General anesthetics work by depressing the central nervous system starting with the cerebral cortex. They are used during surgery to induce unconsciousness and abolish pain sensation. There are several stages of anesthesia from analgesia to medullary paralysis. General anesthetics are classified as inhalation agents like halothane, dissociative agents like ketamine, and ultra short-acting barbiturates like methohexital. Inhalation agents directly reach the lungs and bloodstream while others must pass the blood brain barrier. These drugs work by potentiating GABA, glycine, or inhibiting NMDA receptors to produce neuronal inhibition.

1. General anaesthetics
Fine Drops of water

2. General anaesthetics
1. Introduction
2. Mechanism of action of General anesthetics
3. Stages of anesthetics
4. Classification
 Inhalation
 Ultra short acting
 Dissociation
 Synthesis and Drug profile

3. 1. Introduction
 General anaesthetics are group of drugs that
produces loss of consciousness, and therefore, loss
of allsensations.
 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 basalganglia,
the cerebellum, and finally the spinal cord.

4.  These drugs are used in surgical operations
to induce unconsciousness and, therefore,
abolish the sensation of pain.
 Horace Wills, a dentist, in 1844 successfully
used N,O as an anaesthetic for tooth
extraction.
 Mortan,a dentist, demonstrated ether as an
anaesthetic agent and it became popular.
 In 1847, chloroform was used by Simpson in
Britain for obstetrical purposes.
 The first intravenous anaesthetic,
thiopentone, was introduced in 1935.

5.  In 1901, Mayer and Overton pointed out a direct
parallelism between lipid/water partition
coefficient of general anaesthetics and their
anaesthetic property known as minimal alveolar
concentration (MAC)
 MAC is the lowest concentration of an anaesthetic
in pulmonary alveoli that is needed to produce
immobility in response to a painful stimulus in 50%
of the individuals.

6.  MAC of a number of general anaesthetics shows
excellent correlation with their oil/gas partition
coefficients.
 However, this only reflects the capacity of
anaesthetics to enter into the CNS and attain
sufficient concentration in the neuronal membrane.
 The basic molecular targets show that the ligand-
gated ion channels are the major target of
anaesthetic action.
 Many inhalation anaesthetics, such as barbiturates,
benzodiazepines, and propofal potentiate the action
of inhibitory transmitter GABA to open chloride
channels.

7.  The action of glycine transmitter, which also
activates chloride channels in the spinal cord and
medulla, is augmented by barbiturates, propofol,
and many other inhalation anaesthetics. N2O and
ketamine do not act on GABA or glycine, but they
selectively inhibit the excitatory N-methyl D-
aspartate(NMDA) type of glutamate receptor.

8. 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.

10.  N2O and ketamine do not affect the GABA
or glycine gated Cl–channel,
 but they selectively inhibit the excitatory
NMDA-type of glutamate receptor,
 which belongs to calcium-gated channels
in the neurons and leads to neuronal hyper-
polarization.

11. STAGES of Anaesthesia

12. STAGES OF ANAESTHESIA
1. Stage I ( analgesia):
 The patient is conscious and experience
sensations of warmth, remoteness, drifting,
falling, and giddiness.
 There is a marked reduction in the
perception of painful stimuli.
 This stage is often used in minor surgery

13. Stage II ( delirium):
This stage begins with the loss of
consciousness.
Depression of higher centres produces
variety of effects including excitement,
involuntary activity, and increased
skeletal muscle tone, and
 the respiration is typically irregular.

14. Stage III ( surgical anaesthesia):
 This is the stage of unconsciousness and
paralysis of refl exes, respiration is
regular and blood pressure is maintained.
 All surgical procedures are carried out in
this stage.

15. 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.

16. Classification of General Anesthetics
General anaesthetics
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 Inhalation Dissociation ultra short acting
Anesthetics Anesthetics Barbiturates
- Halothane - ketamine - Methohexital
- Enflurane Hydrochloride sodium
- Sevoflurne - Thiamylal
- Isoflurane sodium
- Desflurane - Thiopental sodium

17. Inhalation Anesthetics
 These anaesthetics directly reaches the lungs and then trans-
ferred from the alveolar space of the lungs to the blood and
finally to the brain.
 They do not have to cross the blood brain barrier.
 These drugs are generally volatile in nature and chemically
classified into-
 I) Ethers
 I|) Halogenated carbons
 III) Gases

18. 1. Ethers
 Diethyl ether (C2H5OC2H5,) was the first
drug discovered in this category. It has
serious effects like it causes irritation on
the mucus membrane, it is flammable and
is explosive when mixed with oxygen and
nitrous oxide. Due to its side effects it is
replaced by various halogenated
anaesthetics. Halogenated ethers are clear,
colourless and non-flamable in nature.

19. 2 ) Halogenated Carbons :
 Ethers gets replaced by non flammable
halogenated hydrocarbon
 These halogenated hydrocarbons depresses
respiration and produces hypotension
 chloroform and trichloro ethylene were
discovered in this category
 because of many serious side effects like
hepatotoxicity and nephrotoxicity Halothane was
developed
 Halothane had rapid onset and is not flammable.

20. 3) Gases :
 Nitrous Oxide and cyclopropane belongs to
this category.
 Nitrous oxide is used in combination with
other drugs and produces unconsciousness
through inhibition of NMDA-receptors (N-
methyl-D-aspartate)
 Cyclopropane is rarely used as it is
flammable and becomes explosive with
oxygen or fresh air.

21. Synthesis and drug profile
1)Halothane

22. Synthesis:

23.  Properties : It is a clear, colourless liquid. It
is non-flammabbel in nature. It is
slightlysoluble in water and miscible with
ethanol, chloroform and ether.
 Mechanism of Action : Halothane activates
GABA and glycine receptors. lt also inhibits
Acetylcholine and Sodium channels and
activates 5HT3, and K* -ion channels.

24. Uses :
It is generally used to start or to
maintain anaesthesia.
It is not explosive when mixed with
oxygen and is generally given as an
inhalation.
It served as a model for the halogenated
ether anaesthetic drugs.

25. B)Ultra short acting Barbiturates
 Ultrashort acting barbiturates are also
used as general anaesthetics. They are
generally used to induce anaesthesia before
using an inhalational anaesthetic. Ultra
short acting barbiturates are given by
intravenous route. These drugs produces
rapid anaesthesia i.e. within seconds of
their administration. The sodium salt of
barbiturates are administered by
intravenous route in aqueous solution for
the induction of anaesthesia.

26. Drugs belonging to this category are:
Methohexital or Methohexitone sodium

27. Synthesis:

28.  Mechanism of Action: It binds to a site
which is associated with CF ions pores
presenton the GABA receptors. It opens the
Cl ions pores and inturn produces inhibitory
effect i.e causes depression of the CNS.

29. Uses:
It is a ultra short acting barbiturate and
commonly used in the induction phase of gen-
eral anaesthesia.
It is also used to induce anaesthesia in
animals.
It is commonly used to induce deep sedation
for surgery and in dental procedures.
It also decreases the seizure threshold, so
useful as an anaesthetic during electroconvul-
sive therapy.

30. Dissociation anesthesia
 Dissociative anaesthesia is a type of anaesthesia which is
associated with catalepsy, catatonia, analgesia and
amnesia. It does not always involves loss of consciousness
and does not always produces a state of general
anaesthesia. These agentsproduces their effects by
interfering with the transmission of sensory signals to the
brainand also by interferring the communication between
different parts of the CNS. In this thepatient does not
completely anaes thetized but can swallow and open eyes
but is not able toCommunicate. These agents are generally
used to produce analgesia during superficial op-erative
procedures or diagnostic processes.

31. Drug belong to this category is
Ketamine hydrochloride

32. Synthesis:
Properties: it is a white crystalline powder ,
freely soluble in water

33.  Mechanism of Action:
 It acts as a selective antagonist of NMDA
receptor and glutamtate receptor. It also
interacts with and inhibits the NMDAR. So,
it is a uncompetitive antagonistof NMDA
receptor. It causes inhibition of –
 a) Keuptake of serotonin, norepinephrine
and dopamine
 b) Blocker of sodium and calcium channels
 c) Inhibitor of Nitric oxide synthase

34.  Uses:
 it is mainly used for starting and maintaining
anaesthesi
 It induces trance like state i.e. state of
awareness while providing pain relief,
sedationand some loss of memory.
 It is used as an anaesthetic and in the
management of pain.
 It also has some anti-depressant effect.

35. Group members : Rohini sonare, Darshan
khapekar,Nikhil Thakur, Saurabh Bokde,
Shashank parteki,kunal masram