phrm 82400: exam 1: lecture 2: ionization of drugs

the ionization state of a drug has an impact on the drug's _________

- solubility

- extent of absorption (bioavailability)

- binding to its receptor

charged molecules are (more or less) soluble, but (more or less) likely to cross lipid membranes

more; less

__________ affects the ionization of a drug molecule

pH

what weak acids (pKa < 7) are ionizable functional groups?

- arylcarboxylic acid

- arylamine

- aromatic amines

- alkylcarboxylic acid

what weak bases (pKa > 7) are ionizable functional groups?

- alkyl amines

- phenol

- guanidine

what functional groups are non-ionizable?

- alkyl alcohol

- alkyl aldehyde

- ether

- ester

- ketone

- amide

- quaternary amine

when pH < pKa,

[A-] < [HA]

- acidic

- protonated

when pH > pKa,

[A-] > [HA]

- basic

- deprotonated

water is a __________ solvent

polar

- polar molecules dissolve better in water

what components make a solvent polar?

- H-bond donors and acceptors

- ionic group

better solubility can be achieved by changing _________

pH

hotseat: at pH 7.4, what is the ratio of this drug in the acid form (neutral) to that in the base form (negatively-charged)?

ibuprofen (pKa 4.4)

a. 1000:1

b. 100:1

c. 1:100

d. 1:1000

d. 1:1000

GI tract and blood brain barrier as well as lipid membranes of the target cells act as _________

physical barriers

most drugs are absorbed through membranes by __________

passive diffusion

what is the absorption rate of a drug related to?

drug's lipophilicity

- in general, more lipophilic drugs are absorbed more efficiently

ionized drugs (can or cannot) cross the lipid bilayer

cannot

where is passive diffusion of a drug more efficient?

at a pH where the drug is mostly neutral

even if a drug is mostly ionized at a given pH, why does the drug still diffuse through the lipid bilayer slowly?

- the unionized neutral drug is still in equilibrium with the ionized drug

- the diffusion rate is proportional to the amount of the neutral drug

drugs are absorbed best at pH where they are mostly __________

neutral

what organ are most drugs absorbed?

small intestine (jejunum) where pH is generally between 5 and 7

what organ do acidic drugs tend to be absorbed?

stomach where pH is generally between 1 and 3

hotseat: a drug is an organic base (RNH2) with a pKa of 9.0. assume the stomach has a pH of 1.5 and the small intestine has a pH of 6.5. where will the drug be preferentially absorbe?

a. stomach

b. small intestine

c. equally absorbed in the stomach and small intestine

d. no absorption at either site

b. small intestine