HOW PEOPLE TAKE OPIATES

HOW PEOPLE TAKE OPIATES

Most opiate drugs enter the bloodstream easily from many different

routes because they dissolve in fatty substances and so can cross intocells. Heroin and fentanyl represent one extreme—they are so fat-soluble that they can be absorbed across the mucosal lining of the nose. Most other opiates are not quite that fat-soluble and cannot be absorbed well after snorting. However, some opiates including the natural ingredients of the opium poppy form a vapor if heated and can be absorbed into the body if they are smoked—that is the basis of the use of the "opium pipe" as the traditional device of ancient as well as more recent history. Almost all opiates can be absorbed from the stomach, although injection is a much more efficient route for some, like morphine, that are more poorly absorbed from the stomach than others.

Intravenous injection is the route that delivers opiates into the blood­stream the fastest. Because intravenous injection is more difficult and more dangerous than other routes, many users do not start this way. Instead, they start by skin-popping—injecting drugs subcutaneously (just beneath the skin). Heroin powder is dissolved and injected. Morphine, fentanyl, and meperidine almost always appear as legally prepared injec­tion forms that have been diverted from medical use. Snorting heroin has become a common route for new drug users. In part, users are avoiding the stigma—and risk of infectious diseases including hepatitis and AIDS—that come with injecting a drug. In part, they may believe mistak­enly that they cannot become addicted if they don't inject drugs. Pre­scription opiates like codeine, hydromorphone (Dilaudid), oxycodone (Percodan, OxyContin), meperidine (Demerol), and, of course, metha­done (Dolophine) are available as pills. Sometimes drug users resort to grinding up pills of codeine, hydrocodone, or methadone and injecting the suspension when they cannot get opiates any other way. This is an extremely risky business because the other pill components do not dis­solve in saline. Injecting particles into a blood vessel can irritate the blood vessel, thus setting off a chain of reactions that lead to vascular inflamma­tion and permanent damage. In addition, a pill particle can lodge in a small vessel and block off the blood supply to an area of the body.

OPIATE EFFECTS ON THE BRAIN AND THE REST OF THE BODY

OPIATE EFFECTS ON THE BRAIN AND THE REST OF THE BODY

Morphine hits the backs of the legs first, then the back of the neck, a spreading wave of relaxation slackening the muscle away from the bones so that you seem to float without outlines, like lying in warm salt water. As this relaxing wave spread through my tissues, I experienced a strong feeling of fear. I had the feeling that some horrible image was just beyond the field of vision, moving, as I turned my head so that I never quite saw it. I felt nauseous. A series of pictures passed, like watching a movie: a huge neon-lighted cocktail bar that got larger and larger until streets, traffic and street repairs were included in it; a wait­ress carrying a skull on a tray; stars in the clear sky. The physical impact of the fear of death; the shutting off of breath; the stopping of blood. I dozed off and woke up with a start of fear. Next morning I vomited and felt sick until noon.

The character in William Burroughs's novel Junkie describes his first experience with morphine fairly accurately. 'the only thing missing from this description is the rush that comes with intravenous injection that most users compare to orgasm.

All opiates cause a pleasant, drowsy state in which all cares are forgot­ten (nodding off), and there is a decreased sensation of pain (analgesia). The feelings are the most intense after injection, which brings the rush. After the orgasmic feeling, sexual feelings usually diminish, and people experience decreased sexual desire and performance. This happens because opiates affect the release of many hormones and neurotransmit­ters, including those involved in the regulation of sexual behavior. People under the influence of opiates will often say that they just don't worry about their troubles anymore: they are in a special, safe place where cares are forgotten. The allure is understandable, and at the beginning it is impossible to understand the misery of addiction and withdrawal.

While the opiate user is in a dreamy, pleasant state, breathing slows, pupils are constricted, and he typically experiences nausea and perhaps even vomits. Although the effects on breathing can be quite dangerous, the other physiologic effects are fairly benign. For example, opiates do not produce big changes in blood pressure in healthy individuals. Most of the effects of narcotic drugs are caused by effects of the drugs on specific opi­ate receptors in the parts of the brain involved with the control of breath­ing and other involuntary functions. For example, opiate users vomit because morphine stimulates a center in the brain (the chemoreceptor trigger zone) whose job it is to cause vomiting in response to the ingestion of a toxic substance. So, in the movie Pulp Fiction the injection of adrena­line into the heart to reverse opiate overdose was not accurate. The effects on breathing that were causing the woman to OD were happening in the brain, and injecting a drug directly into the heart to get it started again was good theater, but bad pharmacology. Injecting an opiate receptorblocking drug (naloxone, or Narcan) into the bloodstream instead would have effectively treated the OD. The movie Trainspotting does a much bet­ter job of depicting the reversal of opiate effects with naloxone. The protag­onist is dumped at the doors of a hospital emergency room, taken into a room, and given naloxone. In a matter of seconds he leaps up from the gurney.

One very important effect of opiates on the body has made life easier for generations of foreign travelers. Opiates increase the tension in certain muscles in the gastrointestinal tract so that the normal propulsive move­ments that move food along cannot operate effectively—hence their well-known ability to cause constipation. This can be a good thing if you are in Mexico and have traveler's diarrhea. Diphenoxylate (Lomotil) takes advantage of a neat chemical trick to stop diarrhea without affecting the brain. The typical opiate molecule is slightly changed so that it is not fat-soluble enough to enter the brain. This gives you a very safe, very effec­tive medicine that can treat mild diarrhea without the risk of addiction. Through a similar action, opiates constrict the muscles of the urinary bladder and can cause difficulties in urination.

There is active research ongoing to use a similar strategy to develop drugs that bind to one special population of mu receptors that are not behind the blood-brain barrier but still involved in suppressing pain. This could be the holy grail of narcotics research—a nonaddictive nar­cotic drug.

HOW OPIATES MOVE THROUGH THE BODY

                 HOW OPIATES MOVE THROUGH THE BODY

The rate at which opiates enter the brain depends mainly on how the user takes them. The fastest way to get high is to inject the drug directly into the bloodstream. The second fastest is to smoke it. When opiates are smoked or injected, peak levels in the brain occur within minutes. Fentanyl is the most fat-soluble and achieves maximum brain concentrations in seconds. Heroin is a little slower; it takes a couple of minutes. Mor­phine is slower still, but not by much (five minutes). The faster the buzz, the greater the danger of death by overdose, because drug levels in the brain can rise so quickly. Snorting heroin causes slower absorption because the drug must travel through the mucous membranes of the nose to the blood vessels beneath.

After taking a pill, the high is much slower because the drug must be absorbed from the small intestine into the bloodstream, then pass through the liver, which can metabolize much of a dose, before it ever gets into the circulation. This process takes about thirty minutes, so there's no rush after oral administration. This lack of a "rush" is why methadone is so useful in treating addicts, and as a pain medication. Sometimes users figure out how to circumvent opiate preparations that are designed to have a slow onset—the formulation of OxyContin provides a now-notori­ous example. OxyContin is a delayed-release form of oxycodone that is designed to release drug gradually, providing pain relief over hours. How­ever, users discovered that crushing the pills causes a quick release of drug and gives a "high" that the manufacturer did not intend. Following its introduction in 1996, OxyContin rapidly gained a reputation as the hot "new" drug of abuse. It has since been reformulated to make abuse more difficult.

The duration of action depends upon how quickly the drug-metaboliz­ing enzymes in the liver degrade the particular drug. Most of the drugs mentioned last for four to six hours. The exact time can vary from two hours (morphine) to up to six or so (propoxyphene), but all opiates are pretty similar. There are two important exceptions. Methadone lasts for twelve to twenty-four hours, so it can be given as a single daily dose. Fen­tanyl goes to the other extreme: the effects are over within an hour.

WHAT OPIATES ARE

WHAT OPIATES ARE

Opiate drugs are any drugs, natural or synthetic, that produce the charac­teristic opiate effects: the combination of a dreamy, euphoric state; less­ened sensation of pain; slowed breathing; constipation; and pinpoint pupils. Sometimes scientists use the more generic term opioids, which includes drugs resembling the substances in the opium poppy as well as endogenous opioids that serve as neurotransmitters in the brain.

Opium refers to a preparation of the opium poppy (Papaver som­niferum). It is obtained in a very low-tech, labor-intensive manner throughout the world. Opium farmers cut the developing seedpod of the opium poppy and collect the gummy fluid that oozes out of the cut over the next few days. The sap is refined in several ways. It may be dried into a ball and used directly (gum opium) or dried and pounded into a powder (opium powder). Raw opium appears as a brown tarry substance. Opium can also be made into an alcohol-water extract called tincture of opium. This is the famous laudanum of your great-great-grandmother's era, or the paregoric of that age.

Morphine, which is one of the mainstays for pain management, is a major constituent of the seedpod. It is a potent opiate and is used in injectable or pill form to relieve pain after surgery and for extreme pain, such as in advanced cancer. Codeine is a much less potent opiate that is used mainly in pill form for milder pain. Many people have encoun­tered it as an acetaminophen-codeine preparation that is used com­monly for dental pain or in prescription cough medicine. To compensate for the lower potency of codeine, some drug abusers simply drink an entire four-ounce bottle, which does contain an intoxicating amount. These cough syrups used to be available over the counter until recre­ational use became too popular. Now most states require a prescription for codeine-containing cough syrups.

Heroin is a chemically modified form of morphine that is created from partially purified morphine, usually in "refineries" close to sites of opium production. It is broken up into small amounts and usually appears on the street in bags of loose powder containing about one hundred milligrams. The actual color can range from white to brown to black depending upon the source and quality of the preparation technique. Highly purified her­oin hydrochloride is a white powder that is prized for its purity, while Mexican "black tar" heroin at the other end of the spectrum is recognized by its black appearance. 'The user either snorts the powder directly or dis­solves it in saline and injects it. The actual composition of the powder depends upon the supplier and can range from 10 to 70 percent heroin (in combination) with various contaminants, including talc, quinine, and baking powder, making up the balance.

Opium poppies grown in Southeast Asia (Burma and Thailand), Afghanistan, South America (Colombia), and Mexico provide the start­ing material for illegal heroin that enters the United States. Southeast Asian poppies mostly provide heroin for Europe, although some makes its way to the United States. Heroin production from Afghanistan still represents the majority of worldwide production (tenfold more than the next highest supplier, which is Mexico), but heroin in the United States mainly comes from South America (East Coast) or from Mexico (West Coast) (US Department of Justice National Drug Intelligence Center, Threat Assessment 2011).

The purity of heroin varies widely. In the most recent report from the DEA (from 2011), the average purity in the United States was 30 percent, with ranges from 5 percent to 66 percent, depending upon the location. If heroin is just morphine that has been slightly changed chemically, what advantage does it have? In fact, once heroin enters the brain, it is con­verted back to morphine. However, the improved fat solubility does serve a useful purpose—it gets heroin into the brain faster. Many physicians are lobbying for its use in terminal cancer patients, as this difference means

faster pain relief The government is weighing the balance between this medical benefit and heroin's long and unpopular legal history.

Scientists have made many derivatives of morphine. the original hope was to find a drug that would eliminate pain but not cause tolerance or addiction. That mission has been unsuccessful—all of the effective opiate analgesic drugs are also addictive. However, the attempt has led to many man-made opiates with desirable characteristics for particular clinical uses. There are at least five important opiate analgesics that are either direct products of the seedpod of the opium poppy or minor modifica­tions of it. These chemically modified drugs are widely used in medicine, and prescription opiate abuse is a major health concern today. Ten times more people abuse prescription opiates than abuse heroin, and rates have increased dramatically in the last ten years, as have overdose deaths from these drugs. Therefore, we will spend some time describing them in detail.

Some of the most widely used and abused prescription narcotics are mod­ifications of morphine. These are hydromorphone, oxycodone, and hydroco­done. Hydromorphone (Dilaudid), a very strong opiate, is an effective analgesic that is widely abused. Oxycodone is synthesized from a nonanal­gesic in opium (thebaine) and ranks between morphine and codeine in its effectiveness against pain. Its use has spread dramatically in the United States in the last few years, due in part to its appropriate use to treat pain. It is also marketed in combination with aspirin under the prescription name Percodan. Hydrocodone (Vicodin) is a moderately strong opiate that is also widely abused.

Meperidine (Demerol) is used like morphine for intense postsurgical pain, but it works well even with oral use. Meperichne has a definite downside: it can cause seizures at high doses--a feature that has led to decreased use by physicians in recent years. Methadone is a long-lasting opiate that is taken as a pill. Its unique time course makes it particularly useful for replacement therapy for treating opiate addiction as well as chronic pain. The gradual and mild onset of action staves off withdrawal signs but doesn't provide a "high." Its use for these purposes is controver­sial in some circles: although tolerance and physical dependence clearly develop, it provides safe and effective treatment without the same liability for abuse. One important characteristic of methadone is its very long half­life—it remains in the body for hours. This is a helpful characteristic in suppressing opiate withdrawal and in treating chronic pain. However, it also represents a danger to people who do not follow instructions about its use. Overdose deaths from methadone have increased 800 percent in the last five to ten years. Most of these deaths have occurred in people who were using it for pain relief, not abusing it. Fentanyl (Sublimaze) and its relatives are very fat-soluble, very fast-acting analgesics that anesthesi­ologists use when they put patients to sleep. Fentanyl is also used in patches that release the drug slowly through the skin to provide more long-lasting pain relief. Its most unusual formulation is a lollipop designed to deliver the drug to young children before surgery. Many addicts use fentanyl in its injectable form, and it is a common cause of overdose. Fentanyl's high comes on fast and is intense, brief, and just a step away from fatal suppression of breathing. Finally, there is propoxy­phene (Darvon). This drug is such a poor opiate that most physicians won't use it, because clinical studies find it to be no more effective than a placebo. However, some people swear by it, although it's really little stron­ger than aspirin.

All the opiate drugs bind to the same molecule in the brain, but they do so with varying degrees of success. What follows is a list of drugs that bind very well, bind okay, and bind poorly. The clinical use of these drugs is determined in large part by this quality. Obviously, a drug like codeine won't do much good with the pain caused by major abdominal surgery, and hydromorphone would be overdoing it for a simple headache. There­fore, the form in which each of these is prepared and administered is tai­lored to its typical use.

OPIATE DRUGS

High Efficacy                    Medium Efficacy           Low Efficacy

morphine                      hydrocodone                   codeine

hydromorphone             oxycodone                       propoxyphene

meperidine

fentanyl

OPIATES

OPIATES

Drug Class: Opiate analgesics. All of the drugs mentioned in this chapter are scheduled by the Drug Enforcement Administration, but they vary from Schedule 1 (heroin) to Schedule IV (propoxyphene) based on their likelihood of abuse and medical use.

Individual Drugs: Opium, heroin, morphine, codeine, hydromorphone (Dilaudid), oxycodone (Percodan, OxyContin), meperidine (Demerol), diphenoxylate (Lomotil), hydrocodone (Vicodin), fentanyl (Sublimaze), propoxyphene (Darvon)

Common Terms: Chinese molasses, dreams, gong, 0, skee, toys, zero

(opium); Big H, dreck, horse, mojo, smack, white lady, brown (heroin);

speedballs (heroin and cocaine); Oxys, OCs, Hillbilly heroin (oxycodone)

The Buzz: People who inject opiates experience a rush of pleasure and then sink into a dreamy, pleasant state in which they have little sensitivity to pain. Their breathing slows, and their skin may flush. Pinpoint pupils are another hallmark of opiate effects. Opiates taken by ways other than injection have the same effect, except that a pleasant drowsiness replaces the rush. Nausea and vomiting can accompany these effects, as well as constipation. An injected heroin/cocaine combination (speedball) causes intense euphoria, the dreaminess of heroin, and the stimulation of

cocaine. People who take opiates by mouth experience the same effects, but the pleasure has a slower onset and is less intense.

Overdose and Other Bad Effects: Opiate overdose can be lethal whether users inject it or take pills. This is not a cumulative effect of years of mis­use—it can happen the first time. Breathing slows to the point that it ceases. Fortunately, the opiate antagonist naloxone (Narcan) can almost immediately reverse the dangerous effects of opiates if the user gets medi­cal help quickly. Opiate overdoses are most common with injectable forms of drug but can occur with any dosage form if enough is taken. Medical attention is critical.

Dangerous Combinations with Other Drugs: Opiates are especially dan­gerous when used in combination with other drugs that suppress breath­ing. These include alcohol, barbiturates (e.g., phenobarbital), Quaaludes (methaqualone), and Valium-like drugs (benzodiazepines).

WHERE OPIATES CAME FROM

No less a cultural icon than Dorothy of The Wizard of Oz has experienced the effects of opiates (remember the field of poppies?). As we saw in The Wizard of Oz, you pretty much have to lack a brain to resist the effects of opiates. For those with a more classical bent, morphine derives its name from Morpheus, the Greek god of dreams, who was often depicted with a handful of opium poppies. Use of opiates began in prehistoric times, probably with teas prepared from opium poppies. The oldest historical references to the medicinal use of opiates arise from the Sumerian and Assyrian/Babylonian cultures (about five thousand years ago). Opium pipes recovered from archeological sites in Asia, Egypt, and Europe docu­ment the smoking of opium between 1000 and 300 sc. Arab traders intro­duced opiates to China between AD 600 and Al) 900. Paralleling developments in Europe, medical use gradually evolved into recreational use, and the number of opium addicts grew. "lhe importation of opium into China became a major source of trade for England and helped start a war between China and England when China banned its importation in the early nineteenth century.

Use (and abuse) of opiates in Europe was common during the Middle Ages. One agent of its popularity was Paracelsus, who coined the term laudanum—meaning "to be praised"—for an opiate preparation. Later, many poets (Samuel Taylor Coleridge and Elizabeth Barrett Browning, among others) used and abused opium. Coleridge reported an opium experience in his famous "Kubla Khan."

Opium has been used widely in the United States throughout its his­tory It was popular long before the wave of Chinese immigration intro­duced opium smoking to this country. Opium was a major ingredient in many of the patent medicines available before the FDA was started, and the average housewife was a major consumer in nineteenth-century America. As in the story of cocaine, the rising availability of increasingly potent preparations led to greater recognition of the drug's toxicity and addictive qualities.

In 1805 morphine, the major active ingredient in the opium poppy, was purified; in 1853 Alexander Wood invented the hypodermic syringe. The first major wave of addiction to injectable narcotics followed the wide use of injected morphine during the American Civil War. The final improve­ment came courtesy of the Bayer Company in 1898, when the company's scientists discovered that adding an extra chemical group onto morphine

made it more soluble in fat, so that it would enter the brain faster. This improvement produced heroin, once a trade name for the narcotic pro­duced by Bayer.

Today, opiate drugs are a mainstay of the medical treatment of pain. There just aren't substitutes for their effectiveness at reducing pain. How­ever, all opiate drugs are addictive. Some doctors so fear addiction in their patients that they withhold needed treatments. This was the reason for the introduction of national programs that rightly promoted the use of ade­quate medication to treat pain. Unfortunately, this opened the door for a small number of unscrupulous doctors to run "pill mills" that prescribe these drugs to patients with very little verification of their medical need for such medication. Unfortunately, opiate drugs are also the form of drug more abused than any other except alcohol and marijuana. The majority (90 percent) of opiate abusers use pills that have been diverted from medi­cal use, although heroin use remains a significant problem as well.