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