GENERAL

ANAESTHETICS
Definition
 General anesthetic is a class of CNS
depressant drugs which produce partial or
total loss of the sense of pain with a
controlled and reversible depression of the
functional activity of CNS
Anaesthesia
 Stages of anesthesia-
Stage I - Analgesia
Stage II- Delirium or stage of excitement
Stage III- Surgical anesthesia
Stage IV- Respiratory paralysis or medullary

paralysis
Overton-Meyer Hypothesis-
-Lipophilic and unionised drugs pass rapidly in CNS
- Increase in concentration – increased CNS penetration thus
increased depth of anesthesia
- Increased partition coefficient- increased effect
Modified Mullins hypothesis-
Besides membrane concentration , its volume expressed as
volume fraction (mole fraction X partial molar volume) of
anesthetic drug is important
Preanesthetic medication
 Hypnotic
 Atropine (Anticholinergic)
 Morphine

Anaesthetics is given by IV or rectal route

followed by gaseous or volatile anesthetic to
maintain anaesthesia
Ideal characteristics
1. Rapid & pleasant induction
2. Rapid & pleasant withdrawal
3. Adequate relaxation of skeletal muscles
4. Potent to allow oxygen admixture
5. Wide range of safety
6. Nontoxic
7. Absence of adverse effects
8. Non flammable/ non explosive
9. Chemically compatible with devices
10. Non reactive
11. Inexpensive
Features of General anaesthetics
available
 Structurally diverse thus no strict SAR
 Non specific in action
 Required in high concentrations
 Have access to all part of the body
Mechanism of action
 Bind allosterically to GABAA receptors to potentiate
the effect of GABA in opening chloride channels
 Increased glycinergic potentiation
 Inhibit glutamic acid binding to glutamic acid
receptors subtypes NMDA, kainate and quisqualate
(decreased conductance of Na+)
 Increased K+ conductance at K+ channels-decreased
neuronal excitation
Classification based on physical state
1. Volatile anaesthetic-
Ether, chloroform, halothane, vinylether,
methoxyflurane etc.
2. Gaseous anaesthetics-
Nitrous oxide, cyclopropane
3. Non-volatile anaesthetics-
Ultra short acting barbiturates, ketamine and
propanidid
Chemical Classification
Sr. Class Examples
No.
1. Hydrocarbon Cyclopropane, Ethylene
2. Halogenated Halothane, Ethyl chloride
hydrocarbon
3. Ether Diethyl ether, Vinylether
4. Alcohol Trichloroethanol
5. Ultrashort acting Thiopental sodium, Methohexital
barbiturates sodium
6. Miscellaneous Nitrous oxide, Ketamine,
Propanidid
Hydrocarbons
 Anaesthetic activity is directly proportional to
chain length
 Toxicity increases simultaneously

Ethylene

Cyclopropane
Halogenated hydrocarbons
Substitution of hydrogen with halogen in
hydrocarbons and ethers

Increase in potency
Decrease in flammability

Toxicity
Hepatotoxicity
Nephrotoxicity
 Cl F Br
F F F
Cl
F Cl
F O H
Cl
F H F F H
chloroform
Desflurane Halothane

2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane 2-bromo-2-chloro-1,1,1-trifluoroethane

Cl F F
F Cl F

H O H
F O H

F F F
F H F
Enflurane Isoflurane

2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane 2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane
 Cl F H

H O H
F
Cl F H
F C F F
Methoxyflurane
H O H
2,2-dichloro-1,1-difluoro-1-methoxyethane

F C F H

F H2 CH CH2
F3C C
Sevoflurane O
Fluroxene
1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane
(2,2,2-trifluoroethoxy)ethene
Ethers
 Highly potent ,significant analgesic and
Neuromuscular relaxing effect
But highly flammable, explosive, slow and
unpleasant induction, increased bronchial
secretion and prolonged recovery with
vomitting, undergo oxidation to form
peroxides, cardiac stimulation
Examples- Diethyl ether and Divinylether
Alcohols
 Halogenated alcohols are potent hypnotics
e.g. Trichloroethanol
Ultrashort acting barbiturates
 Advantages-
 Smooth induction
 Good muscular relaxation
 Absence of salivary secretions
 Non explosive
 Short & uncomplicated recovery
 Side effect-
 Respiratory depression
 H
O N S

N- O
+
Na
Na+
N-
O

O N O

Sodium-5-ethyl-5-(1-methylbutyl)-2-thiobarbiturate Sodium-1-methyl-5-allyl-5(1-methyl-2-pentynyl) barbiturate

Methohexital sodium
Thiopental sodium
 H
O N S

N-
Na+

Sodium-5-allyl-5-(1-methylbutyl)-2-thiobarbiturate
Thiamylal sodium
Miscellaneous
OH Cl

NHCH3 HCl
O

Propofol
Ketamine
2,6-diisopropylphenol
2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride

O
C2H5 N
OCH2C N
C2H5 O
OCH3 N
C OC2H5
H

H3C

CH2COOC3H7
Etomidate
Porpanidid
ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate
 CH3

C O

HO
Alfaxalone