Pharmaceutics Exam 1 Lecture 3
If acetic acid (pKa 4.75) is dissolved in a solution with pH 7.8, what is the fraction of ionized and unionized acetic acid?
% Ionized = 100 / 1 + 10^(4.75-7.8) = 99.9% ionized Ratio = 0.999 to 0.001
What does a lower pKa indicate?
- higher Ka - stronger acid - weaker conjugate base
What does a higher pKa indicate?
- lower Ka - weaker acid - stronger conjugate base
What is the percent ionization of a weakly acidic drug (pKa 4.43) at pH 6.2?
100 / 1 + 10^pKa - pH = 98%
Water's own dissociation constant Kw equals...
10^-14
An acidic drug is at least 99% unionized when the pH of the solution is at least ________ units lower than the drug pKa.
2
Ionization of drugs reduces their passive reabsorption from the renal tubules back to the blood. The renal excretion of amphetamine is highly dependent on urinary pH. Would you expect alkaline urine to increase or decrease elimination of amphetamine? pKa = 9.9
Alkaline urine pHs result in less ionization and reduced renal elimination
1. What is the isoelectric point of cysteine? (acidic pKa: 1.86, amine pKa: 10.25, side chain pKa: 8.00)
COOH pKa = 2.05, amine pKa = 10.25, side chain pKa = 8.00 2.05 + 8.00 / 2 = 5.025
Examples of basic drugs
Clopidrogel bisulfate Metformin HCl
Ionization affects drug behavior from formulation to excretion...
Formulation - salt forms, aqueous solubility, stability A - partitioning across membranes and absorption D - protein binding and distribution M - binding to metabolic enzymes E - renal excretion D - drug interactions (ionic interactions)
How do proton pump inhibitors affect gastric pH? normal gastric pH = 1.5
Increases pH to 4.7-6.4
In terms of a drug, what is a salt?
a crystal form of an ionized acidic or basic drug and counterion
Examples of acidic drugs
atorvastatin calcium levothyroxine sodium
The amount of acid/base needed to change the pH of a 1 liter of solution by 1 pH is called ____________________.
buffer capacity
What species has greater solubility?
charged species
When calculating the isoelectric point of a zwitterion with only 1 positive and 1 negative charge, you will take the ______________ of the pKas.
mean
Salts of cationic basic drugs have __________ counterions
negative
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?
pH = pKa + log [A-] / [HA] 5.2 = pKa + log (0.8/1) 5.2 - log (0.8/1) = pKa pKa = 5.30
Aspirin has a pKa of 3.4. What is the ratio of A- to HA in (a) the blood (pH 7.4) and (b) the stomach (pH 1.4)?
pH = pKa + log [A-]/[HA] 7.4 = 3.4 + log [A-]/[HA] 4.0 = log [A-]/[HA] 10^4 = [A-]/[HA] 10000 = [A-]/[HA] pH = pKa + log [A-]/[HA] 1.4 = 3.4 + log [A-]/[HA] -2.0 = log [A-]/[HA] 10^-2 = [A-]/[HA] 0.01 = [A-]/[HA]
Salts of anionic acidic drugs have _________ counterions
positive
The dissociation constant, Ka, equals the concentrate of __________ times the concentration of the _______________ divided by the concentration of _______________.
protons, conjugate base, acid
What are the uncharged and charged species for bases?
uncharged = BH+, charged = B
What are the uncharged and charged species for acids?
uncharged = HA, charged = A-
What kind of drug crosses membranes more readily?
unionized drug
Buffers are a mixture of a __________ and its ________________.
weak acid, conjugate base
The isoelectric point is the pH when an ________________ molecule has no net charge.
zwitterion