pKa and Drug Solubility – Absorption and Distribution | Pharmacokinetics (PK)

00:01 Okay. Let's talk about a new topic. Something called pKa.

00:06 Now look at this question. Spend a little bit of time reading it.

00:11 And then we will try and go through the answer together. Okay so hopefully you have read the question.

00:19 What I want to do is I want to focus a skill that you need for your exam.

00:25 When you are writing an exam and you see a long stem like this especially for the USMLE exam.

00:31 Look at the last sentence first. Because what that's going to do it's gonna focus your attention.

00:37 Now in this particular question, the last sentence says that it has a pKa of 3.8 and what percentage of the drug will be hydrophobic.

00:47 Well, all of a sudden you have realised that the first half of that question is completely useless to getting your answer.

00:54 So you can actually just ignore a lot of that clinical information and get to the answer much quicker.

01:00 So now what we do is we want to pick between the answers.

01:03 100%, 50%, 10% and 1%.

01:06 So what percentage of the drug will be hydrophobic at a pH of 4.8 if the pKa is 3.8.

01:14 Well what is pKa? Let's go over that together.

01:18 So, aspirin has a pKa of 3.8. So what is pKa? The pKa is that pH level at which a drug is 50% protonated and 50% non-protonated.

01:33 So the ratio of protonated and non-protonated forms is 1:1.

01:38 For weak acids and you can see that because the pKa is 3.8 which is less than 7, that's an acid.

01:45 So, for all weak acids, the ratio changes to 1:10 or 10% at 1 pH unit more alkali than the pH.

01:55 And the ratio changes to 1:100 or 1% at 2 pH units. So remember that pH is a logarithmic.

02:02 So 1 unit is 10, 2 units is a 100, 3 units is a 1000.

02:07 So if you have a pKa of 3.8, and the pH of 5.8, you've got a pretty significant difference in ratio.

02:16 So 2 pH units is 1:100. So let's take a look at pyrimethamine.

02:22 Pyrimethamine is another drug that has a pKa of 7.42. That makes it a weak base, right.

02:30 Because the 7.42 is actually higher than 7.0 so anything above 7.0 is a base.

02:38 The pKa is the point at which a pH that gives you 50% protonated and 50% non-protonated drug so the ratio is 1:1.

02:50 For weak acids and bases the ratio changes by 1:10 or 1:100 for each 1 or 2 pH units you are from your pKa.

03:00 Now because it's a base, the more alkali the pH is it makes less soluble or less polar in the protonated form.

03:09 So to go over it again for weak bases, they are ionized.

03:14 They are more polar when protonated and more soluble when protonated.

03:19 With weak acids, they are not ionized. They are less polar when protonated and less soluble when protonated.

04:27 So speaking of questions let's go back to our question and our case.

04:31 The ratio changes from 1:1 to 1:10 at 1 pH unit more alkaline than the pKa.

04:38 And it changes to a ratio of 1:100 at 2 pH units that are more alkaline than the pKa.

04:44 So in the case of this question, we were saying the bottle label says that the substance has a pKa of 3.8.

04:51 What percentage of the drug will be hydrophobic or lipid soluble or lipophilic in the small bowel at a pH of 4.8.

05:01 Well what's the answer? So the answer is C, 10%.

05:07 1 pH unit difference, 10%. 1:10 ratio.

05:26 Now, why do you care about a pKa? This sounds like alot of chemistry that you left behind in pre-med.

05:33 Well the reason why we need to know this is because we need to know how to enhance excretion of a toxin.

05:41 So for example in aspirin overdose we want to alkalinize the urine.

05:46 When we alkalinize the urine with sodium bicarbonate we trap the aspirin molecules in the urine so it can't get reabsorbed back into the body.

05:55 That's how we treat an aspirin overdose.

05:58 It's also useful when we want to design a drug and when we want to mix medications.

06:03 So in the pharmacy world, it's also something that's very important.