Interactions, drug clinical importance

Pirmohamed M, Orme MLE. Drug interactions of clinical importance. In Davies DM, Ferner RE, de GlanvUle H, editors. Davies textbook of adverse drug reactions. 

D.I. Quinn, R.O. Day, Drug interactions of clinical importance An updated guide. 

Oral contraceptives alter the metabolism of some benzodiazepines that undergo oxidation (alprazolam, chlordiazepoxide, diazepam) or nitroreduction (nitrazepam) (166). For these drugs, oral contraceptives inhibit enzyme activity and reduce clearance. There is nevertheless no evidence that this interaction is of clinical importance. It should be noted that for other benzodiazepines that undergo oxidative metabolism, such as bromazepam or clotiazepam, no change has ever been found in oral contraceptive users. Some other benzodiazepines, such as lorazepam, oxazepam, and temazepam, are metabolized by glucuronic acid conjugation. The clearance of temazepam was increased when oral contraceptives were coadministered, but the clearances of lorazepam and oxazepam were not (167). Again, it is unlikely that this is an interaction of clinical importance. 

An established interaction of clinical importance. Avoid ferrous sulfate and other iron compounds while taking cefdinir. It is not yet known how far apart these drugs must be separated to avoid this interaction, but 3 hours improves the situation considerably even if it does not totally solve it. There is no information to suggest that other eephalosporins interact in this way. 

Fairly well-documented and established interactions of clinical importance. Prothrombin times should be regularly monitored in patients taking warfarin and other coumarins and requiring fluorouracil, capecitabine or other fluorouracil pro-drugs, anticipating the need to reduce the warfarin dose. Note that, from a disease perspective, when treating venous throm-... 

The weight of evidence shows that no interaction of clinical importance normally occurs between phenytoin and the antidiabetic drugs (most of the studies involved sulphonylureas). No special precautions seem normally to be necessary. 

A very well documented and well established interaction of clinical importance. Not every combination of guanethidine and tricyclic antidepressant has been studied but all are expected to interact similarly. Concurrent use should be avoided unless the effects are very closely monitored and the interaction balanced by raising the dosage of the antihypertensive. Note that the use of guanethidine and related adrenergic neurone blockers has largely been superseded by other antihypertensive drug classes. 

An established interaction of clinical importance. If maximal absorption is needed the administration of the two drugs should be separated to avoid mixing in the gut. Two hours or so has been found enough for most other drags which interact similarly. There seems to be nothing documented about other antacids. 

Following concurrent administration of two drugs, especially when they are metabolized by the same enzyme in the liver or small intestine, the metabolism of one or both drugs can be inhibited, which may lead to elevated plasma concentrations of the dtug(s), and increased pharmacological effects. The types of enzyme inhibition include reversible inhibition, such as competitive or non-competitive inhibition, and irreversible inhibition, such as mechanism-based inhibition. The clinically important examples of drug interactions involving the inhibition of metabolic enzymes are listed in Table 1 [1,4]. 

Drug Interactions. Table 1 Examples of clinically important drug interactions due to enzyme inhibition... 

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

Patients are placed on imatinib at the time of diagnosis. Patients should be monitored for a dose-dependent myelo-suppression, Cl intolerance, edema, and rash. Drug interactions with CYP450 3A4 inducers are clinically important and should be monitored. 

Compounds of the same therapeutic class may profoundly differ as to QT prolonging potential in addition, the assessment of the proarrhythmic risk must take into account pharmacokinetic aspects including metabolism, since a very low baseline proarrhythmic risk may become clinically important in case of drug interactions leading to higher than expected plasma levels. 

Carbamazepine, phenytoin, pheno-barbital, and other anticonvulsants (except for gabapentin) induce hepatic enzymes responsible for drug biotransformation. Combinations between anticonvulsants or with other drugs may result in clinically important interactions (plasma level monitoring ). 

Aminoglycosides remain clinically important antibiotics. NMR provided the initial breakthrough in structural understanding of aminoglycoside action on the ribosome, and it remains a powerful tool for the biophysical characterization of drug-RNA interaction. The combined use of NMR, X-ray crystallography, thermodynamic and functional assays, and computational methods is needed to drive forward the development of new aminoglycosides with improved clinical properties. The rich data described above, combined with the application of new synthetic methods, bode well for the future. 

Pharmacodynamics. Although this chapter concentrates on clinical pharmacokinetics, it would be wrong to omit mention of pharmacod)mamic interactions in a section on drug interactions. It is difficult to generalise, but drugs with marked pharmacological effects, particularly on the cardiovascular system and CNS are potentially subject to clinically important pharmacod)mamic interactions. 

Drug/Food interactions Food increased the AUC of loratadine by approximately 40% and the metabolite by approximately 15% absorption was delayed by 1 hour. Although not expected to be clinically important, take on an empty stomach. 

Stockley s Drug Interactions. The most complete listing of drug interactions. Includes mechanisms, as well as advice on clinical importance and actions. Chapter one gives an excellent introduction to the field. 

This chapter reviews the main mechanisms of drug interactions. It gives some clinically important examples of these, and suggests how they can be assessed and managed. It focuses on drug interactions that may have an adverse clinical outcome, rather than those that are used to therapeutic advantage. The issues of pharmaceutical incompatibility and drug interactions with food and alcohol will not be covered here. 

Baxter K, editor. Stockley s drug interactions. A source book of interactions, their mechanisms, clinical importance and management. 8th ed. London Pharmaceutical Press 2007. 

Quinn DI, Day RO. Clinically important drug interactions. In Speight TM, Holford HG, editors. Avery s drug treatment. 4th ed. Auckland Adis International 1997. p. 301-38. 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

Eilers H, Niemann C. Clinically important drug interactions with intravenous anaesthetics in older patients. Drugs Aging 2003,20 969-980. 

Table 1.7.5 Some clinically important drug interactions.

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