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L7 General Anesthesia
L7 General Anesthesia
L7 General Anesthesia
Dr Mohammed Alsbou
Professor of Clinical Pharmacology
College of Medicine, Ajman University
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Objectives
Describe the mechanism of action, pharmacokinetics,
pharmacodynamics, classifications and adverse
reactions to common drugs used in general anesthesia
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General anesthesia (GA) is essential to surgical
practice, because it renders patients analgesic,
amnesic, unconscious and provides muscle
relaxation and suppression of undesirable reflexes.
No single drug is capable of achieving these effects
both rapidly and safely.
Rather, several different categories of drugs are
utilized to produce optimal anesthesia
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General anesthetics are classified into two groups
according to their route of administration:
o Inhaled anesthetics
o Intravenous anesthetics
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PATIENT FACTORS IN SELECTION OF
ANESTHESIA
Liver and kidney: they influence the distribution &
clearance of anesthetic agents and can also be target
organs for toxic effects
Respiratory system: The condition of the respiratory
system must be considered if inhalation anesthetics are
indicated. All inhaled anesthetics depress
respiratory system.
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Preanesthetic medications
Preanesthetic medication serves to calm the patient,
relieve pain and protect against undesirable effects of
the subsequently administered anesthetic or the surgical
procedure
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o Antiemetics
o Antihistamines
o Benzodiazepines
o Muscle relaxants
o Opioids
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Preanesthetic medications
These agents facilitate smooth induction of anesthesia,
they lower dose of anesthetic required to maintain stage
III of anesthesia (surgical anesthesia)
Benzodiazepines, such as midazolam or diazepam, to
relief anxiety & facilitate amnesia
Antihistamines, such as diphenhydramine, for
prevention of allergic reactions
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Ranitidine, to reduce gastric acidity
Opioids, such as fentanyl, for analgesia
Skeletal muscle relaxants, facilitate intubation and
suppress muscle tone to the degree required for
surgery
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Stages of Anesthesia
Anesthesia can be divided into three stages: induction,
maintenance & recovery
Induction is defined as the period of time from onset of
administration of anesthetic to development of effective
surgical anesthesia in the patient.
Maintenance provides a sustained surgical anesthesia
Recovery is the time from discontinuation of
administration of the anesthesia until consciousness and
protective physiologic reflexes are regained.
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Induction of anesthesia depends on how fast effective
concentrations of the anesthetic drug reach the brain;
Recovery is the reverse of induction and depends on
how fast the anesthetic drug diffuses from the brain
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Induction
GA is normally induced with an intravenous
anesthetic like thiopental or propofol;, which
produce unconsciousness within 25 seconds after
injection
At that time, additional inhalation or intravenous
drugs may be given to produce surgical (Stage III)
anesthesia
This often includes coadministration of intravenous
skeletal muscle relaxant to facilitate intubation &
relaxation (pancuronium, atracurium and
succinylcholine)
For children, without intravenous access, such as
halothane or sevoflurane, are used to induce general
13 anesthesia
Maintenance of anesthesia
Maintenance is the period during which patient is
surgically anesthetized
Anesthesiologist monitors vital signs & response to
various stimuli to carefully balance amount of drug
inhaled and/or infused with depth of anesthesia
Anesthesia is usually maintained by administration
of volatile anesthetics, because these agents offer
good minute-to-minute control over depth of
anesthesia
Opioids, such as fentanyl, are often used for pain
along with inhalation agents
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Recovery
Postoperatively, the anesthesiologist withdraws
anesthetic mixture and monitors return of patient to
consciousness
Anesthesiologist continues to monitor patient to be sure
that he or she is fully recovered with normal
physiologic functions (for example, is able to breathe
on his/her own)
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Depth of anesthesia
The depth of anesthesia has been divided into four
stages
Each stage is characterized by increased CNS
depression, which is caused by accumulation of
anesthetic drug in brain
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Stage I—Analgesia: Loss of pain sensation results
from interference with sensory transmission in
spinothalamic tract. The patient is conscious &
conversational
Stage II—Excitement: The patient experiences
delirium and possibly violent & irregularity in blood
pressure. To avoid this stage of anesthesia,
propofol or a short-acting barbiturate, such as
thiopental, is given IV before inhalation anesthesia is
administered
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Stage III—Surgical anesthesia: Regular respiration
and relaxation of skeletal muscles occur in this stage.
Surgery may proceed during this stage
Stage IV—Medullary paralysis: Severe depression
of the respiratory and vasomotor centers occur during
this stage
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INHALATION ANESTHETICS
Inhaled gases are the mainstay of anesthesia and are
used primarily for the maintenance of anesthesia
after administration of an intravenous agent
Inhalation anesthetics have a benefit that is not
available with intravenous agents:
o because depth of anesthesia can be rapidly altered by
changing concentration of drug
o Inhalation anesthetics are also reversible, because most
are rapidly eliminated by exhalation
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Mechanism of action
The focus is on interactions of inhaled anesthetics with
proteins comprising ion channels
The general anesthetics increase the sensitivity of the
γ-aminobutyric acid (GABA) receptors to
neurotransmitter, GABA
This causes a prolongation of inhibitory chloride ion
current, reduce neuronal excitability
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Inhaled anesthetics
o Halothane
o Desflurane
o Enflurane
o Isoflurane
o Nitrous oxide
o Sevoflurane
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Halothane
This agent is the prototype to which newer inhalation
anesthetics have been compared.
When halothane was introduced, its ability to induce
anesthetic state rapidly and to allow quick recovery
made it an anesthetic of choice.
However, with the recognition of adverse effects &
availability of other anesthetics that cause fewer
complications, halothane is being replaced in
developed countries
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Therapeutic uses
Whereas halothane is a potent anesthetic, it is a
relatively weak analgesic.
Thus, halothane is usually coadministered with nitrous
oxide, opioids
Halothane is not hepatotoxic in pediatric patients
(unlike its potential effect on adults), and combined
with its pleasant odor, this makes it suitable in
children for inhalation induction.
Halothane is metabolized in body to tissue-toxic
hydrocarbons (fever, anorexia, nausea & vomiting),
and patients may exhibit signs of hepatitis.
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Adverse effects
Cardiac effects: vagomimetic (bradycardia), cardiac
arrhythmias, hypotension. Should it become necessary
to counter excessive hypotension during halothane
anesthesia, it is recommended that vasoconstrictor,
such as phenylephrine, be given
Malignant hyperthermia: In a very small percentage
of patients, may induce malignant hyperthermia (due
increase myoplasmaic calcium concentration)
Should a patient exhibit symptoms of malignant
hyperthermia, dantrolene is given
Therefore, halothane has been replaced by new agents
as sevoflurane & isoflurane
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Isoflurane
It is widely used; is not tissue toxic.
Unlike the other halogenated anesthetic gases, isoflurane
does not induce cardiac arrhythmias and does not
sensitize heart to the action of catecholamines.
it produces hypotension due to peripheral vasodilation.
It also dilates the coronary arteries, increasing coronary
blood flow. This property may make it benefecial in
patients with ischemic heart disease.
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Sevoflurane
Rapid onset & recovery
Not irritating to the airway
Suitable for induction in children
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Nitrous oxide
Nitrous oxide (“laughing gas”) is a potent analgesic but
a weak anesthetic.
It is not used alone in general anesthesia
It is therefore frequently combined with other, more
potent agents to attain pain-free anesthesia.
It has no effect on cardiovascular system, and it is the
least hepatotoxic of the inhalation anesthetics
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INTRAVENOUS ANESTHETICS
Intravenous anesthetics are often used for the rapid
induction of anesthesia, which is then maintained with
an appropriate inhalation agent.
They rapidly induce anesthesia and must therefore be
injected slowly
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INTRAVENOUS ANESTHETICS
o Barbiturates
o Benzodiazepines
o Etomidate
o Ketamine
o Opioids
o Propofol
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Barbiturates
Thiopental is a potent anesthetic but a weak
analgesic
When thiopental is administered intravenously, it
quickly enters CNS & depress function, often in
less than 1 minute
All barbiturates can cause apnea, coughing,
laryngospasm, and bronchospasm
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Benzodiazepines
The benzodiazepines are used in conjunction with
anesthetics to sedate the patient
The most commonly employed is midazolam, which
is available in many formulations, including oral.
Diazepam and lorazepam are alternatives.
All three facilitate amnesia while causing sedation
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Opioids
Because of their analgesic property, opioids are
frequently used together with anesthetics
The most frequently employed opioid is fentanyl
They are administered either intravenously, epidurally, or
intrathecally.
Opioids can cause hypotension, respiratory depression,
and postanesthetic N & V
Opioid effects can be antagonized by naloxone
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Ketamine
A short-acting, induces a dissociated state in which patient
is unconscious but appears to be awake and does not feel
pain
This dissociative anesthesia provides sedation, amnesia &
immobility
Ketamine interacts with N-methyl-D-aspartate (NMDA)
receptor
It also stimulates central sympathetic outflow, which in
turn, causes stimulation of heart & increased blood pressure
& cardiac output. This property is especially beneficial in
patients with either hypovolemic or cardiogenic shock
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However, it is not widely used, because it induces
postoperative hallucinations “nightmares”
particularly in adults
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Propofol (Diprivan)
Is an intravenous sedative/hypnotic used in
induction or maintenance of anesthesia
It is widely used due to its rapid onset of action &
rapid recovery (40 seconds of administration).
Supplementation with narcotics for analgesia is
required
Propofol is widely used and has replaced thiopental
as first choice for anesthesia induction and sedation,
because it produces a euphoric feeling in patient &
does not cause postanesthetic N & V
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