General Principles of Pharmacology Flashcards
Henderson-Hasselbach effect on drug absorption and excretion
When pH = pKa, what is the relationship between protonated and unprotonated weak acid or weak base?
Protonated and unprotonated are equal.
Remember that pKa is the value at which protonated and unprotonated are at equilibrium– it is a set value for that specific acid or base. pH is variable and is dependent on the degree of protonation of the weak acid or base.
In what form are weak acids and weak bases ionized? (Note: Ionized means it has a charge)
Weak acids are ionized as A- and H+. When the pH is greater than the pKa, the acid is ionized and unprotonated (in order to get more free H+ and lower the pH).
Weak bases are ionized as BH+. When the pH is less than the pKa, the weak base is protonated an ionized (in order to remove free H+ from the environment and raise the pH to match the pKa).
In each of these, think about what you would need to do to free H+ concentration in order to match the pH to the set pKa. (A higher pH needs more free H+ to get back down to pKa)
In the intestine (pH 8.0), which will be better absorbed, a weak acid (pKa 6.8) or a weak base (pKa 7.1)?
A weak base.
Drugs absorb through membranes better when they are UNCHARGED. At the levels shown, the base will be unprotonated and unionized (B + H+) in order to lower the pH. B is uncharged, so it is absorbed well.
The weak acid will be unprotonated and ionized (A- and H+) in order to bring down the pH. Because A has a charge, it will not be absorbed as well
If we alkalinize the urine to a pH of 7.8, will a lower or higher percentage of a weak acid (pKa 7.1) be ionized, compared with when the urine pH was 7.2?
Higher.
The pH or the urine is increased. That means that the acid wants to decrease the pH even more in order to match the pKa. The acid will be more unprotonated and ionized to form more H+ (will be more A- and H+ as the pH increases away from the pKa)
More weak acid will be ionized the more the pH exceeds the pKa.
When the pH is GREATER THAN the pKa, what forms are the weak acids and bases in?
Remember that when pH is greater, we want more H+ to lower the pH to match pKa.
Weak Acid– H+ and A- (ionized, unprotonated)
Weak Base– B and H+ (nonionized, unprotonated)
** BOTH are unprotonated when pH is greater in order to get lots of free H+!!
When the pH is LESS THAN the pKa, what forms are the weak acids and bases in?
Remember that when pH is lower, we want less H+ in the environment in order to raise pH to match pKa.
Weak acid– HA (nonionized, protonated)
Weak base– BH+ (ionized, protonated)
** acid and base are both protonated when the pH is lower in order to remove H+ from the environment
What does “ionized” mean, and in which situation are weak acids and bases ionized?
Ionized means that the acid or base has a charge. Bases will be ionized with a positive charge, and acids will be ionized with a negative charge.
Acids– ionized as H+ and A- when the pH is HIGHER than the pKa
Bases– ionized as BH+ when the pH is LOWER than the pKa
Describe the concept of “ion trapping” as it relates to acid and base accumulation on either side of the membrane.
In general, cells are more acidic on the inside. In an acidic environment, we want less free H+ floating around. Therefore, bases are BH+ (ionized, protonated), and acids are HA (nonionized, unprotonated).
Things without a charge are able to cross the membrane a lot easier. So, basic drugs will build up on the acidic side of the membrane, because the pH is low and the base is ionized as BH+ – cannot cross membrane easily.
Acids would build up on the basic side of the membrane. The pH here is higher, so the acid is in the ionized, unprotonated form in order to decrease pH (A- and H+). Because the acid is charged, it does not easily cross the membrane and is “trapped” on the basic side.
“Ion trapping is an important determinant for where, when, and how much drug absorption, distribution, and excretion takes place”.
(TR) A patient is prescribed codeine, a weak base (pKa = 8.2) for pain management. According to the pharmacokinetics of codeine, which of the following is true?
Acidification of urine will increase excretion rate.
Free drugs are filtered into the urine through glomerular filtration. Some drugs are taken back up into blood through distal tubular reabsorption– this is the part that depends on the pH of the urine.
When the urine pH is decreased, the base wants to raise it to match pKa, so it decreases the amount of H+ in the environment (BH+ is predominant). Because the base is ionized, it is not able to cross the membrane (ion trapping), so it is excreted in the urine.
When the pH of the urine is basic and the renal clearance increases, what kind of drug (acidic or basic) is being excreted?
A weak acid/acidic drug is being excreted.
Clearance = rate at which drug is cleared from the body. (Rate of drug removal / plasma concentration of drug)
When the pH is basic, drugs want to increase the amount of free H+. Acids will be unprotonated and ionized (A-) and bases will be unprotonated and unionized (B). Therefore, the basic drug can cross from the kidney back to the bloodstream, but the acid is charged and remains in the kidney to be excreted in the urine.
In the stomach, which forms do acidic and basic drugs have?
Acids are nonionized in the stomach (HA) and bases are ionized (BH+). This is to decrease the H+ in the environment in order to raise the pH of the stomach to match the pKa of the drugs.
