Fentanyl

Chemical

Synthetic opioid of PHENYLPIPERIDINE CLASS

Rapid acting, intermediate duration

Use

  1. Labour analgesia
  2. Cardiac analgesia
  3. Epidural analgesia
  4. Chronic pain – patch

Presentation

PARENTERAL: clear, colourless, 50mcg/mL ampoule

TOPICAL PATCH: 25, 50, 75, 100mcg/hr Q72hrs

  • Partition coefficient 860 → HIGH LIPID SOLUBILITY (due to piperidine ring)
  • High lipid solubility

→ Rapid onset

→ Shorter DoA

→ More potent

Dose

X 100 more potent than morphine

  • IV analgesia = 1mcg/kg
  • Blunt response to laryngoscopy = 20mcg/kg
  • Surgical anaesthesia (sole agent) = 100mcg/kg
  • Epidural = 50 – 100mcg
  • Intrathecal = 5 – 20mcg
  • Transdermal = 25, 50, 75, 100mcg/hr Q72hrs

Onset / DoA

  • Rapid onset → due to lipid solubility
  • Effect site equilibrium 4-6 mins
  • Short DoA 2° lipid solubility → redistributes quickly to skeletal m. & fat 

MoA

MOP +++

kOP +

δ OP –

PD

CNS – Analgesia

CVS – ↓HR more common cf. M

RESP – respiratory depression → most marked of all opioids. POTENT ANTITUSSIVE & chest wall rigidity

GI – less N&V

IMMUNO – less histamine release

PK

A

Transdermal patch peak plasma 18hrs (∴ not for acute analgesia)

D

4L/kg

Larger cf. M

↑lipid solubility = rapid & extensive tissue penetration

PPB 80%

Tissue affinities

  • Lungs → large, inactive storage site; 75% dose = pulmonary uptake
  • Fat & skeletal m. → redistribution sites

M

Liver

N-Demethylation

  • To norfentanyl
  • Less potent cf. F

High HER

∴depends on HBF

Half times

  • Elim t ½

→ short DoA

→ Prolonged elim t 1/2, longer cf. M

→ Due to larger VD

→ F taken up to ‘inactive sites’ (lungs, fat, skeletal m) is redistributed back into plasma

  • CSHT

→ CSHT = time required for plasma drug [  ] ↓50% after discontinuing an infusion

→ very long

→ as duration of infusion exceeds 2hrs, it saturates the ‘inactive sites’

→ so when an infusion is terminated, the plasma [  ] cannot ↓by redistributing to these sites

→ so for plasma F to ↓ it must be eliminated by hepatic metabolism  

E

Norfentanyl excreted by kidneys

10% unchanged

(Given in renal failure as metabolites are not pharmacologically active)

Adverse Effects

  • Chest wall rigidity
  • Respiratory depression
  • Dependence