Section 1 - Review of biochemistry & Human physiology Flashcards
Why is pH so important in pharmacology?
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.
If a drug is charged, it will have difficulty ________ the membrane.
Why?
Partitioning
Charged molecules do not diffuse through membranes well.
pKa is a ______ term from pH.
different
What is Keq?
Ratio of products to reactants.
A + B C + D
Keq = [C][D]/[A][B]
Acids are _____ donors.
Bases are _____ acceptors.
acid = proton donors
base = proton acceptor
An acid is a substance that can dissociate to give __ and a negative ion (anion) called the ______ ______.
H+
conjugate base
The general equation for dissociation of an acid is?
HA H+ + A-
HA - acid
H+ - proton
A- - conjugate base
An acid is referred to as _______ or ________.
The conjugate base, on the other hand, is referred to as ______ or _________.
unionized - undissociated (acid)
ionized - dissociated (c.b.)
_______ compounds do not partition well.
Charged
Ka is associated with the ________ constant or acid dissociation.
equilibrium
If Ka is 1/10^5, what does that mean?
for an acid
This means that only 1 molecule in 100 000 of that acid is dissociated.
if the Ka is 10^-5, what is the pKa?
5
pka = -logKa
Weak acids are what? (defn)
Ionize partially in water.
______ can function both as a weak acid or base.
water
__% of the drugs we use are weak acids or bases.
Why?
99
Strong acids are corrosive - cannot swallow, will burn mouth.
- strong base also a similar issue
What is the Henderson-Hasselbach equation?
pH - pKa = log [(deprotanated form)/(protonated form)]
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.
Meaning:
At pH 7, 100 molecules in 101 of acetic acid are dissociated (ionized).
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
stable –> stronger
(can also reverse both)
acidity
lowering
What are the factors affecting the strength of an acid?
- 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
What do stable negative charges result from?
Lowering the electron density on the atom.
Which is the stronger acid?
pKa = 0.9
pKa = 10
0.9
the lower the pKa, the stronger the acid
Which is a stronger acid, trichloro-acetic acid or phenol?
Trichloro acetic acid
(Chlorine stabilizes the negative charge due to high electronegativity.
What is the general equation for base protonation?
BH+ B + H+
The conjugate acid is also referred to as what? (______ form)
ionized/undissociated
The base is also referred to as what? (________ form)?
unionized, dissociated
Weak ______ tend to absorb well in our bodies.
A lot of drugs isolated from nature tend to be ______.
bases
basic
What is a weak base?
Ionizes partially in water.
Basicity means ________ of electrons.
availability
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.
lone pair - base
availability, strength
aromatic, aliphatic
What is an aromatic amino acid?
Aromatic - conjugate system - move in resonance in benzene ring - less available to accept proton compared to aliphatic.
A strong base will have a higher or lower pKa?
higher
pH changes can influence the ratio of ______ to _______ forms of a drug.
ionized: unionized
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?
Following absorption, the majority of the weak acid drug remains in the vascular system because they are ionized and cannot return into the gut.
Why is it Important to study the pKa values for acidic and basic drugs:
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.
If the pH shifts the balance towards the unionized form, the drug would be _______.
absorbed
If the pH shifts the balance towards the ionized form, the drug would be ________.
not absorbed
How can an increase in absorption occur for a topical treatment?
Add neutralizing agent in dosage form.
If a person has stomach ulcers but needs to take aspirin, what can be done?
Coat it with buffer in the dosage form (tablet) so it will instead be absorbed in the small intestine.
(since aspirin is acidic)
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.
Absorption occurs in the stomach rather than the small intestine.
ratio of ionization: 100:1.
Much lower in the small intestine.
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?
The greatest absorption will occur in the small intestine.
Sometimes, for an acidic drug, it doesn’t absorb well in the small intestine but, this is still adequate. Why?
The SI has such a large surface area that a decent quantity can still be absorbed.
For acids, which form will partition better?
Bases?
Acids
- HA : protonated - partitions better
- A- : deprotonated - partitions worse
Bases:
- B : deprotonated form, partitions better
- BH+ - protonated form, partitions worse
What is the ratio for describing %ionization for acidic drugs?
Basic drugs?
Acidic drugs:
= deprotonated/protonated or conjugate base/acid
Basic drugs
= deprotonated/protonated or base/conjugate acid
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?
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.
Is loratadine basic or not (refer to posted powerpoint)?
Why?
Basic
The reason being there are no carboxylic groups and two nitrogens with lone pairs.
