Drug Absorption Lesson 4. Drug T A Blood Brain CTZCTZ Organs & Tissues.
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Transcript of Drug Absorption Lesson 4. Drug T A Blood Brain CTZCTZ Organs & Tissues.
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Drug Absorption
Lesson 4
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Drug
T
A
Blood
Brain
CTZ
Organs &
Tissues
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Absorption Movement from administration site
into circulatory system Complete when...
concentration at target equals site of administration
Controlled by membranes cell capillary walls blood-brain barrier placental barrier ~
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Cell Membranes
Lipid bilayer semipermeable
Fluid Mosaic Model Phospholipids Proteins ~
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Membrane Proteins
OUTSIDE
INSIDE
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Movement Across Membrane
Passive diffusion thru un-gated channels
Carrier assisted transport diffuse through gated channels
Active transport requires energy ~
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Capillaries
Exchange of materials b/n blood and cells
Capillary walls one cell thick Pores Spaces between cells materials can move in/out ~
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Barrier b/n circulatory system & brain peripheral vs. CNS blood supply
Capillaries cells in wall tightly packed
astrocytes glia wrap around capillaries tight seal ~
Blood-Brain Barrier (BBB)
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BBB: Function
Maintains stable brain environment large fluctuations in periphery
Barrier to poisons Retains NTs & other chemicals
Regulates nutrient supplies glucose levels active transport ~
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TypicalCapillary
Blood-Brain Barrier BrainCapillary
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BBB: Development
Incomplete at birth up to 2 yrs old vulnerable during pregnancy
Weakening of BBB trauma infection aging ~
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Chemical Trigger Zone (CTZ)
Area Postrema in brainstem BBB weaker
Substances can enter brain safety mechanism neurons monitor blood rapid in blood concentration
triggers vomiting dopaminergic neurons ~
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Placental Membrane
Exchange nutrients & wastes w/ mother Less selective than BBB
all lipid soluble substances Fetus is vulnerable
incomplete BBB lack enzymes for metabolism ~
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Placental Membrane
Teratogens chemicals that cause birth defects alcohol, nicotine, cocaine, etc.
Smoking CO reduced O2 levels brain damage ~
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Solubility
Ability to dissolve in a medium water-soluble lipid-soluble
easily crosses membranes also BBB
Molecular size small absorbed easily ~
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Solubility: Ionization
Ionization decreases solubility ion = charged particle
Lipid-soluble little ionization Water-soluble ionizes easily
requires carrier assisted or active transport ~
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Polarity positive & negative poles H2O
Polar hydrophilic tend to ionize will not cross membrane
Non-polar hydrophobic crosses membrane easily ~
Solubility: Polarization
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OH
H
Water
+ -
Polar
Ethanol
C
H
H
H C
H
H
OH
Non-polar
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Solubility: pH
pH scale: 0-14 Drugs in solution can ionize
H2O H+ and OH- # of H+ in solution relative to OH-
High % H+ = acidic Low % H+ = basic (alkaline) ~
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pH Scale
7.00 14
acidic alkaline
Water = neutral
GI = 1.2 Blood = 7.4
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Ion Trapping
Drug & pH important Ionization decreases solubility
acidic drug in alkaline ionize alkaline drug in acidic ionize
Per Os ? acidic drug best ~
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Redistribution
Ion trapping: Dynamic equilibrium maintained Example: acidic drug in blood 40% ionized to 60% un-ionized
Redistribution: as drug is metabolized some ionized un-ionized ratio ionized to un-ionized retained
4:6 ~
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Best Absorption
Lipid soluble Small Non-polar Un-ionized
pH matches environment ~