Common Features

Property Effect
Uses Analgesia, sedation, elimination of sympathetic response to laryngoscopy/surgical stress response
Resp CNS sensitivity to CO2 causing respiratory depression (↓ RR > ↓ VT) - ↑ reliance on hypoxic drive (therefore respiratory depression may be potentiated by high FiO2)
CVS HR. May ↓ BP due to histamine release (less with synthetic agents). ↑ PVR
CNS Sedation, euphoria. Nausea and vomiting due to CTZ stimulation. Meiosis due to stimulation of the Edinger-Westphal nucleus. ↓ MAC up to 90%
Renal ADH, ↑ ureteric and sphincter tone
MSK Muscle rigidity, pruritus (especially with intrathecal administration)
Metabolic ACTH, prolactin, gonadotrophic hormone secretion. ↑ ADH secretion
GIT ↓ Peristalsis and GIT secretions with subsequent constipation
Immunological Impaired: chemotaxis, lymphocyte proliferation, and antibody production

Comparison of Naturally Occurring Opioids

Property Morphine
Receptor MOP, KOP
Route of Administration SC/IM/IV/Intrathecal
pKa 8.0, 23% unionised at physiologic pH.
Absorption Low (relative) lipid solubility - slower onset and SC absorption. PO preparations absorbed in small bowel, bioavailability 30% - high first pass metabolism.
Distribution ~35% protein binding. VD 3.5L.kg-1
Clearance (ml.kg-1.min-1) 15
Metabolism Hepatic glucuronidation to 70% inactive morphine-3-glucuronide and 10% active morphine-6-glucuronide, which is 13x as potent as morphine. t1/2β of 160 minutes.
Elimination Renal elimination of active metabolites - accumulation in renal failure
Time to Peak Effect (IV) 10-30 minutes
Duration (IV) 3-4 hours
Equianalgesic Dose (IV, to 10mg IV morphine) 10mg

Comparison of Semisynthetic Opioids

Property Oxycodone Buprenorphine
Receptor MOP, KOP, DOP Partial MOP agonist, KOP antagonist (antanalgesic effect)
Route of Administration PO/IV Topical
pKa 8.5, < 10% is unionised at physiologic pH.
Absorption PO bioavailability 60-80% Significant 1st pass metabolism
Distribution As lipid soluble as morphine, 45% protein bound, VD 3L.kg-1. More rapid onset than morphine despite higher pKa potentially due to active CNS uptake
Clearance (ml.kg-1.min-1) 13
Metabolism Hepatic demethylation to noroxycodone (80%, via CYP3A) and the more potent and active oxymorphone (20%, via CYP2D6). t1/2β 200 minutes. Hepatic to active norbuprenorphine
Elimination Renal elimination of active drug and metabolites 70% biliary, 30% renal elimination, t1/2β 40 hours
Time to Peak Effect (IV) 5 minutes
Duration (IV) 4 hours
Equianalgesic Dose (IV, to 10mg IV morphine) 10mg. Note 10mg PO oxycodone is ≈ 15mg PO morphine due to higher first pass metabolism of morphine

Comparison of Synthetic Opioids

Property Fentanyl Alfentanil Remifentanil
Receptor MOP MOP MOP
Route of Administration SC/IM/IV/Epidural/Intrathecal/Transdermal IV IV (contains glycine, so cannot be administered intrathecally)
pKa 8.4, < 10% unionised at pH 7.4 6.5, 90% unionised at pH 7.4 conferring rapid onset 7.3 means 58% unionised at physiologic pH.
Absorption Rapid onset of action (< 30s, peak at 5min) due to lipid solubility (600x that of morphine). 90x more lipid soluble than morphine, but more rapid onset than fentanyl. This is due to:
1. Low pKa means a greater proportion is unionised at physiological pH.
2. Lower potency of alfentanil compared to fentanyl means a greater dose is required (Bowman's Principle)
20x more lipid soluble than morphine.
Distribution 600x as lipid soluble as morphine conferring a larger VD (4L.kg-1). 85% protein bound. 90x as lipid soluble as morphine, small VD of 0.6L.kg-1. 90% protein bound 20x as lipid soluble as morphine, very small VD of 0.4L.kg-1. 70% protein bound. CSHT is constant due to rapid metabolism.
Clearance (ml.kg-1.min-1) 13 6 40
Metabolism Significant first pass pulmonary endothelial uptake. Hepatic demethylation to inactive norfentanyl. t1/2β of 190 minutes, longer than morphine due to higher lipid solubility and VD. Shorter elimination t1/2β than fentanyl (100 minutes) despite lower clearance due to lower VD. Prolonged with administration of midazolam due to CYP3A3/4 competition. Rapid metabolism by plasma and tissue esterases - t1/2β 10 minutes
Elimination Renal elimination of inactive metabolites Renal elimination of metabolites Renal of inactive metabolites
Time to Peak Effect (IV) 5 minutes 90 seconds 1-3 minutes
Duration (IV) Variable depending on dose and distribution. With doses > 3μg.kg-1 tissues become saturated and the duration of action is significantly prolonged 5-10 minutes Offset 5-10 minutes from ceasing infusion
Equianalgesic Dose (IV, to 10mg IV morphine) 150mcg 1mg 50mcg


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  3. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  4. ANZCA July/September 2010
  5. Schug SA, Palmer GM, Scott DA, Halliwell R, Trinca J. Acute Pain Management: Scientific Evidence. 4th Ed. 2015. Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine.
Last updated 2020-08-11

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