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General anesthesia
• General anesthesia was not known until the
mid-1800’s
• Diethylether was the first general anesthetic
used for surgery
• General Anesthetics are divided into two
classes:
– Inhaled anesthetics (usually halogenated
compounds)
– Intravenous anesthetics or induction agents
Modern Anesthesia
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It combines the following:
Analgesia
Sleep (loss of consciousness)
Skeletal Muscle relaxation
amnesia
Abolition sensory & autonomic
reflexes
No single drug can produce all these
effects
Ideal anesthesia is
• Induce loss of consciousness smoothly
and rapidly
• Allow for prompt recovery of cognitive
function after its administration is
discontinued
• Possess wide margin of safety
• Have no side effects
• No single drug can produce all these
effects
Stages of anesthesia
• Stage 1:analgesia
Decreased pain awareness, sometimes with amnesia
,conscious may be impaired but not lost
• Stage 2:disinhibition
Delirium, excitation, amnesia, enhanced reflexes, irregular
respiration and incontinence
• Stage 3:surgical anesthesia
Unconsciousness ,no pain reflex, regular respiration and
maintained blood pressure
• Stage 4:medullary depression
Severe CVS and respiratory depression and the patient
require pharmacological and ventilatory support
Anesthesia protocols
• For minor procedure, conscious sedation
conscious sedation techniques that combine IV
agent with local anesthetics are often used ;these
can provide profound analgesia, with retention of
the patient ability to maintain a patent airway
and response to verbal commands
• For extensive surgical procedure protocol
commonly includes IV drug for induction, inhaled
agent(with or without IV)for maintenance and
neuromuscular junction blockers to cause muscle
relaxation
General Anesthetics
• Absence of sensation associated with a reversible
loss of consciousness, skeletal muscle relaxation, and
loss of reflexes.
• Drugs used for anesthesia are CNS depressants with
action that can be induced and terminated more
rabidly than conventional sedative and hypnotics
• Most sensitive site of action for general anesthetics is
the reticular activating system of the brainstem (RAS)
• Anesthetic dose: does not cause depression of
cardiac, vasomotor or respiratory centers
• Has a small margin of safety
Inhaled Anesthetics
• Include:
Nitrous oxide
Halothane
Enflurane
Isoflurane
Desflurane
Intravenous Anesthetics
• Include:
– Barbiturates
• Thiopental & Methohexital
– Opioids
• Alfentanil, Meperidine, Fentanyl, Sufentanil
(agonists)
• Naloxone (antagonist)
– Benzodiazepines
• Diazepam, Midazolam
• Flumazenil (antagonist)
Intravenous Anesthetics
• Miscellaneous Agents
– Etomidate – non-barbiturate hypnotic agent without
analgesic properties
– Droperidol - Neuroleptic (similar to Haloperidol) combined with Fentanyl and is used for
neuroleptanalgesia (state of analgesia and amnesia)
– Ketamine - dissociative anesthetic
– Propofol
General Uses of IV Anesthetics
• Primary Use = induction of general anesthesia
– Supplement general anesthesia
– maintain general anesthesia
– provide sedation
– control Blood Pressure
Intravenous agents
• Mechanism of action
– Act at cell surface receptors
• Barbiturates and benzodiazepine act at GABA-A
receptors to increase Cl- influx
• Opioids act on m and other subtypes
• Ketamine antagonizes PCP site on NMDA receptors
(prevent excitation)
• Pharmacokinetics
– Rapid induction = shorter acting
– Duration of effect proportional to redistribution from
brain to other tissue
Barbiturates: Thiopentone
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Ultra-short acting hypnotic with no analgesic action
High lipid solubility promotes rapid entry to the brain
Eliminated by the liver
Has rapid onset of action and recovery
M.O.A.= potentiates GABA, decrease glutamate activity,
increase chloride ion conductance
Adverse reactions: decreased myocardial and
respiratory activity
Etomidate
• Imidazole derivative that provide induction with minimal
change in cardiac function and respiratory rate and has
short duration of action
• It is not analgesic , and its primary advantage is in
anesthesia for patient with limited respiratory and
cardiac reserve
• Activates GABA receptors
• Uses
– Induction of anesthesia
• Side effects
– Myoclonus
– Post-operative nausea and vomiting
Ketamine
• This drug produce dissociative state in which the
patient is patient remains conscious but has
marked catatonia, analgesia, and amnesia
• It is a chemical congener of the psychotomimetic
agent, phencyclidine (PCP)
• It is a cardiovascular stimulant drug and this action
may cause increase ICP
• Emergency reactions include disorientation
,excitation and hallucination which can be reduced
by preoperative administration of benzodiazepines
• Uses- Induction of anesthesia
– in children
– in severely hypovolemic patients
• Contraindications
– Increased intracranial pressure
– Ischemic heart disease
– Psychological disorders
• Effects
– Analgesic with dissociative anesth. properties
– Dreaming in children
Propofol
• Uses
– Induction and maintenance of anesthesia
– As anesthetic agent at outpatient surgery
– Also effective in producing prolog sedation in patient
in critical care setting
• Contraindications
– Cardiovascular instability due to marked reduction in
the peripheral resistance
• Effects
– Hypnosis ,Antiemetic
– Fast acting, short duration. Fewer peripheral side
effects compared to barbiturates
Opiates
• Potent analgesics
– Fentanyl -Potency 50-100X >Morph
– Alfentanil -Potency 25-30X > Morph
– Sufentanil -Potency 5-10X >Fentanyl
– Meperidine
• Uses
– Supplementation of general anesthesia or analgesia
• Effects
– respiratory depression
– nausea and vomiting
– muscle rigidity
INHALATION ANESTHETICS
MAC(minimal alveolar concentration)
• MAC of anaesthetic measures potency of
anaesthetic vapour. High MAC means low
potency
• Defined as the concentration of anesthetic
that prevents movement induced by a painful
stimulus in 50 % of subjects.
Mechanism of Action
• Potency is correlated with lipid solubility
– Olive oil:gas partition coefficient
• The greater the number, the more potent
the anesthetic
Methoxyflurane>halothane>isoflurane etc.
Theories for Mechanism of Action
• Theory #1
– Gas movement into lipid membrane disrupting ion
channels and action potential propagation
• Increased Atmospheric pressure will reverse
effects
• Theory #2
– Binding theory = anesthetics bind to hydrophobic
portion of the ion channel
• Theory #3
– Neuromodulator theory = anesthetics bind to cellsurface receptors.
• increased Cl- flux (possible GABA mediation)
Pharmacokinetics of Inhaled Anesthetics
• Factors influencing the effects of inhaled anesthetics
– Amount that reaches the brain
• Indicated by oil:gas ratio (lipid solubility)
– Partial pressure of anesthetic
• 5% anesthetic = 38 mmHg (10% =76 mmHg)
– Solubility of gas into blood
• The lower the blood:gas ratio, the more
anesthetic will arrive at the brain
– Cardiac Output
• Increased CO = greater Induction time
Rate of Entry into the Brain:
Influence of Blood and Lipid Solubility
General Actions of Inhaled Anesthetics
• Respiration
– Depressed respiration
• Kidney
– Depression of renal blood flow and urine output
• Muscle
– High enough concentrations will relax skeletal muscle
General Actions of Inhaled Anesthetics
• Cardiovascular System
– Generalized reduction in arterial pressure and
peripheral vascular resistance. Isoflurane
maintains CO and coronary function better
than other agents
• Central Nervous System
– Increased cerebral blood flow and decreased
cerebral metabolism
Toxicity and Side Effects
• Depression of respiratory drive
• Depressed cardiovascular drive
• Fluoride-ion toxicity from methoxyflurane
– Metabolized in liver = release of Fluoride ions
• Decreased renal function allows fluoride to
accumulate = nephrotoxicity
• Malignant hyperthermia
– To treat this, rapidly cool the individual and
administer Dantrolene to block release of Calcium
from muscle sarcoplasmic reticulum
Advantages and Disadvantages of Selected
Inhaled Anesthetics
• Isoflurane
– Cardiac output is maintained
– Arrhythmias are uncommon
– Potentiates the actions of muscle relaxants
– Minimally metabolized and no reports of heptato- or
nephrotoxicity
– most widely used agent
– MAY CAUSE MALIGNANT HYPERTHERMIA
Advantages and Disadvantages of
Selected Inhaled Anesthetics
• Desflurane
– More irritating to airways than other agents
– Rapid recovery
– No reports of malignant hyperthermia
Preanaesthetic
Medication
Focus Points
1 Induction of anesthesia is through use of any of the IV
agents (Barbiturates: Thiopental, Opiate: Fentanyl,
Benzodiazepines: Midazolam, Dissociative: Ketamine,
Others: Propofol, Etomidate and Droperidol)
2 Majntenance of anesthesia is through use of any of the
ihalation agents
-N2O (70% in oxygen) is not suitable alone
- N2O is usually combined with another inhalation agent
or with opioids e.g. fentanyl
A comparison
halothane
Speed of induction intermediate
Potency
v.potent
MAC=2%
Muscle relaxation
some
Cardiac arrhythmia yes
Liver damage
yes
Recovery
slow
N2O
fast
weak
MAC 80%
none
no
no
rapid
• NOTES:
• Enflurane releases flouride ions which may cause
renal failure
• All inhalation anesthetics can cause resp. depression,
myocardial depression, cardiac arrhythmias,
hypotension and PONV
• A mixture of N2O(50-70%) and haothane 1% is
usually used in anesthesia.
Nitrous Oxide
• Characterized by inert nature with minimal
metabolism
• Colorless, odorless, tasteless, and does not
burn
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Simple linear compound
Only anesthetic agent that is inorganic
Major difference is low potency
MAC value is 80 - 105%
Weak anesthetic, powerful analgesic
Needs other agents for surgical anesthesia
Low blood solubility (quick recovery)
GOOD LUCK