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Printable Handouts
Navigable Slide Index
- Introduction
- Physiological factors in drug metabolism
- Physiological regulation of drug metabolism
- Genetics, environment and drug metabolism
- Challenges in studying human drug metabolism
- Effect of gender on drug metabolism
- Sex and barbiturate metabolism
- Sex-dependent liver drug & steroid metabolism (1)
- Sex-dependent liver drug & steroid metabolism (2)
- Sex-biased drug-metabolizing enzymes (DMEs)
- Gonadal & pituitary control of P450
- Gender differences in human drug metabolism
- Gender differences in human P450
- Growth hormone regulation of drug metabolism (1)
- Growth hormone regulation of drug metabolism (2)
- Sex-biased hepatic gene expression mechanisms
- Regulation of sex-specific liver gene expression
- Ontogenesis of CYP2C expression
- Drug metabolism in development
- Studying DME development
- DME expression patterns during development
- Variability of CYP expression during development
- 3 classes of drug metabolizers
- Qualitative metabolism changes in development
- Transcriptional control of DME ontogenesis
- Drug metabolism and aging
- Regulation of drug metabolism in pregnancy
- Drug metabolism in pregnancy (considerations)
- Summary of studies on drug clearance/PK
- Hormonal induction of enzymes in cell culture
- Regulation of human CYP2D6 in transgenic mice
Topics Covered
- Effect of physiological and pathophysiological conditions on drug-metabolizing enzymes (DMEs)
- Role of growth hormones and transcription factors in sex-dependent expression
- Drug clearance and age
- Developmental regulation
- Impact of infection and inflammatory disease on DME expression
- Clinical consequences
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Talk Citation
Morgan, E.T. (2017, July 31). General factors affecting drug metabolism: effect of physiological factors and disease 1 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 10, 2024, from https://doi.org/10.69645/JZUA4120.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Edward T. Morgan, Grants/Research Support (Principle Investigator): One research grant from the National Institutes of Health
General factors affecting drug metabolism: effect of physiological factors and disease 1
A selection of talks on Pharmaceutical Sciences
Transcript
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0:00
Drug-metabolizing enzymes are highly regulated by chemicals in the organisms environment.
In this presentation, we'll discuss
several physiological and pathophysiological factors
that affect drug metabolism in distinct populations.
0:17
This slide lists some of the most important factors.
For the purposes of this presentation,
I'll focus on the first four of these important regulatory mechanisms:
gender, pregnancy, development and aging,
and inflammation and infection.
0:34
In most cases, the reason for this regulation is not known,
but may be related to the enzymes abilities to
catabolize physiological substrates, such as steroids,
bile acids and thyroid hormones or to synthesize bioactive metabolites,
such as hydroxylated and epoxidized carcinoids.
Regardless of the reasons,
the potential consequences for human and animal drug therapy
for susceptibility to toxicants and for drug development are clear.
1:05
As a general principle,
it's important to appreciate that none of these physiological factors
affecting drug metabolism operate in isolation.
Ultimately, the expression of an enzyme, and therefore,
the responses to drugs that it metabolizes will be an integration of
all the non-genetic factors that can control
the enzyme impinged upon the individual's genetic constitution.
So a 50% decrease in the metabolism of a given drug due to, for example,
a viral infection might not have a significant effect
on most people's response to a drug that has a good safety margin.
However, the same infection could have an adverse effect in
someone who has a predisposition to metabolize that drug early.
For example, someone who is heterozygous for
an inactivating mutation in a cytochrome P450 enzyme.
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