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Alphaprodine is a phenylpiperidine derivative that is approximately one fourth as potent as morphine and has a rapid onset and a relatively short duration of action. It has been a popular analgesic for labor pain. It was reported that alphaprodine (39 ± 4 mg IV) produced no effects on neonates when given to parturients 197 ± 96 minutes prior to delivery. [451]
Codeine (methylmorphine) is half as potent as morphine, has a high oral-parenteral potency ratio (2:3) and a plasma half-life of 2 to 3 hours. Codeine has mild to moderate analgesic but strong cough-suppressant properties after oral administration. Cytochrome P-450 2D6 (CYP2D6) is the enzyme responsible for O-demethylation of codeine to morphine.[452] Intravenous codeine produces profound hypotension and is neither approved nor recommended. [453]
Heroin (diacetylmorphine) is approximately twice as potent as morphine and has a 4- to 5-hour duration of action. Heroin is rapidly hydrolyzed to 6-acetylmorphine and morphine.
Hydromorphone is structurally related to morphine but is approximately five to ten times as potent. Analgesia after hydromorphone lasts 4 to 5 hours.[454] The effects of hydromorphone are essentially indistinguishable from those of heroin. [455] It was recently reported that hydromorphone PCA provided adequate postoperative analgesia with improved mood, and that it can be an alternative to morphine PCA.[456]
Levorphanol is a semisynthetic opioid with a long (12 to 19 hours) half-life. It is five times as potent as morphine with an intramuscular/oral potency ratio of 1:2. Levorphanol may have particular utility in patients with chronic pain and who demonstrate morphine tolerance, perhaps because of differences in opioid receptor activity.
Methadone has an equivalent potency but longer duration of action than morphine.[457] Its major clinical applications are in the prevention of opioid withdrawal symptoms and in the treatment of chronic pain. The plasma half-life of methadone is very long and variable (13 to 100 hours). Despite this property, many patients require dosing every 4 to 8 hours to maintain analgesic effects.
Oxymorphone, also structurally related to morphine, is almost ten times as potent, and has a similar duration of action.
Pentamorphone, a morphinan derivative, is two to eight times as potent as fentanyl and produces analgesia of similar duration without hemodynamic disturbances or increases in plasma histamine.[458] Although respiratory depression may be limited with analgesic doses (0.1 µg/kg), higher doses produce typical opioid-induced respiratory depression.
Phenoperidine is chemically related to meperidine but is 100 times as potent as an analgesic. Onset of its effect is rapid and duration is moderate (2 to 6 hours). Phenoperidine has long been used for sedation in Europe.[459]
Piritramide, a synthetic opioid structurally related to meperidine, is devoid of emetic activity, and is used for postoperative analgesia in several European countries.[460] Pharmacokinetic analysis showed that piritramide is distributed extensively and eliminated slowly, and it is recommended for intermittent bolus administration.[461]
Tramadol is a synthetic 4-phenyl-piperidine analog of codeine with a dual mechanism of action. Tramadol stimulates the μ-receptor, and to a lesser extent the δ- and κ-opioid receptors; like tricyclic antidepressants, it also activates spinal inhibition of pain by decreasing the reuptake of norepinephrine and serotonin.[462] A recent report suggested that tramadol may have a direct serotonin-releasing action.[463] Tramadol is one fifth to one tenth as potent as morphine. In rats, tramadol reduced the MAC of isoflurane in a naloxone-sensitive manner.[464] It was shown that intravenously administered tramadol was effective for post-thoracotomy pain relief.[465] Analgesic doses of tramadol may produce less respiratory depression in part because of its non-opioid receptor-mediated actions.[466] Tramadol has minimal effects on gastrointestinal motor function.[467]
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Equianalgesic IM Dose (mg) | Duration of Analgesia (hr) | Oral: IM Efficacy Ratio |
|---|---|---|---|
| Morphine | 10 | 4–5 | 1:6 |
| Buprenorphine | 0.3–0.4 | >6 | 1:2 * |
| Butorphanol | 2 | 3–4 | — |
| Nalbuphine | 10 | 3–6 | 1:4–5 |
| Pentazocine | 40 | 3 | 1:3 |
Sameridine possesses both local anesthetic and opioid properties. In patients subjected to arthroscopic knee joint surgery, sameridine was administered intrathecally and provided clinically adequate anesthesia.[470] A large intravenous dose of sameridine depressed resting ventilation and the hypercarbic ventilatory response, whereas a smaller clinical dose did not.[471] [472]
Morphine-6-glucuronide (M6G) is a potent metabolite of morphine. The molar M6G:morphine potency ratio is approximately 13:1 in rats.[473] In trials using M6G as an analgesic, Osborne and associates. reported that M6G (0.5–4 mg IV) was effective for cancer pain for 2 to 24 hours without nausea and vomiting.[474] M6G (100 µg and 125 µg) given intrathecally provided excellent analgesia after total hip replacement, as did intrathecal morphine sulfate (500 µg).[475]
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