Biological Response to Drug

VINCENT MARKS, W. EDWARD LINDUP, AND E. MARY BAYLIS 

These examples are given to show that a simplistic approach to therapy, which is based upon clinically useful but unproved hypotheses of disease causation, can lead to the neglect of studies into the relationship between blood drug levels and clinical response, as determined by morbidity and mortality, rather than by some easily measured but possibly irrelevant chemical parameter. 

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Biological response to drug binding, OCCUPANCY THEORY OF DRUG ACTION... 

Ritter, J.K. (2007) Intestinal UGTs as potential modifiers of pharmacokinetics and biological responses to drugs and xenobiotics. Expert Opinion on Drug Metabolism and Toxicology, 3, 93—107. 

Variability in responses to drugs has been observed as long as drugs have been tested systematically. These variations have been designated as "biological" and have been considered a necessary evil by those who have sought to develop a systematic science of pharmacology. Much attention has been paid to the mathematical treatment of the data obtained from such tests, but little to the basic reasons for the variability. Krantz and Carrl state frankly "The mechanism of idiosyncrasy is not understood."... 

Generally, to produce a biological response, a drug molecule must first cross at least one biological membrane. The biological membrane acts as a lipid barrier to most drugs and permits the absorption of lipid-soluble substances by passive diffusion while lipid-insoluble substances can diffuse if at all across the barrier only with considerable difficulty. The interrelationship of the dissociation constant, lipid solubility, and pH at the absorption site and absorption characteristics of various drugs are the basis of the pH-partition theory. 

Consider the difference in response to drugs between older and younger people. Treatment should reflect biological age (rather than chronological). Pharmacokinetics, pharmacodynamics, tolerability, adverse reactions, economy and patient choice will all influence therapy chosen. Most commonly, car-bamazepine or sodium valproate are chosen for older people as their effects in older people are well documented. Both show a favourable balance of safety, efficacy and economy. Phenytoin is less preferable because of drug interactions, adverse effects and potential for toxicity (zero order kinetics). 

Fluorescence microscopy has long been a powerful tool for cell biology as well as drug discovery research. It can measure both the contents and locations of multiple biomolecules or probes in cells simultaneously. Thus it provides unparalleled levels of detailed information about cellular responses to drug treatment or other perturbations. It has been particularly useful for rapidly validating drug leads in multiple cellular systems relevant to their efficacy and toxicity profiles. 

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