Interactions, drug

The clinically established drug interactions can be minimized to some extent by the avoidance of combined drug therapy, which are proven to be incompatible. 

in certain cases, the single drug is effective only to a certain degree or stage of disease condition. The multiple/combined drug therapy is required in many medical and dental conditions. 

The use of combined drug therapy can not be avoided in certain cases to attain a desired therapeutic level, but the risk of incompatibility/interactions involved in the treatment increases. 

Pharmacokinetic, which occur at the level of absorption, distribution, metabolism and excretion of one drug by another. 

Pharmacodynamic, which occur at the site of drug action involving the receptors. 

Upon completion of this chapter, you will have the ability to  

A large fraction of clinically significant drug interactions are mediated by one of the following  

The bottom line on any drug interaction is whether we expect the effect of the drug to increase, decrease or remain the same after an interaction with another drug. The effect of a drug which has reached steady-state equilibrium is directly (but not linearly) related to the concentration of unbound (free) drug at steady state, (CJss. 

The concentration of unbound drug at steady state is calculated from  

The term Css is given by a different formula depending on whether the drug is administered orally or intravenously. 

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Lethal drug interactions of new antiviral, sorivudin [l-(3-D-arabinofuranosyl-( )-5-(2-bromvinyl)uracil], with anticancer prodrugs of 5-fluorouracil structure 97YZ910. 

These, such as the black box that was the receptor at the turn of the century, usually are simple input/output functions with no mechanistic description (i.e., the drug interacts with the receptor and a response ensues). Another type, termed the Parsimonious model, is also simple but has a greater number of estimatable parameters. These do not completely characterize the experimental situation completely but do offer insights into mechanism. Models can be more complex as well. For example, complex models with a large number of estimatable parameters can be used to simulate behavior under a variety of conditions (simulation models). Similarly, complex models for which the number of independently verifiable parameters is low (termed heuristic models) can still be used to describe complex behaviors not apparent by simple inspection of the system. 

Wienkers, L. C., and Heath, T. G. (2005). Predicting in vivo drug interactions from in vitro drug discovery data. Nature Rev. Drug Discovery 4 825-833. 

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

Drug Interactions During Absorption Changes In Gastrointestinal pH... 

Drug Interactions. Figure 1 Increase in drug concentration caused by pharmacokinetic interactions. Shadow represents the therapeutic range. 

Drug Interactions During Distribution Displacement from Plasma Protein Binding Sites... 

Drug Interactions During Metabolism Enzyme Inhibition... 

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 During Excretion Changes In Urinary pH... 

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

Shitara Y, Sato H, Sugiyama Y (2005) Evaluation of drug-drug interactions in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 45 689-723... 

Hansten PD, Horn JR (2000) The top 100 drug interactions a guide to patient management. Edmonds H H Publications,... 

Ito K, Iwatsubo T, Kanamitsu S et al (1998) Prediction of pharmacokinetic alterations caused by drug-drug interactions. Pharmacol Rev 50 387-411... 

Diug metabolism, to predict whether a diug candidate will cause drug-drug interactions... 

Na+/Ca2+ Exchangers. Figure 4 Molecular properties of drugs interacting with NCX. Scheme summarizing the potency, the mode of selectivity, the molecular site of action and the isoform specificity of drugs interfering with NCX activity. 

The following drug interactions are the most important that can occur when conventional NSAEDs are co-administered with other agents ... 

Direct inhibition of P450 enzymatic activity is the most common reason for drug-drug interactions. 

Drug Interactions Drug-Receptor Interaction G-protein-coupled Receptors Tolerance and Desensitization Transmembrane Signaling... 

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