The First Pass Effect in Pharmacology

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  • 0:00 The First Pass Effect
  • 1:11 The Stomach
  • 1:41 The Intestines
  • 2:52 The Liver
  • 3:41 Lesson Summary
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Lesson Transcript
Instructor: Artem Cheprasov
Did you know that when you take a pill, only a fraction of that pill actually makes it into general circulation? Do you know why this is so? It has something to do with the first pass effect.

The First Pass Effect

When you take a medication by mouth, it doesn't just magically get into your body and start doing its thing. It actually has to go through a whole host of organs and a big number of biochemicals in order to finally enter general circulation and actually exert its intended effect upon your body. In fact, the amount of a drug that is actually delivered to your general circulation is less than the total amount you initially took by mouth as a result of all of this. This concept is known as the first pass effect.

This is like someone hiking through the woods trying to get back to their car. They don't just magically teleport to the car. No! They have to go through various sections of the woods and avoid perils like wild animals that could rip off some clothing or even an arm! What's left of the person after they get back to the car is due to their own kind of first pass effect.

In other words, some of the drug is lost as it passes through the gastrointestinal system and the liver prior to reaching general circulation. That's what the first pass effect is all about. Let's explore why this is the case.

See if you can spot the organs we discuss in this lesson that are involved in the first pass effect.
Digestive system

The Stomach

Imagine taking a pill. Once you swallow that pill, it plops into the stomach. The stomach is a vat of acid. It has some very low pH (so it's acidic). We all know seriously acidic stuff can destroy even metal. Well, stomach acid can destroy some parts of a drug. As if that wasn't enough for the poor drug particles, next these guys are pumped out into the intestine from the stomach. It's not much safer here for what's left of the pill.

The Intestines

The gastrointestinal tract can contribute significantly to the first pass effect. This happens in many ways.

  • The first is by bacterial enzymes. These are proteins that speed up biochemical reactions. Basically, the enzymes might chop up and degrade the drug.
  • Next we have intestinal membrane enzymes. Again, the enzymes here may destroy the drug or convert it into something useless.
  • We also have to look at complexion with food. The drug combines with some food particles, which deactivates or degrades the drug, or it may mean that because the drug is mixed in with the food, it won't be fully absorbed. Instead, a part of the total drug taken by mouth will be simply excreted in the feces.
  • Other medications taken alongside or too closely time-wise to the drug in question can also disable the drug or interfere with its absorption into the body.
  • Finally, p-glycoproteins; interestingly enough, even if the drug is absorbed by the intestine, the intestine may spit the drug back out into what will become feces. It does so through transporters called P-glycoproteins.

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