BBB Pharm Flashcards
What is the purpose of the BBB?
to prevent free-passage of molecules from the periphery to the CNS, and vice-versa to prevent neurotransmitters from leaking
What are some things that can contribute to BBB breakdown?
diease or aging
temporarily post MI, following a marked rise in BP, or after injection of hypertonic solutions
What forms the BBB?
Formed by endothelial cells at the levels of the cerebral capillaries. These endothelial cells interact with perivascular elements such as basal lamina, astrocyte feet-processes, and pericytes to form a BBB
These cerebral endothelial cells are unique in that they form complex tight junctions produced by the interaction of several transmembrane proteins that effectively seal the paracellular pathway. There are also adherens junctions, which stabilize cell-cell interfaces
What others things contribute to the BBB?
the presence of intracellular and extracellular enzymes such as amonoamine oxidase (MAO), y-glutamyl transpeptidase (y-GT), alk phosphatase, peptidase, P450s, and others maintain metabolic activity at the BBB interface
BBB under normal and disrupted (e.g. aging) conditions. Normally, the presence of tight junctions measn that passage of drugs must occur trans-cellularly.
Whereas water, CO2, O2, and lipid-soluble free forms of steroid hormones penetrate the brain with ease, other substances like drugs do not.
These are active processes but know that polymorphisms can affect their efficiacy
_________ is important for a drug to gain access to the CNS
lipophilicity (measured experimentally by an octanol/water partition coefficient which compares drug equilibration in the octanol (lipid) phase vs the water (aqueous) phase
more lipid= easier access in CNS
glucose is very poorly absorbed so it needs active transport
Things that get into the brain easy:
diazepam
nicotine
heroin and ethanol
phenytoin
What parameters allow a drug to enter the CNS?
lipophilic
free-drug (not protein bound as these bear a charge, which is prohibited)
Non-ionized
In general, all ______ and _______ are prevented from accessing the CNS
proteins and polypeptides
What are some CNS P-gp inhibitors?
Amiodarone, cyclosporin,
nifedipine, verapamil
quinidine
protein binding= bad
nasal passage can bypass the BBB
pegylated is actually taken up into CNS less avidly
