Class 3

pKa

-logKa

1. What will be the fraction of unionized species for a weakly basic drug with a pKa of 8.4 in a solution of pH 9.4? 0.99 0.90 0.50 0.10

0.90

1. What is the pH of a buffer solution with a pKa of 4.50, an acid concentration of 0.02M, and salt concentration of 0.01M? 3.20 4.20 4.80 5.20

4.20 pH = pKa + log (salt/acid)

percent free acid at equilibrium

50

bases counterion

negative - anion but not always...look under description/section 11

Buffers

solution that resists change in pH - typically a mixture with a conjugate acid base pair

Percent Ionization

the concentration of ionized acid in a solution divided by the initial concentration of acid multiplied by 100%

Dissociation Constant

(Ka) expresses the amount of dissociation of a compound in water.

what will the fraction of unionized species for a weakly basic drug with a pKa of 8.4 in a solution of pH 6.9

0.01

1. If the drug is in a solution where pH equals the drug's pKa, if you decrease pH by 1 unit, ___ of the drug will exist as HA and __ as A-.

1. If the drug is in a solution where pH equals the drug's pKa, if you decrease pH by 1 unit, __90%_ of the drug will exist as HA and __10%__ as A-.

1. The dissociation constant, Ka, equals the concentrate of __ times the concentration of the __ divided by the concentration of ___.

1. The dissociation constant, Ka, equals the concentrate of __protons_ times the concentration of the __conjugate base_ divided by the concentration of ___acid (HA)__.

1. Water's own dissociation constant, Kw, equals ___.

10E-14

1. An acidic drug is >99% unionized when the pH of the solution is at least ___ units lower than the drug pKa. 2 3 4

2

physiological pH

7.4

1. What is the isoelectric point of cysteine? -COOH pKa: 2.05, amine pKa: 10.25, side chain pKa: 8.00.

A: 5.03 (2.05 + 8.00) / 2 = 5.03

Basics on solubility

Bases are more soluble at a lower pH where they are ionized Acids are more soluble at a higher pH where they are ionized Ionized is more soluble Unionized is more lipophilic / more able to dissolve in fats, oils and lipids

free acid

HA

Strong bases (pKa >10)

Ionized at all pH values Poorly absorbed from GIT

Equilbrium - constant is

Ka = [H3O+] [A-]. / [HA] Kb = [OH-] [BH+] / [B]

Isoelectric Point

The pH value at which the amino acid exists as a zwitterion

Very weak acids (pKa > 8.0)

Unionized at all pH values Absorbed along the entire GIT

Very weak bases (pKa < 5)

Unionized at all pH values Absorbed along the entire GIT

1. The isoelectric point is the pH where an ____ molecule has no net charge.

__zwitterion__

drug ionization is a result of

acid-base equilibrium

Le Chatelier's Principle

if a system at equilibrium is subjected to a stress, the equilibrium is shifted in the direction that tends to relieve the stress

pharmaceutical salt

ionizable drug that has been combined with a counter-ion to form a neutral complex

Strong acids (pKa < 2.5)

ionized at all pH values Poorly absorbed from GIT

1. Unionized, neutral compounds have (higher / lower) solubility in a polar solvent.

lower

1. A buffer at a given concentration will have a (maximum / minimum) buffer capacity when the ratio of base to acid is 1:1.

maximum

When calculating the isoelectric point of a zwitterion with only 1 positive and 1 negative charge, you will take the (sum / mean) of the pKa's

mean

Zwitterion

net charge is zero

When pH is over two units away from pKa

over 99% of the drug will exist in one form

1. What is the pH of a buffer solution containing 0.025 mol of ethanoic acid (pKa = 4.76) and 0.035 mol of sodium ethanoate in 1 liter of water?

pH = pKa + log ([A-]/[HA]) [A-] from sodium ethanoate [HA] from weak ethanoic acid pH = 4.76 + log (0.035 M/0.025 M) pH = 4.76 + 0.15 = 4.91

Henderson-Hasselbalch Equation

pH = pKa + log [A-]/[HA]

-logKa =

pKa

pKa values do not tell you hwether a compound is an acid or a base

pKa tells the relative strength of an acid

Brønsted-Lowry Acid

proton donor

1. Buffers are mixtures of a (weak acid / strong acid) and its conjugate base.

weak acid

The higher the pKa the

weaker. the acid

1. The amount of acid/base needed to change the pH of 1 liter of solution by 1 pH unit is called ___.

buffer capacity

drug salt

crystal form of an ionized acidic or basic drug and a counterion

More dissociation leads to higher concentration of conjugate which leads to

higher Ka or. Kb value

The lower the pKa the

higher Ka, stronger acid, weaker conjugate base

1. If the pH of the solution begins much lower than an acidic drug's pKa, but is then titrated so that pH approaches the pKa, the percent ionization (increases / decreases).

increases

Buffer Capacity

magnitude of resistance - amount of acid/base needed to change pH of 1 liter of solution by one unit ...depends on magnitude of [A-] and [HA] separately

uncharged species are ___ and have ___ solubility than a charged species

more readily absorbed less solubility

1. What is the pKa of a weakly acidic drug when, upon dissolving in a solution with a pH of 5.2, the ratio of salt: acid (i.e. A-:HA) is measured to be 0.8:1?

A: 0.0575 M pH = pKa + log([A-]/[HA]) 1.2 = pKa + log(0.8/1) 1.3 = pKa

Alkaline urine pHs result in __ ionization and __ renal elimination

Alkaline urine pHs result in less ionization and reduced renal elimination

acids counterion

positive - cation ex: Warfarin has Na+ ....having this positive counterion warfarin is an acid

Brønsted-Lowry Base

proton acceptor - usually has a lone pair

pH<pKa, the species is

protonated. A protonated acid is unionized, but a protonated base is positively charged

amphoteric

a substance that can act as both an acid and a base