Lecture 10 - Intro to Ionic Equilibria pt. 1

Ionized forms?

are MORE water soluble, less lipid soluble

Non-ionized forms?

are MORE lipid soluble, so more permeable to lipid membranes

Changes in ionization state can directly affect what?

Drug solubility

Absorption and bioavailability

Acids

A species that can donate a proton

The strength of an acid depends on what?

Its ability to donate a proton

The stronger it is, the more easily it can donate a proton

Bases

A species that can accept a proton

Add an acid to water what happens?

pH goes down below 7

H3O+ Increases

OH- Decreases

Add a base to water what happens?

pH goes up above 7

H3O+ decreases

OH- Increases

When a free form unionized acid donates a proton what does it become?

A conjugate base, ionized and deprotonated

When a free form unionized base donates a proton what does it become?

A conjugate acid, ionized and protonated

Conjugate species are related by what?

By the loss or gain of a single proton H+

What is K_a a measure of?

Its the acidity constant

Its a measure of strength of the acid

A strong acid you would expect what?

That it would complete dissociate and the Ka would be large, (pka would be very small/negative)

A weak acid you would expect what?

That very little of the free form acid would dissociate and Ka would be small

General guideline as the strength of an acid increases

H3O+ Increase

Ka Increases

pka decreases

Can you tell if a drug is an acid or base based on pka alone?

NO you need to look at the molecular structure was well

What does pka of a base imply?

It is referring to the pka of the conjugate acid of the weak base

Rank the weak acids from strongest to weakest

Sulfonic acids

Carboxylic acids

Aryl sulfonamides

Phenols

Imides

Thiols

Rank the weak bases from strongest to weakest

Guanidines

Aliphatic nitrogens

Amidines

Ar-NH2

Aromatic Nitrogens

Nonelectrolyte

No acid or base functionality

Monoprotic acid

Capable of donating 1 proton/molecule

Monoprotic base

Capable of attaching 1 proton/molecule

Polyprotic acid

Capable of donating more than 1 proton/molecule

Polyprotic base

Capable of attaching more than 1 proton/molecule

Ampholyte

Has both acid and base functionality

Strong Acids

HCl Hydrochloric acid

H2SO4 Sulfuric Acid

HI Hydroiodic Acid

HClO4 Perchloric Acid

HNO3 Nitric Acid

HBr Hydrobromic acid

Strong Bases

LiOH Lithium hydroxide

NaOH Sodium hydroxide

KOH Potassium hydroxide

Ca(OH)2 Calcium hydroxide

Mg(OH)2 Magnesium hydroxide

Ba(OH)2 Barium Hydroxide

Would you expect basic drugs to be consistently better absorption in the stomach?

No, because the pH of the stomach is low the basic drug would be mostly ionized leading to less permeability and absorption

When pH = pka?

The drug is 50% ionized and 50% free form (unionized)

A pH below pka?

Ionized base

Free form acid

favored

pH above a pka?

Ionized acid

Free form base

Favored