Opioid Analgesics and Opioid Antagonists

By opioid is meant any drug, regardless of chemical structure, that acts like morphine. The term opioid is preferred to the older term, opiate, for two reasons: first, because opiate implies presence in or derivation from opium, which indeed contains the analgesic drugs morphine and codeine but also contains thebaine, a strong stimulant (convulsive) drug with minimal analgesic properties, and also papaverine and noscapine, which have no analgesic actions; and second, because of a host of purely synthetic drugs with actions qualitatively similar to those of morphine and codeine that, unlike the analgesics found in opium or derived therefrom, lack the phenanthrene nucleus (e.g., methadone, meperidine, d-propoxyphene). Opium is prepared from the sap of the poppy Papaver somniferum and contains about 10% by weight of morphine and about 0.5% by weight of codeine. Analgesic compounds that are derived from morphine and that retain the phenanthrene nucleus and are classed as opioids include heroin (diacetylmorphine), hydromorphone (Dilaudid), oxymorphone (Numorphan), and oxycodone (Percodan). Purely synthetic analgesic compounds that lack the phenanthrene nucleus but are classed as opioids include methadone (Dolophine), meperidine (Demerol), d-propoxyphene (Darvon), levorphanol (Levo-Dromoran), and phenazocine (Prinadol). In man, the analgesic potencies of these drugs relative to morphine (all drugs given subcutaneously) are codeine, one-twelfth; heroin, 2–3 times; hydromorphine, 6–8 times; oxymorphone, 7–10 times; oxycodone, two-thirds to equipotent; methadone, equipotent; meperidine, one-tenth to one-eighth; levorphanol, 2–3 times; and phenazocine, 3 times. By the oral route, 65 mg of d-propoxyphene is equivalent to 32–45 mg of codeine for analgesia, but 32 mg of d-propoxyphene may be no more effective than placebo. A newer synthetic compound, pentazocine (Talwin), exerts some morphinelike effects (analgesia, respiratory depression, sedation) in doses of 30–50 mg given parenterally (equivalent to 10 mg of morphine) or of 50 mg given orally (equivalent to 60 mg of codeine); at higher doses, pentazocine also produces dysphoric and psychotomimetic effects that can be reversed by naloxone, but not by nalorphine. In addition, pentazocine has weak opioid-antagonistic actions and can precipitate abstinence phenomena in morphine-dependent individuals. Though not in clinical use, etorphine (Immobilon), an opioid derived from oripavine and ultimately from thebaine, is of interest because of its extreme potency. In man, it is about 400 times as potent as morphine, though its duration of action is much shorter; in animals, its potency is even greater than in man, and it is used for immobilizing large game animals (Harthoorn & Bligh, 1965). Although of all these opioid analgesics, heroin is the most widely abused in the United States, its pharmacological effects (including the development of tolerance and physical dependence) do not differ qualitatively from those of morphine. The same is true also of hydromorphone, oxymorphone, oxycodone, levorphanol, phenazocine, and methadone, but the pharmacological effects of meperidine, d-propoxyphene, and pentazocine present more prominent differences with regard to “toxicity” and/or physical dependence. The pharmacological effects of morphine serve here as a prototype of the actions of opioids in general, and deviations from this prototype are noted for some particular opioid analgesics.