THIS CHAPTER IS A PART OF MEDICINAL CHEMISTRY-I SYLLABUS AS PER GTU

1. PREPARED BY:
Shreyanshi Raval
TwinkleJoshi
GUIDED BY :
Ms. KHUSHBU PATEL
ASSISTANT PROFESSOR,
SVBIP.

2. ◤
Definition
 To conduct various surgical operation ,a state of
absence of all type of sensation.
 Ex:unconsciousness is required
 This is State can be achieved by the use of drugs
which produce unconscious and such drugs
known as general anaesthetics.
 General anaesthetics are group of drugs that
produce loss of consciousness and therefore loss
of sensation.

3. ◤
 The term anaesthetics Is greek origin and
means without perception or insencebility,
They caused selective and reversible CNS
depression
 General anaesthetics is about desending
depression of CNS, starting with the
cerebral cortex,the basal ganglia.

4. ◤
Stages of anaesthesia
• When an inhalation anaesthetics is
administered to a patient some of the
following well defined stages are produced by
increasing the blood concentration of the
agent ,they are

5. ◤
Stage-1 (analgesia)
 This stage begins with the inhalation of
anaesthetics gas and ends with the beginning of
loss of consciousness.
 The patient progressively loss pain

6. ◤
Stage -2 (Delirium and excitement)
 This stage starts with the loss of
consciousness.
 This state of irregular and specific breathing
to the re-establishment of regular breathing.
 The patient may laugh, vomit or struggle.

7. ◤
Stage -3 (surgical anaesthetics)
 This stage involves unconsciousness and
paralysis of reflexes.
 In this stage excitement is lost and
skeletal muscle relaxation is produced.
 Most type of surgeries are done in this
stage.

8. ◤
Stage -4 (medullary paralysis)
 This stage should be avoided.it starts with
respiratory paralysis and ends with cardiac
failure and death.
 Overdose of the anaesthetics may bring the
patient to this stage.
 Respiratory and circulatory failure occur in
this stage.

9. ◤
Classification of general anaesthetics
 General anaesthetics are classified
according to their nature as follow:
 1) Inhalation anaesthetics
 2) Ultra short acting barbiturates
 3) Disaccoiative anaesthetics

10. ◤
Inhalation anaesthetics
1. Halothane
 Stucture:

11. ◤
Synthesis of Halothane
• The commercial synthesis of halothane
starts from trichloroethylene, which is
reacted with hydrogen fluoride in the
presence of antimony trichloride at 130
°C to form 2-chloro-1,1,1-
trifluoroethane. This is then reacted
with bromine at 450 °C to produce
halothane.

12. ◤
Mechanism of action
 Halothane produce action on multiple ion channels
due to which there is depression in nerve
conduction, breathing and cardiac
contractility.
 It binds with potassium channel and
produces immobilizing effects.
 They also bind with NMDA and calsium Chanel
and causes hyperpolarazation.

13. ◤
Properties & uses:
 It is a clear, colourless, heavy,
nonflammable liquid, slightly soluble in
water, miscible with ethanol, and with
trichloroethylene.
 Halothane lacks flammability.
 It may produce any depth of anaesthesia
without causing hypoxia.

14. ◤
 Being a nonirritant, it’s inherent hypotensive
effect retards capillary bleeding and renders a
comparatively bloodless field.
 It is a potent, relatively safe general inhalation
anaesthetics used in conjunction with N²O .
 For skeletal muscle relaxation,it is used with
succinyl choline or tubocurarine.

15. ◤
Methoxyflurane
 Structure:

16. ◤
Mechanism of action
 It decreases the gap junction channel opening
times and increase gap junction channel
closing time, which induces reduction in
junctional conductonce.
 Methoxyflurane also binds with D subunit of ATP
synthase,GABA receptors,glutanate receptors,
glycine receptors,NADH dehydrogenase.

17. ◤
Properties &uses
 It is a clear, colourless liquid, noninflammable
and nonexplosive in air or oxygen in
anaesthetic concentration.
 It is the most potent of the inhalation agent.
 It is employed to cause light anaesthesia with
deep analgesic and muscle relaxation feature,
which makes it convenient for surgical
operation.

18. ◤
Enflurane
 Structure:

19. ◤
Mechanism of action
 It produces depressive effects by
binding with GABA and glycine
receptors.
 The cardio depressive effects is
produced due to the binding of the drug
with calcium channel.

20. ◤
Properties & uses
 It is clear, colourless liquid , volatile liquid with
pleasant hydrocarbon- like odour.
 Soluble in water, miscible with organic
solvents, chemically it is extremely stable.
 It is a noninflammable halogenated ether
anaesthetics and provides rapid induction with
ni excitement.

21. ◤
Savoflurane
 Structure:

22. ◤
Mechanism of action
 Sevoflurane decrease the gap juntion channel opening
time and increase gap Junction Channel closing time
which induces reduction in junctional conductor.
 It also binds with D sub unit of ATP synthase,GABA
receptors, glutanate receptors, glycine receptors ,NADH
dehydrogenase.
 The exact mechanism of action of this genaral
anaesthetics is not clear.

23. ◤
USE & PROPERTY
 It is a inhalation anaesthetic agent used for
induction and maintenance of general anesthesia
during surgical procedure.
 It also called fluromethyl,is an ether
inhalation anaesthetic agent used for
induction and maintenance of general
anesthesia.

24. ◤
ISOFLURANE
 Structure:

25. ◤
Mechanism of action
 It reduce pain sensitivity and relaxes
muscles.
 It increases glycine receptor activity which in
term decrease motor function.
 It also activates Calcium ATPase by
increase membrane fluidity.

26. ◤
USE & PROPERTY
 It is a genaral inhalation anaesthetics used for
induction and maintenance of general
anesthesia.
 It induces muscle relaxation and reduce
pain sensitivity by altering tissue
excitability.

27. ◤
DESFLURANE
 Structure:

28. ◤ Mechanism of action
 It is a positive modulator of GABA &
glycine receptors while negative
modulator of acetyl choline receptor.
 It depress the CNS & reduce perception of pain
producing unconsiousness.

29. ◤
USE & PROPERTY
 It is indicated as an inhalation agent for
mentainance of anaesthesia for inpatient and
outpatient surgery in adult.
 After induction of anaesthesia which agent other
than desflurane and tracheal intubation, desflurane
is indicate for maintenance of anaesthesia in
infants and childrens.

30. ◤Ultra short acting barbiturates
 Methohexital sodium:
 Structure:

31. Synthesis of methohexital sodium:
◤
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.

32. ◤Mechanism of action
 Methohexital binds at a distinct binding
site associated with a Cl- ionopore at the
GABA receptor, increasing the duration
of time for which the Cl- ionopore is
open. The post-synaptic inhibitory effect
of GABA in the thalamus is, therefore,
prolonged.

33. ◤
USE & PROPERTY
 Methohexital is primarily used to induce
anesthesia, and is generally provided as a
sodium salt (i.e. methohexital sodium). It is only
used in hospital or similar settings, under strict
supervision. It has been commonly used to
induce deep sedation or general anesthesia for
surgery and dental procedures.

34. ◤
Thiamylal sodium
 Structure:

35. ◤
Mechanism of action
 Thiamylal binds at a distinct binding site
associated with a Cl- ionopore at the GABA
receptor, increasing the duration of time for
which the Cl- ionopore is open.
 The post-synaptic inhibitory effect of GABA
in the thalamus is, therefore, prolonged.

36. ◤
USE & PROPERTY
 Thiamylal, a barbiturate, is used in combination
with acetaminophen or Aspirin and caffeine for
its sedative and relaxant effects in the treatment
of tension headaches, migraines, and pain.

37. ◤
Thiopental sodium
 Structure:

38. ◤
Mechanism of action
 Thiopental binds at a distinct binding site
associated with a Cl- ionopore at the GABA
receptor, increasing the duration of time for
which the Cl- ionopore is open. The post-
synaptic inhibitory effect of GABA in the
thalamus is, therefore, prolonged.

39. ◤
USE & PROPERTY
 Sodium thiopental is a synthetic ultra-short- acting
barbiturate and has been used commonly in the
induction phase of general anesthesia.
 Its use has been largely replaced with that of
propofol, but may retain some popularity as an
induction agent for rapid- sequence induction and
intubation, such as in obstetrics.

40. ◤ Dissociative anaesthetics
 Ketamine hydrochloride:
 Structure:

41. ◤Synthesis of ketamine hydrochloride

42. ◤
Mechanism of action
 Ketamine interacts with N-methyl-D- aspartate
(NMDA) receptors, opioid receptors,
monoaminergic receptors, muscarinic
receptors and voltage sensitive Ca ion
channels.
 Unlike other general anaesthetic agents,
ketamine does not interact with GABA
receptors.

43. ◤ USE & PROPERTY
 Ketamine Hydrochloride is a prescription medicine
used as a sedative for diagnostic and surgical
procedures.
 Ketamine Hydrochloride may be used alone or with
other medications.
 It is a white and almost white crystalline powder, fairly
soluble water, methanol and ethanol.

44. ◤
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