INTRO

bbb transport mechanisms

passive, facilitated, active, carrier mediated, endocytosis/transcytosis, efflux transport

Passive Diffusion

Movement down concentration gradient without energy; favors lipid soluble drugs (benzodiazepines, antidepressants, antipsychotics, anesthetics); primary route for most CNS drugs

Facilitated Diffusion

Carrier mediated transport without energy expenditure; allows essential nutrients (glucose via GLUT1) to enter CNS

Active Transport

Carrier mediated transport requiring ATP; moves amino acids, ions, certain metabolites; maintains CNS homeostasis and selective drug entry

Carrier Mediated Transport

Specific transport proteins facilitate passage across BBB; explains why levodopa crosses BBB but dopamine cannot; also transports amino acids

Endocytosis/Transcytosis

Vesicular transport of large molecules across endothelial cells; important for biologics and endogenous proteins (insulin, transferrin, peptides)

Efflux Transport Systems

Active removal of substances from CNS back into circulation; P glycoprotein substrates, certain antiepileptics and antiretrovirals; may reduce CNS drug concentrations and therapeutic effectiveness

Acetylcholine

Neurotransmitter located in cerebral cortex, basal ganglia, limbic/thalamic regions, and spinal interneurons; general effect is EXCITATION

Norepinephrine

Neurotransmitter from neurons originating in brainstem and hypothalamus projecting throughout brain; general effect is INHIBITION

Dopamine

Neurotransmitter located in basal ganglia and limbic system; general effect is INHIBITION

Serotonin

Neurotransmitter from neurons originating in brainstem projecting upward to hypothalamus and downward to spinal cord; general effect is INHIBITION

GABA (gamma aminobutyric acid)

Neurotransmitter found in interneurons throughout spinal cord, cerebellum, basal ganglia, and cerebral cortex; general effect is INHIBITION

Glycine

Neurotransmitter found in interneurons in spinal cord and brainstem; general effect is INHIBITION

Glutamate and Aspartate

Neurotransmitters found in interneurons throughout brain and spinal cord; general effect is EXCITATION

Substance P

Neurotransmitter in pathways in spinal cord and brain that mediate painful stimuli; general effect is EXCITATION

Enkephalins

Neurotransmitters in pain suppression pathways in spinal cord and brain; general effect is EXCITATION