Definition, Classification, mechanism of action, Structure activity relationship, synthesis and uses of General anesthetics

1. General anesthetics
Dr. Gopal Krishna Padhyp y
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2. DefinitionDefinition
General anesthetics are CNS depressant drugs that inducep g
absence of perception of all sensations and loss of pain.
They depress the CNS non selectively but reversibly.y p y y
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3. Classification
DefinitionInhalation anesthetics
Halogenated
Halothane Enflurane Isoflurane
M h fl D fl S flMethoxyflurane Desflurane Sevoflurane
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4. Non-Halogenatedg
Cyclopropane DiethyletherCyclopropane Diethylether
N ON2O
Nitrous oxide
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5. Non-Inhalation anesthetics
Barbituric acid derivatives
2 5
2
3
23
3
Thiopental Sodium Methohexital Sodium
22
2
3
23
Thiamylal sodium 16-04-2020

6. Miscellaneous
Ketamine
Hydrochloride
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7. Halothane
MOA: Halothane causes anesthesia due to its actions on
multiple ion channels, which ultimately depresses nerve
conduction, breathing, cardiac contractility. Its effects haveg y
been attributed to its binding to potassium channels in
cholinergic neurons. Halothane's effect are also likely due tog y
binding to NMDA receptor and calcium channels, causing
hyperpolarization.yp p
Uses: Halothane is a modern and widely used inhalation
anesthetic. It is used in both short and long-lasting surgical
operations. It acts very quickly, which is pleasing to patients,
and it is very safe.
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8. Methohexital Sodium
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9. Mechanism of action of methohexital
It is believed that methohexital decreases the electrical
Mechanism of action of methohexital
It is believed that methohexital decreases the electrical
nerve activity in the CNS that leads to general anesthetic
actionaction.
Methoxehital binds to GABA-BZD receptors-Chloride ion
channel complex This binding increases affinity of GABAchannel complex. This binding increases affinity of GABA
for the GABAA receptor.
It leads to increase in chloride ion conduction via anIt leads to increase in chloride ion conduction via an
increase in the frequency of the chloride channel opening. At
higher dose it directly increase conductance of Cl- ion andhigher dose, it directly increase conductance of Cl ion and
inhibit calcium dependant release of neurotransmitter.
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10. I ddi i b i l d l i d dIn addition to above it also depress glutamate induced
neuronal depolarization through AMPA receptor. At very high
d b bi d N + d K+ i h l ldose barbiturates depress Na+ and K+ ion channels also.
Uses:
I i i il d i d h i I i l d iIt is primarily used to induce anesthesia. It is only used in
hospital under strict supervision. It has been used to induce
d d ti f d d t l ddeep sedation for surgery and dental procedure.
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11. Ketamine Hydrochloride
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12. Reaction mechanism for step-5
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13. Ketamine show multiple therapeutic properties like
Mechanism of Action
Ketamine show multiple therapeutic properties like
analgesic, anesthetic and sympathomimetic effects by acting
on different sites.on different sites.
N-methyl-D-aspartate (NMDA)-receptor antagonism is the
most important neuropharmacological mechanism for themost important neuropharmacological mechanism for the
analgesic effects of ketamine.
Effects on opiate receptors may contribute to the analgesicects o op ate ecepto s ay co t ute to t e a a ges c
proporties as well as to dysphoric reactions.
 Sympathomimetic properties are mediated by enhancedy p p p y
central and peripheral monoaminergic transmission.
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14. Inhibition of central and peripheral cholinergic transmission
may contribute to the induction of anaesthetic state andy
hallucinations.
Uses:
Ketamine is a specific drug for non-inhalation anesthesia. It is
used in brief surgical procedures. It is indicated as the soleg p
anesthetic agent for diagnostic and surgical procedures.
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15. Enflurane Isoflurane
MOA: Enflurane acts as a
positive allosteric modulator ofp
the GABAA receptor. It also
inhibits receptor activity in they
NMDA glutamate receptor
subtypes. These yield a decreased
MOA: Similar to enflurane.
Uses: Used for the
depolarization and therefore,
tissue excitability which results
induction and maintenance
of general anaesthesia
in anesthesia.
Uses: Used for the induction
during surgery and cesarean
section and also used for
and maintenance of general
anaesthesia during surgery and as
analgesia during child
delivery.
analgesia during child delivery. 16-04-2020

16. Methoxyflurane Desflurane
MOA: Similar to enflurane. MOA: Similar to enflurane.
Uses: Used for the induction
and maintenance of general
Uses: Used for the induction
and maintenance of generalg
anaesthesia during surgery and
for analgesia during child
g
anaesthesia during surgery
and cesarean section and alsog g
delivery. used for analgesia during
child delivery.y
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17. Sevoflurane Thiopental Sodium
NC2H5
O
SNa
NH
CH
O
CH2
CH3
CH2H3C
lMOA: Similar to enflurane.
Uses: Used for the induction
MOA: Similar to
methohexital sodium.
h land maintenance of general
anesthesia during surgery
Uses: Thiopental is an
extremely short acting
b b h k
g g y
and also as analgesia during
child delivery.
barbiturate that makes
anesthesia pleasant and
h f h
y
smooth for the patient. It
has been used to induce
d d fdeep sedation for surgery
and dental procedure.16-04-2020

18. Thiamylal sodium
CH
O
CHH C
NH
NCH2
CH
SNa
CH2
CHH2C
CH2CH3
MOA: Similar to
CH
O
CH2
CH3
CH2CH3
methohexital sodium.
Uses: It has sedative, hypnotic
and anticonvulsant properties
and is used as a short acting
sedative. It is used primarily
for induction of surgical
hanesthesia or as an
anticonvulsant to counteract
d ff f hside effects from other
anesthetics. 16-04-2020

19. BOOKS FOR FURTHER READING
Wil d Gi ld T b k f i M di i l
BOOKS FOR FURTHER READING
Wilson and Gisvold,Text book of organic, Medicinal
and Pharmaceutical Chemistry.
Foyes Principles of medicinal chemistry byWilliams
O. Foye.y
AText book of medicinal chemistry (Synthetic and
Biochemical Approach) vol I& II by SN PandeyaBiochemical Approach) vol. I& II by SN Pandeya.
Synthesis of Essential Drugs by R.S.Vardanyan and
VJ H bV.J. Hruby
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