pKa, Acid-Base Equilibria, and Partition Coefficients in Pharmacology

pKa

the pH at which an acid (or base) is 50% ionized and 50% unionized.

pH greater than pKa

environment is more basic and weak acids are mostly ionized (charged).

pH less than pKa

environment is more acidic and weak acids are mostly unionized.

Large Ka

strong acid → small pKa.

Small Ka

weak acid → larger pKa.

Negative number when subtracting pH from pKa

indicates that the acid or protonated form is predominant (unionized).

Positive number when subtracting pH from pKa

indicates that the base or unprotected form is predominant (ionized).

Rule of thumb for pH and pKa problems

if the pH is 3 subunits from the pKa you will have 98.99 percent ionized.

pH 1 unit away from pKa

90 percent ionized.

pH 2 units away from pKa

99 percent ionized.

pH 3 units away from pKa

99.9 percent ionized or like 98.99 percent ionized.

pH of plasma is 7.5

ratio of phenobarbital to its conjugate base in the plasma is 10^0=1, so 50/50.

pH equals pKa

No need to calculate every time; 10^0 is 1 and indicates 50/50 concentration.

pKa in a base

describes how easily the protonated form (BH⁺) loses a proton.

Relationship between base and BH+

The B (weak base) can accept a proton; BH+ is the ionized/protonated form of the base.

pKa of a base

actually the pKa of the protonated base (BH⁺).

Partition coefficient

the larger the (p) partition coefficient the less water soluble it is.

Partition coefficient equal to 1

the substance is equally soluble.

Estimating log P values of compounds

by summing up their fragment constants.

Groups with negative pi values

make the log P more polar.

High P

lipophilic.

Low P

hydrophilic.

P less than 1

drug is hydrophilic.

P greater than 1

drug is lipophilic.

Acidic environment for acidic functional groups

primarily unionized.

Basic environment for acidic functional groups

primarily ionized (polar).

Basic environment for basic functional groups

primarily unionized (non-polar).

All alcohols are hydroxyls but not all hydroxyls are

Alcohols

Adding a acid to a base

Polarizes, moves into the aqueous phase. P decrease lip p decrease

Adding a base to a base

Less polar, prefers octantal higher log p high p.

Acid in acid

P increases, log p increases

Base in acid

P decrease, log p decreases

P increases=

More in the octanol and more lipophilic

What drug can not absorb into the GI tract well?

Extreme. Very hydrophilic, very lipophilic

Finding oct give the aqueous (decimal)

Decimal times the aq

Finding the oct given the aqueous (whole)

Remove the o's

Aromatic rings do not participate in

Dipole-dipole interactions because they don't have permanent dipoles

What is a chelating agent

It is a substance that forms multiple bonds with a single metal ion, creating a more stable complex

The metal ion doesn't need to be present for the molecule to be a

Chelating agent

What are some possible donating atoms for a chelating agent

Nitrogen oxygen sulfur phosphorus