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- Introduction
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1. Editor's foreword
- Prof. Ann Daly
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2. Introduction to drug metabolism enzymes
- Dr. Dennis Smith
- General factors affecting drug metabolism
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3. General factors affecting drug metabolism: effect of physiological factors and disease 1
- Prof. Edward T. Morgan
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4. General factors affecting drug metabolism: effect of physiological factors and disease 2
- Prof. Edward T. Morgan
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5. Drug metabolism in liver disease
- Dr. Nathalie Zgheib
- Prof. Robert Branch
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7. Prediction of pathways of drug metabolism
- Dr. Maurice Dickins
- Phase I metabolizing enzymes: cytochrome P450s
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8. Cytochrome P450 1 family: the roles of 1A1, 1A2 and 1B1 in drug metabolism
- Prof. F. Peter Guengerich
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9. CYP2 family
- Prof. Ann Daly
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10. Why study the cytochrome P4503A (CYP3A) family?
- Dr. Erin Schuetz
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11. Pharmacogenomics: an update
- Prof. Magnus Ingelman-Sundberg
- Phase I metabolizing enzymes: non-cytochrome P450s
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12. Non-P450 oxidative metabolism: characteristics and drug substrates
- Dr. Christine Beedham
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13. UDP-glucuronosyltransferases
- Prof. Abby Collier
- Phase II metabolizing enzymes: conjugating enzymes
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14. Glutathione transferases
- Prof. Ralf Morgenstern
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15. Arylamine N-acetyltransferases 1
- Prof. Edith Sim
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16. Arylamine N-acetyltransferases 2
- Prof. Edith Sim
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17. Arylamine N-acetyltransferases 3
- Prof. Edith Sim
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18. Methyltransferases
- Prof. Richard Weinshilboum
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19. Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Clinical aspects
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20. Clinical significance of enzyme induction and inhibition
- Prof. Kim Brøsen
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21. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism
- Prof. Julia Stingl (formerly Kirchheiner)
- Latest Updates in the Field
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22. Mammalian flavin-containing monooxygenases
- Prof. Allan Rettie
- Archived Lectures *These may not cover the latest advances in the field
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23. Glucuronidation and the UDP - glucuronosyltransferases
- Prof. Peter Mackenzie
- Prof. John Miners
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25. Catalytic cycle of cytochrome P450s
- Prof. Gordon Roberts
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26. Drug metabolism and liver disease
- Prof. Robert Branch
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27. Crystal structures of drug-metabolizing P450 monooxygenases
- Prof. Eric Johnson
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28. Sulfation and human cytosolic sulfotransferases
- Prof. Charles Falany
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29. Laboratory methods for the in vitro study of drug metabolism
- Dr. Charles Crespi
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30. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism: psychopharmacology and pain
- Prof. Julia Stingl (formerly Kirchheiner)
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32. Pharmacogenomics
- Prof. Magnus Ingelman-Sundberg
Printable Handouts
Navigable Slide Index
- Drug metabolism in liver disease
- Questions
- Clinical relevance
- Outline
- Hepatic drug elimination
- Hepatic drug clearance
- Hepatic elimination - high clearance
- Hepatic elimination - low clearance
- Outline
- HAC - basis for liver disease
- Liver blood flow
- Presystemic "first pass" effect
- Metabolism of mephenytoin
- S-mephenytoin in cirrhosis
- The effect of liver disease
- Outline
- Antipyrine - normal/liver disease
- Outline
- Child-pugh score
- The child-pugh score - limitations
- Drug metabolism - chronic liver dis.
- Outline
- High intrinsic clear. - comparison
- Drug disposition in liver disease
- Intact hepatocyte
- Intact nephron
- Intact nephron hypothesis
- Intact hepatocyte hypothesis
- Intact nephron/hepatocyte hypoth.
- Drug clearance - renal/hepatic dis.
- Differential effects of liver disease
- Infl. of liver dis. on drug oxid./conj.
- Infl. of liver dis. on morphine clear.
- Probe drugs
- CYPs & severity of chronic liver dis.
- CYPs regulation in chronic liver dis.
- Liver transplantation - CYP activity
- Cholestatic dis. - CYP proteins
- Effect of liver dis. on drug clearance
- Future application of pharmaco.
- Outline
- Gene expression & protein function
- Drug-gene-environment model
- Summary
- Acknowledgements
Topics Covered
- Liver disease and drug clearance
- Mechanistic explanations
- Intact hepatocyte hypothesis
- Sick cell theory
- Sequential progressive model of liver disease
- Viral liver disease
- Alcoholic liver disease
- Hepatocellular carcinoma
- Liver transplantation
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Branch, R. (2007, October 1). Drug metabolism and liver disease [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved May 13, 2025, from https://doi.org/10.69645/TSII9764.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Robert Branch has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Drug metabolism and liver disease
A selection of talks on Metabolism & Nutrition
Transcript
Please wait while the transcript is being prepared...
0:00
From the outside, I would like
to acknowledge my co-workers
at my institution who are involved
with me in the study of drug
metabolism in liver disease.
And if there is any
interest, there is
contact information
in terms of my email
and also in terms of a website.
And we move to the next slide.
0:25
During this presentation
I would like
to address a number of questions.
The first question is, do
diseases of different etiology
alter the metabolism
of different drugs
being given to a variable extent?
In other words, is there selectivity
of the effect of the disease
process based on the
underlying etiology?
Second question that
I'd like to address,
is there a differential
effect of liver disease
on different routes of metabolism?
This is the selectivity
with respect to the drug
metabolizing enzymes
or active processes
involved in drug elimination.
Thirdly, does the severity of the
underlying liver disease influence
the magnitude of the change?
Is there a sensitivity
of these processes
to the presence of liver disease?
And then finally, are
the changes sufficiently
large to justify dosage
modification and therefore
be of clinical relevance?
And we move to the next slide.
1:33
From the perspective
of clinical relevance,
I think it's also important
to address the questions,
can the extent of
change be anticipated
in an individual patient when
faced with a therapeutic decision?
And secondly, can
these changes be used,
in fact, to assess hepatic
function as discrete entities?
Thirdly, can we use this
information in predictive rules
if we are faced with giving
drugs that are just being
introduced to the
market, where we know
the disposition in normal people?
Can we anticipate when
there will be change
in the presence of liver disease?
And we move to the next slide.