Second lec& 3rd
Transcript of Second lec& 3rd
Physicochemical Properties of Drugs
The Effect of pH and pKa on Drug Action
most drugs are small organic molecules that behave in solution as either weak acids or
weak bases.Acid-Base properties of drugs greatly
influences their biodistribution and partitioning characteristics.
What does it mean to say that a certain molecule is an acid or base?
Arrhenius definition.
and Base Strength ِAcid ِ
Percentage Ionization
ExampleWhat is the ratio of ephidrine to ephedrine
HCl (pKa 9.6) in the intestinal tract at pH 8.0?
What is the percentage ionization of: 1. ephedrine HCl (pKa 9.6) and 2. indomethacin (pKa 4.5) in an intestinal tract with pH 8?
pKa for the base is the pKa of its conjugate acid.
Ephedrine pKa =9.6Ammonia pKa=9.3
What is the significance of Ka and pKa values?
How can the drug pKa value be used?
Rules
Acid drugs – become more NON ionized in acidic pH
Basic drugs – become more NON ionized in basic pH (alkaline pH)
Acid Drug Basic Drug
Acid pH Environment
Basic pH Environment
Rules
Acid drugs – become more NON ionized in acidic pH
Basic drugs – become more NON ionized in basic pH (alkaline pH)
Acid Drug Basic DrugBasic Drug
Acid pH Environment
Basic pHBasic pH EnvironmentEnvironment
NON-ionized
NON-ionized
Rules
Acid drugs – become more NON ionized in acidic pH
Basic drugs – become more NON ionized in basic pH (alkaline pH)
Acid Drug Basic DrugBasic Drug
Acid pHAcid pH EnvironmentEnvironment
Basic pH Environment
NON-ionized
NON-ionized
IONIZED
Rules
Acid drugs – become more NON ionized in acidic pH
Basic drugs – become more NON ionized in basic pH (alkaline pH)
Acid DrugAcid Drug Basic Drug
Acid pH Environment
Basic pHBasic pH EnvironmentEnvironment
NON-ionized
NON-ionized
IONIZED
IONIZED
Rules
Hydrophilic = Ionized molecules (charged)
Lipophilic = Non-ionized molecules
) non charged(
Lipophilic molecules penetrate membranes
Hydrophilic molecules dissolve in water
Depending if a molecule is ionized or not determines if it can pass through a
cell membrane
C E
L L M E
M B
R A
N E
Ionized Molecule
Non-Ionized Molecule
Need three things to figure out whether drug is MAJORITY in
lipophilic or hydrophilic form
1. Whether the drug is an acid drug or a base drug.
2. The pKa of the drug (pH at which number of ionized = number of nonionized molecules)
3. pH into which the drug is going to be placed
Acid Drug
=Non ionized molecules
=Ionized molecules
Acid drugs – become more NON ionized in acidic pH
pH 2
N I
pH 6
N I
pH 9
I
pH 8
IN
Basic Drug
=Non ionized molecules
=Ionized molecules
Basic drugs – become more NON ionized in basic pH
pH 9
N I
pH 8
N I
pH 2
I
pH 6
IN
WHEN GIVEN:1. Acid / Base nature of the drug
2. Drug’s pKa
3. Environmental pH drug is put into
Be able to predict whether majority of drug is in the ionizedionized form or non-ionizednon-ionized form
Be able to state whether majority of drug is in the hydrophilichydrophilic form or lipophiliclipophilic form
Be able to predict whether it can be absorbed across membrane or dissolved in water
Examples
Carboxylic Acids
Phenols
The End