HOW DRUGS MOVE THROUGH THE BODY

HOW DRUGS MOVE THROUGH THE BODY

GETTING IN

Drugs must get to their receptors to act. Even a skin cream like a corti­sone ointment that relieves the itch of poison ivy must be able to pass through the fatty membrane that surrounds most cells to heal the cells that are irritated by poison ivy toxin.

Most drugs must go much farther than the skin to act. Drugs used to treat tumors deep inside the body must travel from where they are placed, through the bloodstream, to be delivered to distant organs. A few drugs pass through cells so well that when they are rubbed on the skin they travel through all the skin layers down to the layer of the skin where the smallest blood vessels (capillaries) are, through the capillary walls, and into the bloodstream. Nicotine is one, which is why the nicotine skin patch works. There is also a motion-sickness drug that can travel through the skin to the brain. What is unique about such drugs is their ability to pass through a cell membrane that is very fatty However, most drugs just don't dissolve well enough in these fatty membranes to travel all that dis­tance. Such drugs prefer water to oil, and they have a great deal of trouble passing through cells: these often only enter the body well after injection.

Applying drugs to the mucous membranes is a more effective way to get some drugs into the body, because the mucous membrane surfaces of the body (as in the nose) are much thinner, and the capillaries are much closer to the surface. For these reasons, placing drugs in the nose, mouth, or rectum provides a pretty efficient route for administering some drugs. Cocaine and amphetamine enter the bloodstream easily from these sites, which is why people snort them. In contrast, antibiotics, an example of drugs that prefer water to oil, cannot cross through cell membranes and cannot be given nasally.

The most efficient way to get a drug into the bloodstream is to put it there directly. The invention of the hypodermic syringe provided the most direct means we have of getting drugs into the body: we inject them directly into a vein. The drug then goes to the heart and is distributed throughout the entire body. After intravenous injection, peak drug levels in the bloodstream occur within a minute or two. Then levels begin to fall as the drug crosses the capillaries and enters the tissues.

There are other places that drugs can be injected. Most immunizations are done by injecting the vaccine into the muscle (intramuscular). The drug is delivered a little more slowly this way, because it must leave the muscle and enter capillaries before it is distributed to the body. Drugs can also be injected beneath the skin (subcutaneously). This "skin-popping" is a route used by many beginning heroin users who have not yet started injecting heroin intravenously.

Inhaling drugs into the lungs can deliver a drug to the circulation almost as quickly as intravenous injection. Anyone who smokes tobacco takes advantage of this characteristic to deliver nicotine to the brain. The drug simply has to dissolve through the air sacs of the lungs and into the capillaries. The surface area of the lungs is very large and fat-soluble drugs like nicotine can move quickly across a large surface. In addition, the blood supply of the lungs goes directly to the heart and then out to the other tissues. Therefore, smoking can deliver the drugs to the tissues very quickly. However, only certain drugs enter the body efficiently this way. They must be very fat-soluble, and they must form a vapor or gas when they are heated. Several drugs, including cocaine and metham­phetamine, easily form vapors if they are in their uncharged form, which occurs when they are crystallized from an alkaline (basic) solution. In this case, the nitrogen that is present in each molecule is uncharged (it has no positive charge from a hydrogen ion). 'I hese qualities allow drugs to cross into the circulation very quickly. Drug users call this method of delivery "freebasing." Cigarette manufacturers create the same effect by making tobacco leaves alkaline (basic).

The most common way that people get drugs into their system is by swallowing them. Drugs that enter this way must pass through the walls of the stomach or intestine and then enter the capillaries. A large part of any drug that is swallowed never gets to the rest of the body because it is removed by the liver and destroyed. The liver is placed cleverly to do this job. All the blood vessels that take nutrients from the intestine to the body must go through the liver first, where toxic substances can be removed. This protects the body from toxic substances in food. Swal­lowing may be the easiest way to deliver drugs, but it is the slowest way to deliver a drug to the body That is why your headache is not gone five minutes after you take an ibuprofen tablet.

To recapitulate, the way people take a drug (the route of administra­tion) and the amount they take determine the drug's effects. Injecting drugs intravenously or smoking them results in nearly instantaneous effects because the levels of drug in the blood rise very rapidly. This speed accounts for the lure of injecting heroin intravenously or smoking crack. The drug effect occurs much more rapidly than if the drug was snorted. Injecting a drug intravenously or smoking it also offers the greatest risk of overdose. Drugs like heroin can be lethal because they take effect so quickly after intravenous injection that the drug user can reach fatal drug levels before it would be possible to get help. The same dose of drug taken orally will never exert as great an effect—some of it will be lost to metabolism because the process of absorption is gradual.

WHERE THEY GO

Once drugs are in the circulation, getting into most tissues is no chal­lenge. There are big holes in most capillaries, and drugs are free to go into most tissues. The brain is an important exception because it has an espe­cially tight defense—the blood-brain barrier--that prevents the move­ment of many drugs into it. All of the drugs we discuss in this book are psychoactive, in part because they easily pass through this blood-brain barrier.

Although there are myths that drugs "hide" in specific places in the body (such as Ecstasy or LSD hiding in the spinal cord for months), they don't really. Because most psychoactive drugs are fat-soluble enough to enter the brain, they also accumulate in body fat. TI-IC (the active com­ponent in marijuana) and PCP (phencyclidine, or angel dust) are partic­ularly prone to accumulate in fat. As the drug eventually leaves the fat, it enters the bloodstream again and can enter the brain but usually at lev­els so low it produces negligible effects.

There is a legal consequence to this storage in fat. Drugs like 'clic are so well stored in fat that they remain detectable in urine for weeks after the last time the drug was used. It is common in drug-treatment pro­grams for people who have been testing "clean" to show drugs in their urine suddenly if they have been losing weight during their rehabilitation. The drug is simply driven out of the fat as the fat deposits shrink.

GETTING OUT

Most drugs do not leave the body the way they came in. Although a few drugs, like the inhalants, enter and leave through the lungs, most leave through the kidneys and the intestine. Many are changed in the liver to a form that is easily excreted in the urine. This process of metabolism and excretion in the urine determines how long the drug effect lasts. It is very  difficult to change this rate, so once a dose of drug is ingested, there is no

hurrying the recovery. In extreme cases, there are emergency room pro‑

cedures that can accelerate the removal of some drugs by the kidneys, but otherwise we must wait.

Some drugs, like cocaine, leave the brain and bloodstream quickly. The combination of quick onset of action and rapid removal can lead to cycles of taking the drug repeatedly. Drug levels shoot up, then plummet, taking the user to an intense high followed by a "crash," which motivates him to take another dose of the drug. Some cocaine users get into "runs" of repeated doses and end up using grams of cocaine in a single sitting. This pattern often leads to overdosing—the user takes another dose as the drug effect wanes but before the earlier dose has been completely eliminated. Drug levels in the brain gradually accumulate to dangerous levels.

Marijuana presents the opposite problem. THC, the active compound, is extremely fat-soluble (and thus accumulates in body fat), and its break­down products are also active compounds. So, as the body tries to remove it, the metabolic products continue to have psychological effects. These

two characteristics of marijuana mean that users can be under its influ­ence for many hours or even days after it is smoked.