2. -The Unitary theory of Anesthesia – Meyer – Overton rule (1901)
-Mechanisms of GA
--1-Lipid – Water partition coefficient
a-GA (gases) are highly lipid soluble and therefore can easily
enter in Neurons
b-After entry causes disturbances in physical chemistry of
neuronal membranes “fluidization theory”
c-Finally – obliteration of sodium(Na+) channel and refusal of
depolarization
--2-Potency gas correlated with its solubility in olive oil
(olive oil – water) – lipid bilayer as the only target for
Anesthetic action
THE MORE LIPID SOLUBILITY IS ASSOCIATED WITH MORE POTENCY
--3-Clear exceptions have been found out now
--4-The “Unitary Theory” has been discarded now
3. --1-Mainly acts via interaction with membrane proteins
--2-Different agents:-Different molecular mechanism
--3-Major sites:-Thalamus and RAS, Hippocampus and spinal cord
--4-Major Targets:-Ligand gated (Not Voltage gated) ion channels
--5-Important one are
--A-GABAA receptor gated Cl channel complexes e.g
a-Many inhalational anesthetics
b-Barbiturates
c-Benzodiazepines and
d-Propofol
--B-Potentiates the GABA to open the Cl channels
--C-Also direct activation of Cl channel by some inhaled anesthetics
and Barbiturates
-MODERN THEORY ON
MECHANISM OF
GENERAL ANESTHESIA
4. --1-Five(5) subunits arranged around a central pore
(2-Alpha 2-Beta 1-Gamma)
--2-The receptor sits on the membrane of its neuron
at the synapse
--3-GABA, an endogenous compound, causes GABA
to open
--4-Drugs (GA) don’t bind at the same side with GABA
--5-GA Receptors:-They are located between an Alpha
and Beta subunits
--6-Normally, GABAA, receptor mediates the effects of
gamma – amino – butyric acid (GABA) the major
inhibitory neurotransmitter in the brain
-GABA RECEPTORS
6. --GABA receptor found throughout the CNS like
a-Most abundant, fast inhibitory, ligand gated
ion channel in the Mammalian brain
b-Located in the post synaptic membrane
c-Ligand binding causes conformational changes
leading to opening of central pore and passing
down of Cl- along concentration gradient
d-Net inhibitory effect reducing activity of Neurons
--General anesthetics bind with these channels and
cause opening and potentiation of these inhibitory
channels – leading to inhibition and anesthesia
-GABA RECEPTORS
7. --GLYCINE:-These activates Cl- channel in the spinal cord and
Medulla Barbiturates, Propofol, and other inhalational
Anesthetics
--N – methyl D – aspartate (NMDA) type of Glutamate
receptors Nitrous Oxide and Ketamine selectively inhibit
--Inhibit neuronal channels gated by Nicotinic cholinergic
receptors analgesia, and amnesia (Barbiturates and
Fluorinated anesthetics)
-OTHER MECHANISMS
8. There are Four(4) stages of General anesthesia
--1-Traditional description of signs and stages of
GA – Also called “Guedel’s signs”
--2-Typically seen in case of ETHER anesthesia
--3-Show slow action as it is very much lipid soluble
--4-There is Descending depression of CNS
--5-Higher to Lower areas of Brain are involved
--6-Vital centers located in Medulla are paralyzed last
-STAGES OF
-GENERAL ANESTHESIA
9. ---This stage starts from beginning of Anesthetic
inhalation and lasts upto the loss of
consciousness
--In this stage Pain is progressively abolished
--Patient remains conscious, and can Hear and See
and feels a dream like state
--Reflexes and respiration remain normal
--It is difficult to maintain – use is limited to short
procedures only
-STAGE-1
Stage of Analgesia
10. --1-From loss of consciousness to beginning of regular respiration
--2-Excitement:-Patient may shout, struggle and hold his breath
--3-Muscle tone increases, jaws are tightly closed.
--4-Breathing is Jerky:-vomiting involuntary micturition or defecation
may occur
--5-Heart rate and BP may rise and pupils dilate due to sympathetic
stimulation
--6-No stimulus or operative procedure carried out during this stage
--7-Breath holding are commonly seen:-Potentially dangerous responses
can occur during this stage including vomiting, Laryngospasm and
uncontrolled movement
--8-This stage is not found with modern anesthesia – Preanesthetic
medication, rapid induction etc.
-STAGE-11
Stage of “Delirium and excitement”
11. --B-It extends from onset of regular respiration to
cessation of spontaneous breathing. This
has been divided into Four(4) planes
--Plane 1 :- Roving eye balls. This plane ends when
eyes become fixed
--Plane 2 :- Loss of corneal and laryngeal reflexes.
--Plane 3 :- Pupil starts dilating and light reflex is used.
--Plane 4 :- Intercostal paralysis, shallow abdominal
respiration, dilated pupil
-STAGE 111= STAGE OF
-SURGICAL ANESTHESIA
12. --1-Cessation of breathing failure
of circulation death
--2-Pupils widely dilated
--3-Muscles are totally Flabby
--4-Pulse is imperceptible
--5-BP is very low
--STAGE IV MEDULLARY
-RESPIRATORY PARALYSIS
14. -THAT IS NOT SEEN THESE DAYS BECAUSE
--1-Availability of rapidly acting agents – IV as well as inhalation
--2-Mechanical control of respiration
--3-Pre – operative and Post – operative drugs
---ATROPINE:-Dilated pupil, Opioid – depressing of respiration
-IMPORTANT SIGNS OBSERVED BY ANESTHETISTS
--1-If no response to painful stimulus – stage – 111
--2-On incision – rise in BP, respiration etc. – light Anesthesia
--3-Fall in BP, Respiratory depression – deep anesthesia
