Drug Absorption

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Drug Absorption

• Lecture 3

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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
• 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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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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Blood-Brain Barrier

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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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Solubility Polarization

• Polarity
• positive negative poles
• H2O
• Polar ? hydrophilic
• tend to ionize
• will not cross membrane
• Non-polar ? hydrophobic
• crosses membrane easily

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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
7.0
0
14
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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
• 46

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Best Absorption

• Lipid soluble
• Small
• Non-polar
• Un-ionized
• pH matches environment