Acids, Bases, and pH Calculations in Pharmacology

Acids

Proton donors.

Bases

Proton acceptors.

H2O

Serves as both a base and an acid, referred to as amphoteric.

pKa

Calculated as -log Ka, where Ka is the acid dissociation constant.

Ka

The acid dissociation constant, expressed as Ka = ([H3O+]x[A-])/[HA].

Henderson-Hasselbalch Equation

pKa = pH - log ([A-]/[HA]).

pH of plasma

If the pH of plasma is 7.5, the ratio of phenobarbital to its conjugate base is 1:1.

Base Strength

pKa < 2 = NO BASIC PROPERTIES; pKa 4 - 6 = VERY WEAK BASE; pKa 8-10 = WEAK BASE; pKa > 12 = STRONG BASE.

Strong Acid

Has a weak conjugate base.

Weak Acid

Has a strong conjugate base.

Strong Base

Has a weak conjugate acid.

Weak Base

Has a strong conjugate acid.

Percentage Ionization of a Drug

HA is unionized and A- is the ionized form of the drug.

Polar Drug

Dissolves readily in an aqueous solution but not in non-polar solvents.

Non-Polar Drug

Does not dissolve in an aqueous solution but dissolves in organic or non-polar solvents.

Like Dissolves Like

A principle stating that polar solvents dissolve polar substances and non-polar solvents dissolve non-polar substances.

Fragment Constants

Used to estimate log P values of compounds by summing their pi values.

Phenyl

Fragment constant value of 2.13.

CH3

Fragment constant value of 0.50.

CH2

Fragment constant value of 0.50.

Br

Fragment constant value of 0.86.

Cl

Fragment constant value of 0.71.

NO2

Fragment constant value of -0.80.

NH2

Fragment constant value of -1.23.

OH

Fragment constant value of -0.67.

Le Chatelier's Principle

States that if a stress is applied to a system at equilibrium, the system shifts in the direction that relieves the stress.

When PH is equal to the PKA

50% is ionized and 50% is nonionized

partition coefficient

How lipid soluble the drug is

The larger P is

The less soluble it is in water

If P is equal to 1

Than it is equally as soluble

We should be able to calculate the log P using

Fragment constants

If the partition coefficient (P) is greater than 1, what does this indicate about the drug?

The drug is more lipophilic (lipid-soluble) → it prefers the lipid (oil) phase over the aqueous (water) phase.

he partition coefficient (P) is less than 1, what does this indicate about the drug?

The drug is more hydrophilic (water-soluble) → it prefers the aqueous (water) phase over the lipid phase.