Extensive summary of the course molecular therapy including pictures, notes on important topics, and possible exam questions mentioned during the lectures . Chapter 15 and 16 from the book Molecular cell biology, Lodish 8th edition are incorporated into the summary. It also includes chapter 4 from ...
2.0 Week 2 ..................................................................................................................................................... 16
2.1 Lecture Drug delivery part 1 ....................................................................................................................... 16
2.2 Drug targeting and delivery part 2 ............................................................................................................. 25
2.3 Lecture Drug development ......................................................................................................................... 35
,1.0 Week 1:
Objectives:
- Introduction to the field of personalized healthcare, molecular biomarkers and system
biology, whilst stressing the importance of improving the quality of translational research.
- To refresh knowledge obtained in BSc curriculum on pharmacology and pharmacokinetics.
- To apply the basics of pharmacology/pharmacokinetics to comment on the significance of
membrane transporters in drug disposition and bioavailability.
Objectives of the workgroup:
- Evaluate dosage requirements using the HDK simulation program.
- To indicate which drug and patient characteristics may be important for the
pharmacokinetic behavior of a certain drug in the body.
- Calculate simple clinical pharmacokinetic parameters from the cases given, and use these
parameters to design and, where necessary, adjust dosing regimens.
1.1 Introductory lecture
Therapeutic options
Interventions using
- Chemical approaches -> pharmacology
- Biological approaches -> medical biotechnology
- Physical approaches -> surgery/ radiology
1.2 Lecture personalized healthcare
Exponential developments in omics technologies
Genomics
- Testing 3.000.000.000 DNA bases in 1 assay
Proteomics, glycomics, metabalomics
- Testing of 10.000- 50.000 proteins and metabolites in 1 assay
On personalized diagnosis:
- Technology innovation is driving impact in personalized healthcare.
- Combination of genetic and metabolic screening is a strong approach towards
identifying mechanism of disease.
On personalized medicine:
- Impressive effects of uridine therapy
- Increase quality of life for patient and family
- Frequent issues regarding expensive medication versus cheap supplements
,Technology innovation is driving impact in personalized healthcare
Analysis of dynamic biomarkers is key in monitoring minimal residual disease to
Mass spectrometry has added value and good potential
Collaboration between clinic, lab specialists, proteomics labs + between academics and
industry is needed and works
- Analytical development
- Clinical validation
Diagnosis of (new) disease mechanisms
- Deep learning/ AI
- Integrated diagnostics
- System biology
Advantages digital biomarkers
- Continuous monitoring versus 1 snapshot observation.
- Real world data versus data from clinically controlled circumstances.
- More comprehensive and rich data sets.
- Truly personalized.
- Strong potential in molecular + clinical + digital + environmental biomarkers for
optimal insight in complex biological systems.
- Better basis to drive personalized health(care).
- Better support for phase 1,2,3,4 clinical trials.
Personalized health(care) model
Primary prevention: Avoiding that you
get ill.
Secondary prevention: When you have an
increased risk for instance genetics or
diabetes, it is not so bad that you develop
complications.
Tertiary prevention: You are seriously ill
and you want to avoid that you get
complications, for instance you have
cancer and you want to avoid
progression.
, 3 translation innovation gaps
1. Research to research
2. Research to clinic
3. Research to society
1.3 Tutorial Pharmacology and drug disposition
Pharmacology is the science that is concerned with the uses, effects, and modes of action of
chemicals on the function of living system.
Pharmacology can be studied at the molecule, cell, organ, organism, family or population
level.
Pharmacokinetics: what the patient does with the drugs (e.g. if a drug is taken up and
transported from the intestine into the blood and then it is taken up by cells and removed
again by urine, the body moves the drug through a certain pathway).
Pharmacodynamics: what the drug does with the patient (what it does to our body for e.g.
when it binds to a target and changes the receptors or the reaction of the receptor).
Together this is called the rational pharmacotherapy.
Note: You must be able to answer a question to determine what response it is.
Rational pharmacotherapy is ‘mechanism-based pharmacotherapy’
‘evidence-based pharmacotherapy’: it does not matter how it works, as long as it works
Pharmacological phases in pharmacotherapy
Agonist: stimulates a receptor
Antagonist: blocks the receptor
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