salicylates and Disease

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

A population-based case-control interview study of 486 adult leukemia cases and 502 healthy controls was carried out in Shanghai, People's Republic of China during 1987-89 to evaluate the etiologic role of prior medical conditions, medications, and diagnostic X-rays. Risks were examined separately for 236 cases with acute non-lymphocytic leukemia (ANLL), 79 with chronic myeloid leukemia (CML), 81 with acute lymphocytic leukemia (ALL), and 21 with chronic lymphocytic leukemia (CLL). Little difference was found between cases and controls for prior history of diabetes, hypertension, allergic conditions, most medications, and diagnostic X-rays. A few significant associations were observed for appendectomy, tuberculosis, and for several other chronic disorders with specific leukemia cell types, but the odds ratio estimates for most of these ranged from two to three and, with the exception of the two specified above, were based generally on five or fewer exposed controls. In contrast to an association with childhood leukemia in Shanghai, prior use of chloramphenicol was not linked with ANLL or other forms of adult leukemia. Further research is needed to clarify the relation of specific medical conditions and exposures with particular subtypes of leukemia, and to examine reasons for the low incidence of CLL in China and other Asian populations.

Topics: Adolescent; Adult; Age Factors; Aged; Appendectomy; Case-Control Studies; China; Disease; Female; Humans; Hyperthyroidism; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Salicylates; Tuberculosis

Topics: Dermatitis; Dermatitis, Seborrheic; Disease; Humans; Keratolytic Agents; Salicylates; Scalp; Sebaceous Gland Diseases; Skin Diseases

Topics: Adrenal Cortex; Arthritis; Disease; Drug Combinations; Glycosaminoglycans; Humans; Knee; Knee Joint; Salicylates; Salicylic Acid; Tissue Extracts

Topics: Biphenyl Compounds; Dermatitis, Seborrheic; Disease; Salicylates; Scalp; Skin Diseases

Topics: Analgesics; Anesthetics; Anesthetics, Local; Disease; Leg; Lower Extremity; Salicylates

Topics: Disease; Knee; Knee Joint; Osteoarthritis; Salicylanilides; Salicylates

Topics: Disease; Humans; Leg; Lower Extremity; Narcotics; Pain; Salicylates

Topics: Bile Ducts; Common Bile Duct; Common Bile Duct Diseases; Disease; Humans; Salicylates

Topics: Adrenochrome; Diabetes Complications; Diabetic Retinopathy; Disease; Glaucoma; Humans; Retina; Retinal Diseases; Salicylates

Topics: Cardiomyopathies; Disease; Heart; Heart Diseases; Joint Diseases; Myocardium; Rheumatic Diseases; Salicylates; Sodium Salicylate

Topics: Abdomen; Disease; Gastrointestinal Diseases; Rheumatic Diseases; Salicylates

Topics: Analgesics; Disease; Humans; Injections, Intra-Articular; Knee; Knee Joint; Salicylates; Synovitis

Topics: Arthritis; Arthritis, Rheumatoid; Disease; Humans; Neuritis; Peripheral Nerves; Salicylamides; Salicylates

Topics: Disease; Salicylates; Solanum lycopersicum; Tospovirus; Virus Diseases; Virus Inactivation; Viruses