GENERAL ANESTHETICS... Drugs made surgeries possible...

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Introduction:
General anaesthetics are the drugs which makes the patient not to respond for the painful stimulus and he will not even feel the pain during surgical procedures. (1)

They give the systemic effect as they act mainly on the CNS, whereas the local anaesthetics act on the peripheral nerves produce the local effect. (1)
To be a good general anaesthetic the drug action including the initiation of its effect and recovery should be done according to condition required. (1)
Their action should be reversible. (2)

Stages of anaesthesia: (3)
In anaesthesia, depression of the main physiological activities takes first. The lower segments are first effected by anesthetic increases, the important centers present in medulla are paralyzed.
Using either as anaesthetic the following four stages are described.
a) Stages of analgesia: this stage lasts between the drug inhalation to loss of consciousness. The patient can hear and can see and will be conscious. The stage lasts for small period of time.
b) Stage of delirium: The patient will excite in this stage. Subject may shout, will close jaws very tightly, may vomit, micturition or defecation occurs without subject's knowledge. Chances are there to increase in heart rate and blood pressure. Surgical procedures should not be done in this stage.
c) Surgical anaesthesia: it is divided into four planes as follows.
Plane 1: During this plane, the eye balls will wander and will fix at the end of the plane.
Plane 2: corneal and laryngeal reflexes will be stopped.
Plane 3: Dilation of pupil will begin and there will be no reflex action for light.
Plane 4: Intercoastal paralysis will takes place.
d) Medullary paralysis: Breathing may stop and circulation may fail and death may occur.

Mechanism of action:
It can be explained by following theories.
Lipid theory: This is proposed by Meyer. According to him "narcosis commences when any chemically indifferent substance has attained a certain molar concentration in the lipids of the cell."(1)
This theory showed that lipid solubility and anaesthetic effect were releated. The potency can be estimated by Minimum Alveolar Concentration. It is the minimum concentration of the anaesthetic that should be maintained in the alveoli to prevent pain at least 50% of the patients during surgery. It does not change with the change in other conditions. More the MAC, less is the potency. Membrane fluidity and volume expansion theories were failed to explain completely. Hence glance was turned towards proteins rather than lipids. (1)
Action on ion channels:
Proteins and lipids are the targets for binding of the anaesthetics. When the anaesthetics reached the required concentration then they are capable to inhibit excitatory receptors. (e.g. 5-hydroxy tryptamine, acetylcholine) and increase the GABA and glycine receptors whch are inhibitory in action. GABA is the main binding site for benzodiazepines and intravenous anaesthetics( e.g. thiopental, propofol). TREK which is the two pore domain potassium channel which when activated decreas3es the membrane excitability.(1)

What is their effect on nervous system...??
Their effect on the axonal conduction is not significant but their action is by stopping the synaptic transmission; which can be done either by decreasing the synaptic release or stopping the transmitter's action or by decreasing excitability of post synaptic membrane.(1)
Decrease in the release of transmitter occurs in the peripheral synapsis, whereas post synaptic membrane excitability decreases at the peripheral and central synapses . inhibion of thalamic sensory nuclei and reticular formation is responsible for the loss of consciousness and decrease in pain(1)
At low concentration these causes amnesia for short span and the subject cannot remember the effect of the drug during that time. This is because action of drug on hippocampus.
Reflex activity and motor control will be affected as the concentration of anaesthetic at high concentration. Since several areas are effected in the brain, it is not possible to find the particular area which is the target for the anaesthetic. If artificial respiration is not provided in case of high concentrations it leads to death of patient.(1)

What is their effect on cardiovascular system...??
The contraction of heart decreases but cardiac output and blood pressure varies accordingly because of mixed action on sympathetic nervous system as well as on vascular smooth muscle.
Halothane and also some other anaesthetics increases the number of ventricular systoles then normal conditions and the patient will be safe.(1)

What is their effect on respiratory system...??
All the anaesthetics decreases the respiration and results in increased level of pCO2. But nitrous oxide and ketamine do not follow this. Desflurane causes laryngospasm and bronchospasm. (1)

References:
1. Rang and Dales Pharmacology, 6th edition, Churchil livingstone publishers, page no 523 to 525.
2. A text book of Medicinal chemistry by Surendra nath Pandeya, volume 1, SG publishers, page no 63.
3. Essentials of Medical pharmacology by KD Tripathi, 5th edition, Jaypee publishers, page no334 to 335

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