Pharmacogenomics

Pharmacogenomics (PG) (pharmaco=drug; genomics=study of gene) is a branch of science that deals with how human gene has an impact or response to drugs. This field has evolved to improve the efficacy and reduce the side effects of administered drugs. Mostly, the majority of the drugs administered to the patient fulfil the cause and are also responsible for some adverse side effects. When a drug is administered to a patient, it has to reach its target through the bloodstream, act on the target, and finally come out of the body. After the targeted point is reached, the drugs are then finally absorbed, distributed, metabolized, and eliminated by the body. This whole process is eased by pharmacokinetic (PK) genes. These genes affect the ADME process (absorption, distribution, metabolization, and excretion) of a drug. On the other hand, the action of a drug on its target is facilitated by the pharmacodynamic (PD) genes which are mainly responsible for the desired clinical outcome. These PK and PD genes are involved in two different processes called intentional (on-target) and unintentional (off-target) (Karczewskietal., 2012). The intentional process involves desired therapeutic outcome, whereas unintentional process results in causing adverse events. Therefore, genetics plays a critical role in both adverse and desired events in a living organism, especially in determining optimal drug dose for an individual. For example, warfarin and clopidogrel, anticoagulant drugs, have different therapeutic doses based on the genetic makeup of an individual (Karczewskietal., 2012). Currently, research community is working to discover the genes engaged in PK and PD pathway genes. This could help in understanding the effect of drug action and to improve dosing. The overview of PG is illustrated in Figure 1.1.

In 1950s, a child suffering with leukemia was treated with mercaptopurine (a drug used as myelosuppressant), and the child began experiencing unexpected immunosuppression and bone marrow toxicity. However, later in 1990s researchers realized that genetics could explain the reason for the life threatening bone marrow toxicity (Abbott, 2003). Succinylcholine, a drug that came into market in 1950sand was used as a muscle relaxant by anesthesiologists during operations, was found to cause horrific respiratory arrest in about 1 in 2,500 individuals. Thus, there is an increasing need to understand the interaction between human genetics and drugs to formulate modern and personalized medicine.