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Chapter: Basic & Clinical Pharmacology : Introduction

Pharmacology & Genetics

It has been known for centuries that certain diseases are inherited, and we now understand that individuals with such diseases have a heritable abnormality in their DNA.

Pharmacology & Genetics

It has been known for centuries that certain diseases are inherited, and we now understand that individuals with such diseases have a heritable abnormality in their DNA. During the last 10 years, the genomes of humans, mice, and many other organisms have been decoded in considerable detail. This has opened the door to a remarkable range of new approaches to research and treatment. It is now possible in the case of some inherited diseases to define exactly which DNA base pairs are anomalous and in which chro-mosome they appear. In a small number of animal models of such diseases, it has been possible to correct the abnormality by gene therapy, ie, insertion of an appropriate “healthy” gene into somatic cells. Human somatic cell gene therapy has been attempted, but the technical difficulties are great.

Studies of a newly discovered receptor or endogenous ligand are often confounded by incomplete knowledge of the exact role of that receptor or ligand. One of the most powerful of the new genetic techniques is the ability to breed animals (usually mice) in which the gene for the receptor or its endogenous ligand has been “knocked out,” ie, mutated so that the gene product is absent or nonfunctional. Homozygous knockout mice usually have complete suppression of that function, whereas heterozy-gous animals usually have partial suppression. Observation of the behavior, biochemistry, and physiology of the knockout mice often defines the role of the missing gene product very clearly. When the products of a particular gene are so essential that even heterozygotes do not survive to birth, it is sometimes possible to breed “knockdown” versions with only limited suppression of function. Conversely, “knockin” mice, which overexpress certain proteins of interest, have been bred.

Some patients respond to certain drugs with greater than usual sensitivity to standard doses. It is now clear that such increased sensitivity is often due to a very small genetic modification that results in decreased activity of a particular enzyme responsible for eliminating that drug.) Pharmacogenomics (or pharmacogenetics) is the study of thegenetic variations that cause differences in drug response among individuals or populations. Future clinicians may screen every patient for a variety of such differences before prescribing a drug.


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Basic & Clinical Pharmacology : Introduction : Pharmacology & Genetics |


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