Sedatives

Phamaceutics

• Stable in water, air, light, room temperature; no reconstitution
• Long shelf life
• Widely compatible
• Cheap

PK

• A: Onset in 1 arm-brain time
• D: Highly lipid soluble \(\to\) rapidly crosses BBB; but no CSHT
• M: Organ-independant metabolism to inactive metabolites
• E: Rapid clearance with short duration of action \(\to\) titratable

PD

• MOA: Known, with antagonist available for reversal
• CNS: Anxiolysis, anterograde amnestic, analgesic, capable of inducing GA, \(\downarrow\)CMRO2 \(\to\ \ \downarrow)ICP
• CVS: No effect; no histamine release
• RESP: No effect on control of breathing
• GI: Antiemetic
• IMMUNE: No anaphylaxis

Phamaceutics

• Water insoluble \(\to\) stored in emulsion of soybean oil + lethicin
• No reconstitution required
• Long shelf life but not stable once opened, oil/emulsifiers promote bacterial growth
• Incompetible with most drugs
• Expensive

PK

• A: Onset in 1 arm-brain time
• D: Highly lipid soluble \(\to\) rapidly crosses BBB; CSHT less extreme than midazolam (but can ultimately reach 8 hours!). Rapid offset due to distribution \(\to\) titratable
• M: Glucuronidated hepatically and extrahepatically \(\to\) inactive.
• E: Metabolites eliminated in urine. Accumulation \(\to\) propofol infusion syndrome.

PD

• MOA: Partially known (GABA PAM, NMDA antagonist), no reversal agent.
• CNS: Anxiolysis, anterograde amnestic, capable of inducing GA, \(\downarrow\)CMRO2 \(\to\ \ \downarrow)ICP. No analgesia.
• CVS: Direct negative inotrope. Indirect sympatholysis \(\to\) indirect negative chronotrope, inotrope, vasodilation \(\to \ \downarrow\)CO and \(\downarrow\)MAP
• RESP: May induce apnoea
• GI: Antiemetic
• IMMUNE: Anaphylaxis rare (1:50,000)

Phamaceutics

• Water soluble, stable, not reconstituted
• Long shelf life
• Widely compatible
• Cheap

PK

• A: 10 minute IV onset.
• D: Highly lipid soluble \(\to\) rapidly crosses BBB. Exhibits CSHT (max ~ 6 hours)
• M: Hepatically metabolized by CYP3A4 \(\to\) 95% inactive, 5% active. High HER
• E: Short bolus DoA due to distribution. Metabolites excreted in urine.

PD

• MOA: GABAA PAM \(\to\) potentiates GABA. Antagonist (flumazenil).
• CNS: Anxiolysis, anterograde amnestic. No analgesia. Need big dose to induce GA. Little effect on ICP.
• CVS: Mildly indirect decreased TPR.
• RESP: Can induce apnoea
• GI: Antiemetic
• IMMUNE: Anaphylaxis rare

Phamaceutics

• Stable in water, air, light, room temperature; no reconstitution
• Long shelf life
• Racemic mix of S-ketamine (more potent, fewer AE) and R-ketamine
• Widely compatible
• Cheaper than propofol

PK

• A: OBA 17%, IM 95%
• D: Highly lipid soluble \(\to\) rapidly crosses BBB; but no CSHT
• M: High HER. Hepatic metabolism \(\to\) partially active norketamine \(\to\) inactive.
• E: Metabolites excreted in urine. T1/2=2.5 hours.

PD

• MOA: Known (NMDA antagonist, sialogogue unknown mechanism, indirect sympathomimetic)
• CNS: Dissociative anesthesia (dissociates thalamus from cortex), Analgesia with partial reversal of opioid tolerance, anterograde amnestic, \(\uparrow\)CMRO2 \(\to\ \ \uparrow)ICP. Emergence delirium common.
• CVS: Direct negative inotrope. Indirect positive inotrope, chronotrope, vasoconstrictor; these usually predominate except in severe shock when catecholamine system is at max efficacy already.
• RESP: Does not reduce MV. Preserves laryngeal reflexes. Bronchodilator. Increases secretions.
• GI: Increased BGL by indirect \(\beta\)-2 agonism
• IMMUNE: Anaphylaxis rare

Phamaceutics

• Stable in water, air, light, room temperature; no reconstitution
• Long shelf life
• D-isometer of metetomidine (other isomer is inactive)
• More expensive than propofol

PK

• A: OBA 17%
• D: Highly protein bound 94%. Vd 1.3L/kg. Onset 15 minutes.
• M: High HER. Hepatic metabolism \(\to\) inactive.
• E: Metabolites excreted in urine. T1/2=2 hours.

PD

• MOA: Known (\(\alpha_2\) agonist. \(\alpha_2\) in CNS \(\to\) sedation and reduced SNS outflow, in A\(delta\)/C fibers \(\to\) analgesia)
• CNS: Sedation, anxiolysis. Analgesia. Not amnestic. Cannot progress to GA. , \(\downarrow\)CMRO2 \(\to\ \ \downarrow)ICP. May reduce delirium compared to other sedatives.
• CVS: Direct vasoconstrictor (initial hypertension). Indirect negative chronotrope, vasodilator (subsequent bradycardia, hypotension). No effect on inotropy.
• RESP: Does not reduce MV. Preserves laryngeal reflexes.
• IMMUNE: Anaphylaxis rare