Blood brain barrier: (BBB)
  • A physical / functional barrier which does not permit ionized and non lipid soluble drugs to pass through into the Central Nervous System
  • It is mainly formed by the endothelial cells of the CNS blood vessels. Its purpose is to protect the brain from the chemical environment of the rest of the body due to the delicate balance between excitation and inhibition maintained within the CNS.
  • The brain capillaries do not contain fenestrations (holes). There are more tight junctions in brain capillaries decreasing the rate of diffusion through interstitial spaces. Glial cells ensheath the brain capillaries providing a second set of cell membranes which must be traversed as well as a second intracellular compartment where cellular metabolic processes can transform entering substances
  • Chemical or enzymatic barrier - MonoAmineOxidase, cholinesterase - This barrier prevents 5 HT, catecholamines, ACh from entry into CNS
  • Carrier mediated transport – to facilitate exit of drugs
  • Highly lipophilic drugs enter easily because they cross membranes. (Fig. 18) Unionized forms of drugs enter more easily than ionized forms. Penicillin, streptomycin, gentamicin – do not cross the BBB
  • Chloramphenicol - can cross the BBB

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