L29 - Recap Of Bioavailability, Dissolution And Membrane Transport Flashcards
What is pharmacodynamics?
What the drug does to the body
What is pharmacokinetics?
what the body does to the drug
What is bioavailability?
A quantitative measure of the amount of a drug that reaches its site of action and of the rate at which it gets there
What does LADME stand for?
Liberation
Absroption
Distribution
Metabolism
Excretion
What two steps does drug appearance in blood demand?
- release - drug dissolves at administration site
- absroption - drug crosses biomembrane to reach blood
What is typical of hydrophilic molecules?
Drugs is rapidly released, membrane transport is slow
What is typical of lipophilic molecules?
A poorly soluble drug, easily permeates the biological membrane
What two steps are involved in the dissolution of a solid crystal in a liquid?
- solvation - create a stagnat layer of saturated solution
- diffusion - dissolved molecules move across layer into bulk solution
What is the solubility of weakly acidic/basic drug can be predicted by?
- pH of the solution
- pKa
- solubility of free (unionised) form of drug
What is the equation of weak acids as a function of pH?
Log Cs-S0/S0 = pH - pKa
What is the equation of weak bases as a function of pH?
Log S0/Cs-S0 = pH - pKa
What are the different types of membrane transport?
- transcellular pathway
- paracellular pathway
What is passive diffusion?
(Main pathway of drug absorption)
- solutes diffuse into cells down a conc grad, partition into the lipid bilayer and out again into cytoplasm
What are the different types of transcellular absorption?
- passive diffusion
- aqueous pore
- facilitated diffusion
- active transport
What is the aqueous pore pathway?
Hydrophiic channel created by transmembrane aquaporin protein
- allow transport of small neutral solutes such as urea and glycerol
What is facilitated diffusion?
Carrier nediated transport of a drug down a conc grad
What is active transport?
Carrier mediated transport of a drug down or against a conc grad
- requires energy input
When does flux occur?
A system not in eq moves towards eq
- flow/flux must occur
What factors affect flux?
- conc
- velocity
- area
When does flux increase?
with membrane SA (A)
What is flux inversely proportional to?
Membrane thickness (deltax)
What is flux directly correlated to?
difference between drugs conc on either side of membrane
What are membrane properties, drug properties and drug & membrane properties in fick’s first law of diffusion?
Membrane - membrane thickness, area
Drug - conc grad, parition coefficient
Drug & membrane - diffusivity
What is the partition coefficient?
K
Quantifies distribution of drug between membrane and aqueous phases which it separates
What does a drug’s lipophilicity affect?
- absorption
- distribution
- elimination
What must a drug be like in terms of lipophilicity?
Lipophilic to cross cell membranes
- not too lipophilic as may be deposited in fatty tissue
What is the pH parition hypothesis?
Drug accumulates on the sideof the membrane where pH favours ionisation
What is membrane transport like when AH and B (unionised drug) is lipophilic?
Optinal membrane transport
What is membrane transport like when A- and BH+ (ionised drug) is hydrophilic?
Reduced membrane transport
What are the limitations of the pH partition hypothesis? (7)
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
Why and what is lipinki’s Ro5 used for?
- considers physiochemical properties of a drug candidate in terms of potential bioavailability
- predicts good oral bioavailability
What is the criteria for a good oral bioavailability with Ro5?
- MW < 500
- logP < 5
- H bond donors < 5
- H bond acceptors < 10
- all units are multiples of 5
