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