Fentanyl, Sufentanil and Remifentanil

Mechanism

Mechanism of action

Opioids act on G_i/o family protein-coupled receptors (MOP or µ receptors) located in the pre- and postsynaptic cell membranes of the periaqueductal gray matter, the rostroventromedial medulla oblongata, and the spinal posterior horns.

The binding of the agonist causes the dissociation of the βγ subunit, which inhibits the opening of pre-synaptic N-type voltage-gated calcium channels (reducing the exocytosis of nociceptive neurotransmitters such as glutamate and substance P) and activates post-synaptic internal rectifier potassium channels (GIRK), promoting persistent cellular hyperpolarization.

Pharmacokinetics

Exceptional Metabolism of Remifentanil

Remifentanil is an anilidopiperidinic derivative that has an ester-type functional group in its binding side chain. This structural chemical modification allows the drug to be degraded almost instantaneously by the catalytic action of nonspecific plasma and tissue esterases, yielding an inactive carboxylic acid metabolite (with a potency 1/4600 times lower).

Remifentanil Plasma Esterases Metabolite GI90291 (Inactive)

Its metabolism is totally independent of kidney function, liver clearance or the plasma concentration of pseudocholinesterases. Its context-sensitive half-life remains constant and invariably fixed at approximately 3 to 5 minutes, regardless of the time and duration of the continuous infusion administered (even after 12-hour infusions).

Pharmacokinetic Class Differentiation

Indicators and dose

Dosage and Clinical Adjustment

• Fentanyl (Induction): 1.5 - 3.0 µg/kg IV. Maintenance: boluses of 1.0 - 2.0 µg/kg intermittently depending on the patient's response.
• Remifentanil (TCI Balanced Anesthesia - Minto Model): Target concentration at the site of action of 2.0 - 8.0 ng/mL, or standard continuous infusions of 0.05 - 0.5 µg/kg/min.
• Sufentanil (Cardiac Anesthesia): 0.5 - 2.0 µg/kg IV.

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Critical Adverse Effects

• Chest Wall Rigidity (Timber Chest): The rapid administration of moderate or high doses of short-acting opioids can induce a tonic spasmodic contraction of the supralaryngeal and thoracic skeletal muscle by stimulation of central GABAergic interneurons, making manual mechanical ventilation by mask impossible. Immediate treatment: neuromuscular relaxants or naloxone.
• Respiratory Depression: They decrease the sensitivity of the bulbar respiratory center to carbon dioxide pressure (pCO₂) in a dose-dependent manner.
• Bradyarrhythmias: Central vagal tonic stimulation at the level of the dorsal motor nucleus of the vagus nerve.