Hi guys, Jessica here, and welcome to CritIC, the pharmacokinetics series. Let's hop directly into absorption. Absorption is the process of a drug getting into the systemic circulation. This is obviously governed by how you take the drug.
If you take it intravenously, Captain Obvious here, 100% of what you give the patient gets into the main bloodstream. We say that the bioavailability, denoted as F, is 100%. Now, if you take a drug orally, it needs to be absorbed by the gut. If only 50% of what you give the patient gets into the systemic circulation, We say that the bioavailability of that drug is 50%.
An example of this is furosemide. Let's take a look at the way a drug travels through the body. When you take a drug orally, the drug will first encounter the stomach and its acid.
It then needs to cross the cell membrane of the intestine to get into the portal circulation. It then passes the liver and enters the systemic circulation. So what factors can influence these steps of absorption and thus bioavailability?
First, your patient needs to actually take the darn pill. Though it's not considered pharmacokinetics, never forget compliance when it comes to judging the effectiveness of your treatment. Anyway, when the drug reaches the stomach, it will be exposed to the acidity of the stomach fluid.
pH influences absorption in two ways. If a drug is chemically unstable, Acidity, meaning low pH, will degrade it. This is why benzyl penicillin, or penicillin G, cannot be given orally. I'll get back to the second way in a minute.
The stomach could contain food or other medication that influences absorption. For example, calcium or iron in the stomach will decrease absorption of certain antibiotics, like cyprofloxacin and doxycycline, by forming insoluble complexes. Next, the drug travels to the intestine, where it needs to cross the cellular membrane.
You can imagine that the amount of drug that can cross the membrane depends on the surface area of the intestine, and how long a drug gets to be there. Patients that underwent bariatric surgery will miss a large portion of their stomach and small intestine, so absorption could very well be a problem for them. Also note, most bariatric patients will need to use supplements like iron, that can influence absorption as well, as explained earlier. Exposure time is decreased in patients with diarrhea and could be increased in patients with ileus. Also remember that certain medication can increase or decrease gut motility, examples being metoclopramide and opioids respectively.
Decreased splanchnic blood flow will result in less absorption, which is the case for patients in shock and patients with advanced atherosclerosis. In order for the drug to actually cross the lipid-rich cellular membrane, it will need to be lipid-soluble enough. This is why some drugs, like gentamicin, cannot be given orally. And this brings us to the second way pH influences absorption. Uncharged molecules, i.e. non-ionized molecules, are more lipid-soluble and can cross cell membranes.
Therefore, lipid solubility is highly dependent on the acid dissociation constant of a drug versus the pH of its environment. Most drugs are either weak acids or weak bases. In an acidic environment like that of the stomach, weak bases will be ionized, so they will not be absorbed. In more alkaline environments like in the intestine, these weak bases will not be ionized and can be absorbed. For drugs that are weak acids, it's vice versa.
And just for reference, about 12% of people in my country use proton pump inhibitors, so go figure. It should be mentioned that there are several transporters on the intestinal cell membrane that can actively pump drugs in or out of the cell. An important one is P-glycoprotein, or PGP, which actively pumps the drug out of the cell, decreasing absorption. PGP and other transporters are also expressed in other areas of the body, like the tubular cells of the kidney. These transporters are of great interest in pharmacokinetics because these transporters can be induced or inhibited by other drugs.
I'll come back to transporters like PGP in the excretion video. After the drug crosses the cell membrane, it gets into the portal circulation, not the systemic circulation. The portal blood flow determines the rate at which the drug is presented to the liver.
So before the drug can go to any other organ, the liver will have its fair share, and will metabolize some of the drug. This is called the first pass effect, and it can be quite large. For example, nitroglycerin for angina. Ever wonder why we use a spray or tell people to place the pill under their tongue? This is because the first-pass effect of nitroglycerin is so large, almost nothing reaches the systemic circulation.
So why is all this important? Remember the bioavailability of furosemide being 50%? Well, imagine a patient that normally uses 80 milligrams of furosemide a day.
He's admitted to your hospital and isn't allowed to eat because of a procedure that day. How would you dose it intravenously? Well you know the bioavailability of furosemide is 50%, so only 50% of that 80mg, being 40mg, makes it into the systemic circulation. This means that 80mg of furosemide orally equals 40mg intravenously.
You would have doubled their dose if you didn't adjust for this. So, bioavailability is important in converting drugs from oral to IV dosage and vice versa. And you need to know what factors can influence this. This is it for absorption. If you liked this video, please give it a thumbs up and share it, and be sure to check out the next one, where we'll talk about what happens with a drug once it has entered the systemic circulation in distribution.
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