Drug Absorption

Lesson 4

Drug

T

A

Blood

Brain

CTZ

Organs &

Tissues

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 ~

Cell Membranes

Lipid bilayer semipermeable

Fluid Mosaic Model Phospholipids Proteins ~

Membrane Proteins

OUTSIDE

INSIDE

Movement Across Membrane

Passive diffusion thru un-gated channels

Carrier assisted transport diffuse through gated channels

Active transport requires energy ~

Capillaries

Exchange of materials b/n blood and cells

Capillary walls one cell thick Pores Spaces between cells materials can move in/out ~

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)

BBB: Function

Maintains stable brain environment large fluctuations in periphery

Barrier to poisons Retains NTs & other chemicals

Regulates nutrient supplies glucose levels active transport ~

TypicalCapillary

Blood-Brain Barrier BrainCapillary

BBB: Development

Incomplete at birth up to 2 yrs old vulnerable during pregnancy

Weakening of BBB trauma infection 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 ~

Placental Membrane

Exchange nutrients & wastes w/ mother Less selective than BBB

all lipid soluble substances Fetus is vulnerable

incomplete BBB lack enzymes for metabolism ~

Placental Membrane

Teratogens chemicals that cause birth defects alcohol, nicotine, cocaine, etc.

Smoking CO reduced O2 levels brain damage ~

Solubility

Ability to dissolve in a medium water-soluble lipid-soluble

easily crosses membranes also BBB

Molecular size small absorbed easily ~

Solubility: Ionization

Ionization decreases solubility ion = charged particle

Lipid-soluble little ionization Water-soluble ionizes easily

requires carrier assisted or active transport ~

Polarity positive & negative poles H2O

Polar hydrophilic tend to ionize will not cross membrane

Non-polar hydrophobic crosses membrane easily ~

Solubility: Polarization

OH

H

Water

+ -

Polar

Ethanol

C

H

H

H C

H

H

OH

Non-polar

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) ~

pH Scale

7.00 14

acidic alkaline

Water = neutral

GI = 1.2 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 ~

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 ~

Best Absorption

Lipid soluble Small Non-polar Un-ionized

pH matches environment ~