microvesicular steatosis associated with neutrophil infiltration and Mallory bodies, occasionally with satellitosis. These alterations were most abundant in zone 1 of the periportal region, less common in zone 2 and rare in zone 3. There was also confluent periportal necrosis with sinusoidal fibrin deposits associated with intense ductal metaplasia and an infiltrate of inflammatory cells that included plasmocytes and a few eosinophils, as well as focal biliary damage. This morphology, that may be referred as "predominantly periportal steatohepatitis", was distinct from that associated with non-alcohol and alcohol-induced steatohepatitis, both initiated in acinar zone 3 and subsequently extended to other zones.

Topics: Acute Disease; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biopsy; Chemical and Drug Induced Liver Injury; Enalapril; Fatty Liver; Humans; Liver; Male; Necrosis; Neutrophil Infiltration