PubMed · 5190952
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H Goldenberg. 1969. Drug interactions.. https://pubmed.ncbi.nlm.nih.gov/5190952/
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Despite the fact that the combination of vancomycin and a beta-lactam antibiotic are known to act synergistically on vancomycin-susceptible Staphylococcus aureus (VSSA), some MRSA have emerged showing antagonism to the combination of vancomycin and a beta-lactam antibiotic. These MRSA are called beta-lactam antibiotic-induced vancomycin resistant MRSA (BIVR). A method based on this antagonistic phenomenon has been devised to detect BIVR strains. The method inhibits the VSSA strain but allows the BIVR strain to grow. Forty-six commercially available beta-lactam antibiotics induced the vancomycin-resistance. Using this detection method, 717 MRSA clinical isolates obtained from eight institutes throughout Japan were thus screened and 6.3% of these were detected as BIVR when judged at 48 h.
A large number of drugs are introduced every year, and new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely on memory alone to avoid potential drug interactions. Multiple drug regimens carry the risk of adverse interactions. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. Regularly updated manuals of drug interactions and CD-ROM-formatted programs are useful office references.
Drug interactions can be classified according to their pharmacodynamic and pharmacokinetic mechanisms. Pharmacodynamic interactions are observed when two drugs share a common effect or have the same effect on different receptors of a common function. They can be predicted if the elementary effects of each drug are known. Such are pharmacodynamic interactions are particularly interesting as they are selective for the common effect(s). Pharmacokinetic interactions are more difficult to predict. They occur when one drug modifies the pharmacokinetic parameters of a second drug. Modification may involve variations in oral absorption, tissue distribution, rate of metabolism and/or rate of renal excretion. This interaction cannot be selective as drug concentrations are modified, affecting all the concentration-dependent effects. Mastering drug interactions involve the knowledge of the underlying mechanisms. Answers to following questions are needed: does the association produce conjugated effects? can one drug modify pharmacokinetic parameters of another? Potentially toxic effects may be suspected when at least one drug involved is known for its toxicity. Risk is increased when it also exhibits a narrow range between active and toxic concentrations. Many databases in printed form or as interactive software provide information on drug interactions. Clinicians can also consult a Pharmacovigilance Center for a safe prescription procedure. Finally, the main danger lies in the simultaneous prescriptions by different practitioners unaware of their colleagues prescription. In this case, the pharmacist plays an important role of evaluation of the drugs prescribed.