Anybody want to discuss pKa?

[traumaguy8]

So, I am taught that an anesthetic's pKa is important because it is important to know how the drug's actions will be altered across varying levels of plasma pH.

Well, I get the importance of knowing how the drug's actions will be altered across varying levels of plasma pH but I can figure this out without knowing the drug's pKa. In other words, as long as I know whether the drug is a weak acid or base and the value of the patient's pH, I can figure out how the drug's actions will be altered.

Right?! Or am I missing something?

For example, say we have patient X that recieves "medication A." Medication A is a weak acid and the patient's pH is 7.4. The medication is distributed at a textbook onset of action time. Now, lets say the patient plugs off or something causes a new pH of 7.25 and medication A is given again.

Q: "What changes would you expect to see in the effects of medication A the second time it is given?"

A: Medication A is a weak acid that is being introduced into the blood with a lower than physiologic pH; therefore, the non-ionized (lipophilic) form of medication A will dominate and be distributed to the site of action faster causing a faster onset of action.

If the above is correct, then I can come to this conclusion without knowing medication A's pKa. So, why is it important?

[Mully]

I'll take a stab at it. Others can correct me if I'm wrong...

Ok, in the sense of the question you posed, you could technically figure out at which pH the drug would be more ionized vs. unionized. The problem comes in when you want to know exactly how much the drug is or is not ionized quantitatively. This is important because say the drug that you gave at pH 7.4 and pH 7.25 had a pka of 4. The drug would have such microscopic amounts of non-ionized form that in both scenarios, you would see no effect. Technically speaking, placing it in the 7.25 pH pt would have a tiny, tiny, tiny bit more non-ionized, but it would be inconsequential.

However, say the patient took the medication orally. The drug would enter the patient's stomach which say had a pH of 2.5. Now you're placing an acid drug in a more acidic environment (2.5>4 acidity-wise). This means you will have much more non-ionized drug than ionized and the drug can cross membranes (until it makes it to the bloodstream however).

Does this make sense?

You must know 3 things when considering all this. The action of the drug (whether it's a base or acid), the pH of the solution it is entering, and the pka.

Not exactly a scholarly reference, but this site explains it pretty well:

determine drug absorption by pKa

[traumaguy8]

I've totally used that website before! Your answer does answer my question. Basically, the pKa will help you know to what extent a change in the solution's pH will effect the ionization of the drug. I plugged the pKa of STP into the calculator on that website and a change from physiologic pH to a dangerously low serum pH (7.2) didn't change the ionization all that drastically. But when I compared that to a mildly high serum pH, the change in ionization was enough that it could noticeably change the pharmacokinetics enough to warrant an attenuation of the dosing for STP.

So I guess I understand but if I didn't have that calculator, It would take me way to long to work this out if I were in the OR. Is this skill ever really needed of is it just something that I need to have a basic understanding of?

[Mully]

I may not be the best one to answer that as I am only in semester 2 of anesthesia school, but so far it hasn't come into play much. It's definitely important for people who create the drugs (obviously). The only thing people have said to me is that you use this to know why certain drugs may not work in highly acidic people.

Or here's one that I just learned, it's called ion trapping in the pregnant patient. Basically you have a basic drug given to mom such as morphine. In mom's pH, the drug is mostly lipid soluble, so it crosses the placental barrier. However, baby's pH is more acidic at baseline, so the drug becomes ionized in the baby's system and doesn't cross back over to mom, essentially becoming "trapped" in baby's circulation and having a prolonged effect.

FIGURE 4-8 The effects of changes in fetal pH on the transfer of opioids during in vitro perfusion of the human placenta. This figure demonstrates the ion trapping” of opioids, which is similar to that of local anesthetics. Clearance index = clearance drug/clearance creatinine (a reference compound).

I think I'll have more applications of this in the future, but this is about all I can give you right now. Good discussion.