This document discusses different types of general anesthetics. It begins by defining general anesthesia and describing its stages. It then covers various classes of general anesthetics including inhalation anesthetics like nitrous oxide and halothane, ultra short-acting barbiturates like thiopental sodium, dissociative anesthetics like ketamine, and narcotic and non-narcotic analgesics. For each type, it provides details on properties, mechanisms of action, advantages, and synthesis when applicable. The document aims to provide an overview of common general anesthetics used in medical practice.

1. By- Prof. Samruddhi Khonde
P. R. Patil Institute of Pharmacy, Talegaon.

2. Content
1. General anesthetics
2. inhalation anesthetics
3. Ultra short acting barbiturates
4. Dissociative anesthetics
5. Narcotic and non Narcotic analgesics:
A. Morphine and related drugs
B. Narcotic antagonists
C. Anti-inflammatory agents
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General Anesthetics
Anaesthesia is a medical technique used to induce a state of unconsciousness in a patient, allowing for
pain-free surgical procedures or medical interventions. It involves the administration of medications that
cause the patient to lose consciousness, become unresponsive to pain, and have a temporary loss of
memory.
 General anaesthetics are group of drugs that produces loss of consciousness, and therefore, loss of all
sensations.
The absolute loss of sensation is termed as anaesthesia. General anaesthetics bring about descending
depression of the central nervous system (CNS), starting with the cerebral cortex, the basal ganglia, the
cerebellum, and finally the spinal cord. These drugs are used in surgical operations to induce
unconsciousness and, therefore, abolish the sensation of pain.
General anaesthesia is a class of CNS depressant drugs which produces partial or total loss of the
senses of pain with a controlled and reversible depression of the functional activity of CNS.
Propofol (Diprivan®) is the most commonly used IV general anaesthetic.

4. Stage of Anaesthesia
Stage I
Stage of Analgesia
This is the period from the beginning of
anaesthetic administration to the loss of
consciousness.
The patient will progressively loses pain.
Stage II
Stage of Delirium
This period extends from the loss of
consciousness through a stage of irregular
and specific breathing to the
reestablishment of regular breathing.
The patient may laugh, vomit or struggle
and for this reason it is called the stage of
excitement.
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5. Stage of Anaesthesia
Stage III
Stage of surgical anaesthesia
In this stage excitement is lost and
skeletal muscle relaxation is produced.
Most types of surgeries are done in this
stage.
◦ Stage IV
Stage of medullary depression
Overdose of the anaesthetic may bring
the patient to this stage.
Respiratory and circulatory failure
occur in this stage.
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6. Ideal characteristic of general anaesthetic
An Ideal general anaesthetic should possess the following characteristic features:
It should be inert
 It should be potent and non-inflammable
 It should be non-irritating to mucous membrane
 It should produce rapid and smooth anaesthesia
 It should produce analgesia and muscle relaxation in addition to anaesthesia
 It should not produce severe hypotension
 It should not produce nausea and vomiting
 It should be compatible with adjuvant drugs used in anaesthesia
 It should be economical
 It should be stable to heat, light and alkalies
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General
Anaesthetics
Volatile or
Inhalation general
anaesthetics.
Gaseous
Nitrous
oxide (N₂O)
Liquids
Halothane,
enflurane,
isoflurane,
desflurane,
sevoflurane
methoxyflur
ane
,
Non-Volatile or
Intravenous
anaesthetics.
Ultra short-
acting
Barbiturates
•Thiopental
sodium,
•Methohexital
sodium
Dissociative
Ketamine
hydrochloride
Narcotic
analgesics
Nalorphine
hydrochloride
Morphine,
Fentanyl citrate,
Morphine
sulfate,
Methadone
hydrochloride
Non-Narcotic
analgesics
(NSAIDS)
Ibuprofen,
aspirin,
Mefenamic
acid ,ketorolac,
acetaminophen
Classification of
GeneralAnaesthetics Classified according to their nature
(volatile or non-volatile) at Room
temperature

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Inhalational Anaesthetics: These are gases or vapours that are inhaled by the patient. They
work by enhancing the activity of GABA or by blocking the activity of excitatory
neurotransmitters such as NMDA (N-methyl-D-aspartate) receptors. They also affect other
cellular targets in the brain, such as potassium channels and calcium channels, which lead to a
decrease in neuronal activity.
Examples: Isoflurane, Sevoflurane, Desflurane, Nitrous oxide
Intravenous Anaesthetics: This class of anaesthetics is administered via injection into the veins.
They work by enhancing the action of GABA (gamma-aminobutyric acid), which is an
inhibitory neurotransmitter in the brain. This results in a decrease in neuronal activity and
produces sedation and unconsciousness.
Examples: Propofol, Etomidate, Thiopental Sodium, Ketamine
Opioids: These drugs are primarily used for pain management during surgery. They work by
binding to specific receptors in the brain and spinal cord, known as mu, delta, and kappa
receptors, which inhibit the transmission of pain signals.
Examples: Fentanyl, Morphine, Remifentanil, Alfentanil
Mode of Action

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Dissociative anaesthetics
 Dissociative anaesthetics are a class of drugs that induce a state of dissociation
between the mind and the body. These drugs produce a profound alteration in
perception and consciousness, leading to a loss of sensory and motor function.
 Intravenous anaesthetics.
 It was first synthesized in 1962 and has since been used as an anaesthetic and
analgesic in both humans and animals
 The most commonly used dissociative anaesthetic is Ketamine, which has been used
in medical settings for decades. It is primarily used for surgical procedures, but it can
also be used for pain relief and as an antidepressant. Administered through injection
or intravenous infusion, and its effects typically last for about an hour.

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Mechanism of Action:
 Ketamine works by blocking the N-methyl-D-aspartate (NMDA) receptors in the brain.
 The NMDA receptors are involved in the transmission of pain signals and are also responsible
for the induction of long-term potentiation, which is thought to be important for learning and
memory. By blocking these receptors, ketamine reduces the transmission of pain signals and
produces a dissociative state.
 Ketamine also acts on other receptors in the brain, including the mu-opioid receptor, the sigma
receptor, and the alpha-7 nicotinic receptor. These receptors are involved in pain perception,
mood regulation, and cognition.
 By modulating these receptors, ketamine produces a wide range of effects, including pain
relief, sedation, and altered mental states.

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 Barbiturates are central nervous system (CNS) depressants (medicines that cause drowsiness).
Barbiturates produce a wide spectrum of CNS depression, from mild sedation to coma, and have
been used as sedatives, hypnotics, anaesthetics and anticonvulsants.
 Have a rapid onset and short duration of action.
 They act by enhancing the activity of GABA, a neurotransmitter that inhibits the activity of
neurons in the brain, leading to a general suppression of the central nervous system (CNS) and
induction of anaesthesia. Among the ultra short-acting barbiturates, Thiopental sodium is one of
the most commonly used and studied drugs in this category.
 Mechanism of action: Thiopental sodium, like other barbiturates, binds to the GABA receptor and
enhances the activity of GABA, leading to a decrease in the activity of neurons in the brain. The
drug binds to a specific site on the GABA receptor called the barbiturate site, which enhances the
ability of GABA to open the ion channel, leading to hyperpolarization and reduced neuronal
activity. Thiopental sodium also increases the duration of the open state of the GABA receptor ion
channel, further enhancing the inhibitory effects of GABA.
Ultra Short Acting Barbiturates

12. Advantages associated with the ultra short acting agents
Smooth induction Ultra short-acting agents provide a smooth and rapid induction of anaesthesia,
which means that the patient falls asleep quickly and without discomfort.
Fair muscular relaxation These agents provide fair to good muscular relaxation, which is
important for surgical procedures.
Absence of salivary secretion These agents do not stimulate salivary secretion, which reduces
the risk of aspiration during anaesthesia
Non-explosive nature These agents are non-explosive, which means that they can be safely used
in operating rooms where there is a risk of fire.
Short and uncomplicated recovery. Patients recover quickly and without complications after
anaesthesia.
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13. SYNTHESIS AND DRUG PROFILE
Inhalation general anaesthetics.
NITROUS OXIDE
Nitrous oxide was the first anaesthetic. Joseph Priestly first reported nitrous oxide preparation in
1772. It is prepared by heating ammonium nitrate to 2000C.
NH4NO3 N2O + H2O.
Properties
• Nitrous oxide is available as a colourless, tasteless and odourless gas
• It is supplied in blue coloured metal cylinders
• It is soluble in water, alcohol and ether
Uses
• Sir Humphry Davy in 1800 was first recognized its anaesthetic properties. Nitrous oxide is used to
induce anaesthesia and is followed by ether, halothane or methoxyflurane.
• It is also used for short dental operations.
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14. HALOTHANE
 Chemically halothane is 2-bromo, 2-chloro, 1,1,1-trifluoroethane. It is prepared from
trichloroethylene by the following chemical reactions.
 Properties
 Halothane is a colourless, non-inflammable liquid having chloroform like odour
 It is non-irritant to the skin and mucous membrane
 Uses
Halothane is one of the most widely used potent anesthetic agents (2-2.5%). It is a potent, relatively
safe general inhalation anaesthetic used in conjunction with N2O. more rapid induction and
recovery compared to ether (generally discouraged as an explosive hazard) and methoxyflurane
 It is more potent than chloroform and ether
 Some disadvantages of halothane are;
 It reduces cardiac output
 It causes peripheral vasodilation leading to
hypotension or low blood pressure
 It is a dose-dependent respiratory depressant
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15. ENFLURANE
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 Chemically enflurane is 2-chloro-1,1,2-
trifluoroethyldifluoromethylether.
 Synthesis
 It is prepared from……….. by the
following chemical reactions.
 Uses
 It is used as an alternative to
halothane.
 The induction and emergence from
anaesthesia of enflurane is smooth and
moderately rapid.
 It is a non-inflammable halogenated ether
anaesthetic and provides rapid induction
with no excitement.

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Intravenous Anaesthetic
THIOPENTONE
 Ultra Short Acting Barbiturates belonging to the category of an intravenous anaesthetic.
 Synthesis
 It is a barbituric acid derivative and is synthesized by condensing thiourea with ethyl
(ethyl 1-methyl butyl) malonate.
 Properties
 Thiopentone is available as thiopentone sodium
 It is a yellowish hygroscopic powder, having characteristic odour and bitter taste
 Uses
 Thiopentone sodium solutions (2.5%) are administered by intravenous route to produce
anaesthesia. It has short duration of actions.
 It is also used to control convulsions

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METHOHEXITAL SODIUM
 Methohexital is a derivative of barbituric acid.
 Synthesis
 It is prepared by condensation of ethyl cyanoacetate with 2-chloro-3-pentyne in presence of
sodium ethylate yields ethyl-1-methyl-2-pentnyl cyanoacetate which on further condensation
with allyl bromide yields ethyl(1-methyl-2-pentynyl)allylcyanoacetate.
 Reaction with N-methyl urea yields the iminobarbituric acid which on acid catalyzed
hydrolysis forms methohexital.
 Properties
 Methohexital is available as methohexital sodium
 It is a colourless or slightly yellowish crystalline powder
 Methohexital sodium is freely soluble in water
 Uses
 It is used as a general anaesthetic and hypnotic.
It is administered either by intravenous route
or intramuscular route
 It is more potent than thiopentone sodium

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KETAMINE HYDROCHLORIDE
 Ketamine is a cyclohexanol derivative belonging to the category of
Dissociative anaesthetic.
 Chemically ketamine is (+) 2 (o-chlorophenyl)-2
methylaminocyclohexanone.
 Synthesis
 Ketamine is prepared by Griganard reaction of o-chlorobenzonitrile
with bromocyclopentane in presence of strong alkali to form an
expoxy compound, which converts to an imine by the action of
methylamine. The imine rearranges to ketamine on heating with HCl.
 Properties
 It produces unpleasant hallucinations and strong feelings of
dissociation from the environment.
 It is a rapidly acting nonbarbiturate general anaesthetic that
produces anaesthesia and is characterized by profound analgesia.
 Uses
 Ketamine is used as a
general anaesthetic.
 It also has analgesic
effect.
 Ketamine relaxes
skeletal muscles.

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21. Opium is a dark brown resinous material obtained from the poppy
(Papaver somniferum) capsule.
It has two types of alkaloids; Phenanthrene derivatives and
Benzoisoquinoline derivatives.
Opium has been known from 1500 BC. Sreturner, a pharmacist
isolated the active principle of opium in 1806 and named it morphine.
The term opiates refers to narcotic analgesics that are structurally
related to morphine.
Narcotic analgesic agents cause sleep in conjunction with their
analgesic effect. If a narcotic is used for a long time, it may become
habit-forming (causing mental or psychological dependence) and
physical dependence may lead to withdrawal side effects.
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History of Opium
Opium

22. Narcotic Analgesics
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Analgesics are agents that relieve pain by acting centrally to elevate pain
threshold without disturbing consciousness or altering other sensory modalities.
 The general anaesthetics act by relieves pain by producing unconsciousness,
Analgesics are classified into two major categories:
1. Opioid analgesics or narcotic analgesics ( centrally acting).
2. Nonopioid analgesics ( peripherally acting).
1. Opioid Analgesics
 Opioid analgesics are drugs that denote all naturally occurring, semisynthetic
and synthetic drugs, which have a morphine-like action, namely, relief from pain
and depression of CNS associated with the drug dependence.

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 The term opioid is used generally to designate collectively the drugs, which bind
specifically to any of the subspecies of the receptors of morphine and produce
morphine like actions.
 They tend to produce euphoria, which is an important factor in their addictive
property that limits their use.
 Other limitations include, respiratory depression, decreased gastrointestinal
motility leading to constipation, increased biliary tract pressure, and pruritis due to
histamine release.

24. 1. Write synthesis of Ibuprofen.
2. What are NSAID’S ? Write in detail about Chemical classification of NSAID’S. Give the synthesis of
Ibruprofen.
3. Explain in detail about narcotic analgesics
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Assignment Question
1. Define and classify general anaesthetics. Outline the synthesis of any two drugs
that belongs to intravenous anaesthetics. 10M
2. Write the structure, chemical name, and uses of two drugs from each class. 5M
3. Name the four derivatives of barbiturates that are used abundantly as intravenous
anaesthetics. Write their structure, chemical name, and uses. 5M
4. What is dissociative anaesthetic? How it works? Write synthesis of Ketamine
hydrochloride. 5M
5. Write the different stages of anaesthesia and explain the mode of action of general
anaesthetics.

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