Fentanyl

Question 1

Brand name for Fentanyl

Answer 1

Sublimaze, Duragesic (transdermal formulation)

Question 2

Drug Class

Answer 2

Opioids. Fentanyl is a synthetic opioid agonist belonging to the phenylpiperidine class

Question 3

Mechanism of Action

Answer 3

Fentanyl binds to mu receptors in the CNS and spinal cord. Binds to Gi protein -> inhibits adenylate cyclase -> decreases cAMP -> closes voltage gated calcium channels presynaptically and closes K channels post synaptically causing neuronal hyperpolarization

Question 4

Receptors and physiologic effects

Answer 4

Mu receptor activation.
Mu 1- Supraspinal analgesiaBradycardiaSedationPruritusNausea and vomiting
Mu 2 - Respiratory depressionEuphoriaPhysical dependencePruritusConstipation

Question 5

Indications

Answer 5

pre/intra/postop analgesia, monitored anesthesia care (MAC), blunting SNS response to intubation/surgical stress

Question 6

MAC sparing effect of Fentanyl

Answer 6

Administration of 1-2mcg/kg of Fentanyl decreases inhalational anesthetic and propofol requirements by 50%

Question 7

Potency of Fentanyl

Answer 7

100 times more potent then morphine

Question 8

Fentanyl: General pharmacokinetics (VD, protein binding, keo)

Answer 8

Fentanyl is highly lipophilic and has a high VD. Rapidly penetrates the BBB.
It is highly protein bound (79-87%).
About 75% of fentanyl undergoes 1st pass pulmonary uptake.
High keo compared to morphine, effect-site equilibration time is 6.4 minutes

Question 9

Fentanyl: Metabolism

Answer 9

Extensive hepatic metabolism.
N-demethylation via CYP3A4.
Metabolites have minimal pharmacologic activity

Question 10

Fentanyl: primary elimination route

Answer 10

Renal excretion of metabolites.

Question 11

Elimination half life

Answer 11

Short CLINICAL duration (10-20min)
Fentanyl actually has a long elimination half life due to its large Vd/extensive tissue binding.

Question 12

Fentanyl: context sensitive half time

Answer 12

After over 2 hours of infusion context sensitive half time largely increases

Question 13

Special populations

Answer 13

Elderly- elimination half-time increases (due to reduced hepatic clearance, and higher fat)
Patients on any CYP3A4 inhibitors

Question 14

Fentanyl: side effects

Answer 14

Respiratory depression, decreased CO2 responsiveness

bradycardia
(no histamine release)

sedation, analgesia, euphoria

pruritis, nausea and vomiting, constipation, contraction of sphincter of oddi, miosis

Chest wall rigidity

Question 15

Contraindications/caution in

Answer 15

patients with OSA.
Premature neonates and elderly = more sensitive
Transfers through placenta and breast milk.
Opioid dependence.
Allergies.

Question 16

Dosing

Answer 16

1-2mcg/kg for induction