Pharm Topic 2: Drug Absorbtion And Distribution

Front 1

5 ways drugs cross membranes

Back 1

1) Simple diffusion
2) Facilitated diffusion (carrier mediated)
3) Active Transport (carrier mediated)
4) Diffusion through pores
5) Pinocytosis

Front 2

Passive diffusion flux equation (Fick's Law)

Back 2

J = -DA deltaC/deltaX

J = flow across membrane
D = diffusion coefficient which is proportional to the lipid permiability of the drug and the temp and inversely proportional to drug size.
A = Surface area diffusing across (SA of stomach or intestine)
delta C = Difference in concentration across a membrane
delta X = thickness of membrane

Front 3

Determinants of passive transport

Back 3

1) Drug permeability
2) Concentration gradient
3) Absorptive surface area
4) Temperature

Front 4

What determines drug permeability

Back 4

Drug related:
1) Lipid solubility of drug - More hydrophobic the better the absorption
2) PK of drug - b/c only uncharged form of drug can be passively transported.
3) Size of the drug
Non-Drug related:
1) pH of medium (most drugs are weak bases or weak acids)

Front 5

Lipid partition coefficient

Back 5

Measure of lipid solubility. High partition coefficient easily pass through lipid bilayer.

Front 6

What is the effect of pH on acid/base ionization

Back 6

For an ACID, as you Increase pH you Increase the amount of acid Ionized
For a BASE, as you Increase the pH, you Decrease the amount of base Ionized.

Front 7

Ion Trapping

Back 7

When a drug is passing to a medium with a different pH, it is possible to accumulate ions on the other side despite the fact that ions are not passively permeable.
For example, if an acid is transported from a more acidic environment to a more basic, it may start unionized, but once it crosses into the more basic environment, it will have a tendency to ionize, thus building up charge.

Front 8

What is pKa?

Back 8

pKa is the PH vaule at which 50% of the drug is ionized.

Front 9

Relationship between pKa of drug and pH of medium equations

Back 9

pH = pKa + log[A-] / [HA]

pH = pKa + log[B] / [BH+]

Front 10

Compare and Contrast the 2 types of carrier mediated transport

Back 10

Facilitated and Active transport are both independent on surface area and proportional to the number of carriers, They also both show saturation kinetics (dependent on concentration of drug until saturated) and both have specific transport mechs.
However, facilitated transport cannot transfer from a high gradient to a low while active can.

Front 11

How does carrier mediated transport differ from passive diffusion

Back 11

1) Rate of permeation is faster for carrier mediated
2) Carrier mediated is saturable
3) Carrier mediated has a high degree of specificity. Structural analogs can competitively compete.

Front 12

Factors effecting drug distribution

Back 12

1) Exit from circulation
2) Rate of distribution
-Blood perfusion
3) Extent of distribution
-Lipid solubility
-pH-pKa
-Plasma protein binding
-Intracellular binding

Front 13

Ways in which a drug can distribute

Back 13

1) Within vascular system (very little leaves circulation)
2) Uniform distrib throughout body
3) Concentrated in specific tissues
4) Non uniform distribution (most drugs, often in liver and kidneys).

Front 14

What determines where a drug goes

Back 14

1) Rate of distribution:
-blood perfusion
-Plasma protein binding
-Capillary permeability (most important for BBB)
2) Extent of distribution
-Intracellular binding

Front 15

Factors that limit fat deposition

Back 15

Low partition coeficient and low blood supply.

Front 16

Enteral and Parenteral drug delivery

Back 16

Enteral - Oral, Sublingual, rectal
Parenteral - IV, Sub Q, IM, Spinal, topical, inhilation

Front 17

What percentage of a cell is considered water?

Back 17

70%

Front 18

Whats considered enteral vs parenteral

Back 18

Enteraal - oral, sublingual, rectal
Parenteral - IV, sub Q, IM, spinal, topical, inhillation.