G5 Pharmacogenetics | 58 | v4 | BIOS Instant Notes in Genetics

ABSTRACT

Key Notes https://www.niso.org/standards/z39-96/ns/oasis-exchange/table">

Pharmacogenetics

Pharmacogenetics is the practice of examining the response of individual genotypes to specific drugs and adjusting the treatment accordingly. These differences arise from differences in the expression levels or structure of proteins affecting drug uptake, metabolism, or the drug target. In the USA, over 100 000 people die and over two million are adversely affected by reactions to drugs. Many promising drugs cannot be used because a few patients would suffer a severe reaction to them. Some drugs only work on a part of the population, so are wasted when prescribed to many patients. A similar study involves cancer treatment, where mutation considerably alters the specific genomes of the cancer cells and affects their response to treatment. The deciding factor in pharmacogenetics is the cost-benefit trade-off of how beneficial the drug, or how serious its potential harm, and how expensive the drug is (if it is likely to be ineffective) compared to the cost of doing genetic tests before using the drug.

Examples

Enzymes which normally degrade drugs are missing in most of the cases where drugs fail, so that normal doses become effectively massive overdoses. Examples are butyrylcholinesterase which breaks down a muscle relaxant; glucose-6-phosphate deficiency and sensitivity to certain antimalarial drugs; cytochrome P450 oxidase family (CYP) of liver enzymes that detoxify (or activate) a range of drugs; and thiopurine S-methyltransferase (TPMT) which metabolizes thiopurines used in various chemotherapies.

Ethics

The application of screening to patients before drug treatment may not be given for reasons related to ethics. The cost of testing may be prohibitive; it may be cheaper to start the drug carefully and see what happens, stopping if there are adverse signs; or the drug may be deemed too risky to use at all. There are also issues of civil rights. Testing for genetic variants that affect drug metabolism would produce a genetic profile which could be used to identify the subject. Racial differences in reaction to drugs are common, but to withhold a drug from an ethnic group who would not benefit from it has been construed as racist.