The Anesthesia Record

What the heck is pKa? Back in the Fall last year I made the mistake of explaining pKa to Amy.  Ever since then she has been asking me to write a post to help others grasp this concept.  I would love to sit here and pretend that this is an altruistic exercise, but the truth is that I continually get these questions wrong on exams and am writing this post as much for my own benefit as anyone else's.  So here it goes…

Figuring out pKa questions is easier if we remember one rule and ask two questions.  The rule to remember is: pKa DOES NOT equal pH.  We will get to the questions a little later. pH and pKa are related, but totally different….kind of like Stephan and Alec Baldwin.  Put simply pKa is a quality that drugs have.  It is the pH at which the drug is 50% ionized and 50% unionized. Ionization is important because drugs that are ionized cannot cross lipid membranes.  If they can’t cross lipid membranes they can’t get to their sites of action.  The site of action might be the brain, or a nerve axon, or whatever.  So ionization is bad.  The nonionized portion of the drug is the portion that crosses the lipid membrane and gets to the site of action.  This is the portion of the drug that “works”, therefore the nonionized part is good.

I’m gonna go way back in the memory banks here and bring back some basic chemistry.  Remember how acids and bases behave?  Acids donate H+ and bases accept them.  (H+) + (OH-) <==> HOH.  When acids and bases are mixed together they are in a constant flux of ionization (which is bad).  But, if we mix a base in a basic environment or an acid in an acidic environment ionization doesn’t happen; there is nothing there to donate an H+ to and nothing there to accept one.  The drug is less ionized (or more nonionized), which is good.

This brings us to the first question we need to ask:  Is the drug we are examining an acid or a base?  Examples of basic drugs are local anesthetics and opioids; some of our acidic drugs are the barbiturates. 

So let’s pretend we are dealing with the basic drug lidocaine, whose pKa is 7.74.  So at a pH of 7.74 there is exactly 50% ionized lidocaine and 50% unionized.  Is this drug an acid or a base?  A base, like we just talked about. 

This brings us to our second question:  Are we placing our drug into a relatively more acidic or basic environment compared to the drugs pKa?  What is normal body pH?  Anyone, anyone…Bueller…7.4.   So, if we put this basic drug which is 50/50 at a pH of 7.74 into a relatively more acidic environment (body pH is 7.4, therefore relatively more acidic than 7.74) will we get more ionized or unionized drug?  I really hope you all said more ionized. 

Let’s deal with an acidic drug, like the barbiturates. The pKa of methohexital is 7.92.    So, we know this is an acidic drug that is 50/50 at a pH of 7.92.  Now we inject that into the body with a relatively more acidic pH of 7.4, will there be more ionized or nonionized drug?  Please say more nonionized. 

Did anyone notice that this acidic drug had a pKa greater than 7.0?  This is an excellent example of our #1 rule: pKa DOES NOT equal pH.

On exams I always find it super helpful to draw it out.  Here are some extreme examples (Click on each to enlarge):