Summary of the lectures about pharmacokinetics and -dynamics. Plus further reading and E-learning summary
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Course
Molecular Therapy (NWIBM0782023KW1V)
Institution
Radboud Universiteit Nijmegen (RU)
This English written document contains the first lectures of molecular therapy about pharmacotherapy. It also contains further reading and E-learning. And it contains many pictures.
Molecular therapy
Inhoudsopgave
Week 1 Pharmacodynamics and pharmacokinetics................................................................................ 4
LE Personalized healthcare (Alain van Gool) ....................................................................................... 4
LE Pharmacology and Pharmacokinetics (Jan Koenderink) ................................................................. 5
Further reading interactive clinical pharmacology (catch-up on toxicology course BA) .................... 8
LE Drug transporters & metabolism .................................................................................................. 14
Transporters .................................................................................................................................. 14
LE Biotransformation......................................................................................................................... 16
E-learning Biotransformation of Xenobiotics .................................................................................... 18
General principles.......................................................................................................................... 18
Phase I reactions............................................................................................................................ 19
Phase II reactions........................................................................................................................... 21
E-learning transporters ..................................................................................................................... 24
Introduction ................................................................................................................................... 24
Week 2 Drug delivery & development .................................................................................................. 29
LE Drug Targeting and Delivery (Part I) (Rik Oude Egberink) ............................................................ 29
LE Drug Targeting and Delivery (Part II) ............................................................................................ 34
Antibody drug conjugates (ADCs) = antibody with cytotoxic conjugate ....................................... 34
Factors that influence tissue targeting: ......................................................................................... 35
Targeted Cytokines ........................................................................................................................ 35
Targeting:....................................................................................................................................... 35
Cellular molecule import: .............................................................................................................. 35
Oligonucleotides ............................................................................................................................ 36
Cellular uptake............................................................................................................................... 37
Oligonucleotide-based therapeutics ............................................................................................. 37
LE Drug Development ........................................................................................................................ 38
History of therapeutics .................................................................................................................. 38
Current small molecule drug development pipeline: different stage & assays ............................ 38
Small molecule drugs vs biologics (protein therapeutics) ............................................................. 40
Week 3 Genetic therapy for retinal disease .......................................................................................... 43
LE Genetic Therapy for inherited Retinal Disease ............................................................................. 43
LE Gene Augmentation Therapy........................................................................................................ 44
LE Splicing modulation / RNA therapy .............................................................................................. 45
, LCA ................................................................................................................................................. 45
Stargardt disease ........................................................................................................................... 46
LE Genome editing therapy ............................................................................................................... 47
Types of genome editing methods ................................................................................................ 47
Partly removing intron .................................................................................................................. 48
Base editing ................................................................................................................................... 48
PRIME editing ................................................................................................................................ 48
RNA editing .................................................................................................................................... 48
Week 4 Therapy of renal tubulopathies (jojanneke huck phd, neurophysiologist department of
medical biosciences RUMC) .................................................................................................................. 49
Renal Physiology................................................................................................................................ 49
Current studies and therapy of renal tubulopathies ......................................................................... 50
How to test the 3 functional defects in channels/transporters: ................................................... 50
Proximal tubule ............................................................................................................................. 51
Thick ascending lis of Henle (TAL) ................................................................................................. 52
Distal convoluted tubule ............................................................................................................... 52
Collecting duct (principle cell) ....................................................................................................... 53
Collecting duct (a-intercalated cell) .............................................................................................. 53
Drug-induced renal pathologies ........................................................................................................ 54
Classification Drug-induced renal failure: ..................................................................................... 54
Diagnosis of acute renal failure: .................................................................................................... 55
Week 5 Modern cancer therapies ......................................................................................................... 56
Tutorial Lecture Receptor Tyrosine Kinases ...................................................................................... 56
Cytokine receptors ........................................................................................................................ 56
Receptor tyrosine kinases (RTKs) .................................................................................................. 57
Cancer therapeutics .......................................................................................................................... 62
Molecular mechanisms of cancer.................................................................................................. 62
Common therapeutics ................................................................................................................... 62
Novel therapies targeting signaling molecules ............................................................................. 63
Lung cancer mechanisms/treatment ............................................................................................ 65
Modern cancer therapeutics Clinical aspects in lung cancer treatment........................................... 65
Week 6 Modern pain management ...................................................................................................... 67
LE GPCRs mediated signaling ............................................................................................................ 67
Signaling molecules ....................................................................................................................... 67
Intracellular receptors ................................................................................................................... 67
Cell-surface ion channels............................................................................................................... 68
, Cell-surface GPCRs......................................................................................................................... 68
Activation mechanism of GPCRs ................................................................................................... 68
Heterotrimeric G proteins ............................................................................................................. 69
Different effector systems............................................................................................................. 70
Common concepts in signaling ...................................................................................................... 72
De-activation ................................................................................................................................. 72
Crosstalk ........................................................................................................................................ 73
LE GPCRs and pain management....................................................................................................... 73
Opioid receptors ............................................................................................................................ 78
GPCR oligomerization ........................................................................ Error! Bookmark not defined.
Biased agonism .................................................................................. Error! Bookmark not defined.
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