General Anesthetics

“Anesthetic are the drugs which depress the vital functions of all type of cells but especially
those of nervous tissues & produce temporary insensibility to pain in whole body or a particular
organ which has to undergo the surgical operation.”

Properties of ideal anesthetic agent:

An ideal anesthetic agent should have following properties:
i. It should be inert.
ii. It should be potent and non-inflammable.
iii. It should produce rapid and smooth induction without irritation.
iv. It should be non-irritating to mucous membrane.
v. It should produce the analgesia and muscle relaxation.
vi. It should be nontoxic to brain, liver,heart and kidney tissues.
vii. It should not produce nausea and vomiting.
viii. It should be economical.
ix. It should be stable to light and heat.
x. It should have a quick/short recovery period without discomfort.
xi. It should not produce severe hypotension.

General Anesthesia:
General anesthesia is the controlled, reversible depression of the functional activities of CNS.
The state of general anesthesia includes:

 Analgesia
 Amnesia
 Loss of consciousness
 Inhibition of sensory & autonomic reflexes
 Skeletal muscle relaxation

General anesthetics:
“General anesthetics are the drugs that depress the central nervous system to such an extent that
all sensitivity to pain is lost and the individual suffers loss of consciousness.”

Mechanism of Action of General Anesthesia

 In contrast to the local anesthesia, general anesthesia alters the physical properties of
nerve membranes through non-specific interactions with lipid bilayer or the receptor/
ionic channel proteins. Therefore, reduce membrane excitability through a number of
possible mechanisms including:
i. Changes in membrane fluidity
ii. Changes in membrane permeability
iii. Changes in receptor/channel functions
 Two main mechanisms involved are:
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 a. General anesthesia can hyperpolarize neurons, thereby inhibiting generation,
propagation and conduction of impulses.
b. Both inhalation and IV anesthetic have substantial effects on synaptic function.
 Inhalation anesthesia has been shown to inhibit excitatory synapses and enhance
inhibitory synapse.
 Most of IV agents act predominantly by enhancing inhibitory neurotransmission.

Signs and stages of general anethesia:

Generally the anesthetic effects are divided into four stages of increasing depth of central
nervous system depression.
Stage I (stage of analgesia):
It begins with administration of anesthetics and lasts till consciousness is lost.

 Initially there is analgesia without amnesia.

 Later both analgesia and amnesia ensures.
Stage II (stages of excitement):
It starts after loss of consciousness and proceeds to the beginning of surgical anesthesia.
i. Patient appears to be delirious and excited but is amnesic.
ii. Respiration is irregular both in volume and rate.
iii. Nausea and vomiting may occur.
iv. Incontinence and struggling may occur.
v. Pulse becomes rapid.
vi. B.P is increased due to increase in level of circulating catecholamine.
Stage III (stage of surgical anesthesia):
It begins with the recurrence of regular respiration and normal B.P and extends to complete
cessation of spontaneous respiration.
Stage III is subdivided into four planes in terms of changes in ocular movements, eye reflexes
pupil size which under specified conditions may represent signs of increasing depth of
anesthesia.
Stage IV (stage of medullary depression):
When spontaneous respiration ceases, stage IV is present. This stage of anesthesia includes
severe depression of the vasomotor centre (the vasomotor center is the portion of medulla
oblongata together with the cardiac centre and respiratory center that regulates blood pressure
and other homeostatic processes) in the medulla as well as the respiratory center. Without full
circulatory and respiratory support, death rapidly ensures.

Classification:
General anesthesia are classified as:

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 1. Inhalational agents:
A-Volatile liquids:
a) Ethers:
i. Diethyl ether
ii. Divinyl ether
b) Halogenated agents:
i. Halothane
ii. Chloroform
iii. Enflurane
iv. Tricholoroethylene
v. Ethyl chloride
B- Gases:
i. Nitrous oxide
ii. Cyclopropane
2- Intravenous agents:
A-Thiobarbiturates:
i. Thiopental
ii. Methohexital
B-Benzodiazepines:
i. Diazepam
ii. Midazolam
iii. Lorazepam
C-Neuroleptics and opioid analgesics:
i. Droperidol
ii. Fentanyl citrate
D-Arylcyclohexylamine:
i. Ketamine
E-Micellaneous:
i. Etomidate
ii. Disopropofol
3- Basal anesthetics:
i. Paraldehyde
ii. Tribromoethanol
iii. Trichloroethylene

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 1- Inhalational Anesthetics:
Method of synthesis:
1)Diethylether: (C2 H5 -O-C2 H5 )
i- from alcohol:
C2 H5 OH + H2SO4 → C2 H5 HSO4 + H2O
C2 H5 HSO4 + C2 H5 OH → C2 H5 –O- C2 H5 + H2 SO4
( diethyl ether)
ii- from ethylene:
H2 C = C H2 + H2 SO4 → C2 H5 HSO4
C2 H5 HSO4 + C2 H5 OH → (C2 H5 )2 O + H2 SO4
( Diethyl ether)
2)Ethyl chloride:
C2 H5 OH + NaCl + H2 SO4 → C2 H5 Cl + NaHSO4 + H2 O
(ethyl chloride)
3)Halothane:

4)Nitrous oxide:
NH4 NO3 (2000C) → N2 O + 2H2 O
5)Chloroform:
It may be prepared from bleaching powder and ethanol after a series of chemical reaction.
CaOCl2 + H2 O → Ca(OH)2 + Cl2
(Bleaching powder) (slaked lime)

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 C2 H5 OH +Cl2 → CH3 CHO + 2HCl
CH3 CHO + 3Cl2 → Cl3 C . CHO + 3HCL
(trichloroethanal)
2Cl3 C . CHO + Ca (OH)2 → 2CHCl3 + (HCOO)2 Ca
(chloroform)
6)Cyclopropane:

7)Trichloroethylene:

Pharmacological Actions:
A- Effect on CVS:
 Decreased arterial blood pressure.
Increased cutaneous blood flow.
 Depressed mayocardial contractility.
 Decreased cardiac sympathetic activity i-e, bradycardia.
 Interference with norepinephrine action, thus antagonises the sympathetic response to
hypotension.

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  Increased cardiac automaticity especially in presence of adrenergic agonists, cardiac
diseases, hypoxia and electrolyte abnormalities.
B- Effect on central nervous system:
 Dilation of cereberal blood vessels, thus increasing cerebral blood flow and CSF
pressure.
 Shivering occur during recovery.
C- Effect on respiratory system:
 Respiration becomes rapid and shallow.
 Minute volume is reduced
 Ventilatory response to CO2 is decreased
 Bronchodilation occurs
 Depressed airway mucociliary functions
D- Effect on kidney:
 Decreased glomerular filtration rate (GFR) and effective renal plasma flow and increased
filtration fraction.
E- Effect on liver:
 Decreased hepatic blood flow ranging from 15-45% of the preanesthetic flow.
F- Effect on uterine smooth muscle:
 Relaxation of uterine muscle

Uses:
 Inhaled anesthetics are rarely used alone. They are usually combined with IV agents and
the combination called “Balanced Anesthesia”
 Halothane is not used in adults but still used in pediatric anesthesia.
 Chloroform is not used now because of hepatoxicity.
 Cyclopropane and diethyl ether were previously most commonly used but now no longer
used because of their flammable and explosive characteristics.

Toxicity:
1) Acute toxicity:
 Hepatoxicity
 Nephrotoxicity
 Malignant hyperthermia ( it is an autosomal dominant genetic disorder of skeletal muscle
includes tachycardia and severe hypertension, severe muscle rigidity, hyperthermia,
hyperkalemia, acid-base imbalance)
2) Chronic toxicity:
 Mutagenicity (that damage DNA)
 Carcinogenicity (causing cancer)
 Hematotoxicity ( destruction of RBCs)

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 2- Basal Anesthetics:
It represents a degree of anesthesia short of surgical stage i.e, the patient is unconscious but yet
not sufficiently depressed for surgical operations.
1)Tribromoethanol:

2)Paraldehyde or 2,4,6 trimethyl-s-trioxame:

It is cyclic acetal of acetaldehyde.

Uses:
+Basal anesthesia
+For preanesthetic medication to produce hypnosis.

3)Trichloroethylene:

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