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Pharmacology of
General Anesthetics
Post-Doctoral Fellow
Department of Pharmacology
University of British Columbia
Vancouver, BC, Canada
Learning Objectives
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Extracted from M.H Ossipov
History of Anesthesia
Joseph Priestly – discovers N2O in 1773
Sir Humphrey Davy – experimented with N2O, reported loss of pain,
euphoria
1842, Crawford Long – First used ether. Did not publicize. Tried to
claim credit after Morton’s demonstration but…
Important lesson learned – if you don’t publish it, it didn’t
happen.
1846, William Morton, dentist – Diethyl Ether – First demonstration of
successful surgical anesthesia
1847, James Simpson – Chloroform
1930s, Intravenous Barbiturates
1940s, d-Tubocurarine to induce skeletal muscle relaxation
1956, Halothane (halogenated hydrocarbon)
1981, Isoflurane (currently most popular) Extracted from M.H Ossipov
5
Anesthesia
• Cognitive:
-Absence of intraoperative awareness
-Absence of recall of intraoperative events
• Motor:
-Absence of movement & adequate muscular relaxation
• Autonomic:
-Absence of hemodynamic response
-Absence of tearing, flushing, sweating 7
Modified slide of Dr. Peter Smith
General Anesthetics
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General Anesthetic Protocols
9
Modified slide of Dr. Peter Smith
General Anesthetic Protocols
12
Extracted from M.H Ossipov
Stages of General Anesthesia
Stage I: Disorientation, altered consciousness
Stage II: Excitatory stage, delirium, uncontrolled movement, irregular breathing. Goal
is to move through this stage as rapidly as possible.
Stage III: Surgical anesthesia; return of regular respiration.
Plane 1: “light” anesthesia, reflexes, swallowing reflexes.
• Intravenous
– Safe, pleasant and rapid
• Mask
– Common for children under 10
– Most inhalational agents are pungent, evoke coughing
and gagging
– Avoids the need to start an intravenous catheter before
induction of anesthesia
– Patients may receive oral sedation for separation from
parents/caregivers
• Intramuscular
– Used in uncooperative patients 14
Extracted from M.H Ossipov
Types of General Anesthetics
Inhalation:
Gas: Nitrous Oxide
Volatile Liquids: Ether, Halothane, Enflurane, Isoflurane,
Desflurane, Sevoflurane
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Types of General Anesthetics
Inhalation:
Gas: Nitrous Oxide
Volatile Liquids: Ether, Halothane, Enflurane, Isoflurane,
Desflurane, Sevoflurane
Intravenous:
Barbiturates (thiopental)
Benzodiazepines (midazolam, diazepam)
Opioid Agonists (morphine, fentanyl, sufentanil, remifentanol)
Others: Propofol, etomidate
Ketamine = ‘Dissociative Anesthesia’
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Droperidol = ‘Neurolept anesthesia’
Minimum Alveolar Concentration
(MAC)
o Concentration (i.e the % of an alveolar gas mixture) that
results in immobility in 50% of patients when exposed to
a noxious stimulus such as a surgical incision
o Analogous to ED50
Substan(a gela(nosa
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Spinal Cord and Pain
o Substantia gelatinosa = termination of pain fibers in dorsal
horn of spinal cord
20
Organ Systems Affected By Volatile
Anesthetics
o Cardiovascular System
o Can lower blood pressure, some act on cardiac output
others lower peripheral resistance
o Sensitization of myocardium to action of catecholamines
(CAT are potentially dysrhythmogenic and can cause
ventricular dysrhythmias)
o Respiratory System
o Decrease tidal volume and increase respiratory rate
o Decrease overall minute respiration
o Decrease ventilatory response to hypoxia
o Depress mucocilliary function: pooling of mucous in lungs
(mucous secretion is attenuated by atropine and used for
premed) 21
Modified slide of Dr. Peter Smith
Toxicity
o Nephrotoxicity
o F- from hepatic metabolism
o Malignant Hyperthermia
o Rare, potentially fatal: a pharmacogenetic hypermetabolic state of
skeletal muscle induced in susceptible individuals by inhalational
anesthetics and/or succinylcholine (and maybe stress or exercise)
o Mechanism of Action
o Barbiturates, benzodiazepines, propofol and (ethanol)
potentiate movement of Cl- ions through the GABAA
receptor channel
o Barbiturates and
benzodiazepines bind
at different sites on the
GABAA channel
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h-p://thebrain.mcgill.ca/flash/i/i_04/i_04_m/i_04_m_peu/i_04_m_peu.html
Intravenous Anesthetics – GABAA
Receptor modulation
o Benzodiazepines increase the frequency of channel opening
o Thiopental
27
Modified slide of Dr. Peter Smith
Neuroleptanesthesia
o Reduces anxiety
28
Modified slide of Dr. Peter Smith
Others
o Propofol
o Expensive 29
Modified slide of Dr. Peter Smith
Others
o Etomidate
o No analgesic effects
30
Modified slide of Dr. Peter Smith
Others
o Ketamine
o Cardiovascular stimulation
o Stages of anesthesia
Heidi.boyda@ubc.ca
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