This is the presentation for B. Pharm. IV Semester Students. It includes details like introduction, mechanism of action, classification along with structures and nomenclature, synthesis, uses and adverse effects of General Anaesthetics.

1. GENERAL
ANAESTHETICS
Ms. Pradnya Gondane
Gurunanak College of Pharmacy, Nagpur

2. GENERAL ANAESTHETICS
They are the groups of drugs that produces loss of
consciousness, and therefore, loss of all
sensations. The absolute loss of sensation is
termed as anesthesia. 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.

3. GENERAL ANAESTHETICS
• Basic molecular targets show that ligand-gated ion
channels are major target of anaesthetic action.
• Many inhalation anaesthetics, such as barbiturates,
benzodiazepines & propofol potentiate action of
inhibitory transmitter GABA to open chloride
channels.
• Action of glycine transmitter, which also activates
chloride channels in the spinal cord & medulla, is
augmented by barbiturates, propofol & many other
inhalation anaesthetics.
• N2O & ketamine do not act on GABA or glycine, but
they selectively inhibit excitatory N-methyl-D-
aspartate (NMDA) type of glutamate receptor.

4. Types of General Anaesthetics
General anaesthetics are usually given through
inhalation or by intravenous injection.
• Inhalation anaesthetics: Nitrous oxide, a gas
at an ambient temperature and pressure
continues to be an important compound of
many anaesthesia regimens. Halothane,
enflurane, isoflurane, desflurane,
sevaflurane, and methoxyflurane are volatile
liquids.

5. Intravenous anaesthetics
Several drugs are used intravenously, alone, or in
combination with other drugs to achieve an anaesthetic
state for minute surgery of the patients in the intensive
care unit. These drugs include the following:
1. Barbiturates (thiopental,methohexital)
2. Benzodiazepines ( midazolam,diazepam)
3. Opiod analgesics ( morphine, fentanyl,afentanil)
4. Propofol
5. Ketamine
6. Miscellaneous: droperidol, etomidate, dexmedetomide

6. Ideal properties of General
Anaesthetics
• Loss of all sensation, especially pain.
• Sleep (unconsciousness) and amnesia.
• Immobility and muscle relaxation.
• Abolition of somatic and autonomic reflexes.
• It should be pleasant, non-irritating.
• It should not cause nausea or vomiting.
• Induction and recovery should be fast with no
other effects.

7. Comparative features of General
and Local Anaesthesia
General
anaesthesia
Local
anaesthesia
1. Site of action CNS Peripheral nerves
2. Area of body involved Whole body Restricted area
3. Consciousness Lost Unaltered
4. Care of vital functions Essential Usually not needed
5. Physiological trespass High Low
6. Poor health patient Risky Safer
7. Use in non-cooperative patient Possible Not possible
8. Major surgery Preferred Cannot be used
9. Minor surgery Not preferred Preferred

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. Nitrous oxide and Ketamine do
not affect the GABA or glycine gated chloride
channel, but they selectively inhibit the excitatory
NMDA type of glutamate receptor, which belongs to
the calcium-gated channels in the neurons and
leads to neuronal hyperpolarization.

9. Diagrammatic representation of
MOA of general anaesthetics

10. STAGES OF ANAESTHESIA
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.
Stage II (delirium): This state 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.

11. STAGES OF ANAESTHESIA
Stage III (surgical anesthesia): 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.
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.

12. Classification
1. Volatile/Inhalational Anaesthetics:-
Eg:-
i. Chloroform ii. Diethyl ether

13. Other examples of volatile
anaesthetics
iii. Halothane iv. Enflurane v. Isoflurane

14. Uses of volatile anaesthetics
• Halothane:-
• It may produce any depth of anaesthesia without
causing hypoxia.
• Being a nonirritant, its inherent hypotensive
effect retards capillary bleeding & renders a
comparatively bloodless field.
• It is a potent, relatively safe general inhalation
anaesthetic used in conjunction with N2O.
• For skeletal muscle relaxation, it is used with
succinyl choline or tubocurarine.

15. Uses of volatile anaesthetics
• Enflurane:-
• The induction of an emergence from
anaesthesia & adjustment of anaesthetic
depth during maintenance is smooth and
moderately rapid.
• It is a noninflammable halogenated ether
anaesthetic and provides rapid induction with
no excitement.

16. Uses of volatile anaesthetics
• Isoflurane:-
• It resembles isomer enflurane in its
properties.
• It is not flammable in air or oxygen.
• The depth of anaesthesia can be rapidly
adjusted with it.
• Used for induction and maintenance of
general anaesthesia.

17. Other examples of volatile
anaesthetics
• Methoxy Flurane Sevoflurane
• CHCl2CF2OCH3 F3C(CF3)CHOCH2F
2,2-Dichloro-1,1-difluoro ethyl
(methyl) ether 1,1,1,3,3,3-Hexafluoro-2-
(fluoromethoxy) propane
• Desflurane
• F2COFCHCF3
• 1,2,2,2-tetrafluoroethyl difluoromethyl ether

18. Uses of volatile anaesthetics
• Methoxy Flurane:-
• It is the most potent of the inhalational
agents.
• It is employed to cause light anaesthesia with
deep analgesic & muscle relaxation feature,
which makes it convenient for surgical
operations.

19. Uses of volatile anaesthetics
• Sevoflurane:-
• It is nonflammable, nonirritating agent.
• The physical properties of this compound result in a more
rapid induction & termination of anaesthetic when observed
with currently used agents.
• Desflurane:-
• Like halothane, enflurane, and isoflurane, it is a racemic
mixture of (R) and (S) optical isomers (enantiomers).
• Together with sevoflurane, it is gradually
replacing isoflurane for human use, except in economically
undeveloped areas, where its high cost precludes its use.
• It has the most rapid onset and offset of the volatile
anesthetic drugs used for general anesthesia due to its low
solubility in blood.

20. 2. Non volatile or intravenous
anaesthetics
A. Ultra short acting barbiturates :-
Eg:-
i. Methohexital sodium ii. Thiopental sodium

21. Non volatile or intravenous anaesthetics
• Uses of Methohexital sodium:-
• More potent & has shorter duration of action.
• Used for induction of anaesthesia through IV
administration.
• 2 advantages over thipental sodium.
• First, has less affinity towards fatty tissues & second,
has greater potency.
• Useful for short surgical operations, such as oral
surgery, gynaecological investigation, genitourinary
procedures, & electroconvulsive therapy.

22. Non volatile or intravenous anaesthetics
• Uses of Thiopental sodium:-
• Used for production of complete anaesthesia of a
short duration.
• Onset is rapid (about 30 sec.) & duration is brief
(10-30 min.).
• By rectal route, administered as a solution,
suspension, or suppositories as basal anaesthetic.
• Also used as a sedative, hypnotic and
anticonvulsant.

23. 2. Non volatile or intravenous
anaesthetics
• Ultra short acting barbiturates :-
Thiamylal Sodium:-

24. Non volatile or intravenous anaesthetics
• Uses of Thiamylal Sodium:-
• Strong but short acting Sedative,
anticonvulsants & hypnotic .
• Is still in current use, primarily for induction in
surgical anaesthesia or as anticonvulsant to
counteract side effects from other
anaesthetics.

25. B. Aryl cyclohexylamines
Eg :- Ketamine (Dissociative anaesthetic)
2-(2-chloro phenyl)-2-(methylamino)-cyclohexanone

26. Aryl cyclohexylamines
• Uses of Ketamine:-
• Also called Dissociative anaesthetic because it
produces unpleasent hallucinations and
strong feelings of dissociation from the
environment.
• Rapidly acting nonbarbiturate general
anaesthetic that produces anaesthesia & is
characterized by profound analgesia.

27. Doses of Anaesthesia
Lowest dose - Sedative
Lower dose - Hypnotic agent
Low dose - Local anaesthetic
More than low dose - General anaesthetics
High dose - Coma
Higher dose - Death

28. Applications of General anaesthetics
• Used in major surgeries.
• Used as an analgesic agent.
• Used as a muscle relaxant.
• Used as a hypotensive agent.( in excess
quantity leads to drug abuse)
• Can also be used in low doses for minor
surgeries.
Eg :- Dental surgery.

30. Administration of general
anaesthetics in patients

31. Inhalational route of administration
of GA in patient

32. Machinery for monitoring the effect of
GA in patient

33. Intravenous route of administration of
GA in patient

34. Synthesis of Ketamine

35. Synthesis of Methohexital sodium

36. Synthesis of Halothane

37. Questionarie
• Write short notes on
– General Anesthetics & its importance
• Stages of General Anesthesia
• General anaesthetics
• What are General Anesthetics? Give a detailed
account of drugs used as ‘General Anesthetic’ &
receptors as their site of action.
• Define & classify general anaesthetics. Explain
ketamine as general anaesthetics.
• Differentiate between general & local
anesthetics.

38. References
• Textbook of Medicial Chemistry by
Algarswamy Volume I
• Foye’s Principle of Medicinal Chemistry
• Willson & Giswold’s Textbook of Organic
Medicinal and Pharmaceutical Chemistry