2.2 - Transport Mechanisms Flashcards
– How drugs move across cell membrane
– Drug must be in aqueous solution EXCEPT Pinocytosis
Transport Mechanisms
Transport Mechanisms
- Passive Diffusion
- Carrier-Mediated Transport
- Convective Transport
- Ion-Pair Transport
- Vesicular Transport
– Dominant
– Slowest; NON ENERGY requiring
– ALONG the concentration gradient (DOWNHILL)
– Passage across cell membrane
Passive Diffusion
Governing Principle of Passive Diffusion
Fick’d Law of Diffusion
dQ/dt
Rate of diffusion
D
Diffusion coefficient
A
Surface area
K
Partition coefficient
(CGi - Cp)
– Concentration Gradient
– Difference in concentration between 2 immiscible phases
h or l
– Length of the membrane
– Membrane thickness
D x A x K. (Cgi - Cp)
DIRECTLY Proportional
h
INVERSELY Proportional
Factors Affectig Rate of Diffusion
- Surface Area (A)
- Concentration Gradient (Cgi - Cp)
- Membrane thickness (h or l)
- Diffusion Coefficient (D)
Surface Area
⬆️A = ⬆️dQ/dt
Concentration Gradient (Cgi - Cp)
⬆️(CGi - Cp) = ⬆️dQ/dt
Membrane Thickness (h or l)
⬆️h = ⬇️dQ/dt
– Propert of a drug in relation to property of the mebrane
– 2 determinants
Diffusion Coefficient
2 determinants
- Particle Size
* Lipophilicity
Particle Size
⬇️PS = ⬆️ A = ⬆️dQ/dt
Lipophilicity
⬆️Lipophilicity = ⬆️dQ/dt
2 Factors
- Degree of Dissociation/ Ionization
* Partition Coefficient (K)
[HA] — LUNA
• Non-ionized
• Non-polar
• Lipophilic
A B S O R B E D
H + A — WIPE
• Ionized
• Polar
• Hydrophilic
E X C R E T E D
Ka — DossociatiobnRate Constant
⬆️Ka = ⬇️Lipo = ⬇️dQ/dt
pKa — -log Ka
⬆️pKa = ⬇️Ka = ⬆️lipo = ⬆️dQ/dt
Partition Coefficient
— Lipid-H2O coefficient
⬆️K = ⬆️Lipo = ⬆️dQ/dt
Carrier-Mediated Transport
- Features/ Characteristics
* Examples
Features/ Characteristics
- Specificity/ Selectivity
- Subject to Inhibition, Competition, Antagonism
- Saturable
Carriers recognize specific molecules
Selectivity/ Specificty
- Ex: Amino Acid transportrers — Recognized L-dopa but not dopamine
- Ex: A.A Transporters — A.A in food can compete with L-dopa for CNS Transport
Subject to Inhibition, Competition, Antagonism
– Based on the presence of limited # of carriers
– Displays MICHAELIS-MENTEN Kinetics/ Saturation Kinetics/ Nonlinear Kinetics
Subject to Saturability
Examples
- Active Transport
* Facilitated Diffusion
– Energy requiring
– AGAINST concentration gradient (UPHILL)
– Fastest
Active Transport
– Non-enwrgy requiring
– ALONG concentration gradient
Facilitated transport
– Linear
– Concentration INDEPENDENT
– Rate of Accumulation = Rate of Elimination
First Order Kinetics
– Non-linear
– Concentration DEPENDENT
– Saturable Kinetics
– Michaelis-Menten Kinetics
Zero Order Kinetics
– Movemement through water-filled PORES/GAP JUNCTIONS
– Only PARACELLULAR transport mechanisms
Convective Transport
Properties of Convectie Transport
- Pore Size/ Diameter
- Change of the Pore Lining
- Movement is by SOLVENT drug
- Movement is ALONG concentration gradient
– 7-10 angstrom
– Allows movement of ions/ molecules with MW 150-400
Pore Size/ Diameter
– Pure (+) or Pure (-)
– Allows movement of ions with charge OPPOSITE of the pure lining
Charge of the Pure Lining
– Mesh of transport for large ions — large exogenous ions form a neutral complex with an endogenous oppositely charged ion
– Ex: Quaternary Amines
Ion-Pair Transport
Vesicular Transport
- Pinocytosis
* Phagocytosis
– Cell EATING – Small molecules; liquids – Requirement: Micelle form – Surfactant: Bile Salts/ Bile Acids – Vesicle-Mediated – Requires energy – Ex: Griseofulvin, ADEL Vitamins
Pinocytosis
– Cell DRINKING
– Large molecules
Phagocytosis
