Genetic Origin of Pharmacokinetic &
Pharmacodynamic variability
M. Sedensky
Physicians
are keenly aware that patients can respond quite differently from
each other given the same dose of a particular drug. Although it has
long been recognized that a drug dose must sometimes be
individualized for a particular patient, the genetic contribution to
an individual’s behavior when exposed to a particular medicine has
been relatively poorly understood. As a whole, the practice of
medicine faces a period of unprecedented growth in our understanding
of how the genetic make up of any given patient may affect a drug’s
potency and disposition.
The
field of pharmacogenetics studies the role of genetic differences in
controlling an individual’s response to drugs; it seeks to explain
and avoid both therapeutic toxicities and failures of standard
dosing regimes. Advances in this field have huge implications for
enhanced drug surveillance, as well as more efficient development of
new drugs. The field of anesthesiology faces many exciting changes
in patient care based on the explosion of knowledge in
pharmacogenetics; it will affect all facets of the anesthesiologist’s
function as a perioperative physician.
Study
of the genetic variations within the P450 family of enzymes was the
initial system that yielded significant information on genetic
contributions to drug potency and safety; this system continues to
be studied in great depth. Many other molecules, including the ß2
adrenergic receptor, are currently under intense investigation.
Study of this receptor and its genetic variants has already yielded
valuable information in our care of the asthmatic or cardiac
patient. The genetic control of pathways that affect pain perception
and response to analgesics is yielding fascinating information that
may revolutionize the ability of anesthesiologists to optimally
manage pain. In the future, it may be that the every patient’s
genetic make up can be perfectly analyzed, and an anesthetic regime
perfectly tailored to optimize that patient’s outcome. A primer of
pharmacogenetics, as well as a review of the influence of genetics
on drugs of relevance to anesthesiologists, will be presented.
