Pharmacology of Intravenous Anesthetics

Pharmacology of Intravenous Anesthetics

Pharmacology of Intravenous Anesthetics

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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). GABA-A receptor structure and drug binding sites

⭐ 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

FeaturePropofol ("Milky Way")Etomidate ("Steady Eddy")
MOA↑GABA$_A$ receptor activity↑GABA$_A$ receptor activity
Induction Dose1.5-2.5 mg/kg IV0.2-0.3 mg/kg IV
CVS EffectsVasodilation, ↓BP, ↓SVRCardiovascular stability (minimal effect on HR, BP)
Respiratory EffectsSignificant depression, apneaMinimal depression
Key Side EffectsPain on injection; PRIS 📌 (PRISMATIC; acidosis, rhabdo, arrhythmias with >4mg/kg/hr >48h)Myoclonus, PONV, Adrenocortical suppression (inhibits $11\beta$-hydroxylase → ↓cortisol)
OtherAntiemetic; Rapid on/off. Fospropofol (prodrug).Rapid on/off. Preferred in shock states.

Etomidate inhibition of 11-beta-hydroxylase

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).

GABA receptor mechanism

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.

Practice Questions: Pharmacology of Intravenous Anesthetics

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Midazolam does not cause which of the following?

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Flashcards: Pharmacology of Intravenous Anesthetics

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_____ is the only anesthetic with no intrinsic antiepileptic property.

TAP TO REVEAL ANSWER

_____ is the only anesthetic with no intrinsic antiepileptic property.

Methohexital

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