Pharm: CNS properites Block 3
Terms
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- Describe the capillary endothelium of the brain.
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-not support vesicular transport
-histamine, 5HT, and NE do not inc. its permeability
-no contractile proteins
-enzymes regulating transport of AA, amines and hexoses - Where else is capillary endothelium of the brain found?
- pia and arachnoid, retina
- How many membranes must CNS drugs cross?
- 2 lipid membranes: the basement membrane from the glial cells and the endothelium layer that is connected by tight junctions
- What is the choroid plexus? type of cells?
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secretes the CSF and lines the ventricles.
CILIATED CUBOIDAL EPITHELIUM - Areas with fenestrated epithelial linings of the CNS? (i.e. no BBB)
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pineal gland
pituitary gland
median eminence
area postrema
wall of the optic recess (suprachaismatic and supraoptic nuclei of the hypothalamus-control bio rhythms and pit. control) - Areas with fenestrated epithelial linings of the PNS?
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*olfactory receptor cells
*terminal endings of *peripheral nerves (site entry for virus)
*sensory ganglia of SC and CN
*part of the optic nerve (P scleral foramen)
*Dura - What impairs the BBB?
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*infarction
*heavy metals (Pb, Hg, Mn)
*degenerative, inflammatory and autoimmune dz
*HTN (>200)
*hypercapnia
*convulsions (electroshock, hypoglycemia) - Factors that facilitate diffusion rate across BBB?
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*lipid/water partition coefficeint
*Carrier-mediated facilitated diffusion - Factors that impede diffusion rate across BBB?
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*level of ionization of the drug in plasma (ionic not cross)
*binding to plasma proteins
*Hydrogen bonding with H20
*enzymatic degradation within endothelial cells - General description of CNS drugs.
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*high lipid solubility
*large Vd,extensively redistributed
*duration of action << half-life
*Cleared by hepatic metabolism
*no diffusion barrier between CSF and ECF, intrathecal admin - Only CNS drug that is not highly lipid soluble?
- L-dopa
- Which class of drugs produces a life threatening withdrawal?
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Sedative hypnotics:
Benzos, barbituates, and alcohol - Name the catecholamines
- NE, epinephrine, dopamine
- What are the neurotransmitters of the CNS?
- NE, Epi, Dopamine, serotonin, histamine
- Name the types of NE receptors and what they are coupled to?
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B-receptors: inc. CAMP--excites
A1R: inc. neuronal excitability
A2R: neuronal inhibition (pre and post-synaptic)--sedation, analgesia, hypotension - Describe the Locus coeruleus.
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*NE cell bodies
*collaterals to entire brain
*stress, nociceptive stimuli, maintenance of waking state.
*Part of Reticular Activating System - Parts of the brain richly innervated by NE neurons
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*dorsal horn-snesory modulation
*intermediolateral cell column-
BP and other sympath. funct.
*most autonomic medularry nuclei
*hypothalamic nuclei (some)
*limbi system - Role of adrenergic neurons in the CNS
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FEW
*central regulation of stress
*autonomic functions
*BP - Location of dopamine cell bodies
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*mesencephalon (ventral tegmental area (VTA), substantia nigra)
*diencephalon (thalamus, hypothatlamus) - Location of Dopamingergic neurons and their role/function
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* Midbrain (substantia nigra)-motor function
*Basal forebrain-personality and affects/motivation and reward
*Hypothalamus- endocrine- inhibit prolactin release - Location of serotonergic cell bodies in CNS
- midline series of brainstem nuclei: raphe nuclei
- Projections of Serotonergic neurons and their function?
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*limbic system-mood
*hypothalamus-appetite and hormone production
*dorsal horn-pain
*intermediolateral column and ventral horn-inc. sympathetic and somatic motor outflows
*brainstem-breathing [infant-respiration; adult-airway diameter] - Describe the cycle of sertonergic neuron action.
- active during waking, less so during SWS and not active in REM.
- Location of Serotonin in the periphery?
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*In platelets-not produced here;absorbed from blood
*Enterochromaffin cells of the GI tract - Location of histamingeric neurons in the CNS
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Not produced in CNS; except for a cluster in the hypothalamus
Receptors H1 and H2 located in a cluster in the hypothalamus
regulation of sleep-waking cycle