Canonical Question
PainPharm – Opiates
Master answer
| Fentanyl Infusion | Morphine Infusion | |
|---|---|---|
| Cost | slightly less | |
| Potency | 50 to 100 times more potent highly lipophilic, which allows rapid penetration of the blood-brain barrier and rapid onset of action (four to six minutes), although maximal analgesic and respiratory depressant effects of fentanyl may not be evident for several minutes | |
| Effective analgesia for surgical trauma causing severe pain during the intraoperative or immediate postoperative period, due to a prolonged duration of action. | ||
| PD | a more rapid onset of action than morphine, which reflects its greater lipid solubility and consequent increased ability to cross the blood–brain barrier | Slower onset of analgesia (within 20 minutes) and slower time to peak analgesic effect compared with fentanyl due to lower lipid solubility and a longer lag time for penetration of the blood-brain barrier. |
| redistribution to inactive tissue sites such as fat and skeletal muscle, with an associated decrease in plasma concentration Furthermore, fentanyl has been reported to have 75% first-pass uptake into the lungs, thus the amount of fentanyl that reaches the systemic circulation is limited | morphine’s first-pass pulmonary uptake is extremely small | |
| Despite fentanyl being a more attractive option than morphine for analgo-sedation, because of its potentially shorter duration of action, other pharmacokinetic properties may limit its usefulness. After initial redistribution, fentanyl’s plasma concentrations are maintained by slow reuptake from the tissues across a concentration gradient | ||
| Effects | no significant difference in amount of pain relief | |
| Minimal effect on myocardial or hemodynamic function. | Unsuitable for patients with hemodynamic instability due to possible exacerbation of hypotension by histamine release, as well as persistence of its effects due to a long context-sensitive half time and the mu-receptor-stimulating properties of its morphine-6-glucuronide metabolite. | |
| Metabolism | Metabolised by N-demethylation in the liver, catalysed by the cytochrome p450 system; major metabolite is norfentanyl and other metabolites are hydroxyproprionyl-fentanyl and hydroxyproprionyl-norfentanyl (all these metabolites have minimal pharmacologic activity) | Metabolised by conjugation with glucuronic acid in hepatic and extrahepatic sites, especially the kidneys; major metabolites are morphine-3-glucuronide (75–85%), morphine-6-glucuronide (5–10%); other metabolites are normorphine and a small amount to codeine |
| Active metabolites | Minimal pharmacological effect | Morphine-6-glucuronide – pharmacologically active undergoes renal clearance and accumulates in patients with renal failure, with clinical effects including prolonged sedation and respiratory depression elimination half-life of about 1.4 hours, but this is increased in patients with renal failure |
| Fentanyl has a high hepatic extraction ratio with clearance approaching liver blood flow | ||
| Excretion | Metabolites are renally excreted and < 10% of fentanyl is excreted unchanged in the urine | Metabolites are renally excreted with 7–10% undergoing biliary excretion |
| Elimination half life | 3.1–6.6 hours | 1.7–2.3 hours |
| fentanyl’s effects may be as prolonged as morphine, even when allowing for potential accumulation of metabolically active metabolites of morphine in renal failure | Cautious use in patients with a history of seizures if renal insufficiency is present, due to neuroexcitation caused by the morphine-6-glucuronide metabolite, with possible occurrence of myoclonus or exacerbation of seizure activity. | |
| Context-sensitive half-time | Consequently, following infusion, the clinical effects of fentanyl become increasingly prolonged owing to its long “context-sensitive half-time” | |
CSHT 4hr inf | 200 minutes | Not applicable |
| CSHT 8hr inf | 300 min | Not applicable |
| longer inf | unpredictably long | Not applicable |
| Adverse effects | Higher incidence of most opioid-related adverse side effects (eg, pruritus, urinary retention, constipation, and nausea), compared with other opioids. | |
| Absence of histamine-releasing properties; thus, fentanyl is appropriate for patients with bronchospasm. | headedness, sedation, drowsiness and euphoria). In addition, morphine contains a tertiary amine group, which causes non-immune-mediated release of histamine and can lead to skin rashes, itchiness and hypotension | |
| Drug-drug interactions | Similar interactions – may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome | |
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2020A Q17 | Discuss the advantages and disadvantages of the use of an intravenous infusion of fentanyl in comparison to morphine. | historical_member | — |