salicylates and Heart-Failure

Topics: Acidosis; Bicarbonates; Biguanides; Diabetes Mellitus; Epilepsy; Ethanol; Fructose; Heart Failure; Humans; Hypoglycemic Agents; Lactates; Leukocytosis; Methanol; Neoplasms; Physical Exertion; Salicylates; Shock

Topics: Asthma; Asthma, Exercise-Induced; Bronchitis; Cough; Diagnosis, Differential; Heart Failure; Humans; Occupational Diseases; Peak Expiratory Flow Rate; Pruritus; Pulmonary Embolism; Radiography, Thoracic; Respiratory Sounds; Salicylates

This article attempts to help in the understanding of the mechanisms responsible for a modified drug pharmacokinetic profile in disease states. The main factors influencing the fate of the drug as it moves from the site of administration to the sites of elimination are depicted. Changes in absorption kinetics can be due to altered gastrointestinal peristalsis and secretions as well as modifications of splanchnic blood flow. Pathological states may affect the binding of drugs to plasma proteins, mainly human serum albumin and alpha 1 acid glycoprotein. The resulting modifications in the free fraction of the drug can cause a change in the volume of distribution. The distribution can also be influenced by circulatory disorders modifying local blood flows and thus impeding drug entry into the tissues. Many diseases can alter hepatic and/or renal clearance. This is not surprising since the elimination mechanisms are dependent upon many factors such the enzymatic status of the liver, plasma protein binding, and blood flow to both the liver and the kidney. Some examples such as the modification of furosemide pharmacokinetics in acute renal failure, the impaired metabolism of opiate analgesics in hepatic insufficiency, the alterations of the usual disposition process in salicylic acid intoxication, and the influence of cardiac failure upon some drugs pharmacokinetics, have been chosen to illustrate some of the aspects discussed. Some simple rules for making a rational selection of drugs in pathological states are also outlined.

Topics: Acute Kidney Injury; Blood Proteins; Disease; Furosemide; Glomerular Filtration Rate; Heart Failure; Humans; Intestinal Absorption; Kidney; Kinetics; Liver Diseases; Narcotics; Pharmaceutical Preparations; Protein Binding; Salicylates; Tissue Distribution

Topics: Acute Kidney Injury; Barbiturates; Blood Volume; Child; Child, Preschool; Costs and Cost Analysis; Heart Failure; Humans; Hyperkalemia; Hypocalcemia; Hypotension; Intestinal Obstruction; Intestinal Perforation; Kidney Failure, Chronic; Metabolic Diseases; Methods; Nutrition Disorders; Peritoneal Dialysis; Poisoning; Renal Dialysis; Salicylates; Time Factors

Topics: Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Aspirin; Child; Cortisone; Digitalis Glycosides; Electrocardiography; Heart Failure; Humans; Injections, Intramuscular; Penicillin G Benzathine; Physical Exertion; Rheumatic Fever; Rheumatic Heart Disease; Salicylates; Streptococcal Infections; Streptococcus; Virulence

To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease.. Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo.. Tertiary referral centre.. 20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 0.40. Twelve patients completed the two parts of the study.. Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids.. The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drug's accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E2 synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed.. The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A2 synthesis effectively in patients with heart failure and no further reduction by salicylate was found.

Topics: Adult; Aged; Angiotensin II; Blood Pressure; Coronary Disease; Creatinine; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Salicylates; Salicylic Acid

ROS have been implicated in the development of pathological ventricular hypertrophy and the ensuing contractile dysfunction. Using the rat monocrotaline (MCT) model of pulmonary arterial hypertension (PAH), we recently reported oxidative stress in the failing right ventricle (RV) with no such stress in the left ventricle of the same hearts. We used the antioxidant EUK-134 to assess the role of ROS in the pathological remodeling and dysfunction of the RV. PAH was induced by an injection of MCT (80 mg/kg, day 0), treatment with EUK-134 (25 mg/kg, once every 2 days) of control and MCT-injected animals [congestive heart failure (CHF) group] was started on day 10, and animals were analyzed on day 22. EUK-134 treatment of the CHF group attenuated cardiomyocyte hypertrophy and associated changes in mRNA expression (myosin heavy chain-beta and deiodinase type 3). It also reduced RV oxidative stress and proapoptotic signaling and prevented interstitial fibrosis. Cardiac MRI showed that ROS scavenging did not affect the 37% increase in end-diastolic volume of the RV in the CHF relative to the control group, but the threefold increase in end-systolic volume was reduced by 42% in the EUK-134-treated CHF group. The improved systolic function was confirmed using echocardiography by an assessment of tricuspid annular plane systolic excursion. These data indicate an important role of ROS in RV cardiomyocyte hypertrophy and contractile dysfunction due to PAH and show the potential of EUK-class antioxidants as complementary therapeutics in the treatment of RV dysfunction in PAH.

Topics: Animals; Antioxidants; Disease Models, Animal; Heart Failure; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Organometallic Compounds; Rats; Rats, Wistar; Reactive Oxygen Species; Salicylates; Ventricular Dysfunction, Right; Ventricular Remodeling

An analysis of 37 patients over the age of 65 years who underwent emergency surgery for complications of peptic ulcer is presented. A major predisposing factor to these complications was the use of ulcerogenic drugs that were prescribed for chronic musculo-skeletal ailments. The overall mortality was 23.5%, and was mainly related to pre-existing cardio-pulmonary disease.

Topics: Aged; Emergencies; Heart Failure; Humans; Indomethacin; Lung Diseases, Obstructive; Peptic Ulcer; Salicylates; Steroids

Topics: Animals; Guinea Pigs; Heart; Heart Failure; In Vitro Techniques; Indomethacin; Lung; Platelet Aggregation; Pulmonary Embolism; Salicylates

Pericarditis complicating acute myocardial infarction assumes increasing importance in this era of quantitating infarct size by precordial ST segment mapping. Early recognition of this complication avoids diagnostic and therapeutic errors. In this study we looked for factors that could alert to the early diagnosis of pericarditis, such as ST elevation measured within 24 hours from onset, extent of CPK, LDH, and SGOT elevation, as well as degree of pump dysfunction. ST segment elevation in millimeters on admission seemed to be one factor that was of predictive value in this condition. Pericarditis occurred in three forms: (1) within a few hours from the onset of myocardial infarction and this form seems to carry a high mortality rate; (2) a more common variety occurs within 24 to 72 hours from onset and carries a higher mortality rate than matched controls; and (3) the late syndrome of Dressler's, not observed in our series. Aside from increased incidence of heart failure, other complications of myocardial infarction and the coronary risk factors were not significantly higher in patients with pericarditis. Salicylate treatment offers immediate relief in the majority of patients.

Topics: Aspartate Aminotransferases; Creatine Kinase; Heart Failure; Humans; L-Lactate Dehydrogenase; Male; Myocardial Infarction; Pericarditis; Radiography; Risk; Salicylates; Tachycardia; Time Factors

Topics: Acidosis; Aged; Blood Urea Nitrogen; Bradycardia; Catheterization; Female; Heart Failure; Hepatic Encephalopathy; Humans; Hyperglycemia; Kidney Failure, Chronic; Male; Methanol; Middle Aged; Peritoneal Dialysis; Pyelonephritis; Salicylates

Topics: Adult; Bicarbonates; Child, Preschool; Chlorides; Emetics; Female; First Aid; Heart Failure; Humans; Intraocular Pressure; Ipecac; Pulmonary Edema; Salicylates; Sodium; Sodium Chloride

Topics: Acetazolamide; Chemoreceptor Cells; Cyanosis; Dexamethasone; Diabetes Insipidus; Feeding and Eating Disorders; Heart Failure; Humans; Hypercapnia; Hypoventilation; Hypoxia; Infant, Newborn; Male; Respiration, Artificial; Salicylates; Syndrome

Topics: Arteriosclerosis; Coronary Disease; Heart Failure; Humans; Protein Binding; Rheumatic Fever; Salicylates

Topics: Adrenal Cortex Hormones; Age Factors; Child; Child, Preschool; Chorea; Endocarditis; Female; Heart Failure; Heart Valve Diseases; Humans; Male; Myocarditis; Penicillins; Rheumatic Fever; Rheumatic Heart Disease; Salicylates; Sex Factors

Topics: Acute Kidney Injury; Aspirin; Blood Chemical Analysis; Bronchopneumonia; Coma; Diagnosis, Differential; Diuresis; Gastric Lavage; Heart Arrest; Heart Failure; Humans; Infusions, Parenteral; Kidney; Kidneys, Artificial; Phenacetin; Poisoning; Pulmonary Edema; Renal Insufficiency; Salicylates; Statistics as Topic; Toxicology

Topics: Adolescent; Blood Sedimentation; C-Reactive Protein; Child; Heart Failure; Humans; Rheumatic Heart Disease; Salicylates; Statistics as Topic; Steroids

Topics: Blood Circulation; Heart Failure; Pulmonary Edema; Rheumatic Fever; Salicylates