pharmacokinetics - acid-base + solubility Flashcards

Question

how does basicity of the heterocyle compare with N, O or S is part of the ring?

Answer 1

N heterocycles are more basic than O O is slightly more basic than S but they are quite similar

Answer 2

fat/lipid loving, aka hydrophobic

Answer 3

the body is made up of both fatty/non-polar environments and aqueous environments, drugs need to be able to pass between these areas to reach their site of action - too hydrophilic and the drug will pass right through + be excreted - too lipophilic and the drug will be too strongly absorbed + stored

Answer 4

a crucial immunological feature of the CNS, provides strucural + functional/chemical barrier to stop contamination of the brain capillaries supplying brain are lined with tight fitting cells without pores located in a fatty layer = thick, non-porous, highly lipophilic / hydrophobic barrier - this blocks most large units e.g. microorganisms, only very fatty molecules can get through

Answer 5

the blood brain barrier is a tightly controlled environment because the brain is so important its made up of endothelial cells with very tight junctions, which prevent drugs/unwanted chemicals from squeezing between cells, anything entering must dissolve through the fat + cell membranes to diffuse across to the brain, only very fatty molecules can get through

Answer 6

the relative distribution of the neutral drug is tested in an octanol/water mixture to determine P, often expressed as logP P = [octanol]/[water], logP = log10(P) - therefore high logP = more lipophilic molecule (+ vice versa)

Answer 7

used to compare the partitioning of a compound between aqueous phase and cell membrane - drugs with logP > 3 are better are passing through lipid bilayer

Answer 8

using partition coefficient, πx, relative to H atoms: πx = logP(x) - logP(H) +ve π means group is more lipophilic than H -ve π means group is less lipophilic than H

Answer 9

yes, π for aromatic substituents are different to π for aliphatic substituents

Answer 10

no, it is defined only for neutral species

Answer 11

this is the effective partitioning coefficient at a specific pH, essentially logP for ionised species, distribution coefficient = D D = [non-ionised]org/([non-ionised]aq + [ionised]aq) logD = log10(D)

Answer 12

a compound is dissolved into a solution and buffered to a specific pH, solution is then added to octanol to measure effective partitioning

Answer 13

logD can be found at pH 7.4 to give an indication of lipophilicity at the pH of blood plasma

Answer 14

for acids: logD(pH) = logP - log(1+10^(pH-pKa) for bases: logD(pH) = logP - log(1+10^(pKa-pH)

Answer 15

the fraction or % of a drug that reaches systemic circulation - influenced by solubility, permeability, clearance

Answer 16

logP/logD describe lipophilicity, which influences solubility, permeability and clearance

Answer 17

'rule of 5: molecule should have no more than 5 hydrogen bond donors, no more than 10 hydrogen bond acceptors, molecular mass under 500 daltons and a log P lower than 5' - if a molecule follows this it means it has good bioavailability/ is orally available

Answer 18

must have a polar surface area (PSA) of less than 140Å^2 and less than 10 rotatable bonds

Answer 19

the sum of the areas of the surfaces of polar atoms within a molecule, reported in Å^2

Answer 20

PS correlates with intestinal absorption, membrane permeability and blood-brain barrier penetration - lower PSA = better permeability

Answer 21

LLE = ligand-lipophilicity efficiency it links potency with lipophilicity - for orally available drugs, logP between 2-3 is often a compromise between permeability and first pass clearance, LLE>6 corresponds to high quality compounds

pharmacokinetics - acid-base + solubility Flashcards

(45 cards)