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.

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GENERAL ANAESTHETICS
Yogesh Tiwari
M Pharma (Pharmaceutics)
Assistant Professor
VIPER, Sagar (MP)

2. CONTENT
 INTRODUCTION
 STAGES OF ANAESTHESIA
 TYPES OF GENERAL ANAESTHETICS
 MODE OF ACTION
 SYNTHESIS , PROPERTY AND USES
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4. INTRODUCTION
 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.
 These drugs are used in surgical
operations to induce unconsciousness
and, therefore, abolish the sensation
of pain.
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5. Cont…..
 In 1844, Horace Wills (dentist)
successfully used N2O as an
anaesthetic for tooth extraction
 In 1847, chloroform was used.
 The first intravenous anaesthetic ,
thiopentone , was introduced in 1935.
 The ligand-gated ion channels are the
major target of anaesthetic action.
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6. STAGES OF ANAESTHESIA
Stage I
( Analgesia)
Stage II
( Delirium)
Stage III
( Surgical
Anaesthesia
)
Stage IV
( Medullary
Paralysis)
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7. Cont…..
1. Stage I ( analgesia):-
 The patient is conscious and experience
sensations of warmth, remoteness,
drifting, falling, and giddiness.
 This stage is often used in minor surgery.
2. Stage II ( delirium):-
 This stage begins with the loss of
consciousness.
 Depression of higher centres produces
 variety of effects including excitement,
involuntary activity
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8. Cont…..
3. Stage III ( surgical anaesthesia):-
 This is the stage of unconsciousness
and paralysis of reflexes, respiration is
regular and blood pressure is maintained
 All surgical procedures are carried out in
this stage.
4. Stage IV ( Medullary paralysis):
 Respiratory and circulatory failures take
place as a result of the depression of the
vital centres of the medulla, and brain
stem occurs.
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9. TYPES OF GENERAL
ANAESTHETICS
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GENERAL
ANAESTHETICS
Inhalation
anaesthetics
Intravenous
anaesthetics

10. Volatile/Inhalation anaesthetics
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S NO. NAME STRUCTURE
1 Halothane* CF3CHClBr
2 Enflurane CHFClCF2OCHF2
3 Methoxy Flurane CHCl2CF2OCH3
4 Isoflurane CF3CHClOCHF2
5 Sevoflurane CF3CHCF3OCH2F

11. Non Volatile/Intravenous
anaesthetics
1 Ultra short acting barbitutrates
 Methohexital sodium* (C14H18N2O3)
 Thiamylal sodium (C12H17N2NaO2S)
 Thiopental sodium (C11H17N2NaO2S)
2 Dissociative anesthetics:
 Ketamine hydrochloride*
(C H Cl NO) 4/29/2020 11

12. Mode of Action
 General anaesthetics target the
ligand gated ion channels and
produce the anaesthetic action.
 The GABA receptor gated chloride
channels are the most important sites
and opens to perform the inhibitory
action.
 N2O and ketamine do not affect the
GABA or glycine gated Cl–channel.
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13. Volatile/Inhalation anaesthetics
1 Halothane (CF3CHClBr)
 Synthesis:-
 Halothane, 2-bromo-2-chloro-1,1,1-
trifluorethane is made by the addition of
hydrogen fluoride to tricholoroethylene
and simultaneous substitution
of chlorine atoms in the presence of
antimony(III) chloride at 130 °C.
 The resulting 2-chloro-1,1,1-
trifluorethane undergoes
further bromination at 450 °C to
form halothane .
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14. Volatile/Inhalation anaesthetics
1 Halothane (CF3CHClBr)
 Synthesis:-
 Properties:-
 It is a clear, colourless, heavy,
nonflammable liquid,
 Slightly soluble in water, miscible with
ethanol, and with trichloroethylene.
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15. Volatile/Inhalation anaesthetics
1 Halothane (CF3CHClBr)
Uses:-
 Halothane is a modern and widely
used inhalation anaesthetic.
 It is a potent, relatively safe general
inhalation anaesthetic.
 It is used with succinyl choline for
skeletal muscle relaxation
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16. Volatile/Inhalation anaesthetics
2 Enflurane (CHFClCF2OCHF2)
 Synthesis:-
 Enflurane (2-chloro-1-(difluoromethoxy)-1,1,2-
trifluoroethane, Ethrane)
 a regioisomer of isoflurane, is
synthesized on industrial scale by free
radical chlorination of methoxy-1,1,2-
trifluoro-2-chloroethane followed
by halogen(chloride to fluoride)
exchange in the presence of HF/SbCl5
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17. Volatile/Inhalation anaesthetics
2 Enflurane (CHFClCF2OCHF2)
 Synthesis:-
 Properties:-
 It is a clear, colourless, volatile liquid
with pleasant hydrocarbon-like odour.
 Soluble in water, miscible with organic
solvents.
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18. Volatile/Inhalation anaesthetics
2 Enflurane (CHFClCF2OCHF2)
 Uses:-
 may be used for induction and
maintenance of general anesthesia.
 may be used to provide analgesia for
vaginal delivery.
 may also be used to supplement
other general anesthetic agents.
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19. Volatile/Inhalation anaesthetics
3 Methoxy Flurane (CHCl2CF2OCH3)
 Synthesis:-
 Methoxyflurane, (2,2-dichloro-1,1-
difluoroethylmethyl ether) is
synthesized from 1,1-difluoro-2,2,2-
trichloroethane, which
undergoes dehydrochlorination
by potassium hydroxide to give 1,1-
dichloro-2,2-difluoroethylene to
which methanol is added in the
presence of potassium hydroxide .
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20. Volatile/Inhalation anaesthetics
3 Methoxy Flurane (CHCl2CF2OCH3)
 Synthesis:-
 Properties:-
 It is a clear, colourless liquid,
noninflammable.
 It is the most potent of the inhalational
agents.
 It is employed to cause light anaesthesia
with deep analgesic and muscle
relaxation feature,
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21. Non Volatile/Intravenous anaesthetics
1 Ultra short acting barbitutrates
 Methohexital sodium* (C14H18N2O3)
 Synthesis:-
 The reaction of malonic ester derivatives with
derivatives of urea. The resulting allyl-(1-
methyl-2-pentynyl) malonic ester is synthesized
by subsequent alkylation of the malonic ester
itself,
 Beginning with 2-bromo-3-hexyne, which gives
(1-methyl-2-pentynyl)malonic ester, and then
by allylbromide.
 In the final step, reaction of the disubstituted
malonic ester with N-methylurea gives
methohexital.
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22. Methohexital
sodium*
(C14H18N2O3)
Synthesis:-
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23. Non Volatile/Intravenous anaesthetics
 Properties and uses:-
 White to off-white hygroscopic powder,
essentially odourless, and
 The solution is alkaline to litmus, soluble
in water.
 It is more potent and has shorter
duration of action.
 It is used for the induction of anaesthesia
through the intravenous administration.
 It is specifically useful for short surgical
operations, such as oral surgery,
gynaecological investigation.
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24. Non Volatile/Intravenous anaesthetics
 Thiopental sodium (C11H17N2NaO2S)
 Synthesis:-
 Thiopental, [5-ethyl-5-(1-methylbutyl)2-
thiobarbituric acid] is synthesized by
the alkylation of
ethylmalonic ester with 2-
bromopentane in the presence
of sodium ethoxide.
 The product ethyl-(1-
methylbutyl)malonic ester
undergoes heterocyclization with
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25. Non Volatile/Intravenous anaesthetics
 Thiopental sodium (C11H17N2NaO2S)
 Synthesis:-
 Properties and uses:-
 A yellowish-white powder, hygroscopic, freely
soluble in water, and partly soluble in ethanol.
 Onset is rapid (about 30 sec) and duration is
brief (10–30 min).
 It is also used as a sedative, hypnotic, and
anticonvulsant.
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26. Non Volatile/Intravenous anaesthetics
Dissociative anesthetics:
 Ketamine hydrochloride* (C13H17Cl2NO)
 Synthesis:-
 The syntheis starts with the reaction of
cyclopentyl Grignard and o-
chlorobenzonitrile to give o-chlorophenyl-
cyclopentyl ketone, followed by alpha
bromination of the ketone.
 Then reaction with methylamine to form an
alpha-hydroxy imine (1-Hydroxycyclopentyl-
(o-chlorophenyl)-ketone-N-methylimine).
 Heating this imine results in Ketamine.
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27. Dissociative
anesthetics:
Ketamine
hydrochloride*
(C13H17Cl2NO)
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28. Non Volatile/Intravenous anaesthetics
 Ketamine hydrochloride* (C13H17Cl2NO)
 Properties and uses:-
 It is a white or almost white crystalline
powder, freely soluble in water,
methanol, and ethanol.
 It produces unpleasant hallucinations
and strong feelings of dissociation from
the environment.
 It is a rapidly acting non barbiturate
general anaesthetic that produces
anaesthesia
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29. Some Questions…..
1. Describe general anaesthetic in
detail.
2. Name some inhalation anaesthetics
and ultra short acting barbiturate.
3. Discuss how general anaesthetics
work.
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