Transporters Flashcards
What is access in terms of the mechanisms of drug variability?
Access is how the drug: gets to the brain, gets to the correct part of the brain, and having the concentration-dependent effects
What is genome variability in terms of the mechanisms of drug variability?
Polymorphisms that lead to alterations in drug metabolism, drug targets, or drug transporters. Some people express it (transporters) more, naturally
What is “disease-related mechanisms” in terms of the mechanisms of drug variability?
Disease progression despite treatment, structural brain alterations and/or network changes, alterations in drug target(s). or alterations in drug uptake into the brain
What is “drug-related mechanisms” in terms of the mechanisms of drug variability?
(Drug) tolerance, induction of drug-metabolizing enzymes or drug transporters, and ineffective mechanisms of drug action (change in receptor number, density)
Define tolerance
Increasing the dosage of the drug in order to get the same effect. It is not the same as addiction
What maintains the Blood-Brain Barrier (BBB)?
The capillary network supplying blood to the brain
True or False: The capillary endothelial cells in the brain are the same as those found in the peripheral tissues
False: The BBB is special and different in many ways
How do tight junctions provide an effective barrier against the paracellular movement of the molecules?
The tight junctions have high electrical resistance since they are spaces with electrical charge, giving high levels of resistance
Where is there good transcellular movement?
Peripheral endothelial cells
True or False: There is no good transcellular movement of molecules in brain endothelial cells
True: Because of gap junctions
What do astrocytes do?
The ends of the astrocytes contact with the brain capillaries, which essentially separate the capillaries from the neurons
The BBB is both _________ and a delicately _________
physical ; balanced set of transport mechanisms
What type of molecules is able to penetrate through the barrier relatively easily?
Lipid-soluble molecules
Why are lipid-soluble molecules able to penetrate through the barrier more easily?
They are able to use the lipid membranes of the cells, as compared to water-soluble molecules (i.e.: ions) that need specialized carrier-mediated mechanisms
Which type of molecules are drugs (for addiction) usually are made of?
Lipid-soluble molecules, because they can easily penetrate through the barrier relatively easily. They are usually very small but the production of these drugs can alter the size
What are the five main points on why the BBB peripheral capillaries are different?
- compounds DIFFUSE across the endothelium
- compounds can use the PARACELLULAR PATHWAY (intercellular pore)
- compounds can use FENESTRATIONS
- compounds can use VESICLES
- compounds can use FACILITATED DIFFUSION and ACTIVE TRANSPORTERS (influx and efflux)
What happens to the cells during fenestrations?
The cell dies, which creates a gap. While the replacement is getting built, there is more opportunity for drugs* to get to the epithelia
What type of compounds can diffuse through the brain capillaries?
Fat-soluble compounds
