Section 1 - Review of biochemistry & Human physiology

Question 1

Why is pH so important in pharmacology?

Answer 1

Our body is an aqueous system.

The pH differs in the different compartments of the body and will thus influence the partitioning of the drug.

Question 2

If a drug is charged, it will have difficulty ________ the membrane.
Why?

Answer 2

Partitioning

Charged molecules do not diffuse through membranes well.

Question 3

pKa is a ______ term from pH.

Answer 3

different

Question 4

What is Keq?

Answer 4

Ratio of products to reactants.
A + B C + D
Keq = [C][D]/[A][B]

Question 5

Acids are _____ donors.

Bases are _____ acceptors.

Answer 5

acid = proton donors

base = proton acceptor

Question 6

An acid is a substance that can dissociate to give __ and a negative ion (anion) called the ______ ______.

Answer 6

H+

conjugate base

Question 7

The general equation for dissociation of an acid is?

Answer 7

HA H+ + A-
HA - acid
H+ - proton
A- - conjugate base

Question 8

An acid is referred to as _______ or ________.

The conjugate base, on the other hand, is referred to as ______ or _________.

Answer 8

unionized - undissociated (acid)

ionized - dissociated (c.b.)

Question 9

_______ compounds do not partition well.

Answer 9

Charged

Question 10

Ka is associated with the ________ constant or acid dissociation.

Answer 10

equilibrium

Question 11

If Ka is 1/10^5, what does that mean?

for an acid

Answer 11

This means that only 1 molecule in 100 000 of that acid is dissociated.

Question 12

if the Ka is 10^-5, what is the pKa?

Answer 12

5

pka = -logKa

Question 13

Weak acids are what? (defn)

Answer 13

Ionize partially in water.

Question 14

______ can function both as a weak acid or base.

Answer 14

water

Question 15

__% of the drugs we use are weak acids or bases.

Why?

Answer 15

99
Strong acids are corrosive - cannot swallow, will burn mouth.
- strong base also a similar issue

Question 16

What is the Henderson-Hasselbach equation?

Answer 16

pH - pKa = log [(deprotanated form)/(protonated form)]

Question 17

Example question:
Calculate the ratio of non-ionized/ionized form of acetic acid at pH 7. The pKa of acetic acid is 5.
Acetic acid = CH3COOH.
Remember to indicate meaning.

Answer 17

Meaning:

At pH 7, 100 molecules in 101 of acetic acid are dissociated (ionized).

Question 18

Factors affecting the strength of an acid:

• The more _____ the conjugate base (anion) formed, the _______ the acid will be
• So, any factor that will stabilize the anion will increase the ________ of the group, such as resonance and induction stabilization
• Stable negative charges results from _______ the electron density on the atom

Answer 18

stable –> stronger
(can also reverse both)

acidity

lowering

Question 19

What are the factors affecting the strength of an acid?

Answer 19

• the more stable the c.b. –> the stronger the acid

Thus, factors stabilizing the anion will increase the acidity of the group
ex: resonance stabilization, induction stabilization

Question 20

What do stable negative charges result from?

Answer 20

Lowering the electron density on the atom.

Question 21

Which is the stronger acid?
pKa = 0.9
pKa = 10

Answer 21

0.9

the lower the pKa, the stronger the acid

Question 22

Which is a stronger acid, trichloro-acetic acid or phenol?

Answer 22

Trichloro acetic acid

(Chlorine stabilizes the negative charge due to high electronegativity.

Question 23

What is the general equation for base protonation?

Answer 23

BH+ B + H+

Question 24

The conjugate acid is also referred to as what? (______ form)

Answer 24

ionized/undissociated

Question 25

The base is also referred to as what? (________ form)?

Answer 25

unionized, dissociated

Question 26

Weak ______ tend to absorb well in our bodies.

A lot of drugs isolated from nature tend to be ______.

Answer 26

bases

basic

Question 27

What is a weak base?

Answer 27

Ionizes partially in water.

Question 28

Basicity means ________ of electrons.

Answer 28

availability

Question 29

Basicity:

• if the atom has an available _____ ____ of electrons, it can act as a _______
• the ________ of these electrons will determine the _______ of the base
• As a result of that, _______ amino groups tend to be weaker bases than ________ ones.

Answer 29

lone pair - base
availability, strength
aromatic, aliphatic

Question 30

What is an aromatic amino acid?

Answer 30

Aromatic - conjugate system - move in resonance in benzene ring - less available to accept proton compared to aliphatic.

Question 31

A strong base will have a higher or lower pKa?

Answer 31

higher

Question 32

pH changes can influence the ratio of ______ to _______ forms of a drug.

Answer 32

ionized: unionized

Question 33

A drug has a pKa of 4.4. It is a weak acid.
The pH of the stomach is 1.4.
That of the blood (tightly associated) is 7.4.
What occurs?

Answer 33

Following absorption, the majority of the weak acid drug remains in the vascular system because they are ionized and cannot return into the gut.

Question 34

Why is it Important to study the pKa values for acidic and basic drugs:

Answer 34

Only the non-ionized forms of a drug can partition biological membranes (provided that the non-ionized form is lipophilic)

The ionized form tends to be water soluble - which is required for drug administration and distribution in plasma.

Question 35

If the pH shifts the balance towards the unionized form, the drug would be _______.

Answer 35

absorbed

Question 36

If the pH shifts the balance towards the ionized form, the drug would be ________.

Answer 36

not absorbed

Question 37

How can an increase in absorption occur for a topical treatment?

Answer 37

Add neutralizing agent in dosage form.

Question 38

If a person has stomach ulcers but needs to take aspirin, what can be done?

Answer 38

Coat it with buffer in the dosage form (tablet) so it will instead be absorbed in the small intestine.
(since aspirin is acidic)

Question 39

Assume the pH of the stomach is 2 and the pH of the SI is 8.
Where would you expect an acidic drug with a pKa of 4.0 to be absorbed?
Remember to add meaning in your answer.

Answer 39

Absorption occurs in the stomach rather than the small intestine.
ratio of ionization: 100:1.

Much lower in the small intestine.

Question 40

Assume the pH of the stomach is 2 and the pH of the SI is 8.

Where would you expect a basic drug with a pKa of 7.8 to be absorbed?

Answer 40

The greatest absorption will occur in the small intestine.

Question 41

Sometimes, for an acidic drug, it doesn’t absorb well in the small intestine but, this is still adequate. Why?

Answer 41

The SI has such a large surface area that a decent quantity can still be absorbed.

Question 42

For acids, which form will partition better?

Bases?

Answer 42

Acids

• HA : protonated - partitions better
• A- : deprotonated - partitions worse

Bases:

• B : deprotonated form, partitions better
• BH+ - protonated form, partitions worse

Question 43

What is the ratio for describing %ionization for acidic drugs?
Basic drugs?

Answer 43

Acidic drugs:
= deprotonated/protonated or conjugate base/acid

Basic drugs
= deprotonated/protonated or base/conjugate acid

Question 44

Loratadine has a pH of 5, is absorbed orally and is a basic drug.
Calculate the %ionization in the stomach and in the SI. (pH of 2 and 8, respectively.)
Where would it be best absorbed?

Answer 44

Stomach: %ionization is 99.9% (1000100/1001)
Intestine: % ionization is 0.1% (1100/1001)

It will be better absorbed from the intestinal membrane, not from the stomach.

Question 45

Is loratadine basic or not (refer to posted powerpoint)?

Why?

Answer 45

Basic

The reason being there are no carboxylic groups and two nitrogens with lone pairs.