Transcript drug absorption

Drug Absorption
Lecture 4
Absorption
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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 ~
Cell Membranes
Lipid bilayer
 semipermeable
 Fluid Mosaic Model
 Phospholipids
 Proteins ~
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Membrane Proteins
OUTSID
E
INSIDE
Movement Across Membrane
Passive diffusion
 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
 materials can move in/out ~
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Blood-Brain Barrier (BBB)
Barrier b/n circulatory system & brain
 peripheral vs. CNS blood supply
 Capillaries
 cells in wall tightly packed
 astrocytes
 glia
 wrap around capillaries
 tight seal ~
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Blood-Brain
Barrier
Blood
T
Brain
Blood-Brain Barrier
astrocytes
Typical
Capillary
Intercellular
cleft
Fenestra
No
fenestra
Brain
Capillary
tight
junction
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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BBB: Development
Incomplete at birth
 up to 2 yrs old
 vulnerable during pregnancy
 Weakening of BBB
 trauma
 infection
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aging ~
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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Chemical
Trigger Zone
Blood
T
Brain
C
T
Z
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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Lipid 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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Solubility: Polarization
Polarity
 positive & negative poles
 H 2O
 Polar  hydrophilic
 tend to ionize
 will not cross membrane
 Nonpolar  hydrophobic
 crosses membrane easily ~
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Water
Ethanol
H
O
+
H
Polar
-
H
H
H
C
C
H
H
Nonpolar
OH
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
Water = neutral
0
7.0
acidic
GI = 1.2
14
alkaline
Blood = 7.4
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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Redistibution
Dynamic equilibrium maintained
 Example: acidic drug in blood
 40% ionized to 60% un-ionized
 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
 Nonpolar
 Un-ionized
 pH matches environment ~
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