Antiemetic (low dose) Amnesia Poor analgesic and amnestic Antipuritic w/neuraxial opiods properties Induction = 1.5 2.5 mg/kg Analgesia = 0.2 0.5 mg/kg Induction = 0.2 0.4 mg/kg – – – IV sedation = 25 100 mcg/kg/min Induction = 1-2 mg/kg IV – Maint. of anesth = 100 300 mcg/kg/min = 4 8 mg/kg IM ( 1-2 mg/kg Onset = 30 60 seconds – – – w/ general anesthesia) Myoclonic movements normal Dosing Elderly hypotension smaller doses Duration of action IV = 5-15 min – – distribution volume IM= 12-25 min. ↓central and clearance rate Peds higher ind. Dose (mg/kg basis) – central distribution volume ↑ and clearance rate Noncompetitive attachment to phencyclidine (PCP) recognition sites on NMDA receptors Inhibits activation of receptor by glutamate Decreases pre-synaptic release of glutamate GABA receptor interaction prolong – Potentiates effect of GABA Mechanism of GABA inhibitory effects receptor interaction prolong GABA – (weak action at GABA receptors) Action Decreases the rate of dissociation of GABA inhibitory effects GABA from the receptor Exerts effect at receptor Opioid µ, ,Κ, – Δ Σ(delirium) MAO antinociceptive action – Muscarinic – anticholinergic,bronchodilation, HTN, delirium, ↑HR VS Na channels acts like local – anesthetic Propofol Ketamine Etomidate Carboxylated Imidazole compound Substituted Isopropylphenol Related to phencyclidine Administered as single isomer R(+) Structure Only one not a chiral compound Racemic mixture Water soluble @ Acidic pH (ring open) Lipid egg soy emulsion b/c it is insoluble S(+) more active isomer Lipid soluble @ phys. pH (ring closed) Short effect-site equilibration time Rapid onset = high lipid solubility Rapid brain penetration peak brain – Uptake + 30 sec. brain effect after dosing Short duration of action= 5-15 min. level in 1 minute Distribution Awakening faster and complete Rapid brain penetration
Antiemetic (low dose) Antipuritic w/neuraxial opiods Amnesia Poor analgesic and amnestic properties Dosing Induction = 1.5 – 2.5 mg/kg IV sedation = 25 – 100 mcg/kg/min Maint. of anesth = 100 – 300 mcg/kg/min Elderly – hypotension – smaller doses ↓central distribution volume and clearance rate Peds – higher ind. Dose (mg/kg basis) ↑ central distribution volume and clearance rate Analgesia = 0.2 – 0.5 mg/kg Induction = 1-2 mg/kg IV = 4 – 8 mg/kg IM ( 1-2 mg/kg w/ general anesthesia) Duration of action IV = 5-15 min IM= 12-25 min. Induction = 0.2 – 0.4 mg/kg Onset = 30 – 60 seconds Myoclonic movements normal Mechanism of Action GABA receptor interaction – prolong GABA inhibitory effects Decreases the rate of dissociation of GABA from the receptor Noncompetitive attachment to phencyclidine (PCP) recognition sites on NMDA receptors Inhibits activation of receptor by glutamate Decreases pre-synaptic release of glutamate Potentiates effect of GABA (weak action at GABA receptors) Exerts effect at receptor Opioid – µ, Δ ,Κ, Σ(delirium) MAO – antinociceptive action Muscarinic – anticholinergic,bronchodilation, HTN, delirium, ↑HR VS Na channels – acts like local anesthetic GABA receptor interaction – prolong GABA inhibitory effects Propofol Ketamine Etomidate Structure Substituted Isopropylphenol Only one not a chiral compound Lipid egg soy emulsion b/c it is insoluble Related to phencyclidine Racemic mixture S(+) more active isomer Carboxylated Imidazole compound Administered as single isomer R(+) Water soluble @ Acidic pH (ring open) Lipid soluble @ phys. pH (ring closed) Uptake + Distribution Short effect-site equilibration time 30 sec. brain effect after dosing Awakening faster and complete Rapid onset = high lipid solubility Short duration of action= 5-15 min. Rapid brain penetration Rapid brain penetration – peak brain level in 1 minute