L29 - recap of bioavailability, dissolution, membrane transport

Question 1

pharmacodynamics

Answer 1

what the drug does to the body

Question 2

pharmacokinetics

Answer 2

what the body does to the drug

Question 3

bioavailability

Answer 3

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

Question 4

LADME

Answer 4

1. Liberation
2. Absorption
3. Distribution
4. Metabolism
5. Excretion

Question 5

after extravascular administration how does the drug enter the blood?

Answer 5

1. release: drug dissolves at administration site
2. absorption: drug crosses biomembrane to reach blood

Question 6

describe what happens if drug is rapidly released but membrane transported is slow?

Answer 6

• this is typical of hydrophilic molecules
• you can increase bioavailability by changing drug structure, e.g increase lipophilicity)

Question 7

describe how to increase bioavailability of a poorly soluble / slowly released drug that easily permeates membrane?

Answer 7

• typical of lipophilic molecule
• optimisation of dosage form

Question 8

dissolution process

Answer 8

1. salvation of drug at crystal surface to create stagnant layer of saturated solution
2. diffusion of dissolved molecules across layer into bulk solution
   - observed rate of dissolution depends on slowest of these 2 steps

Question 9

notes Whitney equation: overall rate of dissolution

Answer 9

dissolution rate = dC/ dt = D x S /h (Cs-Cb)

Question 10

solubility of weak acids as a function of pH

Answer 10

• solubility (Cs) of weakly acidic drug predicted by:
• pH of sol
• pKa
• solubility of ionised drug (S0)

Question 11

solubility of weak bases as function of pH

Answer 11

• solubility of weakly basic drugs can be predicted given:
• pH of sol
• pKa
• solubility of unionised drug (S0)

Question 12

transcellular pathway

Answer 12

• major pathway
• passive diffusion: solutes diffuse down a conc gradient. partiton into lipid bilayer and then out to cytoplasm
• aqueous pore: hydrophilic channel made by aquaporin proteins
• facilitated diffusion: selective, carried protein, down conc gradient
• active transport: selective, against conc gradient

Question 13

passive diffusion

Answer 13

system not in equilibrium moves towards equilibrium, so flux/flow must occur

Question 14

equation for flux

Answer 14

J = C x v x A

conc x velocity x area

Question 15

what is flux proportional to?

Answer 15

change in conc

Question 16

passive transport: ficks first law

Answer 16

• flux increases with membrane surface area
• SA of the SI is bigger than stomach
• flux is inversely proportional to membrane thickness (Δx).
• flux is correlated to difference between drug conc on either side of memb

Question 17

partition coefficient (K)

Answer 17

• k quantifies distribution of drug between membrane and aqueous phases which it separates
• K = Coil/Cw
• K= ratio of drug’s solubility in 2 phases
• K= drugs relative affinity for oil compared to water

Question 18

what is logP?

Answer 18

octanal water partiton coefficient - used to find drugs lipophilicity

Question 19

what does a drugs lipophilicity affect?

Answer 19

absorption, distribution, elimination

Question 20

what could happen if drugs are too lipophilic?

Answer 20

deposited in fatty tissue

Question 21

why are polar functional groups needed on drugs?

Answer 21

to bind to receptors + ensue,es by h bonds

Question 22

octanal water partition coefficient

Answer 22

• measures drug lipophilicity
• P = [drug]oct / [drug]water

Question 23

P and log P of drug that is 10x more lipid soluble than water soluble?

Answer 23

P= 10
LogP = 1

Question 24

P and log P of drug that is 100x more lipid soluble than water soluble?

Answer 24

P= 100
LogP= 2

Question 25

P and log P of drug that is 5x more water-soluble than lipid-soluble?

Answer 25

P= 1/5 = 0.2
LogP = -0.7

Question 26

pH partiton hypothesis

Answer 26

drug accumulates on side where pH favours ionisation.

• unionised drug = optimal memb transport as lipophillic
• ionised drug = hydrophilic = reduced transport

Question 27

limitations of pH partition hypothesis

Answer 27

doesn’t take into account
1. type of epithelium
2. SA of absorption site
3. ionised drugs still absorbed to a small extent
4. AT of drugs
5. residence time of drug at delivery site
6. mass transfer of fluids
7. charged drugs can form ion pairs with oppositely charged species

Question 28

lipinskis rule of 5

Answer 28

• predicts that good oral bioavailability when:
  1. molecular weight ≤ 500
  2. log P ≤ 5
  3. No more than 5 hydrogen bond donors
  4. No more than 10 hydrogen bond acceptors
  5. All units are multiples of five