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Printable Handouts
Navigable Slide Index
- Introduction
- Part II: Internal medicine
- More than 30 years of pharmacogenetic research
- Implementing pharmacogenetics in drug therapy
- Genetic variability in pharmacokinetics
- Polymorphisms affecting drug metabolism
- PGx influencing ADE and outcome: e.g. TPMT
- Azathioprine-induced fatal myelosuppression
- TPMT-activity in humans
- TPMT genetic polymorphisms
- Dose adjustments for thiopurines by phenotype
- Polymorphic drug-metabolizing enzymes
- Cytochrome P450 enzyme 2C9
- The CYP2C genetic locus
- CYP2C9 substrates
- Panel studies in healthy volunteers
- Effect of CYP2C9 polymorphism: clinical examples
- CYP2C9 and glyburide clearance
- Mean clearance of sulfonylureas and CYP2C9*3
- Oral anticoagulants
- Warfarin dose requirements and CYP2C9
- Warfarin dosing based on CYP2C9 and VKORC1
- Differences in pharmacokinetics
- CYP2C9: S- & R-acenocoumarol concentrations
- Phenprocoumon pharmacokinetics and CYP2C9
- Maintenance dose in relation to CYP2C9 genotype
- Bleeding complications risk: CYP2C9*2/*3 alleles
- CYP2C9 and oral anticoagulation therapy
- Risk and benefit of being a poor metabolizer
- Cytochrome P450 2C19 (CYP2C19)
- Substrates of CYP2C19
- Metabolism of PPIs
- CYP2C19 activity & concentration of PPIs (in vitro)
- CYP2C19 and PPI pharmacokinetics in vivo
- Ulcer/H. pylori infection cure rates & CYP2C19
- Guidelines for CYP2C19 dosing
- Cytochrome P450 enzyme 2D6
- CYP2D6 and metoprolol
- Metoprolol plasma concentrations and CYP2D6
- Exercise-induced heart rate after metoprolol
- CYP2D6 and metoprolol clinical utility
- CYP2D6 polymorphism in metoprolol therapy
- Genetics-based dose adjustments
- Pharmacogenetics-based dose adjustments
- Limitations of genetics-based dose adjustments
- Clinical validation of dosage adjustments
- Limitations of genetics-based dose adjustments
Topics Covered
- Genetic variability in pharmacokinetics
- Polymorphic drug-metabolizing enzymes (Cytochrome P450)
- Implementation of pharmacogenetics in drug therapy
- Risks and benefits of being a poor metabolizer
- Limitations of genetics-based dose adjustments
- Future clinical study directions in pharmacogenetics
Links
Series:
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Therapeutic Areas:
Talk Citation
Stingl (formerly Kirchheiner), J. (2016, July 31). Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/DATO5276.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Julia Stingl (formerly Kirchheiner) has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism
A selection of talks on Pharmaceutical Sciences
Transcript
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0:00
My name is Julia Stingl.
Former name was Kirchheiner.
I am a Professor of Clinical Pharmacology at the University Bonn.
And I will talk about clinical importance
of pharmacogenetic polymorphisms affecting drug metabolism.
0:17
Part 2, Internal Medicine.
0:21
We have now more than 30 years of pharmacogenetic research.
But still we may ask ourselves, do we really use it?
Where is the translation into the clinics?
And these are the questions that are most urgent.
What is the patient's benefit?
And how could we increase drug safety with the use of pharmacogenetics?
Or has our drug therapy been improved by genetic diagnostics?
So to come closer to an answer of these questions,
I would like to talk about pharmacogenetics
in internal medicine and, first, give you a short introduction
to the pharmacogenetics variants impacting drug therapy in internal medicine.
1:17
There are genetic polymorphisms affecting both sides of drug action,
pharmacokinetics or pharmacodynamics.
On the pharmacokinetics side, mostly drug metabolism and elimination
is affected, and this can be translated into clinical practice
by giving, for example, dose adjustments.
This can affect the dose amount or the dosing interval.
Whereas on the pharmacodynamic side, genetic variants in drug targets,
they may be translated into the clinics,
for example with companion diagnostic molecular diagnostics.
It may improve therapeutic strategies.
Or it may lead to treatment algorithms.
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