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Printable Handouts
Navigable Slide Index
- Introduction
- DMEs in inflammation and infection
- Inflammation
- Detoxification of pentobarbital sodium (Nembutal)
- Hepatic cytochrome P-450-dependent systems
- Theophylline pharmacokinetics during infection
- LPS model of inflammation & bacterial sepsis
- DME gene expression and LPS in rat/mouse liver
- Endotoxin inhibits P450-mediated drug metabolism
- Regulation of P450s in inflammation/infection
- Infectious/inflammatory stimuli & drug metabolism
- LPS vs. local inflammatory reaction
- In vivo role of cytokines: knockout mice (1)
- In vivo role of cytokines: knockout mice (2)
- Transcriptional & post-transcriptional mechanisms
- Mechanisms of transcriptional downregulation
- Inducible vs. constitutive expression suppression
- P450 & NO activity in inflammation
- Role of physiological NO in CYP suppression
- Infectious/inflammatory stimuli & drugs (humans)
- Inflammation & CYP3A4 in cancer patients
- Disease-dependent drug-drug interaction
- Thanks
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 2 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 5, 2024, from https://doi.org/10.69645/WCOR3227.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 2
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:03
We will now move on to the topic of drug metabolism in inflammatory disease states which,
as we will see, is applicable to a wide variety of diseases in humans.
0:16
The symptoms of inflammation were described more than two centuries ago by Celsus,
tumor, rubor, calor and dolour,
or, swelling, redness, heat and pain.
These symptoms are the result of
a local or systemic response to infection or injury designed to
eliminate or control invading pathogens or to
allow tissue recovery and repair following injury.
But an exaggerated, inappropriate or chronic inflammatory response
can be deleterious and many human diseases have an inflammatory component.
Local inflammation is characterized by vasodilation,
neutrophil recruitment and a cascade of
pro-inflammatory cytokine and they cause node release.
The triggering events of an inflammatory response are many and varied.
But, in the case of infection usually result from the activation by microbial products of
pattern recognition receptors such as
Toll-like receptors on cells of the innate or adaptive immune systems.
Physical or thermally-derived injuries initiate inflammation by activating
mast cells in the tissues which release histamine and tumor necrosis factor alpha,
again initiating the inflammatory cascade.
1:30
Perhaps, the first indication that inflammation could affect
drug metabolism was this publication from 1953 by Samaras and Dietz.
Analogous to the experiments we discussed earlier,
these investigators were studying the metabolism of pentobarbital in
rats by measuring the time the animals slept after a single dose of the barbiturate.
They injected the animals with trypan blue,
an activator of the immune system or saline.
They then injected pentobarbital and measured the sleeping time.
Animals treated with trypan blue slept longer than the control animals
indicating that the metabolism clearance of pentobarbital had been impaired.
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