Fentanyl

1) Receptor-level action → clinical effects

Primary:

μ-opioid receptor full agonist (synthetic phenylpiperidine derivative).

High affinity for μ₁ (analgesia, euphoria, respiratory depression) 

μ₂(respiratory depression, constipation, bradycardia).

Minimal κ-activity (less dysphoria than morphine).

Potency: ~100× morphine.

Other receptor effects (minor):

1. Inhibits substance P release in dorsal horn → spinal analgesia.

2. No histamine release → haemodynamic stability.

3. Mild vagal stimulation → bradycardia.

Clinical effects derived from above:

* CNS: profound analgesia, sedation, blunted stress response.

* CVS: Stable MAP (no histamine vasodilation) but bradycardia from vagal tone; minimal myocardial depression — ideal for cardiac surgery.

* Respiratory: potent dose-dependent depression and chest wall rigidity with rapid large doses.

* GI: constipation, nausea, decreased motility.

* Pupil: miosis.

* No amnesia — combine with hypnotic.

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2) Vial strength, preparation & basic pharmacokinetics (+ disadvantages)

Vials/amps: 

50 mcg/mL (2 mL, 10 mL) common; 2500 mcg/50 mL for infusion (50 mcg/mL).

Pharmacokinetics

* Onset: 1–2 min (very lipid-soluble, rapid BBB entry).

* Peak: 3–5 min.

* Duration: 30–60 min after bolus (redistribution).

* Metabolism: hepatic CYP3A4 N-dealkylation → inactive norfentanyl.

* Elimination: renal excretion of metabolites; elimination t½ = 3–4 h.

* Context-sensitive t½: short initially but lengthens steeply with prolonged infusion (hours → days).

Disadvantages

1. Accumulation with prolonged infusions → delayed awakening.

2. Chest wall rigidity with large rapid IV doses.

3. Requires ventilatory support in almost all anaesthetic doses.

4. No amnesia → needs hypnotic/benzodiazepine adjunct.

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3) Practical dosing

A. Anaesthesia (Cardiac / General)

* Premedication: 

25–100 mcg IV (analgesia, blunting laryngoscopy).

* Induction (cardiac):

 5–20 mcg/kg IV (often 5–10 mcg/kg; up to 30–50 mcg/kg in classical “high-dose opioid” cardiac technique).

* Maintenance:

1–5 mcg/kg IV boluses or infusion 1–5 mcg/kg/h titrated to surgical stimulation.

* Combine with benzodiazepine or propofol for hypnosis.

B. ICU / Analgosedation

Indications: 

ventilated patient analgesia, adjunct to sedation, haemodynamically unstable or renally impaired patients (preferred over morphine).

* Bolus:

25–100 mcg IV q30 min PRN.

* Infusion:

1–2 mcg/kg/h (range 0.5–5 mcg/kg/h).

* In renal failure: safe—no active metabolites.

* Convert to intermittent boluses or enteral opioid once stable.

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4) Special populations — dosing cautions

Pregnancy

* Crosses placenta → neonatal respiratory depression after maternal dosing near delivery.

* Acceptable for cardiac/obstetric anaesthesia when benefit outweighs risk; ensure neonatal resuscitation readiness.

Lactation

* Excreted in breast milk in small amounts; short-term peri-operative use acceptable; monitor infant for sedation/apnoea.

Hepatic impairment

* Metabolised hepatically → reduce dose and titrate slowly.

* Prolonged effect possible in severe liver failure.

Renal impairment

* No active metabolites; safe choice in renal dysfunction (unlike morphine).

* May still accumulate with prolonged high-dose infusion—titrate by effect.

Obesity

* Highly lipophilic → rapid redistribution into fat → accumulation.

* Bolus dose on Lean/Adjusted BW, infusion titrated to effect.

Paediatrics

* Premed:

1–2 mcg/kg IV/IM.

* Induction:

2–10 mcg/kg IV.

* Maintenance:

1–5 mcg/kg/h.

* Neonates/infants: longer elimination t½ → lower maintenance rates.

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5) Drug interactions (clinically key)

1. CNS depressants

(propofol, benzos, volatiles): additive respiratory/CVS depression → titrate carefully.

2. MAOIs / SSRIs / SNRIs / TCAs:

theoretical serotonin syndrome risk (rare).

3. CYP3A4 inhibitors

(azole antifungals, macrolides, protease inhibitors, diltiazem/verapamil, grapefruit): ↓ clearance → prolonged/apnoea.

4. CYP3A4 inducers

(rifampicin, phenytoin, carbamazepine): ↑ clearance → shorter duration.

5. Muscle relaxants:

additive chest rigidity; avoid rapid co-administration without neuromuscular blocker ready.

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6) Significant complications & management

1. Respiratory depression / apnoea

- Due to brainstem μ₂ depression 

* Support airway,

* ventilation, 

* naloxone 40–80 mcg IV q2 min; may need infusion (≈ 60 % of total reversal dose / h). 

2. Chest wall rigidity

- Due to central dopamine-dependent μ effect after rapid large dose

* Prevent with slow injection or give muscle relaxant; 

* if it occurs, suxamethonium 1 mg/kg or naloxone.

3. Bradycardia

- Due to vagal stimulation

* Atropine 0.3–0.6 mg IV or glycopyrrolate; 

*if severe, small epinephrine bolus.            

                         

4. Nausea / vomiting     

       

- Due to CTZ stimulation                                            

* Ondansetron/metoclopramide.                                                                                           

5. Tolerance & dependence

- Due to chronic use.

* Gradual wean; 

* multimodal analgesia. 

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Pocket viva line

Fentanyl is a potent μ-opioid agonist (~100× morphine) providing rapid, haemodynamically stable analgesia ideal for cardiac anaesthesia. 

It causes dose-dependent respiratory depression, bradycardia, and chest wall rigidity with large rapid doses.

Induction 5–20 mcg/kg IV; ICU infusion 1–2 mcg/kg/h; safe in renal failure but accumulates with prolonged use.