Theories of anesthesia
- 1. THEORIES OF ANESTHESIA -Dr Nisar Ahmed Arain Assistant Professor -Anesthesia/Critical care/ER
- 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