Transcript General Anesthetics

General Anesthetics
Learning objectives
At the end of this class, you are able to:
Explain the purpose of application of GAs
Classify the GAs & the typical drugs
Identify the mechanism of action of GAs
Analyze the characteristic ADR of GAs
Definition

The drugs induce the state of general
anesthesia, which create a reversible
condition of comfort, quiescence, and
physiological stability before, during, and
after a surgical procedure.
Why we use general anesthetics?
 Analgesia
 Skeletal
muscle relaxation
 Sedation
 Lack
and reduction of anxiety
of awareness and amnesia
 Suppression
of troublesome reflexes
Pre-anesthetics

Preanesthetic medications – drugs given generally
prior to anesthesia (may be given during or after, as
well) in order to:
 Decrease anxiety
 Sedation
 Provide amnesia
 Relieve pre-and post-operative pain
 Inhibit secretion
 Antiemetic
Preanesthetic Agents
Drug Classification
Generic Name
Desired Effect
Benzodiazepines
Diazepam
Midazolam
Reduce anxiety, Sedation, Amnesia,
“Conscious sedation”
Antihistamines
Hydroxyzine
Sedation
Opioid analgesics
Morphine
Meperidine
Fentanyl
Remifentanil
Sedation to decrease tension,
anxiety, and provide analgesia
Phenothiazines
Promethazine
Sedation, antihistaminic, antiemetic,
decreased motor activity
Anticholinergics
Atropine
Glycopyrollate
Inhibit secretion, bradycardia,
vomiting, and laryngospasms
GI Drugs
Ondansetron
Ranitidine
Metoclopramide
Antiemetic
Decrease gastric acidity
Decrease stomach contents
Classifications of GAs

Inhaled
•
•
•
•
•
Nitrous oxide
Desflurane
Halothane
Isoflurane
sevoflurane

Intravenous
•
Barbiturates
• Benzodiazepines
• Dexmedetomidine
• Etomidate
• Ketamine
• Opioids
• Propofol
Theories of Anesthetic Action

No single theory adequately explains how
anesthetics exert their pharmacological effects.

Physical theories
 Based on physico-chemical properties of
anesthetics, e.g., lipid solubility.
Theories of Action
 Receptor
theories
Anesthetics exert their effects by direct interactions
with proteins (membrane receptors or ion channels).
 Most anesthetics increase the sensitivity of the Ɣaminobutyric acid (GABA) and glycine receptors to
GABA and glycine respectively.
 Anesthetics also generally inhibit the activity of
excitatory transmitters acetylcholine (Nicotinic) and
serotonin.
 Ketamine and nitrous oxide inhibit glutamate activity
via its antagonism of the action of the excitatory
neurotransmitter glutamic acid on the N-methyl-Daspartate(NMDA)

 Thus
neurons are hyperpolarized.
Inhalation Anesthetic Agents

General pharmacological effects
CNS – dose dependent depression of all portions
of CNS. Order of sensitivity (most to least) is
Reticular Arousal System(RAS) and cortex →
hippocampus → basal ganglia → cerebellum →
spinal cord → medulla (irregularly descending
anesthesia)
 Autonomic nervous system
 Inhibition of sympathetics
 Stimulation of parasympathetics
 Nausea and vomiting

Inhalation Anesthetic Agents

General pharmacological effects
Cardiovascular
 Dose related negative inotropic effect
 ↓ BP
 Arrhythmias
 Sensitization to circulating catecholamines
 Respiration
 Dose dependent depression of medullary respiratory
center

Inhalation Anesthetic Agents
 General
pharmacological effects
Hypothermia
 Altered thermoregulatory control and
reduced metabolic rate
 Miscellaneous
 Decrease lower esophageal sphincter tone
 Post-operative cognitive dysfunction

Inhalation Anesthetic Agents


Anesthetic gases – only one is Nitrous Oxide
Volatile liquids





Halothane (Fluothane) : Malignant hyperthermia;
Halothane hepatitis
Isoflurane (Forane) – commonly used anesthetic for
adults
Enflurane (Ethrane) – like isoflurane, except increased
risk of seizures. Rarely used
Desflurane (Suprane) – similar to isoflurane except for
more rapid emergence, and more irritating to airway
Sevoflurane (Ultane) – similar to desflurane except not
irritating to airway
Anesthetic Agents

Intravenous agents
– sodium thiopental
 Propofol (Diprivan) – similar to thiopental
except that it can be used for longer periods
of anesthesia
 Dissociative – ketamine
 Benzodiazepines – diazepam, midazolam
 Etomidate (Amidate)
 Dexmedetomidine (Precedex)
 Barbiturates
Properties of Intravenous Anesthetic Agents
Drug
Speed of Induction
and Recovery
Main Unwanted
Effects
Notes
Thiopental
Fast (accumulation occurs,
giving slow recovery)
Hangover
Cardiovascular and respiratory
depression
laryngospasm
Used as induction agent
declining. Decreases
cerebral blood flow and O2
consumption.
Etomidate
Fast onset, fairly fast recovery
Excitatory effects during
induction and recovery,
including seizures
Adrenocortical suppression
Less cardiovascular and
respiratory depression than
with thiopental, Causes pain
at injection site
Propofol
Fast onset, very fast recovery
Cardiovascular and respiratory
depression.
Pain at injection site.
Most common induction
agent. Rapidly metabolized;
possible to use as
continuous infusion.
Ketamine
Slow onset, after-effects
common during recovery
Psychotomimetic effects
following recovery,
Postoperative nausea, vomiting
and salivation
Produces good analgesia
and amnesia
Midazolam
Slower than other agents
Memory loss, specifically shortterm antegrade amnesia
Little respiratory or
cardiovascular depression
Anesthetic Antagonists
 Naloxone
(Narcan) and nalmefene (Revex)
 Flumazenil
(Romazicon)
Usmle questions
A 20-year-old male patient scheduled for hernia surgery was
anesthetized with halothane and nitrous oxide, tubocurarine
was provided for skeletal muscle relaxation. The patient
rapidly developed tachycardia and became hypertensive.
Generalized skeletal muscle rigidity was accompanied by
marked hyperthermia. Laboratory values revealed
hyperkalemia and acidosis. This unusual complication of
anesthesia is lost likely caused by:
A. acetylcholine release from somatic nerve endings at skeletal
muscle
B. activation of brain dopamine receptors by halothane
C. block of autonomic ganglia by tubocurarine
D. pheochromocytoma
E release of calcium form the sarcoplasmic reticulum

The patient should be treated immediately
with
 A. Atropine
 B. Baclofen
 C. Dantrolene
 D. Edrophonium
 E. Flumazenial
