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The Addicted Brain

Video 2.1

Hello, today we are going to talk about what the body does to drugs after you take them.

Drugs have to get the brain. That’s the only way they can make someone feel different, and

it’s the only way to get high. For drugs to get into the brain, they have to be in the blood,

and various factors determine how much drug gets into the blood and brain, and how long

they remain there.

Overall, what happens to drugs in the body is called drug dynamics.

The first thing that happens after you take a drug orally is that it has to be absorbed from

the stomach and the intestines into the blood. From the blood, it passes into the brain, and

again, all of these drugs have to get into the brain to have an effect. A large fraction of the

blood pumped from the heart goes to the brain.

Drugs that are injected directly into the bloodstream are not absorbed by the stomach, but

are still passed into the brain. Some drugs, such as nicotine or inhalants, are absorbed

directly from the air in the lungs to the blood.

Different drugs have different absorption efficiencies. Some drugs are nearly all absorbed

and others are not.

The next step is that drugs are metabolized or changed. The metabolism or chemical

modification of the drugs can result in the cessation of their action, and metabolism can

also enhance the next step, which is excretion. Drug metabolism usually takes place in the

liver but it can take place in other bodily organs as well; it's the enzymes in the liver and

elsewhere that modify the structures of drugs.

An example is the metabolism of ethanol. Ethanol – or alcohol -‐ is acted upon by an enzyme

called ethanol dehydrogenase (and other enzymes) to form acetaldehyde which is then

changed further into acetate. Acetate is not an active substance, so a metabolite of ethanol

is inactive and the effect of taking ethanol is terminated by its metabolism.

This next example shows the many possible metabolites of nicotine. You can see that it is

extraordinarily complicated and many different kinds of metabolites and chemical

structures are possible. Of course you don't have to remember all of this. I show you this

just to give you an appreciation of how complicated drug metabolism can be.

The next and final step in a drug’s journey in the body is drug elimination. Drugs and their

metabolites are removed from the body, mainly in the urine or feces.

A couple of important concepts related to drug elimination include clearance, which is a

measure of the body's efficiency in eliminating the drug, and the second is elimination half-‐

life. The half-‐life of the drug is a measure of the rate of removal of drug. It's the time needed

to remove or metabolize 50% -‐ or a half) of the drug.

So, we have discussed three main steps: drug absorption, drug metabolism, and drug

elimination.

This graph deals with the idea of half life. It shows the disappearance of two different

substances, A and B, from the blood, and they have different half lives. Drug A has a shorter

half life and Drug B has a half life twice that of A. When we look at the levels of these drugs

in the blood (the solid lines starting at 8) you see that one of the curves falls to zero much

faster than the other, and that means that drug A a has a shorter half-‐life. If the half-‐life is

shorter then the drug disappears faster. Normally for 97% of a drug to be eliminated from

the body it will take five half-‐lives.

But, if a drug is taken orally, then the drug has to be absorbed first and then builds up

slowly in the blood. After it builds up to its peak, then it is eliminated at a rate according to

its half life.

Now I will introduce the topic for next time. One of the practical impacts of a drug being

excreted into the urine is that many drug screens and tests have been developed to screen

for the presence of drugs in the urine. It's interesting that sometimes the metabolites of a

drug persist in the urine for longer periods of time than the drug itself. Therefore the

targets of the tests can be the metabolites.

We’ll discuss this in more detail next time.

Video 2.2

We discussed how the body handles drugs, and having noted the fact that drugs and/or

their metabolites end up in the urine as well as the blood. Now we can talk about a practical

issue-‐-‐something that follows the fact that a drug accumulates in the urine. In this video,

I'm going to talk about the various screens and tests used for detecting drugs and drug use.

I will talk a little bit about the types of tests, how they're done, and what they can show.

There are many variations on the assays and methods, but I’ll present some of the more

typical ones.

We usually use two different words: screens and tests. A “screen” is a broad assay that

looks for many different drugs. A “test” is an assay that is very specific and rigorous. In

general, there are different kinds of assays for screens and tests . There are antibody

detection assays where the shape of the drug is detected by antibodies that bind to it,

because antibodies bind to certain shapes. That is basically what a screen is. Normally,

many different drugs with similar shapes might react in the assay, and that's why we call

them screens.

After we detect the potential presence of a drug in the urine with a screen, we then do a

much more detailed assay, usually using blood. The tests for drugs in the blood are

chemically rigorous and highly specific. Using these tests makes it clear exactly what drug

has been taken. These tests utilize expensive equipment that can include gas

chromatographs and mass spectrometers. They are very precise in their detection

methods.

When carrying out drug screenings in urine, we have to be aware that levels of a drug in

urine will vary in different people. These assays have a detection window that depends on

various factors like: how well was the drug absorbed in this individual, was the drug

metabolized, does the individual have a compromised metabolism, and so forth. All of these

factors will affect whether or not drugs are detected in the urine. I also want to emphasize

that a screen may also focus on detecting a metabolite, because the metabolite itself may

have a longer half-‐life and presence that the drug itself.

This table shows three substances and what is assayed for, and how long after taking the

drug they can be detected. First is cocaine. In many screens the assay detects a metabolite

of cocaine, rather than cocaine itself, and the detection time is 2 to 5 days. This means

cocaine can be discovered for up to 2 to 5 days after taking it. Screens can detect marijuana

as well, and some assays detect a metabolite. In a chronic user, the detection time can be

up to 30 or 60 days, a very long time. A drug like morphine is detected directly (it's not a

metabolite) in many assays, and the detection time is 2 to 4 days. From this information,

you get the idea about what's detected and the detection time, and it may vary depending

on the drug and also on the individual. In spite of the uncertainties, it is accepted that the

drug screens are quite reliable.

Screens often rely on antibodies to indicate the presence of a drug in the urine , and screens

are used because they're less expensive than the more rigorous and reliable chemical tests.

If a screen is positive, then the result can be confirmed using sophisticated analytical

chemical techniques to rigorously identify the drug that was present. Tests are usually

done with blood and the analytic equipment might include gas chromatography and mass

spectrometry.

Here are some questions to think about. First of all, why is the urine a good place to look for

drugs or the metabolites? (PAUSE)

The next question is what's the difference between a “screen” versus a “test”? Thank you

for your attention and I'll see you again soon.

Video 2.3

Hello everybody. As we discussed, a drug must get into the brain in order to have an effect.

During this lecture, we address what the drugs have to do in the brain to generate a feeling

that is positive and something that you want to feel again and again—… To understand this,

we need to discuss synaptic transmission.

Synaptic transmission is a process that occurs in the brain and is fundamental to how the

brain works. Understanding it is required for understanding how the brain functions. It is

also a key for understanding how drugs produce their effects, so this is going to be

important and fun.

Now, there are different words used and I just used the phrase synaptic transmission -‐ this

is the same as neurotransmission. You will see either term or some hybrid of these words

throughout this course.

Here we see a picture of the brain, and like any organ in the body, the brain has cells

specialized for its function. If you take a slice of the brain and look at it under a microscope,

you will see a certain cell type that we call nerve cells or neurons (and others as well).

Neurons are uniquely shaped cells tailor-‐made for an organ like the brain. The nerve cell

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Inne pliki z tego folderu:

2 - 6 - Video 2.6- Drugs are Multifunctional (8-18).mp4 (21925 KB)
2 - 3 - Video 2.3- Synaptic Transmission- The Target of Addicting Drugs (9-55).mp4 (23468 KB)
2 - 1 - Video 2.1- Drug Dynamics- The Fate of Drugs in the Body (6-08).mp4 (14851 KB)
2 - 5 - Video 2.5- Cocaine & Nicotine (6-56).mp4 (16580 KB)
2 - 2 - Video 2.2- Detecting Drugs in the Body (5-17).mp4 (12941 KB)

Week 2 Transcripts.pdf

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