PubMed · 8850856
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C Grüschow, D Blumenberg. [Midazolam].. https://pubmed.ncbi.nlm.nih.gov/8850856/
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Oxazolidinones are potent inhibitors of bacterial protein biosynthesis. Previous studies have demonstrated that this new class of antimicrobial agent blocks translation by inhibiting initiation complex formation, while post-initiation translation by polysomes and poly(U)-dependent translation is not a target for these compounds. We found that oxazolidinones inhibit translation of natural mRNA templates but have no significant effect on poly(A)-dependent translation. Here we show that various oxazolidinones inhibit ribosomal peptidyltransferase activity in the simple reaction of 70 S ribosomes using initiator-tRNA or N-protected CCA-Phe as a P-site substrate and puromycin as an A-site substrate. Steady-state kinetic analysis shows that oxazolidinones display a competitive inhibition pattern with respect to both the P-site and A-site substrates. This is consistent with a rapid equilibrium, ordered mechanism of the peptidyltransferase reaction, wherein binding of the A-site substrate can occur only after complex formation between peptidyltransferase and the P-site substrate. We propose that oxazolidinones inhibit bacterial protein biosynthesis by interfering with the binding of initiator fMet-tRNA(i)(Met) to the ribosomal peptidyltransferase P-site, which is vacant only prior to the formation of the first peptide bond.
OBJECTIVE: The objective of this study is to assess the usefulness of a programme of attention to pharmaceutical prescriptions (APP) so as to detect medicine-related problems. DESIGN: A descriptive study of the findings after six months operation of this programme. SETTING: Five primary care centres in the Bahía-Cádiz Area. PATIENTS: All the patients (499) who requested advice on their drug therapy and were included at the request and on the criterion of their doctor were studied. INTERVENTION: We introduced the APP programme for chronic patients, with two basic aims: Care: to detect medicine-related problems and propose individual solutions. Teaching: to bring drug-therapy skills used in clinical practice into line with the scientific evidence available. MEASUREMENTS AND RESULTS: We focused on the detection of problems related to the most common medicines, with direct and relevant incidence on morbidity and mortality. We detected 236 cases (47%) of possible therapeutic improvement that had important implications for associated morbidity, of which 114 (23%) also had implications for mortality. 56% of the patients took more than 4 medicines, multiple medication that could easily be reduced in 43.5% of cases, so avoiding the use of medicines of low intrinsic value. CONCLUSIONS: The programme was very useful, as numerous very clinically relevant problems were detected and information was gained that the doctor can use to bring drug therapy into line with the available scientific evidence.
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