Version June 2024
| Drug | Drug class | Speed of onset (minutes) | Context-sensitive half time* | Duration of action and elimination half-life | Metabolism and clearance | Drug-drug interactions | Comments |
| Fentanyl | Phenylpiperidine opioid | 4 to 6 minutes | May be prolonged and continues to increase as duration of infusion increases (for example, after infusion for 200 minutes, approximately 200 more minutes are necessary to achieve a 50% decrease in effect site concentration). | Duration of action (after a bolus dose): 30 to 45 minutes. Elimination half-life: 3 to 6 hours. | Metabolized in liver by cytochrome CYP3A4 to norfentanyl (an inactive metabolite). Metabolite excreted by kidney with clearance 8 mL/kg per minute. | Synergistic effects if coadministered with other anesthetic agents. Caution with coadministered serotonergic agents due to increased risk of serotonin syndrome. Caution with CYP3A4 inhibitors (eg, diltiazem, ritonavir, voriconazole), which may increase plasma levels of fentanyl.¶ | Longest duration of action in the phenylpiperidine family. Pharmacokinetics unaffected by renal or hepatic insufficiency. |
| Remifentanil | Phenylpiperidine opioid | 1 to 2 minutes | Approximately 5 minutes. Duration of action is not affected by duration of infusion. | Duration of action: 3 to 10 minutes. Elimination half-life: 10 to 20 minutes. | Metabolized by nonspecific esterases in plasma, red blood cells, and interstitial tissue to remifentanil acid (an inactive metabolite). Metabolite excreted by kidney with clearance of 40 mL/kg per minute. In older adults, clearance reduced by ~25%. | Synergistic effects if coadministered with other anesthetic agents. | Fastest onset and shortest duration of action compared with other opioids. Higher incidence of hypotension compared with other opioids. Need for alternative analgesic agent or technique during emergence and the postoperative period if pain is anticipated. In selected circumstances, may be used for a remifentanil intubation technique. |
| Sufentanil | Phenylpiperidine opioid | 3 to 5 minutes | Context-sensitive half time plateaus at 30 to 45 minutes (shorter than fentanyl). | Elimination half-life: 2 to 4 hours. Prolonged half-life reported in patients undergoing certain procedures.Δ | Metabolized in liver and small intestines by cytochrome CYP3A4 to inactive metabolites. Metabolites excreted by kidney with renal clearance 12 mL/kg per minute. | Synergistic effects if coadministered with other anesthetic agents. Similar to fentanyl, use caution with CYP3A4 inhibitors (eg, diltiazem, ritonavir, voriconazole), which may increase plasma levels of sufentanil¶. | Used for longer procedures when continuous opioid administration and a postoperative analgesic effect are desirable, and rapid emergence is not needed. Likelihood of muscle and chest wall rigidity, particularly if administered rapidly or in high doses. |
| Alfentanil | Phenylpiperidine opioid | 1 to 3 minutes | Context-sensitive half time plateaus at 30 to 45 minutes (shorter than fentanyl). | Elimination half-life: 1.5 to 2 hours. | Metabolized in liver by cytochrome CYP3A4 to noralfentanil (an inactive metabolite). Excreted by kidney with renal clearance 5 mL/kg per minute. | Synergistic effects if coadministered with other anesthetic agents. Similar to fentanyl, use caution with CYP3A4 inhibitors (eg, diltiazem, ritonavir, voriconazole), which may increase plasma levels of alfentanil. | Avoided in patients with risk factors for seizures due to focal activation of the cerebral cortex in susceptible patients. Hepatic metabolism less predictable compared with fentanyl due to inter-individual variability in activity of hepatic CYP3A4. |
| Hydromorphone | Semi-synthetic phenanthrene opioid | Within 10 minutes | N/A | Duration of action: 2 to 4 hours. Elimination half-life: 2 to 3 hours. | Metabolized in liver to glucuronide metabolites. Hydromorphone-3-glucoronide excreted by kidney; may accumulate with renal insufficiency. | Synergistic effects if coadministered with other anesthetic agents. | Suitable for treatment of postoperative pain. Caution with use in patients with renal insufficiency due to likely accumulation of hydromorphone-3-glucoronide, which causes neuroexcitation that may result in myoclonus or exacerbation of seizures; reduce dose and increase dosing interval. |
| Morphine | Phenanthrene opioid | Within 20 minutes | N/A | Duration of action: 4 to 6 hours (but up to 7 hours for active morphine-6-glucuronide metabolite). Elimination half-life: 2 to 3 hours, but 7 hours for active metabolite. | Metabolized in liver to glucuronide metabolites (morphine-6-glucoronide and morphine 3-glucoronide). Morphine-6-glucoronide is an active metabolite and is excreted by kidney with renal clearance 2.2 mL/kg per minute; may accumulate with renal insufficiency. | Synergistic effects if coadministered with other anesthetic agents. | Suitable for treatment of postoperative pain. Unsuitable for use in patients with renal insufficiency (CrCl <30 mL/minute) due to likely accumulation of morphine-6-glucoronide, which produces ongoing analgesia, and possible neuroexcitation that may result in myoclonus or exacerbation of seizures. Histamine release and vagally mediated venodilation, hypotension, and bradycardia may be intolerable in some patients. |
| Methadone | Diphenylheptane synthetic opioid | 6 to 8 minutes | N/A | Redistribution half-life: approximately 6 minutes. Elimination half-life: approximately 30 hours (range 8 to ≥59 hours). Duration of action is highly dependent on dose and frequency. | Metabolized in the liver by cytochrome P450 enzymes, primarily CYP3A4 and 2B6 but also CYP2D6 and other CYP enzymes. No active metabolites. Excretion is primarily fecal. | Extensive drug-drug interactions. CYP3A4 inducers may result in rapid metabolism leading to withdrawal, while inhibitors may result in prolonged effects. Antiretroviral agents including ritonavir-boosted regimens in particular are metabolized via similar mechanisms and have alternating induction, inhibition, or mixed effects on P450 enzymes; refer to UpToDate topic discussion. Caution with coadministered serotonergic agents due to increased risk of serotonin syndrome. Review of interactions with specific agents should be considered before initiation of methadone therapy, especially on a chronic basis¶. | Unique among opioids as it has NMDA antagonist effects as well as serotonin and norepinephrine reuptake inhibition. These effects also contribute to the analgesic efficacy of methadone. May prolong QT interval. Significant risk of accumulation with repeated doses and when titrating. |
| Meperidine | Synthetic opioid | <10 minutes | 3 hours[1] | Approximately 3 to 4 hours. Extended in the setting of hepatic dysfunction. Normeperidine metabolite has half-life up to 48 hours; thus, accumulation can occur with repeat dosing. | Metabolized in the liver by cytochrome P450, primarily CYP3A4. Normeperidine is the most clinically relevant metabolite, with less analgesic effect but more CNS excitability. Excretion of metabolites is dependent on kidney function. | Co-administration with serotonergic agents increases risk of serotonin syndrome. Co-administration with MAOI is contraindicated due to potentially fatal reaction. Interacts with drugs that alter CYP3A4 metabolism¶. | Limited utility for analgesia due to adverse effect profile. Most common use is for postoperative shivering. |
| Nalbuphine | Phenanthrene synthetic opioid | 2 to 3 minutes (IV route), <15 minutes (subcutaneous or intramuscular) | Unknown | 3 to 6 hour duration, and 5 hour half-life. | Hepatic metabolism by UGT2B7 to largely inactive metabolites.[2,3] Fecal/biliary excretion of both active drug and metabolites (80 to 90% within 7 hours of administration). | Administration to patients taking mu-opioid agonists can precipitate opioid withdrawal. | Primary usage is at sub-anesthetic doses (2.5 to 5 mg IV) to reverse opioid-related adverse effects without reversal of analgesia. In opioid-naïve patients, doses of 10 mg IV can provide analgesia. |
IV: intravenous; CYP: cytochrome; N/A: not applicable; CrCl: creatinine clearance; NMDA: N-methyl-D-aspartate; MAOI: monoamine oxidase inhibitor.
* Context-sensitive half time is the time in minutes required for a 50% decrease in effect site concentration after the infusion is discontinued.
¶ Lists of drugs that alter CYP3A4 and CYP2D6 metabolism are available as separate tables within UpToDate. Significant drug interactions may be identified by use of the Lexicomp drug interactions program available through UpToDate.
Δ As examples, a longer half-life of sufentanil has been reported in patients undergoing cardiac surgery (9.9 hours) and abdominal aortic surgery (12 hours)[4,5].آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
