RESUMEN
After a brief recall of the molecular bases of the pharmacological actions, the two main ways of discovery of new drugs are described. On the one hand, the "deductive" approach starts with the elucidation of the pathogenic mechanisms and leads to selective drug designs for the appropriate receptors. The recent contributions of the molecular biology in this way are illustrated by some examples: "knock out" mice for the study of gene functions, discovery of new antibiotics thanks to genomic sequencing of bacteria, new pathogenic concepts about inflammation... On the other hand, the empirical approach is now grounded on two performant methods: High Throughput Screening and Combinatorial Chemistry which together have already given practical results. It is obvious that these two approaches are not opposite, but complementary.
Asunto(s)
Diseño de Fármacos , Farmacología , Animales , Antibacterianos/química , Proteínas Bacterianas/genética , Química Farmacéutica , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica , Genoma Bacteriano , Humanos , Inflamación/etiología , Ratones , Ratones Noqueados , Biología Molecular , Estructura Molecular , Proteínas/genética , Receptores de Superficie Celular/químicaRESUMEN
The hepatic cytochrome P450 enzymes (CYP450) play a prominent part in the metabolism of drugs, toxicants and some endogenous compounds. After a brief recall of their biochemical properties, the recent nomenclature is proposed. They are members of a large superfamily with various functions; the specialization of 3 families, CYP1, CYP2, CYP3 towards the metabolism of foreign and artificial compounds gives way to some evolutive considerations. Three main features are characteristic: these enzymes are poorly selective as a matter of substrates; some display genetic polymorphism; some are highly inducible. The mechanism of induction is detailed for CYP1A1. The consequences in pharmacotherapy are deduced: the CYP450 are the main cause of the variability in pharmacokinetics, of drug interactions and of drug adverse events of type II. Their implication in carcinogenesis, although controversial, deserves attention and requires further studies.
Asunto(s)
Sistema Enzimático del Citocromo P-450/fisiología , Quimioterapia , Carcinógenos/efectos adversos , Citocromo P-450 CYP1A1/fisiología , Sistema Enzimático del Citocromo P-450/clasificación , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Inducción Enzimática , Humanos , Hígado/enzimología , Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Polimorfismo Genético/genética , Terminología como Asunto , Toxinas Biológicas/metabolismoRESUMEN
The problem of drug interactions is particularly important for psychoactive agents and for anticonvulsants because of their large use and of peculiarities of their clinical application. Such interactions may, in a few conditions, explain unforeseen adverse effects, and, more frequently, they disturb the meaning of plasma determinations of the monitored drugs. Some interactions can be pharmacokinetic, principally by way of enzyme induction or enzyme inhibition, and than they lead to disturbances in the plasma levels of the active substances. On the other hand, interactions can take place at the pharmacodynamic level, which is as an important condition although it is less well-known. Some examples are given for both mechanisms.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Psicotrópicos/administración & dosificación , Antidepresivos Tricíclicos/administración & dosificación , Biotransformación , Interacciones Farmacológicas , Inducción Enzimática , Inhibidores Enzimáticos , Humanos , Absorción Intestinal , Cinética , Unión ProteicaAsunto(s)
Líquidos Corporales/análisis , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Preparaciones Farmacéuticas/análisis , Hipersensibilidad a las Drogas , Interacciones Farmacológicas , Humanos , Pruebas de Función Renal , Pruebas de Función Hepática , Preparaciones Farmacéuticas/metabolismoAsunto(s)
Química Clínica , Estadística como Asunto , Femenino , Humanos , Masculino , Valores de ReferenciaAsunto(s)
Toxicología , Sitios de Unión , Química Clínica , Humanos , Laboratorios , Preparaciones Farmacéuticas/metabolismo , FarmacologíaRESUMEN
Measurements of total body water and total exchangeable sodium, by isotopic dilution, and of total body potassium by whole body counting of the naturally occurring 40K isotope, were performed on stabilised paraplegic or tetraplegic subjects. Nineteen patients were investigated by the complete set of tests, six by only body counting. The results of total body potassium are expressed, following a uniform scale, as "relative values", which were established by the processing of reference values, from numberous paired healthy subjects.