PROBLEMS/
DRUG USE/FEATURES
-- Ultra short-acting barbituate
-- Sodium entothal
-- Thiobarbituate – contains S
-- H2O soluble – stable in
aqueous solution for 2 weeks
 2.5% solution preparation
-- Can be given rectally to peds
-- Highly lipophilic
 Rapid onset
 Short duration of LOC
(onset 10-15 s, lasts 5-10
min)  quick distribution
from brain to MG & FG
 “Light anesthesia”
Thiopental
 No analgesia, muscle
relaxation, amnesia,
limited decrease in SNS
-- 75-85% bound to albumin
-- Use during MINOR surgical
procedure as sole anesthetic
-- Used to induce anesthesia or
to maintain anesthesia
-- Smooth induction/transition
to unconsciousness (no
coughing, breath-holding,
laryngospasm)
-- An alkylphenol
-- Egg lechitin soluble
-- “Milk of amnesia” (minimal)
-- Highly lipid soluble (rapid
LOC < 1 min)
-- Excellent anti-emetic (low
Propofol incidence of N/V)
-- Can be used as sedative,
induction agent, component of
maintenance  no analgesia
-- TIVA (total IV anesthesia)
-- Used in OR and ICU
-- Arylcyclohexylamine
 Structure similar to PCP
-- H2O soluble
-- “Dissociative anesthetic”
 Causes functional and
electrophysiological dissoc.
b/w limbic system and
thalamo-neocortical system
Ketamine -- Very lipid soluble (rapid)
-- Sedative, hypnotic, amnestic
(minimal), analgesic
-- IV  LOC in 10-15 min
-- IM for induction
-- Used for trauma, asthmatic
inductions (maintains BP)
-- Used w/ mentally retarded
MOA/PK/RECOVERY
MOA: Binds to barbituate
receptor (postsynaptic) of
GABA complex to modulate
GABAminergic transmission
-- Beta elim. T/2 = 10-12 hrs
-- Clearance: relatively low
-- VDss: relatively large
-- Emergence: Rapid
MOA: Acts as GABA receptor
complex
-- Rapid onset
-- Smooth/pain induction
-- Very rapid recovery: 4-8
min after induction dose
-- Very high clearance rate
-- Beta elim. T/2 = 1-1.5 hrs
-- No active metabolites
MOA: Blocks NMDA receptors
Interacts w/ brain ACh to
cause “dissociation”
-- Excitatory induction
-- Intermediate emergence
-- Has active metabolites
(norketamine)
-- Very high clearance
-- Elim. T/2 = 2-3 hrs
CV EFFECTS
-- Dose-related myocardial
depression (direct)
-- Decreased venous tone,
venous return
-- Net effect: Decreased MAP,
SV, CO; reflex increase in HR
-- Significant depression
(major downside)
-- Decreased MAP, CO, SVR
-- A direct myocardial
depressant
***If SNS is functioning well,
can act as CV stimulant
(increased HR, BP, CO)
-- Increased MAP, SVR, HR, CO
RESP EFFECTS
-- Dose-related respiratory
depression
-- 2-3 large breathes followed
by apnea (will resume upon
distribution to MG & FG)
***Requires positive
pressure ventilation until
breathing resumes***
-- Dose-related depression
***Airway skills necessary to
battle apnea
-- MILD respiratory depressant
-- Bronchodilator
CNS EFFECTS
-- Due to long T/2, residual
CNS depression: decreased
coordination, psycho-motor
testing, fine motor movement
-- Anti-convulsant, cerebral
protectant
-- Decreased CMRO2, CBF, ICP
(via vasoconstriction of brain)
-- Less residual post-op
sedation and psychomotor
impairment than barbituates
-- Same as thiopental:
decreased CMRO2, CBF, ICP
-- Catalepsy
-- Eyes open, nystagmus
-- Corneal & light reflexes
intact
***Difficult to judge depth
-- Intense analgesia  disrupts
spinal cord-brain transmission
-- Cerebrovasodilator:
increased CMRO2, CBF, ICP
***AVOID IN NEUROSURG.
TOXICITY
-- pH > 10
 Irritating to SC tissue
 No pain in vein
 Burns or necroses soft
tissue
***TEST DOSE FIRST
-- Hypoalbuminemia: need to
decrease dose b/c of
increased free drug (less
binding)
-- Liver: no significant changes
-- Renal: decreased CO 
decreased RBF  transient
decreased renal function
-- Side effect: drowsiness
-- Low incidence of venous
irritation
-- Subcutaneous necrosis
-- Intra-arterial injection
gangrene (due to pH)
-- Recovery delayed due to
long T/2
-- Pain on injection  Tx w/
lidocaine
-- Lipid mixture breeds
bacteria  infection
potential
***Cannot leave mixture for
numerous hours
-- Side effect: dizziness
***AVOID IN
NEUROSURGERY DUE TO
INCREASED ICP
-- Hallucinations, emergence
reactions (psychomimetic)
 Countered by pre-Tx w/
benzodiazepines
-- “Special K” on street
 children (needs IM induction)
-- Imidazole
-- Propylene glycol soluble
-- Rapid LOC (5-10 min)
-- Myoclonus during
induction
Etomidate -- No analgesia, minimal
amnesia
-- Used for pt’s w/ CV
dysfunction
-- Used in pt’s w/ increased ICP
-- Benzodiazepine
-- H2O soluble
-- Anxiolytic, sedative,
hypnotic, amnestic
-- No analgesia
-- Versatile:
 Premedication
Midazolam
 Intraoperative sedation
 Induction agent
 Component of
maintenance
-- Replaced diazepam in OR
(less venous irritation, more
rapid, shorter duration)
Fentanyl
-- Used as:
 Premedicants
 Sedatives
 IV anesthetics (high doses
for induction)
 Components of
maintenance
 Post-op analgesics
Sufentanil
 Intraspinal analgesics
-- As IV anesthetics:
 Very high doses
 Unconsciousness,
analgesia, decreases SNS
 Add muscle relaxant =
general anesthetic
-- For cardiac surgery:
 Smooth induction
 CV stability
 Suppresses hemodynamic
Alfentanil
response to changing
surgical stimulus
 Decreases release of
“stress” hormones
 Smooth transition to ICU &
post-op ventilation
Remifentanil
MOA: Works at GABA receptor
-- Pain on injection (propylene
complex
glycol)
-- Myoclonus
-- Metabolized to inactive -- Excellent stability
-- Like barbituates and -- Like barbituates and -- N/V (counter w/ anti-
metabolites -- Minimal effects on MAP, HR,
propofol (minimal) propofol emetics)
-- High clearance CO (useful in pt’s w/ CAD)
-- Transient adrenal steroid
-- Elim. T/2 = 2-5 hrs
synthesis  suppression w/
multiple doses
-- Rapid emergence
-- Intermediate onset
-- Dose-related depression
-- Smooth induction
 Reversible w/ antagonist -- Same as barbituates,
-- Can be given IV, IM, oral (in -- Stable (minimal effects) -- Side effect: drowsiness
(flumazenil) – only IV propofol, etomidate
apple juice for peds)
anesthetic w/ antagonist
-- Intermediate emergence
MOA: as other opioids
-- Equivalent potency (to
morphine):
 Fentanyl = 100
 Sufentanil = 750
-- Clearance (ml/kg/min):
 Fentanyl = 11-21
 Sufentanil = 13
-- Vd (L/kg):
 Fentanyl = 3.2-5.9
 Sufentanil = 2.86
-- Short acting at low doses
-- Long acting at high doses -- Side effects similar to other
-- Termination of effect is opioids
dependent on redistribution
 Long T/2 w/ high doses -- Reversal: Naloxone
leads to accumulation &  Rarely used
increased duration of action
 If used incorrectly 
-- Fentanyl T/2 = 3.1-3.7 hrs
complications
-- Sufentanil T/2 = 2.5-2.8 hrs
-- Rapid onset
-- Short duration of action
-- T/2 less than F & S (1.2-1.6
hrs)
-- Equivalent potency = 25
-- Clearance = 5-7.9
-- Vd = 0.5-1
-- First true ultra-short acting
opioid
-- Hydrolyzed by blood and
tissue non-specific esterases
-- T/2 = 8-10 min
-- Equivalent potency = 100
 -- Clearance = 40-60
-- Vd = 0.1-0.2
-- Agent used for malignant
Dantrolene
hyperthermia
Ondansetron
-- Used for N/V
Promethazine
H2 Blockers
-- Used to reduce stomach acid
PPIs
Metoclopramide -- Prokinetic agent