Interactions, drug pharmacological basis

Simple mathematical calculations by the first pharmacologists in the 1930s indicated that structurally specific drugs exert their action in very small doses and do not act on all molecules of the body but only on certain ones, those that constitute the drug receptors. For example, Clark [407] calculated that ouabain applied to the cells of the heart ventricle, isolated from the toad, would cover only 2.5% of the cellular surface. These observations prompted Clark [407,408] to apply the mathematical approaches used in enzyme kinetics to the effects of chemicals on tissues, and this formed the basis of the occupancy theory for drug-receptor interaction. Thus, pharmacological receptor models preceded accurate knowledge of receptors by many years. 

This section provides a review of the anatomy and physiology of the autonomic nervous system (ANS) accompanied by a brief description of some of the important drugs which modify its actions. A summary of the interaction between the immune system and the ANS is also included. An extensive discussion of the anatomy and physiology of the ANS can be found in the Primer on the Autonomic Nervous System (Robertson, 2004). Detailed information on the pharmacology of the ANS can be found in Goodman Gilman s The Pharmacological Basis of Therapeutics (Brunton et al., 2006). 

Some knowledge of the pharmacological basis of how one drug may change the action of another is useful in obtaining those interactions that are wanted, as well as in recognising and preventing those that are not. 

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. 

Drug Interactions and Side effects Index. (1994) Oradell, NJ Medical Economics Co. Goldstein, A., Aronow, L. and Kalman, S. (1974) Principles of Drug Action The Basis of Pharmacology, 2nd ed. New York John Wiley Sons. 

The interactions of many important drugs, metabolites, and structurally related compounds with HSA have been char-acterized on the basis of their inhibition of its acetylation by p-nitrophenyl acetate. Dissociation constants of 10 5M or lower have been determined for tryptophan, phenylpyru-vate, several pharmacologically important benzodiazepines, several types of small, apolar, anionic drugs and related compounds that interact specifically with the inhibitory site. Two other classes of inhibitory compounds have been identified and similarly characterized, the members of which interact either to a comparable extent or preferentially with one other site. The inhibitory site appears to be elongated, apolar, and has a monoanion binding site near one end. 

Interactions that are predictable on the basis of the pharmacologic activity of the drug, and potential interactions with drugs that are likely to be coadministered with the drug should be identified. 

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