Pharmacology of Inhalational Anesthetics

Introduction & Classification - The Gas Passers

• Inhaled agents inducing reversible CNS depression for anesthesia.
• Classification:
  • Gases (at room temp & pressure):
    • Nitrous Oxide ($N_2O$)
  • Volatile Liquids (liquid at room temp, vaporized for use):
    • Halogenated Ethers: Isoflurane, Sevoflurane, Desflurane.
    • Halothane (historical halogenated alkane).
• 📌 Mnemonic for volatile agents: "DISH" (Desflurane, Isoflurane, Sevoflurane, Halothane).

⭐ Nitrous oxide: sole inorganic gas; analgesic at sub-anesthetic doses.

Pharmacokinetics (PK) - Uptake & MAC Attack

• Uptake: Governed by $F_A/F_I$ rise (alveolar/inspired partial pressure ratio).
  • ↑ $F_A/F_I$ (Faster induction):
    • ↑ Inspired concentration ($F_I$)
    • ↑ Alveolar ventilation
    • ↓ Blood:Gas solubility ($\lambda_{b/g}$)
    • ↓ Cardiac output (especially for soluble agents)
  • 📌 Solubility Slows: Low $\lambda_{b/g}$ (e.g., Sevoflurane, N₂O) = faster onset.
• MAC (Minimum Alveolar Concentration):
  • Conc. at 1 atm preventing movement in 50% of patients to surgical stimulus.
  • Potency $\propto 1/\text{MAC}$. (↓MAC = ↑Potency)
  • ↓MAC: ↑Age, hypothermia, opioids, pregnancy, acute alcohol, IV anesthetics.
  • ↑MAC: Hyperthermia, chronic alcohol, hypernatremia, CNS stimulants.

  ⭐ MAC values are additive: 0.5 MAC Agent A + 0.5 MAC Agent B ≈ 1 MAC effect.

Pharmacodynamics (PD) & System Effects - Body's Response

• Mechanism: Modulate ligand-gated ion channels (↑GABA-A, ↑Glycine; ↓NMDA, ↓nAChR). Potency correlates with lipid solubility (Meyer-Overton).
• CNS Effects:
  • ↓CMRO2; ↑CBF (uncoupling >1 MAC) → ↑ICP.
  • Amnesia, unconsciousness, immobility (spinal).
  • Analgesia: N2O potent; others weak.
• CVS Effects:
  • ↓MAP: Vasodilation (Iso, Sevo, Des); Myocardial depression (Halothane).
  • HR: Iso/Des → ↑HR (esp. rapid induction); Halo/Sevo → ↓/↔HR.
  • Halothane: Arrhythmogenic (sensitizes to catecholamines).
• Respiratory Effects:
  • ↓Ventilation (↓TV, ↑RR → ↓MV), ↑PaCO2.
  • Depressed hypoxic/hypercapnic drive.
  • Bronchodilation (Sevo, Iso, Halo). 📌 SIB: Sevoflurane, Isoflurane, Halothane are Bronchodilators.
  • Desflurane: Airway irritant.
• Other Key Effects:
  • Hepatic: ↓HBF. Halothane hepatitis (rare).
  • Renal: ↓RBF, ↓GFR. Compound A (Sevoflurane) with low flows (<2 L/min).
  • MSK: Muscle relaxation.
  • Uterine: Relaxation (dose-dependent).

⭐ All volatile anesthetics (except N2O) are triggers for Malignant Hyperthermia. Dantrolene is the specific antidote.

Individual Agents - Meet the Vapors

Complications & Contraindications - Danger Zones

• Malignant Hyperthermia (MH): All volatiles (not N₂O). Dantrolene.
• Diffusion Hypoxia: N₂O discontinuation. Give 100% O₂.
• Hepatotoxicity: Halothane.
• Nephrotoxicity: Sevoflurane (Compound A), Methoxyflurane.
• PONV: Common, esp. N₂O.
• Contraindications: Prior MH, severe hypovolemia, ↑ICP (N₂O).

⭐ Malignant hyperthermia: RYR1 gene defect; treat with Dantrolene 2.5 mg/kg intravenously immediately.

High‑Yield Points - ⚡ Biggest Takeaways

• MAC (Minimum Alveolar Concentration) is inversely related to potency (↓MAC = ↑Potency).
• Low Blood:Gas partition coefficient ensures faster induction and emergence (e.g., Desflurane, Sevoflurane, N₂O).
• Halothane is notably linked to hepatotoxicity ("halothane hepatitis") and myocardial sensitization.
• Nitrous Oxide (N₂O) causes diffusional hypoxia and expands gas-filled cavities.
• Sevoflurane, a common bronchodilator, produces Compound A (nephrotoxic) with CO₂ absorbents.
• Malignant Hyperthermia, a life-threatening state, is triggered by volatile anesthetics (except N₂O).