BioChemistry, Biotechnology, Education, Epigenetics, Genetics, Health, Nutriceutical, Pharmacogenetics
(Exercising Your Mind) By Cameron Ward Does your family health
The width of the therapeutic window determines the clinical
significance of the plasma level changes associated with smoking
and caffeine intake. Compared with olanzapine, clozapine has a
much narrower therapeutic window. Several of clozapine’s side effects
are dose related: plasma levels higher than 1,000 ng per milliliter
have been associated with toxicity, including seizure risk and severe
sedation. …
Some trials have shown that having this info on genetic variation can help docs
pinpoint the proper warfarin dosage. And that’s important, because even small
changes in dosage can have big effects, either on the not-enough-thinning side
or the so-much-thinning-it’s dangerous side. …
“Our results suggest the genetic make-up of patients could predispose their
responsiveness to a drug. This could have important implications for the future
of personalized molecular-based or individualized medicine,” …
“They are interested in pharmacogenetic purposes to do case control studies of
adverse drug reactions,” said John Novembre, a co-author of the study published
in Nature. …
Clozapine is a substrate for many CYP450 isozymes, in particular 1A2, 2D6, and
3A4. The risk of metabolic interactions caused by an effect on an individual
isoform is therefore minimized. Nevertheless, caution should be used in patients
receiving concomitant treatment with other drugs that are either inhibitors or
inducers of these enzymes. …
It is well recognized that most medications exhibit wide interpatient
variability in their efficacy and toxicity. For many medications, these
interindividual differences are due in part to polymorphisms in genes encoding
drug metabolizing enzymes, drug transporters, and/or drug targets (e.g.,
receptors, enzymes). …
some differences in drug efficacy response, and some toxicities, are based on
variability in exposure or in pharmacodynamic response, caused by genetic
differences …
The polymorphic forms of the CYP450s are responsible for the
development of a significant number of adverse drug reactions and may
also contribute to drug response. …