Pharmacodynamics

CNS

• NOT an analgesic (but not antanalgesic as thiopental)
• in fact, causes local pain on injection
• hypnosis in 1 arm-brain time (2.5 mg/kg)
• Mechanism of Action: Probably related to action at or near the GABA receptor that enhances the inhibitory effect of GABA on neurotransmission.
• lower doses -> slower onset (but less bad side effects)
• duration 5-10 minutes (2-2.5 mg/kg)
• subhypnotic doses -> sedation and amnesia and antemesis
• alter mood less than thiopental
• general sense of well being; 'amorous' ideation reported
• hallucination and opisthotonus have been reported
• EEG: 2.5 mg/kg + infusion ->
  • log blood concentration proportional to %delta/%beta
  • seizure effect unclear
    • has been used effectively to treat seizures
    • briefer seizure activity after ECT compared to Brevital
• lowers ICP (normal and patients with high ICP)
  • + fentanyll -> less ICP response to ETT
  • normal CO₂ response
  • patients with high ICP: MAP may drop more than ICP -> decreasing CPP
• lowers IOP 35% acutely (> thiopental)
• relevant Cp's (depends also on age and concurrent medications)
  • Cp₅₀ for loss of response to verbal commands = 2.3 - 3.5 mcg/ml
  • maintenance: 1.5-6 mcg/ml
  • awakening: < 1.6 mcg/ml
  • orientation: < 1.2 mcg/ml

Respiratory

• qualitatively similar to barbiturates
• apnea after induction dose: 25-40%
  • more likely to last longer than 30 seconds
  • function of dose, speed of injection, other medications
• 2.4 mg/kg ->
  • slower respiratory rate for 2 minutes
  • smaller V_T for 4 minutes
• 100 mcg/kg/min ->
  • slightly less CO₂ response (compared to 3 mg/kg thiopental)
  • V_T 40% less, respiratory rate 20% greater
• 200 mcg/kg/min ->
  • only slightly more depression of V_T
  • expect p_aCO₂ low 50's

Cardiovascular System

• Induction bolus 2-2.5 mg/kg:
  • BP DOWN: systolic, diastolic, and mean: 24-40%
  • CI, SV DOWN 15-20%
  • LVSWI down 30%
  • HR little changed or significant bradycardia *
  • vasodilation + myocardial depression
• Less depression of CI with spontaneous ventilation (compared to controlled ventilation)
• More CV depression in the elderly and debilitated
• Less CV depression with an induction infusion (avoid boluses)
• Maintenance
  • systolic BP 25% less than preop
  • 100 mcg/kg/min + spontaneous ventilation on room air:
    • CI and SV unchanged
    • HR relatively unchanged
  • MVO₂ and myocardial blood flow lower
  • Myocardial O₂ supply:demand ratio probably preserved
  • ETT: returns BP to baseline

Other -- some nice negatives:

• potentiate NM blockers
• trigger MH
• cause nausea or vomiting
• affect steroid synthesis or ACTH response
• alter hepatic or fibrinolytic function
• cause histamine release

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