Morphine was first identified as the pain-relieving active ingredient in opium in 1806. But morphine was not free of the habit-forming and toxic effects of opium. By the late nineteenth century, the idea of modifying molecules to change their pharmacological actions was well established. It seemed quite reasonable to use this approach to develop new chemical entities that might be free of the problems seen with morphine. In Germany, in 1898, H. Dresser introduced such a new drug—3,6-diacetylmorphine—into medical use; it was named there by the Bayer Company, which produced and marketed it, named it heroin (presumably from heroisch, meaning “heroical”), because it was more potent than morphine.
Although heroin is structurally very similar to morphine, it was hoped that it would relieve pain
without the tendency to produce addiction. Turn-of-the-century medical writings and advertisements, both in Europe and the United States, claimed that heroin was effective for treating pain and cough. Many suggested that it was less toxic than morphine and was nonaddictive. A few even suggested that heroin could be a nonaddicting cure for the morphine habit. Clearly, this was not the case, and within a year or two of its introduction, most of the medical community knew so. By the 1920s, heroin had become the most widely abused of the opiates.
Heroin is a white powder that is readily soluble in water. The introduction of just two esters onto the morphine molecule changes the physical properties of the substance such that there is a significant increase in solubility, permitting solutions with increased drug concentrations. A more subtle advantage of heroin is its greater potency compared to morphine. The volume of drug injected may be particularly important when high doses are used. Thus, 1 gram of heroin will produce the effects of 2 to 3 grams of morphine; by converting morphine to heroin, producers increase both the potency and the value of the drug.
Following injection, heroin is very potent, with the ability to cross the blood-brain barrier and enter the brain. This barrier results from a unique arrangement of cells around blood vessels within the brain, which limits the free movement of compounds. Many factors contribute to the barrier—in general, the less polar a drug, the more rapidly it enters the brain. Heroin, however, has a very short half-life in the blood (amount of time that half the Page 237 | Top of Articledrug remains). It is rapidly degraded by esterases, the enzymes that break ester bonds. The acetyl group at the 3-position of the molecule is far more sensitive to these enzymes than the acetyl group at the 6-position. Indeed, the 3-acetyl group is attacked almost immediately after injection and, within several minutes, virtually all the heroin is converted to a metabolite, 6-acetylmorphine. The remaining acetyl group at the 6-position is also lost, but at a slower rate. Loss of both acetyl groups generates morphine. It is believed that a combination of 6-acetylmorphine and morphine is responsible for the actions of heroin.
The pharmacology of heroin is virtually identical to that of morphine. This probably reflects its rapid conversion to 6-acetylmorphine and morphine. Detailed studies comparing the actions of heroin and morphine in cancer patients with severe pain have shown very little difference between the two agents, other than simple potency. Heroin may have a slightly more rapid onset of action than morphine and it is certainly two to three times as potent (presumably due to its greater facility in crossing the blood-brain barrier). This difference in potency is lost with oral administration. The pain relief (analgesia) from both agents is comparable when the doses are adjusted appropriately. At equally effective analgesic doses, even the euphoria seen with heroin is virtually identical to that of morphine. From the clinical point of view, there is little difference between one drug and the other. Both are effective analgesics and can be used beneficially in the treatment of severe pain. Heroin is more soluble, which makes it somewhat easier to give large doses by injection, with smaller volumes needed. Many of the similar semisynthetic agents, such as hydromorphone, however, are many times more potent than heroin and offer even greater advantages.
One widespread use of heroin in the United Kingdom was in the early formulations of Bromp-ton's Cocktail, a mixture of drugs designed to relieve severe pain in terminal cancer patients. The heroin employed in the original formula is now typically replaced with morphine without any loss in effectiveness. For many years, some groups have maintained that heroin is more effective in the relief of cancer pain than morphine is. Careful clinical studies show that this is not true, but the most important issue is using an appropriate dose. Thus, heroin offers no major advantage over morphine from the medical perspective.
Since heroin has no approved medical indications in the United States, it is only available and used illicitly. The marked variability of its purity and the use of a wide variety of other substances and drugs to “cut” street heroin poses a major problem. This inability to know what is included in each drug sale makes the street drug more than doubly dangerous. Typically, heroin is administered intravenously, which provides a rapid “rush,” a euphoria, which is thought to be the important component of heroin's addictive properties. It can be injected under the skin (subcutaneously, SC) or deep into the muscle (intramuscularly, IM). Multiple intravenous injections leave marks, called tracks, in a much-used injection site, which often indicate that a person is abusing drugs; but heroin can also be heated and the vapors inhaled through a straw (called “chasing the dragon”). It can also be smoked in a cigarette. While the heat tends to destroy some of the drug, if the preparation is pure enough, a sufficient amount can be inhaled to produce the typical opiate effect.
Heroin use is associated with tolerance and dependence. Chronic use of the drug leads to a decreased sensitivity toward its euphoric and analgesic actions, as well as to dependence. Like morphine, the duration of action of heroin is approximately 4 to 6 hours. Thus, addicts must take the drug several times a day to prevent the appearance of withdrawal signs. Many believe that the need to continue taking the drug to avoid withdrawal enhances its addictive potential.
Patients taking opiates medicinally can be taken off them gradually, without problems. Lowering the opiate dose by 20 to 25 percent daily for two or three days will prevent severe withdrawal discomfort and still permit rapid taper off the drug. Abrupt withdrawal of all of the drug is very different—and leads to a well-defined abstinence syndrome that is very similar for both heroin and morphine. It includes eye tearing, yawning, and sweating after about eight to twelve hours past the last dose. As time goes on, people develop Page 238 | Top of Articlerestlessness, dilated pupils, irritability, diarrhea, abdominal cramps, and periodic waves of gooseflesh. The term cold turkey is now used to describe abrupt withdrawal with the associated gooseflesh. The heroin withdrawal syndrome peaks between two and three days after stopping the drug, and symptoms usually disappear within seven to ten days, although some low-level symptoms may persist for many weeks. Babies of mothers dependent on opiates are born dependent, and special care must be taken to help them withdraw during their first weeks. Medically, although miserable, heroin withdrawal is seldom life threatening—unlike withdrawal from alcohol, which can sometimes be fatal.
Overdosing is a common problem among heroin addicts. The reason is not always clear, but wide variation in the purity of the street drug can make it difficult for the addict to judge a dose. Some impurities used to cut the drug may be toxic themselves. With overdose, a person becomes stuporous and difficult to arouse. Pupils are typically small and the skin may be cold and clammy. Seizures may occur, particularly in children or babies. Breathing becomes slow, and cyanosis—seen as a darkening of the lips to a bluish color—may develop, indicating inadequate levels of oxygen in the blood. With respiratory depression, blood pressure may then fall. These last two signs are serious, since most people who die from overdose, die from respiratory failure. Complicating the problem is the fact that many addicts may have taken other drugs, used alcohol, and so on. Some of them may have been taken on purpose, and some may have been a part of the street drug.
Naloxone can readily reverse some opiate problems, since it is a potent opiate antagonist. This drug binds to opiate receptors and can reverse morphine and heroin actions. The appropriate dose may be a problem, however, since naloxone can also precipitate a severe abstinence syndrome in a dependent person.
See also Addiction: Concepts and Definitions; International Drug Supply Systems; Methadone Maintenance Programs; Opioid Complications and Withdrawal; Treatment: A History of Treatment in the United States.
Egendorf, L. K. (2007). Heroin. San Diego, CA: ReferencePoint Press.
Jaffe, J. H. (1990). Drug addiction and drug abuse. In A. G. Gilman et al. (Eds.), Goodman and Gilman's the pharmacological basis of therapeutics (8th ed.). New York: Pergamon. (2005, 11th ed. New York: McGraw-Hill Medical.)
Jaffe, J. H., & Martin, W. R. (1990). Opioid analgesics and antagonists. In A. G. Gilman et al. (Eds.), Goodman and Gilman's the pharmacological basis of therapeutics (8th ed.). New York: Pergamon. (2005, 11th ed. New York: McGraw-Hill Medical.)
Mold, A. (2008). Heroin: The treatment of addiction in twentieth-century Britain. DeKalb, IL: Northern Illinois University Press.
Musto, D. F. (2002). One hundred years of heroin. West-port, CT: Auburn House.
GAVRIL W. PASTERNAK