Compare and contrast the pharmacology of intravenous fentanyl and morphine
Good candidates produced a well-structured answer and highlighted the differences between the two drugs. It was important to include the dose, potency, time course of effect of both agents, and differences in pharmacokinetic and pharmacodynamic effects. Candidates should have specific knowledge of these important drugs. Many candidates failed to focus the question on intravenous fentanyl and intravenous morphine as asked. No marks were given for information about other routes of administration.
|Chemistry||Natural phenanthrene||Synthetic opiate; a derivative of 4-anilinopiperidine. IV presentation is a clear colourless solution.|
|Routes of administration||Oral, IV, epidural, intrathecal, transdermal, subcutaneous, IM||Subcutaneous, IM, IV, epidural, intrathecal, transdermal|
|Absorption||Well absorbed orally, 30% bioavailability||Orally, bioavailability is 33%. Mucosal absorption is poor. Transdermal absorption is slow.|
|Solubility||pKa 8.0, 23% is unionised at pH 7.4; octanol-water partition coefficient ~ 1.42||pKa 8.4; 9% is unionised at pH 7.4. Highly lipid soluble: octanol:water partition coefficient is 717|
|Distribution||VOD = 1-6L/kg; 20-35% protein-bound||VOD is 6L/kg. Highly protein-bound (81-94%).|
|Target receptor||mu-opiate receptor (pre-synaptic G-protein coupled receptor)||mu-opiate receptor (pre-synaptic G-protein coupled receptor)|
|Metabolism||Hepatic metabolism; notable metabolites include morphine 6-glucuronide, an active metabolite||Hepatic metabolism, as well as in the intestine: CYP450 3A4: N-dealkylation to norfentanyl - then hydroxylation (all metabolites are inactive).|
|Elimination||Minimal unchanged drug cleared renally, but most of the metabolites rely on renal excretion||10% unchanged in the urine. Slow hepatic clearance: half life ranges from 2 to 12 hours|
|Time course of action||Slow onset, half-life 2-4 hrs||Rapid onset (2-5 minutes to peak effect); small dose acts for 30-60 minutes, but high doses are effective for 4-6 hours. Offset of effect is due to redistribution into fat and muscle.|
|Mechanism of action||Hyperpolarisation of cell membrane by increasing potassium conductance; reduced production of cAMP and closure of voltage-gated calcium channels||Hyperpolarisation of cell membrane by increasing potassium conductance; reduced production of cAMP and closure of voltage-gated calcium channels|
|Clinical effects||Analgesia, respiratory depression, constipation, miosis, urinary retention. Also has a cardiovascular effect, by inducing a non-immune histamine release (which produces vasodilation)||Vagal bradycardia; blunted cardiovascular reflexes and decreased sympathetic response to intubation; respiratory depression; chest wall rigidity; potent analgesic effect (50-80 times more potent than morphine); miosis; decreased gastrointestinal activity; increased detrusor tone; nausea; vomiting|
|Single best reference for further information||Crow et al (2021)||Smith et al (2016), p.146|
Zöllner, C., and C. Stein. "Opioids." Handbook of Experimental Pharmacology (2006): 31-63.
Crow, Jessica R., Stephanie L. Davis, and Andrew S. Jarrell. "Pharmacology and Pharmacokinetics of Opioids in the ICU." Opioid Use in Critical Care. Springer, Cham, 2021. 31-64.
Cata, Juan P., and Shreyas P. Bhavsar. "Pharmacology of opioids." Basic Sciences in Anesthesia. Springer, Cham, 2018. 123-137.
Armenian, Patil, et al. "Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review." Neuropharmacology 134 (2018): 121-132.