Pharmacodynamic drug interactions

Reviews of ranitidine continue to substantiate its clinical efficacy and selectivity of action. " A multicenter trial in America has been assessed. Drug interactions, pharmacodynamics and pharmacokinetics of ranitidine and clmetldine have been compared. ... 

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

Drug-drug interactions Pharmacokinetic and/or pharmacodynamic interactions Pharmacokinetic and/or pharmacodynamic consequence of multiple drug therapy... 

The major drug interactions of antidepressants are shown in Table 35—6.9,19,30 Antidepressants cause both pharmacodynamic (e.g., additive pharmacologic effects) and pharmacokinetic (e.g., changes in drug levels) interactions with other medications. 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

Pharmacokinetic properties Pharmacodynamic properties Adverse-effect potential Drug-interaction potential Cost... 

Herbette, L. G., Pharmacokinetic and pharmacodynamic design of lipophilic drugs based on a structural model for drug interactions with biological membranes, Pest. Sci. 35, 363-368 (1992). 

Yuan R, Flockhart DA, Balian JD Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam. J Clin Pharmacol 1999,39 1109-1125. 

Pharmacodynamic studies deal more specifically with how the drug brings about its characteristic effects. Emphasis in such studies is often placed upon how a drug interacts with a cell/organ type, the effects and side effects it induces, and observed dose-response curves. 

Therapeutic failure may be the result of nonadherence to medication, development of drug resistance, intolerance to one or more medications, adverse drug-drug interactions, or pharmacokinetic-pharmacodynamic variability. 

Drug interactions with the BZs are generally pharmacodynamic or pharmacokinetic (Table 68-11). The combination of BZs with alcohol or other CNS depressants may be fatal. 

Keywords Pharmacokinetics Pharmacodynamics Drug-drug interactions Adverse drug reactions... 

Human pharmacology (Phase I) Assess tolerance Define/describe pharmacokinetics and pharmacodynamics Explore drug metabolism and drug interactions Estimate activity Dose-tolerance studies Single and multiple dose PK and/or PD studies Drug interaction studies... 

Apart from patient-specific parameters, external factors - most importantly the concomitant uptake of certain other chemicals present in diet, environment and especially other drugs - influence drug actions. Possible effects are manifold and can affect all stages of pharmacokinetic and pharmacodynamic processes in the body. Also direct interaction and inactivation of concomitantly administered substances are possible. Drug-drug interactions via modulation of metabolism present a very hot topic in pharmaceutical research and drug design. 

In previous sections, we discussed pharmacokinetics and pharmacodynamics. Remember, these are simply fancy medical terms for what the body does to a medication and what a medication does to the body. These twin pillars of pharmacology form the basis for understanding and being able to predict drug interactions. 

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. 

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