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.
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.
| Agent | MAC (%) | B:G Coeff. | Key Features/Side Effects |
|---|---|---|---|
| Halothane | 0.75 | 2.4 | Hepatotoxicity, arrhythmias, sensitizes myocardium |
| Isoflurane | 1.15 | 1.4 | Pungent, respiratory depression, coronary steal (controversial) |
| Sevoflurane | 2.0 | 0.69 | Sweet, good for induction, Compound A (soda lime) |
| Desflurane | 6.0 | 0.42 | Pungent, rapid recovery, sympathetic stimulation (high doses) |
| Nitrous Oxide ($N_2O$) | 104 | 0.47 | Analgesic, 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.
| Agent | MoA (Receptor) | Key Use / Feature | Key Adverse Effects (AE) |
|---|---|---|---|
| Propofol | GABA-A | Induction/Maintenance, Anti-emetic, Rapid recovery | Hypotension, Apnea, Injection pain, PRIS (rare) |
| Ketamine | NMDA antagonist | Dissociative anesthesia, Analgesia, Bronchodilation | Emergence phenomena, ↑ICP, ↑BP, ↑HR, Hypersalivation |
| Etomidate | GABA-A | Cardiostable induction (minimal BP/HR change) | Adrenocortical suppression, Myoclonus, PONV |
| Thiopentone | GABA-A | Rapid Sequence Induction (RSI), Neuroprotection (↓ICP) | Laryngospasm, Hypotension, Apnea, Tissue necrosis |
| Midazolam (BZD) | GABA-A | Sedation, Anxiolysis, Amnesia, Co-induction | Respiratory 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.
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.
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