Significance of Drug Interactions

Clinically, drug interactions are important because of their significance in therapeutics. 

Incompatibility, such as that between anionic and cationic antiseptics discussed below, may inactivate the agent(s) involved. 

Study of drug interactions which occur after administration of the drugs to the patient is more difficult. 

A study of drug interactions may also be of value in the understanding of the mechanisms by which drugs act (that is, the forces between the drug and its receptor site ), how they are attached to or transported across cellular structures such as cell membranes, and also in the understanding of pathogenesis of disease states. 

As Albert pointed out, the association between anion dyes and cationic drugs, used as the basis for methods of colorimetric analysis, is a model for the uptake of drug cations by receptors and for carrier-aided passage of agents through semipermeable membranes.  

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Winans EA, Cohen LJ. Assessing the clinical significance of drug interactions in psychiatry. Psychiatr Ann 1998 28 399-405. 

Jorde UP, Horowitz HW, Woimser GP. Significance of drug interactions with rifampin in... 

Melanin has been shown to form adducts with chloroquine, paraquat, and clindamycin. The significance of drug interaction with melanin has been discussed. 

While defining the overall pharmacokinetic or pharmacodynamic basis of botanical-drug interactions may be relatively straightforward, attempts to explain the underlying mechanism of altered drug concentrations or to predict the magnitude and significance of the interaction is certainly not easy. There are several factors that contribute to this difficulty, and they are briefly discussed below. 

Four cases of lack of effect or impotence were reported in patients using sildenafil while on St. John s wort and other concomitant drugs (what are they Are any of them significant from the standpoint of drug interaction ). The age range of the four male patients was between 55 to 73 years. Viagra... 

Buspirone tends to be used preferentially in patients with chronic and persistent anxiety, in patients with comorbid substance abuse, and in elderly patients, because it is well tolerated and has no significant pharmacokinetic drug interactions. What is clear is that buspirone shows reproducible efficacy in certain animal models of anxiety and in GAD, which points to a potentially important role of serotonin in mediating anxiety symptoms through 5HT1A receptors. Buspirone also has a role as an augmenting agent for the treatment of resistant depression, as discussed in Chapter 7. 

Although ethanol is not metabolized by the microsomal drug-metabolizing system, it inhibits it and increases the rate of its synthesis. This effect may create a significant alcohol-drug interaction in both nonalcoholics and alcoholics who are taking medications. 

In addition to these fundamental aspects of drug action, the important area of drug interactions will be considered in Chapter 4. Although this subject does not require exhaustive coverage, it is important to appreciate its ramifications early in the study of pharmacotherapeutics since the coincidental administration of drugs can affect their respective pharmacokinetics. In some cases their interaction can be clinically significant. 

The main route of elimination of benazeprilat is by way of the kidneys, although biliary excretion may also occur [49,51], No clinically significant metabolic drug interactions with benzepril have yet been described [49],... 

Spina E, Perucca E. Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs. Epilepsia 2002 43(Suppl 2) 37-44. 

Significant limitations often exist in trying to predict the results of combination therapy. In the following discussion, guidelines are provided to reduce the risk of the occurrence of drug interactions. 

Table 8 lists commonly used drugs and potential food interactions. This is not a comprehensive list, but rather highlights many of the clinically significant food-drug interactions. ... 

Table 8 Clinically significant drag and food interactions in the elderly Class of drugs Interaction...

Excess caffeine can stimulate the CNS, which can worsen psychosis and thus interfere with the effects of neuroleptic drugs (54). Neuroleptic drugs can precipitate from solution when mixed with coffee or tea (55), but the clinical significance of this interaction is unknown (56). 

Headache, dizziness, and gastrointestinal symptoms are the most frequent adverse effects clinically significant gastrointestinal events include upper gastrointestinal ulceration, with or without hemorrhage or perforation (SEDA-20, 94) (SEDA-21, 107). The profile of drug interactions is similar to the profiles of other NSAIDs (SEDA-21,108). 

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