Hydromorphone addiction

Hydromorphone [466-99-9] (31) and hydrocodone [125-29-1] (32) are isomers of morphine and codeine, respectively. Hydromorphone can be prepared by catalytic rearrangement of morphine (49) or by oxidation of the aliphatic hydroxyl group of dihydromorphine (50). Hydrocodone can be similarly prepared. As an antitussive, hydromorphone is several times more active than morphine and hydrocodone is slightly more active than codeine. Hydromorphone has a much higher addiction potential than hydrocodone. 

Hydromorphone is eight times as potent as morphine but has less bioavailability following oral administration. Its side effects do not differ from those of morphine but are more intense. Hydromorphone is indicated for use in severe pain and in high doses for relief of pain in opioid-addicted patients. 

Side-effects Hydromorphone shows the typical morphinelike side-effects, and has a relatively high potential for addiction and dependence (Hill and Zacny, 2000). 

Dextromethorphan is not classified as a controlled substance under the Controlled Substances Act (CSA) of 1970. The CSA was created as a means to regulate the distribution and use of prescription drugs that are highly addictive, such as codeine, oxycodone, morphine, and hydromorphone. 

Hydromorphone is highly addictive. Its use needs to be carefully monitored by the treating physician. Longterm use of the drug can lead to physical and psychological dependency. Mood can also be affected by hydromorphone and other narcotic analgesics. Infrequently, hallucinations and disorientation can develop. Insomnia develops in a minority of cases. 

A study in the April 5, 2000 issue of the Journal of the American Medical Association found that hydromorphone use for medical indications increased by 19% from 1990 to 1996. This increase coincided with an decrease in the number of hydromorphone drug abuse mentions during this period. The decrease in hydromorphone drug abuse (15%) suggests a low risk of addiction associated with the medical use of hydromorphone in the treatment of severe pain. 

The primary long-term concern of those who use hydromorphone is the risk of addiction. The National Institute on Drug Abuse has determined that persons who become addicted to hydromorphone and other narcotic analgesics are at increased risk of convulsion, overdose, and death. 

Persons with a history of drug abuse of any kind should not receive hydromorphone unless absolutely necessary because of the great potential for addiction. Hydromorphone can become addictive for anyone who has received doses higher than those prescribed by a doctor and in those who use the drug for recreational purposes. In addition, those who receive the drug at prescribed levels for a lengthy period are at a relatively slight increased risk of addiction. 

Addiction to hydromorphone and other prescription painkillers is one of the major reasons behind admittance to drug rehabilitation clinics. Treatment for opiate addiction has been occurring in the United States since the early part of the twentieth century. In these early days of treatment, doctors in private practice prescribed narcotics to those addicted to opiate drugs. Later, governments outlawed this practice and began operating clinics where morphine could be obtained by addicts. Eventually, these clinics were also closed. At that point in time, addicts began to be treated in public health hospitals or placed in jail. 

Codeine, hydrocodone, and hydromorphone decrease the sensitivity of CNS cough centers to peripheral stimuli, and decrease mucosal secretion. These actions occur at doses lower than required for analgesia (see p. 135 for a more complete discussion of the opiates). Dextromethorphan [dex troe meth OR fan], a synthetic derivative of morphine, suppresses the response of the cough center. It has no analgesic or addictive potential, and is less constipating than codeine. 

Studies have been conducted in animals to attempt to clarify the role of varying rates of drug metabolism in humans and animals and the likelihood for development of addiction/dependence to narcotics. Hydromorphone has been studied in several animal models because it is metabolized in humans by specific cytochrome P450 isoenzymes. So far, studies have looked at administration of agents that either block or promote P450 isoenzymes responsible for hydrocodone metabolism and the impact of enhanced or degraded metabolism of hydrocodone on those animal models. Results in rats and rhesus monkeys have demonstrated little effect from modifying hydrocodone metabolism. 

Recently a great deal of attention has been focused on the oxymorphone series (III) of morphine derivatives with an axial OH substituent on the C14 position of hydro-morphone. One reason for this interest is that the N-allyl derivative in this series, naloxone (IIIB) has been found to be a pure antagonist, much more potent than its morphine analogue, nalorphine (IB) and with more morphine-like, rather than nalorphine-like side effects and low addiction capacity. The addition of an OH group on Cl4 also causes an apparent two-fold increase in potency from hydromorphone to oxymorphone. Similarly, a six-fold increase in apparent analgesic potency is observed in going from hydrocodone (IIB) to oxycodone (IIIC) [1]. 

As an oral drug, codeine is much less effective as an analgesic due to its large first-pass hepatic metabolism compared to morphine, hydrocodone and oxycodone. The plasma half-life of codeine is also shorter than many other orally available opiates such as morphine, hydromorphone, and oxymorphone. Like all opioids, continued use of codeine may result in tolerance development and physical dependence. However, when compared to potent mu agonists, codeine is less addictive and is associated with mild withdrawal symptoms. 

Natxirally occurring opiates such as morphine or codeine and semisynthetic opiates such as hydrocodone or hydromorphone have been used as essential pain management components for decades. Since drugs such as these are used chronically in pain treatment and because they possess both euphoric and addictive qualities, they are commonly used illicitly as well. Other drugs, which produce morphine-like effects, are labeled as opioid drugs and are commonly used in similar situations. 

---