Remifentanil

Quick summary

 

 

Usage

What is the drug used for?

Structure

Structure

• Structurally unique because of the ester linkage
  --> Allows hydrolysis by nonspecific plasma and tissue esterase

Thus,

• Short duration of action
• Rapid and easy titration
• Noncumulative effects
• Rapid recovery after discontinuation

Pharmacodynamics

Potency

Analgesic potency is similar to fentanyl
* About 15-20 times as potent as alfentanil

Mechanisms of action

• Selective mu opioid agonist

Effects by systems

CNS

• High dose remifentanil decreases CBF and CMRO2
  * No impairment of CBF autoregulation in response to pCO2
• Seizure-like activity
  * All fentanyl analogs, including remifentanil

Respiratory

After 0.5 microgram/kg IV remifentanil
--> Decrease in slope and downward shift of the CO2 ventilatory response curve
--> Nadir after about 150 seconds after injection
--> Recovery within 15 minutes

 

Propofol and remifentanil
--> Synergistic respiratory depression effect

Acute opioid tolerance

• May be associated with acute opioid tolerance
  * Not all study supports acute opioid tolerance
• Activation of NMDA receptors may be a possible mechanism
  --> NMDA receptor antagonists (ketamine, Mg2+) block opioid tolerance

Others

• PONV
• No histamine release
• No change in ICP or IOP
• Muscle rigidity [PI]

Pharmacokinetics (PK)

Characterised by

• Small Vd
• Rapid clearance
• Low interindividual variability

Absorption

IV infusion

Distribution

• Vd = 0.2 - 0.3 L/kg
  * Small Vd
  * Limited accumulation
  * Steady state is reached within 10 minutes of the start of infusion
• Protein-binding
  = 66-93% [SH4:p93]
  = ?80% [RDM6:p401]

Metabolism

• Ester link in remifentanil
  --> Susceptible to hydrolysis by nonspecific plasma and tissue esterase
  --> Inactive metabolites

Metabolism is by

• Hydrolysis
  * By nonspecific plasma esterase and tissue esterase
  * Remifentanil acid is formed (300 to 4600 fold less potent than remifentanil)
  * The major pathway of metabolism of remifentanil in human
• N-dealkylation
  * Minor pathway

NB:

• Remifentanil is NOT metabolised by butyrylcholinesterases (pseudocholinesterase, plasma cholinesterase)
  --> Remifentanil clearance is not affected by cholinesterase deficiency or anticholinergics
• Esterase metabolism appears to be well-preserved metabolic system and has little interindividual variability

Elimination

• Clearance = 30 - 40 mL/kg/min
  * Very fast clearance
  * Contribute to the lack of accumulation
• Metabolites are excreted by kidneys

Action profile

• Elimination half-time = 0.17 - 0.33 hr
• Context-sensitive half-time (4 hours) = 4 min
  * Nearly independent of infusion duration
• Effect-site equilibration time = 1.1 min

Physicochemical properties

• Weak base
• pKa = 7.3
  --> 58% non-ionised at pH 7.4

Pharmaceutics

[PI on MIMs]

Presentation

• 1mg, 2mg, and 5mg vials
• Diluted to 20, 25, 50, or 250 microgram/mL
• 50 microgram/mL is the recommended concentration in adults
• 20-25 microgram/mL is the recommended concentration for paediatrics

Composition

• Active = remifentanil
• Inactive = glycine

Clinical

Administration

Induction of anaesthesia

• Remifentanil 1 microgram/kg IV over 60-90 seconds

Analgesia

• Remifentanil 0.05 - 2.00 microgram/kg/min

NB:

• Clinical dosing of remifentanil should be based on ideal body mass

 

Contraindications

Spinal or epidural

• Not recommended because the safety of the opioid and/or the vehicle (glycine) have not been determined.

Special consideration

Renal and hepatic disease

• Renal and hepatic disease is unlikely to affect metabolism of remifentanil
  * Esterase metabolism is usually well-preserved

Hypothermic cardiopulmonary bypass

• Decrease in temperature
  --> Decreased blood and tissue esterase activity
  --> Remifentanil clearance is reduced by 20%

Trivia

History

 

Others