Summary: Molecular Therapy
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1 Pharmacodynamics & -kinetics
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Which membrane transporters are there?
ABC and SLC transporters -
Explain the ABC membrane transporters
ABC = ATP binding casette transporters --> efflux (out of the cell)
There are 7 families of ABC (A-G), and they have a membrane and a cytosolic part
G is a half-transporter --> 1 transmembrane and 1 nucleotide-binding domain
Others (A-F) are full transporters (2 domains each) -
What is the function of ABC transporters?
Intestine --> inhibitors could increase the bioavailability
Brain --> maintaining the blood-brain barrier (BBB)
Liver/kidney --> detoxification -
What is the function of P-glycoprotein (P-gp; ABCB1)?
ATP hydrolysis in 2 stept (since 2x ATP need hydrolysis) for chemotherapeutic and antibiotics -
What are 2 ways of measuring transporter activity?
1. Fluorescence + inhibitor
2. ATP assay (in vesicles) --> more controlled -
What are phase II reactions?
More hydrophylic/detoxification (conjugation) --> combine with glycoronide/sulphase/methyl/glutathione --> differ between species -
How is oxidation (most important phase II reaction) catalyzed?
By cytochrome P450 (CYP) enzymes --> the iron in heme of CYP is used for transfer of free electrons -
Why is it hard to access the mitochondria?
It is a double membrane- Outer membrane = permeable for all compounds < 50.000 Daltons (size exlusion)
- Inner membrane = impermeable for all hydrophilic compounts
- Crossing both membranes = lipophilic + charged (matrix is - charged because of the pumped-out protons by the oxphos)
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What are the main components of nanomedicine?
- surface modification
- targeting ligand
- example polymer = PLGA --> will dissolve in the body into natural metabolites (since the drug can't be excreted via the kidney (urine)). -
Name the different drug delivery types
Liposomes, proteins, antibodie conjugates
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