Study Set Content:
These differences are determined by genetic factors and non-
genetic: variables, such as:
Age
Sex
Liver size, liver function,
Circadian rhythm
Body temperature
Nutritional and environmental factors (such as
concomitant exposure to inducers or inhibitors of
drug metabolism).
Genetic difference or Polymorphisms
they don’t have enough fully develop
drug metabolizing enzymes. Small doses are
advised.
Neonates
decreased drug metabolizing capacity.
Elders
might
affect the CYP450 enzymes
Androgens, estrogens and adrenocorticoids
(Faster in women)
Diazepam, prednisolone, caffeine and
acetaminophen
(Faster in
men)
Propanolol, lidocaine and some steroids
Liver diseases can affect the drug’s hepatic
clearance
Liver size, liver function,
Nocturnal Drug plasma level of drugs like
theophylline and diazepam which is lower during the
day
Mild- moderate hypothermia decreases the systemic
clearance of
CYP450.
can alter the amount of
conjugating agent proteins, fatty acids, minerals
and vitamins
Nutritional status
Give rise to distinct subgroups in the population that
differ in the ability perform drug biotransformation
Genetic difference or Polymorphisms
This a result of genetically based variations of
alleles and genes
Individual differences in metabolic rate depend on the(blank)itself.
nature
of the drug
Thus, within the same population, steady-state plasma levels
may reflect a (blank)in the metabolism of one
drug and only a two-fold variation in the metabolism
of another.
30-fold variation
Genetic factors that influence enzyme levels account for some of
these differences, giving rise to
“genetic polymorphisms”
The first examples of drugs found to be subject to genetic
polymorphisms were the muscle relaxant
succinylcholine,
the anti-tuberculosis drug
isoniazid,
and the anticoagulant
warfarin
A true genetic (blank) is defined as the occurrence of
a variant allele of a gene at a population frequency of ≥ 1%,
resulting in altered expression or functional activity of the gene
product, or both.
polymorphism
Well-defined and clinically relevant genetic polymorphisms in
both phase I and phase II drug-metabolizing enzymes exist
that result in altered efficacy of drug therapy or
adverse drug
reactions (ADRs ).
