Pharmacology of Inhalational Anesthetics

Pharmacology of Inhalational Anesthetics

Pharmacology of Inhalational Anesthetics

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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.

FA/FI curves and uptake of inhalational anesthetics

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

AgentMAC (%)B:G Coeff.MetabolismKey Features & Concerns
Halothane0.752.4~20%Sweet; Potent bronchodilator. Risks: Hepatitis, arrhythmias (catecholamine sensitization), ↑ICP. Phased out.
Isoflurane1.171.4<0.2%Pungent; Good muscle relaxant; Stable CV. Economical. Risks: Airway irritant, coronary steal (rare).
Sevoflurane1.80.652-5%Sweet; Rapid onset/offset; Bronchodilator; Ideal for inhalation induction. Risk: Compound A (low with >2L/min flow).
Desflurane6.60.42<0.02%Very pungent; Fastest onset/offset (very low solubility); Needs special heated vaporizer. Risks: Airway irritant, sympathetic surge.
Nitrous Oxide1040.47MinimalGood analgesic; Rapid onset/offset (low solubility). Risks: Diffusion hypoxia, expands cavities, $B_{12}$ inhibition (prolonged). 📌 Laughing gas.

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).

Practice Questions: Pharmacology of Inhalational Anesthetics

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Which of the following statements about Nitrous Oxide (N2O) is true?

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Flashcards: Pharmacology of Inhalational Anesthetics

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Inhaled anesthetics with _____ solubility in blood have a faster onset of action

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Inhaled anesthetics with _____ solubility in blood have a faster onset of action

lower

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