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Biomedical subjects

R Zacest

Publications and source records attributed to R Zacest.

8 recordsLinked to original sources
PubMed1978

Interference in assays for hydralazine in humans by a major plasma metabolite, hydralazine pyruvic acid hydrazone.

The present study showed that published spectrophotometric and GLC methods for hydralazine in plasma do not distinguish between the drug and a major plasma metabolite, hydralazine pyruvic acid hydrazone. These methods involve the acid treatment of the sample, which hydrolyzes that hydrazone back to hydralazine. A specific GLC assay for the hydrazone was developed and involves its selective extraction from plasma and transformation to 3-trifluoromethyl-s-triazolo[3,4-a]phthalazine. This derivative could be sensitively measured by GLC using an electron-capture detector. With this procedure, it was shown that most "apparent hydralazine" in plasma is the hydrazone, which forms rapidly from hydralazine and endogenous pyruvic acid. Previous work indicated that the hydrazone was inactive when administered intravenously to rabbits.

Chromatography, Gas↗
PubMed1977

The ambiguity of adverse drug reactions.

Three clinical pharmacologists independently evaluated 500 untoward clinical events reported by physicians as adverse drug reactions (ADRs). They often disagreed with the reporting physicians and with each other. They judged 14.4-28.2% of the events to be definite, 26.4-38.0% probable, 21.4-31.0% possible and 15.8-28.2% of the events to be definite, 26.4-38.0% probable, 21.4-31.0% possible and 15.8-28.2% unlikely ADRs. In their opinion 19.1-32.4% of the drugs blamed were definitely, 29.8-34.4% probably, 24.9-36.7% possibly and 8.4-14.5% not responsible for the adverse reactions. Evaluators disagreed among themselves about the drug most likely to have been responsible in 36.4% of the events, about ADRs causing hospital admission in 56.8%, about severe ADR morbidity in 55.8%, about ADR prolongation of hospitalization in 67.3% and ADR prolongation of hospitalization in 67.3% and about ADR contribution to death in 71.0%. The divergence of judgements suggests that suspected ADRs are usually ambiguous clinical events, and that incidence, severity, medical consequences and cost of ADRs can only be estimated.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1976

The vasodilator--beta-blocker interaction--some determinants of its clinical success.

A number of structurally dissimilar compounds, sharing the ability to induce vasodilatation have come into clinical usefulness as antihypertensive drugs. Their successful utilisation often depends critically on an appropriate combination with diuretics and beta-blockers. Beta-blockers can specifically inhibit the reflex cardiac stimulation which otherwise may limit the tolerability and haemodynamic value of these drugs. A synergistic antihypertensive effect has been demonstrated with hydrallazine and propranolol and possibly exists with other combinations. Generally, vasodilators are not first-line drugs in chronic therapy but are best added to beta-blockers. Variations of the dose-response and the time-course of effect are stressed as being important determinants of a successful interaction.

Adrenergic beta-Antagonists↗
PubMed1976

Clinical and haemodynamic effects of minoxidil in refractory hypertension.

Thirteen patients whose hypertension had been resistant to conventional drug therapy, had minoxidil added to their regimen in doses from 5 to 60 mg/day. All responded with satisfactory reductions of blood pressure to mean values of 149/90mm Hg (supine) and 143/89mm Hg (standing). A significant portion of their previous antihypertensive therapy was either greatly decreased or withdrawn completely. Although fluid retention occurred in most patients as the dose of minoxidil was increased, this could be successfully checked by the use of diuretics. It was considered that in addition to beta-adrenoreceptor blocking drugs to control the reflexly induced cardiac stimulation, sufficiently aggressive diuretic therapy is mandatory to ensure the successful use of this drug. Haemodynamic evaluations in seven patients clearly showed that lowering of blood pressure was the result of decreases in peripheral vascular resistance as significant increases in the cardiac index occurred in all patients.

Adult↗
PubMed1975

The clinical pharmacology of hypotensive vasodilator drugs.

Drugs which lower arterial blood pressure by direct vasodilator action usually have to be combined with beta adrenergic blocking drugs and diuretics for maximum clinical effectiveness. Appreciation of the pharmacodynamic interactions is necessary to individualize drug programmes rationally. Vasodilator drug therapy is remarkable for the lack of side effects such as central nervous system effects, postural hypotension and sexual difficulties which usually characterize most "antiadrenergic" drug regiments.

Adrenergic beta-Antagonists↗