Opioid Analgesics: Codeine and Other Phenanthrene Derivatives

Codeine and Other Phenanthrene Derivatives

Like morphine, codeine is a naturally occurring opioid found in the poppy plant. Codeine is indicated for the treatment of mild to moderate pain and for its antitus-sive effects. It is widely used as an opioid antitussive be-cause at antitussive doses it has few side effects and has excellent oral bioavailability. Codeine is metabolized in part to morphine, which is believed to account for its analgesic effect. It is one of the most commonly used opioids in combination with nonopioids for the relief of pain. The administration of 30 mg of codeine in combi-nation with aspirin is equivalent in analgesic effect to the administration of 65 mg of codeine. The combina-tion of the drugs has the advantage of reducing the amount of opioid required for pain relief and abolition of the pain via two distinct mechanisms, inhibition of prostanoid synthesis and opioid inhibition of nocicep-tive transmission. When given alone, orally adminis-tered codeine has about one-tenth to one-fifth the po-tency of morphine for the relief of pain. In addition, IV codeine has a greater tendency to release histamine and produce vasodilation and hypotension than does mor-phine. Thus, the use of IV codeine is rare. Codeine is rarely addictive and produces little euphoria.

Adverse effects and drug interactions with codeine are similar to those reported for morphine, although they are less intense. Overdose in children results in the same effects as overdose of morphine, such as respira-tory depression, miosis, and coma; these symptoms are treated with naloxone administration.

Hydrocodone (Hycodan), oxycodone (Roxicodone), dihydrocodeine, hydromorphone (Dilaudid), and oxy-morphone (Numorphan) are derivatives of codeine and morphine. All are indicated for the relief of mild to se-vere pain or for their antipyretic effects; they are often used in combination with nonopioid analgesics. The drugs vary in potency, but their pharmacological effects do not differ significantly from those of codeine or mor-phine.

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

Oxycodone is nearly 10 times as strong as codeine, with absorption equal to that of orally administered mor-phine. Neither hydromorphone nor oxycodone is ap-proved for use in children, and hydromorphone is con-traindicated in obstetrical analgesia and in asthmatics.

Oxymorphone is 10 times as potent as morphine, with actions similar to those of hydromorphone. Oxymorphone, however, has little antitussive activity, and as such is a useful analgesic in patients with pul-monary disease who need to retain the ability to cough.