Variation in response to drug therapy

In Chapter 2, we have seen that responses to drug therapy depend on the four processes of absorption, distribution, metabolism and excretion and there are many factors that affect these four processes. 

It is important to realize that these are principles that have been derived from standard studies of drug action on average or normal individuals during the development process for new drugs. 

Drug development involves investigation of drug action in order to determine suitable and effective dosage regimes, to allow likely adverse effects to be determined and to ensure safety in use as far as possible. 

It is possible to predict, and to some extent avoid, likely adverse effects in particular populations using knowledge of factors that affect the four processes above in different patient groups. 

The elderly are known to suffer a higher frequency of adverse effects to medication and the reasons are many and varied. Knowledge of the possible reasons, together with consideration of the problems and changes caused by the ageing process, means that many of the adverse affects could be avoided or at least reduced in intensity. The lower the TR of a drug, the more important these considerations become. 

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Variation in response to drug therapy can occur due to many factors. At extremes of life absorption, distribution, metabolism and excretion can all be different to normal so that drug action becomes unpredictable. In particular, plasma protein binding, liver and kidney function and the number of drugs being taken concurrently become important in older patients. 

ANTACIDS CONTAINING MAGNESIUM AND ALUMINIUM BETA-BLOCKERS t bioavailability of metoprolol and atenolol, which may produce a mild variation in response to both drugs Variations in absorption of the respective beta-blockers Clinical significance may be minimal but be aware. Monitor BP at least weekly until stable when initiating antacid therapy. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

Eisenhauer, L. A. (1998). Variations in patient responses to drug therapy The role of pharmacodynamics and pharmacokinetics. In L. A. Eisenhauer M. 

Drysdale s recent study, the first of its kind, assessed the effect of combinations of SNPs (haplotypes) on response to the drug, albuterol (146). Variation in 13 SNPs could be organized into 12 haplotypes, and investigation of these haplotypes in several discrete populations (Caucasian, African-American, Asian, and Hispanic-Latino) revealed >20-fold differences among the frequencies of the four major haplotypes. Mean responses to bronchodilator therapy with albuterol of individuals with the five most common (FAR haplotypes varied by greater than twofold, but were unrelated to individual SNPs. 

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