Pharmacology of Intravenous Anesthetics

IV Anesthetics: Classification & Principles - Speedy Sleep Science

• Classification:
  • Barbiturates (Thiopental)
  • Benzodiazepines (Midazolam, Diazepam)
  • Propofol
  • Etomidate
  • Ketamine (Arylcyclohexylamine)
• Mechanisms:
  • GABA-A Receptor Modulation: $↑$Cl⁻ influx (Propofol, Etomidate, Barbiturates, Benzodiazepines)
  • NMDA Receptor Antagonism: (Ketamine)
• Key PK (Pharmacokinetics):
  • Redistribution: Rapid offset after single bolus.
  • Context-Sensitive Half-Time (CSHT): Duration-dependent elimination.
  • Protein Binding: Generally high.
  • Metabolism: Primarily Hepatic.
• Key PD (Pharmacodynamics):
  • CNS: Hypnosis, amnesia.
  • CV: Variable (e.g., Propofol $↓$BP, Ketamine $↑$BP/HR).
  • Resp: Depression (most), Ketamine (minimal).

⭐ The concept of context-sensitive half-time is crucial for understanding drug accumulation and recovery after continuous infusions of IV anesthetics, varying significantly between drugs like propofol and fentanyl.

Propofol & Etomidate - Milky Way & Steady Eddy

Barbiturates & Ketamine - Old Gold & Special K

• Barbiturates (Thiopental, Methohexital)
  • MOA: GABA-A potentiation → CNS depression.
  • PK: Redistribution. "Truth serum".
  • PD: ↓ICP, ↓CMRO2, anticonvulsant. Thiopental dose: 3-5 mg/kg.
  • ⚠️ Laryngospasm; Contra: Porphyria.
• Ketamine ("Special K")
  • MOA: NMDA receptor antagonist → 'dissociative anesthesia'.
  • PD: Analgesia, amnesia. Sympathomimetic: ↑HR, ↑BP, ↑CO, bronchodilation. IV dose: 1-2 mg/kg.
  • Adverse: ↑Salivation, emergence phenomena, nystagmus.
  • 📌 KETAMINE: Kardiovascular stimulant, Emergence reactions, Tachycardia, Analgesia, Muscarinic blockade (salivation), Increased ICP/IOP (controversial), Nystagmus, Eyes open.

  ⭐ Ketamine is unique among IV anesthetics as it produces profound analgesia and cardiovascular stimulation (sympathomimetic effect), making it useful in trauma, shock, and asthmatic patients.

Benzodiazepines & Dexmedetomidine - Chill Pills & Alpha Bliss

• Benzodiazepines (Midazolam, Diazepam, Lorazepam)

  • MOA: Potentiate $GABA_A$ receptors (↑ frequency Cl⁻ channel opening).
  • PK: Variable onset/duration.
  • Effects: Anxiolysis, sedation, amnesia, anticonvulsant. Minimal cardiorespiratory depression alone; synergistic with opioids.
  • Antagonist: Flumazenil.
  • 📌 Mnemonic 'SAD CHF': Sedation, Ataxia, Dependence, Confusion, Hypotension, Flumazenil (antidote).

• Dexmedetomidine ($ ext{\alpha}_2$ Agonist)

  • MOA: Selective $ ext{\alpha}_2$-agonist (locus coeruleus).
  • Effects: 'Cooperative sedation' (arousable), anxiolysis, analgesia, sympatholysis (↓HR, ↓BP). Minimal respiratory depression; opioid-sparing.
  • Dose: Loading 1 mcg/kg over 10 min.
  • ⭐ > Dexmedetomidine provides sedation and analgesia without significant respiratory depression, allowing for 'cooperative sedation' where patients remain rousable and interactive; its antagonist is Atipamezole (not commonly used in humans).

High‑Yield Points - ⚡ Biggest Takeaways

• Propofol: Rapid induction/recovery, antiemetic effect; causes hypotension, apnea; risk of PRIS.
• Etomidate: Hemodynamically stable, preferred in cardiac disease; causes adrenocortical suppression, myoclonus.
• Ketamine: Dissociative anesthesia, potent analgesic, bronchodilator; ↑HR, ↑BP, ↑ICP; emergence delirium.
• Thiopental: Reduces ICP (↓ICP), cerebral protection; risk of laryngospasm, contraindicated in acute porphyria.
• Midazolam: For anxiolysis, sedation, amnesia; flumazenil reverses effects.
• Dexmedetomidine: Sedation without respiratory depression, analgesic; causes bradycardia, hypotension.