Many drugs, insecticides and carcinogens interact with DNA and increase the synthesis of microsomal enzyme protein, specially cytochrome P450 and glucuronyl transferase. As a result rate of metabolism of inducing drug itself and/or other drugs is increased.
MICROSOMAL ENZYME INDUCTION
Many drugs,
insecticides and carcinogens interact with DNA and increase the synthesis of
microsomal enzyme protein, specially cytochrome P450 and glucuronyl
transferase. As a result rate of metabolism of inducing drug itself and/or
other drugs is increased.
Different inducers are
relatively selective for certain cytochrome P450 enzyme families, e.g.:
Anticonvulsants including phenobarbitone,
rifampin, glucocorticoids induce CYP3A isoenzymes.
Phenobarbitone also induces CYP2B1 and
rifampin also induces CYP2D6.
Isoniazid and chronic alcohol consumption
induce CYP2E1.
Polycyclic hydrocarbons like 3methylcholanthrene
and benzopyrene found in cigarette smoke, charcoalbroiled meat and industrial
pollutants induce CYP1A isoenzymes.
Other important enzyme inducers are: chloral
hydrate, phenylbutazone, griseofulvin, DDT.
Since different CYP
isoenzymes are involved in the metabolism of different drugs, every inducer
increases biotransformation of certain drugs but not that of others. However,
phenobarbitone like inducers of CYP3A and CYP2D6 affect the metabolism of a
large number of drugs, because these isoenzymes act on many drugs. On the other
hand induction by polycyclic hydrocarbons is limited to few drugs (like
theophylline, phenacetin) because CYP1A isoenzyme metabolizes only few drugs.
Induction involves
microsomal enzymes in liver as well as other organs and increases the rate of
metabolism by 2–4 fold. Induction takes 4–14 days to reach its peak and is maintained
till the inducing agent is being given. Thereafter the enzymes return to their
original value over 1–3 weeks.
Related Topics
TH 2019 - 2023 pharmacy180.com; Developed by Therithal info.