cardiovascular-agents and Liver-Diseases

Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKβ, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Cardiovascular Agents; Diosmin; Humans; Hypoglycemic Agents; Kidney Diseases; Liver Diseases; Neuroprotective Agents; Retinal Diseases

In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart.

Topics: Cardiovascular Agents; Chemical and Drug Induced Liver Injury; Heart; Heart Failure; Humans; Liver; Liver Diseases

Heart failure affects ≈23 million people worldwide and continues to have a high mortality despite advancements in modern pharmacotherapy and device therapy. HF is a complex clinical syndrome that can result in the impairment of endocrine, hematologic, musculoskeletal, renal, respiratory, peripheral vascular, hepatic, and gastrointestinal systems. Although gastrointestinal involvement and hepatic involvement are common in HF and are associated with increased morbidity and mortality, their bidirectional association with HF progression remains poorly fathomed. The current understanding of multiple mechanisms, including proinflammatory cytokine milieu, hormonal imbalance, and anabolic/catabolic imbalance, has been used to explain the relationship between the gut and HF and has been the basis for many novel therapeutic strategies. However, the failure of these novel therapies such as anti-tumor necrosis factor-α has resulted in further complexity. In this review, we describe the involvement of the gastrointestinal and liver systems within the HF syndrome, their pathophysiological mechanisms, and their clinical consequences.

Topics: Animals; Cardiovascular Agents; Gastrointestinal Diseases; Heart Failure; Humans; Liver Diseases

With recent advances in surgical and anaesthetic management, clinical medicine has responded to societal expectations and the number of operations in patients with a high-risk of perioperative liver failure has increased over the last decades. This review will outline important pathophysiological alterations common in patients with pre-existing liver impairment and thus highlight the anaesthetic challenge to minimise perioperative liver insults. It will focus on the intraoperative balancing act to reduce blood loss while maintaining adequate liver perfusion, the various anaesthetic agents used and their specific effects on hepatic function, perfusion and toxicity. Furthermore, it will discuss advances in pharmacological and ischaemic preconditioning and summarise the results of recent clinical trials.

Topics: Anesthesia, Conduction; Anesthetics, Inhalation; Cardiovascular Agents; Hemodynamics; Humans; Intraoperative Care; Liver; Liver Diseases; Perioperative Care

Topics: Acetaminophen; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Chemical and Drug Induced Liver Injury; Chromans; Contraceptives, Oral, Hormonal; Gastrointestinal Agents; Humans; Liver Diseases; Liver Function Tests; Psychotropic Drugs; Thiazolidinediones; Time Factors; Troglitazone

Cardiovascular drugs are characterized by wide inter-individual variability in dose/plasma concentration/ response (therapeutic and/or toxic) relationships. Therefore, some patients achieve good therapeutic response to their drug therapy, while others do not. Also, some patients experience adverse effects, which vary from mild to life-threatening. The source of variability in patients' response to cardiovascular drugs may be of pharmacokinetic and/or pharmacodynamic origin. Many factors can potentially affect both of them such as genetics, gender, age, disease state, environmental factors like smoking and food, possible drug-drug interactions, and ethnicity (race). Cardiovascular pharmacogenomics is a new field that focus on the roles of genetic polymorphisms in drug metabolizing enzymes and drug targets in development of variable drug response.

Topics: Adrenergic beta-Antagonists; Aging; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Diuretics; Drug Interactions; Drug Resistance; Female; Humans; Liver Diseases; Male

Hepatic impairment can alter the pharmacokinetic profiles of cardiovascular drugs, which can lead to unwanted toxicity. In the presence of cirrhosis, portosystemic shunting occurs and cytochrome P450 activity is reduced. Impaired oxygen uptake caused by changes in the liver's sinusoids, as proposed by the oxygen limitation theory, may also explain the alteration of drug metabolism seen in cirrhosis. With congestive heart failure, sinusoidal congestion and hypoperfusion of the liver are seen. Similar to cirrhosis, the common pathway for hepatic damage in congestive heart failure seems to be liver hypoxia, which may explain the disease's effect on drug metabolism. Since routine hepatic function tests do not always relate to the liver's ability to eliminate drugs, existing guidelines for dosing cardiovascular drugs in patients with hepatic impairment are limited. This article provides guidance for dosing cardiovascular drugs in cirrhotic and heart failure patients based on available research data. Altered drug metabolism, especially in congestive heart failure, tends to be overlooked or not realized in clinical practice. Therefore, further research is needed in congestive heart failure to better elucidate safe prescribing patterns.

Topics: Cardiovascular Agents; Comorbidity; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Humans; Liver Diseases; Pharmacokinetics

The incidence of drug-induced liver disease appears to be increasing, reflecting the increasing number of new agents that have been introduced into clinical use over the past several decades. Among the topics covered, the author discusses incidence, diagnosis, risk factors, clinical presentations, hepatitis, and vascular injury. The author also reviews the hepatic injury seen with commonly prescribed drugs, emphasizing newer developments in the field and recent publications and reports.

Topics: Acetaminophen; Alanine Transaminase; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Cardiovascular Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Hypoglycemic Agents; Incidence; Liver; Liver Diseases; Prognosis; Risk Factors; Vascular Diseases

Topics: Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Biotransformation; Cardiovascular Agents; Humans; Intestinal Absorption; Kinetics; Liver Diseases; Pharmaceutical Preparations; Protein Binding; Psychotropic Drugs; Tissue Distribution

Topics: Animals; Anti-Bacterial Agents; Cardiovascular Agents; Dogs; Drug Interactions; Enzyme Induction; Humans; Intestinal Absorption; Kidney; Kidney Diseases; Kinetics; Liver; Liver Diseases; Mitochondria, Liver; Monoamine Oxidase Inhibitors; Protein Binding; Psychotropic Drugs

Patients with liver disease often show unusual responses to "standard" doses of drugs. Increased variability of response to drugs which are predominantly eliminated by the liver is mainly due to altered pharmacokinetics in the presence of hepatic dysfunction. The possible prediction of abnormal pharmacokinetics in hepatic disease requires a knowledge of the pharmacokinetic characteristics of a particular drug in healthy subjects and of the major pathophysiologic alterations which occur in a given form of liver disease. In all cases with significant impairment of the metabolic capacity of the liver (e.g. acute viral hepatitis), dosage adjustments should be based on decreased (hepatic) clearance rather than on prolongation of halflife of the respective drug. In addition, oral doses of those drugs which under normal conditions are efficiently extracted from sinusoidal blood by hepatocytes should be further reduced in chronic liver disease (e.g. cirrhosis) as marked increases in their systemic bioavailability occur in the presence of altered hepatic blood flow.

Topics: Anti-Bacterial Agents; Anticonvulsants; Benzodiazepines; Biological Availability; Cardiovascular Agents; Humans; Liver Diseases

Topics: Absorption; Alcohol Drinking; Cardiovascular Agents; Diuretics; Drug Interactions; Enzyme Induction; Ethanol; Humans; Hypnotics and Sedatives; Kinetics; Liver; Liver Diseases; Nutrition Disorders; Tissue Distribution; Tranquilizing Agents; Xanthines

Imarikiren hydrochloride (TAK-272; SCO-272) is a novel direct renin inhibitor. The objective of this study was to determine the effects of renal impairment (RI) or hepatic impairment (HI) on the pharmacokinetics and safety of imarikiren.. This phase I, open-label, parallel-group comparative study evaluated the pharmacokinetics and safety of a single 40 mg oral dose of imarikiren in RI [mild, moderate, severe, or end-stage renal disease (ESRD), and on hemodialysis] or HI (mild or moderate) subjects compared with subjects with normal renal or hepatic function.. Following administration of a single 40 mg oral imarikiren dose, the geometric mean imarikiren area under the plasma concentration-time curve from time zero to infinity (AUC. RI and HI are associated with limited changes in imarikiren pharmacokinetics. Imarikiren was safe and well-tolerated, regardless of the severity of RI or HI.. ClinicalTrials.gov Identifier: NCT02367872.

Topics: Adult; Aged; Area Under Curve; Benzimidazoles; Cardiovascular Agents; Enzyme Inhibitors; Female; Humans; Kidney; Kidney Failure, Chronic; Liver Diseases; Male; Middle Aged; Morpholines; Piperidines; Renal Dialysis

Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin.. This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg(-1)  day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls.. A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study.. The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment.

Topics: Area Under Curve; Cardiovascular Agents; Drug Administration Schedule; Female; Germany; Humans; Infusions, Intravenous; Liver; Liver Diseases; Liver Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Recombinant Proteins; Relaxin; Russia; Severity of Illness Index

The aim of the study was to investigate patient-related factors associated with either reliable or poorly reliable measurement results of ultrasound-based shear wave elastography (SWE) of the liver. A total of 188 patients were analyzed prospectively with binary logistic regression using the interquartile range/median as cutoff to define two groups based on reliable and poorly reliable SWE results. SWE results correlated significantly with liver biopsy. Factors associated with reliable SWE results (i.e., no negative impact on measurements) were age, sex, cirrhosis, antiviral and/or cardiovascular medication, smoking habits and body mass index. Factors associated with poorly reliable SWE results were increased skin-to-liver capsule distance (odds ratio = 3.08, 95% confidence interval: 1.70-5.60) and steatosis (odds ratio = 2.89, 95% confidence interval: 1.33-6.28). These findings indicate that the interquartile range/median as a quality parameter is useful in avoiding poorly reliable SWE results. How best to examine patients with increased skin-to-liver capsule distance is a matter of some controversy, as the incidences of obesity, diabetes and metabolic syndrome are increasing worldwide; however, our results indicate that reliable SWE results can be obtained in this group of patients by using ultrasound-based SWE.

Topics: Age Factors; Antiviral Agents; Body Mass Index; Cardiovascular Agents; Elasticity Imaging Techniques; Fatty Liver; Female; Humans; Liver; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prospective Studies; Reproducibility of Results; Sex Factors; Smoking

An adult castrated male pet kinkajou (Potos flavus) presented with dyspnea due to congestive heart failure and was diagnosed with hypertrophic cardiomyopathy (HCM) and suspected pulmonary arterial hypertension. Diagnosis was based on history, clinical signs, clinical pathology, radiographs, abdominal ultrasonography, abdominal fluid analysis, electrocardiography, and echocardiogram. An undetermined hepatopathy also was found at presentation and resolved after metronidazole antimicrobial treatment. Cardiopulmonary medical treatment, including a loop diuretic, an angiotensin-converting enzyme inhibitor, a beta-adrenergic receptor blocker, and a bronchodilator provided improvement of the clinical signs. To the best of our knowledge, this is the first reported case of antemortem diagnosis and treatment of congestive heart failure and cardiomyopathy in a member of the family Procyonidae, suggesting that HCM should be considered as a differential diagnosis in kinkajous displaying clinical signs of dyspnea and exercise intolerance.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Infective Agents; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diuretics; Furosemide; Heart Failure; Liver Diseases; Male; Metronidazole; Procyonidae

Topics: Cardiovascular Agents; Humans; Liver Diseases; Liver Transplantation; Living Donors; Organ Size; Propranolol; Somatostatin; Syndrome

A chronic adverse reaction may occur in some instances of drug-induced liver injury (DILI), even despite drug cessation. In our study, we obtained records from a Spanish registry and evaluated cases of DILI with biochemical evidence of long-term damage. Chronic outcome was defined as a persistent biochemical abnormality of hepatocellular pattern of damage more than 3 months after drug withdrawal or more than 6 months after cholestatic/mixed damage. Data on 28 patients with a chronic clinical evolution (mean follow-up 20 months) between November 1995 and October 2005 were retrieved (18 female; overall mean age 55 yr) and accounted for 5.7% of total idiosyncratic DILI cases (n = 493) submitted to the registry. The main drug classes were cardiovascular and central nervous system (28.5% and 25%, respectively), which, in contrast, represented only 9.8% and 13%, respectively, of all DILI cases. The most frequent causative drugs were amoxicillin-clavulanate (4 of 69 cases), bentazepam (3 of 7 cases), atorvastatin (2 of 7 cases), and captopril (2 of 5 cases). Patients with cholestatic/mixed injury (18 of 194 cases [9%]) were more prone to chronicity than patients with hepatocellular injury (10 of 240 cases; P < .031). In the case of chronic hepatocellular injury, 3 patients progressed to cirrhosis and 2 to chronic hepatitis. In the cholestatic/mixed group, liver biopsy indicated cirrhosis in 1 patient and ductal lesions in 3 patients. In conclusion, cholestatic/mixed type of damage is more prone to become chronic while, in the hepatocellular pattern, the severity is greater. Cardiovascular and central nervous system drugs are the main groups leading to chronic liver damage.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Atorvastatin; Azepines; Captopril; Cardiovascular Agents; Central Nervous System Agents; Chemical and Drug Induced Liver Injury; Chronic Disease; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Heptanoic Acids; Humans; Liver; Liver Diseases; Male; Middle Aged; Pyrroles; Registries; Spain

Topics: Arteriosclerosis; Blood; Blood Protein Electrophoresis; Cardiovascular Agents; Digitalis Glycosides; Diuretics; Drug Therapy; Humans; Liver; Liver Diseases; Oxygen; Oxygen Inhalation Therapy; Pulmonary Heart Disease; Rheumatic Heart Disease; Urine

Topics: Cardiovascular Agents; Electromyography; Humans; Liver Diseases; Muscle Relaxants, Central; Myasthenia Gravis; Neurology; Water-Electrolyte Balance

Topics: Cardiovascular Agents; Decamethonium Compounds; Gallamine Triethiodide; Humans; Jaundice; Jaundice, Obstructive; Liver Diseases; Muscle Relaxants, Central; Succinylcholine; Tubocurarine

Topics: Cardiovascular Agents; Cholecystitis; Humans; Liver Diseases; Muscle Relaxants, Central; Sorbitol

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Glucocorticoids; Humans; Liver Diseases