General Anesthetics

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Introduction & MOA - Knockout Science

  • General Anesthesia (GA): A drug-induced reversible state comprising: unconsciousness (hypnosis), amnesia, analgesia, akinesia (immobility), and autonomic stability.
  • Goals (📌 U-A-A-M-A): Unconsciousness, Amnesia, Analgesia, Muscle relaxation, Autonomic stability.
  • Guedel's Stages (Classic):
    • I: Analgesia/Disorientation
    • II: Excitement/Delirium (⚠️ Avoid)
    • III: Surgical Anesthesia (Target)
    • IV: Medullary Depression (Overdose)
  • MOA - Knockout Science:
    • Meyer-Overton Rule: Potency correlates with lipid solubility. ($Potency \propto Lipid \ solubility$)
    • Protein Targets (Modern View):
      • Enhance Inhibitory: GABA-A (major target), Glycine receptors.
      • Inhibit Excitatory: NMDA receptors, nAChR, K+ channels, Na+ channels.

⭐ Most GAs potentiate GABA-A receptors (↑ Cl- influx, hyperpolarization), except ketamine (NMDA antagonist) & N2O.

Guedel's Stages of Anesthesia Diagram

Inhalational Anesthetics - Potent Gas Vapors

  • MAC (Minimum Alveolar Concentration): Potency index. Concentration for no movement in 50% of patients to surgical stimulus. ↓MAC = ↑Potency.
  • Blood:Gas Partition Coefficient: Blood solubility. Determines speed of induction & recovery. ↓B:G = Faster.
  • Oil:Gas Partition Coefficient: Lipid solubility. Correlates with potency. ↑O:G = ↑Potency.
AgentMAC (%)B:G Coeff.Key Features/Side Effects
Halothane0.752.4Hepatotoxicity, arrhythmias, sensitizes myocardium
Isoflurane1.151.4Pungent, respiratory depression, coronary steal (controversial)
Sevoflurane2.00.69Sweet, good for induction, Compound A (soda lime)
Desflurane6.00.42Pungent, rapid recovery, sympathetic stimulation (high doses)
Nitrous Oxide ($N_2O$)1040.47Analgesic, diffusion hypoxia, second gas effect. 📌 Always with $O_2$

⭐ All potent volatile anesthetics (Halothane, Isoflurane, Sevoflurane, Desflurane) can trigger Malignant Hyperthermia.

Intravenous Anesthetics - Rapid Vein Induction

  • Achieve rapid loss of consciousness for anesthesia induction; smooth, quick transition.

Ketamine HCl Injection Vials

AgentMoA (Receptor)Key Use / FeatureKey Adverse Effects (AE)
PropofolGABA-AInduction/Maintenance, Anti-emetic, Rapid recoveryHypotension, Apnea, Injection pain, PRIS (rare)
KetamineNMDA antagonistDissociative anesthesia, Analgesia, BronchodilationEmergence phenomena, ↑ICP, ↑BP, ↑HR, Hypersalivation
EtomidateGABA-ACardiostable induction (minimal BP/HR change)Adrenocortical suppression, Myoclonus, PONV
ThiopentoneGABA-ARapid Sequence Induction (RSI), Neuroprotection (↓ICP)Laryngospasm, Hypotension, Apnea, Tissue necrosis
Midazolam (BZD)GABA-ASedation, Anxiolysis, Amnesia, Co-inductionRespiratory depression (+opioids), Hypotension

Anesthetic Adjuncts & Concerns - Balanced Smooth Ops

  • Preanesthetic Meds: Goals: ↓Anxiety & amnesia (Benzos), analgesia (Opioids), ↓secretions & vagolysis (Glycopyrrolate), antiemetic (Ondansetron), ↓gastric acid & volume (PPIs/H2 blockers).
  • Balanced Anesthesia: Multiple drugs (IV, inhaled, NMBs, opioids) for hypnosis, analgesia, muscle relaxation & autonomic stability; minimizes side effects & doses.
  • Malignant Hyperthermia (MH):
    • Rare, life-threatening; genetic (RYR1 mutation).
    • Triggers: Halogenated anesthetics (e.g., Halothane, Sevoflurane), Succinylcholine.
    • Signs: Early: ↑ETCO2, tachycardia, tachypnea, muscle rigidity (masseter spasm). Late: ↑Temp (rapidly), rhabdomyolysis, myoglobinuria, acidosis, hyperkalemia, arrhythmias.

    ⭐ Dantrolene (2.5 mg/kg IV, repeat as needed) is the specific antidote for Malignant Hyperthermia, inhibiting calcium ion release from the sarcoplasmic reticulum.

Malignant Hyperthermia Treatment Protocol

High‑Yield Points - ⚡ Biggest Takeaways

  • MAC (Minimum Alveolar Concentration) is inversely related to potency; lower MAC means higher potency.
  • Blood:gas partition coefficient determines induction/recovery speed; lower coefficient means faster action.
  • Propofol: rapid induction/recovery, antiemetic. Ketamine: dissociative anesthesia, analgesia, sympathomimetic.
  • Halothane: risk of hepatotoxicity, malignant hyperthermia. Isoflurane: pungent, good muscle relaxation.
  • Sevoflurane: ideal for inhalation induction. Desflurane: fastest recovery, pungent, requires heated vaporizer.
  • Malignant Hyperthermia: triggered by most volatile anesthetics & succinylcholine; treat with Dantrolene.
  • Nitrous Oxide: good analgesia, weak anesthetic, risk of diffusion hypoxia.

Practice Questions: General Anesthetics

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Anaesthetic agent causing analgesia?

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_____ subunit of the GABAA receptors mediate anxiolysis and muscle relaxation

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_____ subunit of the GABAA receptors mediate anxiolysis and muscle relaxation

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