L29 - Recap Of Bioavailability, Dissolution And Membrane Transport

Question 1

What is pharmacodynamics?

Answer 1

What the drug does to the body

Question 2

What is pharmacokinetics?

Answer 2

what the body does to the drug

Question 3

What is bioavailability?

Answer 3

A quantitative measure of the amount of a drug that reaches its site of action and of the rate at which it gets there

Question 4

What does LADME stand for?

Answer 4

Liberation
Absroption
Distribution
Metabolism
Excretion

Question 5

What two steps does drug appearance in blood demand?

Answer 5

• release - drug dissolves at administration site
• absroption - drug crosses biomembrane to reach blood

Question 6

What is typical of hydrophilic molecules?

Answer 6

Drugs is rapidly released, membrane transport is slow

Question 7

What is typical of lipophilic molecules?

Answer 7

A poorly soluble drug, easily permeates the biological membrane

Question 8

What two steps are involved in the dissolution of a solid crystal in a liquid?

Answer 8

• solvation - create a stagnat layer of saturated solution
• diffusion - dissolved molecules move across layer into bulk solution

Question 9

What is the solubility of weakly acidic/basic drug can be predicted by?

Answer 9

• pH of the solution
• pKa
• solubility of free (unionised) form of drug

Question 10

What is the equation of weak acids as a function of pH?

Answer 10

Log Cs-S0/S0 = pH - pKa

Question 11

What is the equation of weak bases as a function of pH?

Answer 11

Log S0/Cs-S0 = pH - pKa

Question 12

What are the different types of membrane transport?

Answer 12

• transcellular pathway
• paracellular pathway

Question 13

What is passive diffusion?

Answer 13

(Main pathway of drug absorption)
- solutes diffuse into cells down a conc grad, partition into the lipid bilayer and out again into cytoplasm

Question 14

What are the different types of transcellular absorption?

Answer 14

• passive diffusion
• aqueous pore
• facilitated diffusion
• active transport

Question 15

What is the aqueous pore pathway?

Answer 15

Hydrophiic channel created by transmembrane aquaporin protein
- allow transport of small neutral solutes such as urea and glycerol

Question 16

What is facilitated diffusion?

Answer 16

Carrier nediated transport of a drug down a conc grad

Question 17

What is active transport?

Answer 17

Carrier mediated transport of a drug down or against a conc grad
- requires energy input

Question 18

When does flux occur?

Answer 18

A system not in eq moves towards eq
- flow/flux must occur

Question 19

What factors affect flux?

Answer 19

• conc
• velocity
• area

Question 20

When does flux increase?

Answer 20

with membrane SA (A)

Question 21

What is flux inversely proportional to?

Answer 21

Membrane thickness (deltax)

Question 22

What is flux directly correlated to?

Answer 22

difference between drugs conc on either side of membrane

Question 23

What are membrane properties, drug properties and drug & membrane properties in fick’s first law of diffusion?

Answer 23

Membrane - membrane thickness, area

Drug - conc grad, parition coefficient

Drug & membrane - diffusivity

Question 24

What is the partition coefficient?

Answer 24

K
Quantifies distribution of drug between membrane and aqueous phases which it separates

Question 25

What does a drug’s lipophilicity affect?

Answer 25

• absorption
• distribution
• elimination

Question 26

What must a drug be like in terms of lipophilicity?

Answer 26

Lipophilic to cross cell membranes
- not too lipophilic as may be deposited in fatty tissue

Question 27

What is the pH parition hypothesis?

Answer 27

Drug accumulates on the sideof the membrane where pH favours ionisation

Question 28

What is membrane transport like when AH and B (unionised drug) is lipophilic?

Answer 28

Optinal membrane transport

Question 29

What is membrane transport like when A- and BH+ (ionised drug) is hydrophilic?

Answer 29

Reduced membrane transport

Question 30

What are the limitations of the pH partition hypothesis? (7)

Answer 30

Doesn’t take into account
- type of epithelicum
- SA of absorption site
- ionised drug absorbed to a small extent
- active transport of drugs
- residence time of drug at delivery site
- mass transfer of fluids
- charged drug pairs

Question 31

Why and what is lipinki’s Ro5 used for?

Answer 31

• considers physiochemical properties of a drug candidate in terms of potential bioavailability
• predicts good oral bioavailability

Question 32

What is the criteria for a good oral bioavailability with Ro5?

Answer 32

• MW < 500
• logP < 5
• H bond donors < 5
• H bond acceptors < 10
• all units are multiples of 5