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.
The lecture pKa and Drug Solubility – Absorption and Distribution | Pharmacokinetics (PK) by Pravin Shukle, MD is from the course Pharmacokinetics and Pharmacodynamics.
A 44-year-old woman presents to the hospital ER with a low blood pressure of 77/40, a heart rate of 40, and normal pupils. She has an empty bottle of blood pressure pills that have a pKa of 7.5. You want the patient to excrete the drug in the urine. What is the most appropriate action?
A 5-year-old child overdoses on her mother's anti-depression medication. The pKa of the drug is 3.9. The pH of the small bowel is 5.9. What is the ratio of protonated to unprotonated molecules?
A patient has overdosed on pyrimethamine, which has a pKa of 7.42. What percentage of the drug will be trapped in the urine if the urine pH is 5.42?
A patient has overdosed on pyrimethamine (a weak base). It has a pKa of 7.42. What portion of the drug will be hydrophilic at a urine pH of 8.42?
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Rather than giving us mnemonic, I'd rather had him explained. I had to go to Youtube to find out what this means and it took me a lot of time.
I love the course, it's easy to learn and to understand
sorry to say it is really not well explained or concept clearing kindly modify lecture
I found this lecture illuminating. I think adding an image might help to clarify the solubility issue: AH can diffuse through lipid bilayer, but is less soluble in water, so would become "trapped" in urine, and the inverse for bases: B form being soluble in lipids, but not in water. Thank you for the great lecture!