| 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. | 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. | Metabolized in liver and small intestines. Metabolites excreted by kidney with renal clearance 12 mL/kg per minute. | Synergistic effects if coadministered with other anesthetic agents. | 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: 2.4 hours. Elimination half-life: 2.3 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. |
| 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 due to likely accumulation of morphine-6-glucoronide, which produces ongoing analgesia, and possible neuroexcitation that may result in myoclonus or exacerbation of seizures. |
| Methadone | Diphenylheptane synthetic opioid | 6 to 8 minutes | N/A | Redistribution half-life: approximately 6 minutes. Elimination half-life: approximately 30 hours. Duration of action is highly dependent on dosage and frequency. | Metabolized in the liver P450 enzymes, primarily CYP2D6 but also CYP3A4. No active metabolites. Excretion is primarily fecal. | Extensive drug-drug interactions. CYP2D6 or CYP3A4 inducers may result in rapid metabolism leading to withdrawal, while inhibitors may result in prolonged effects. Antiretroviral agents in particular are metabolized via similar mechanisms and have alternating induction, inhibition, or mixed effects on P450 enzymes. 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. |
| 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. | Hepatic metabolism via P450 cytochrome system, and renal excretion. Normeperidine is the most clinically relevant metabolite with less analgesic effect, but more CNS excitability. | Co-administration with serotonergic agents increases risk of serotonin syndrome. Co-administration with MAOI is contraindicated due to potentially fatal reaction. | Limited utility for analgesia due to adverse effect profile. Most common use is for postoperative shivering. |
| Nalbuphine | Phenanthrene synthetic opioid | 2 to 3 minute (IV route), <15 min (subcutaneous or intramuscular) | Unknown | 3 to 6 hour duration, and 5 hr 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. |
