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What is Local anesthetic act by? and explain in detail?
Ans. is 'a' i.e., Na+ channel inhibition * Local anesthetics act by inhibiting Na+ channels from inside.Mechanism of action of LA* Local anesthetics act by blocking Na+ channels. By blocking Na+ channels they block nerve conduction by decreasing the entry (Influx) of Na+ ions during upstroke of action potential.* LAS prolong the inactive state - channel takes longer to recover ->> refractory period of the fiber is increased.* LAS first penetrate the axonal membrane to come inside and then their active species (cationic form) bind to Na+ channel front inside.* Cationic form (active form) is able to approach its receptor only when the channel is open at the inner face - So resting nerve is resistant to block as Na+ channels are not activated and cationic form is not able to approach its receptor.* So blockade develops rapidly when the nerve is stimulated repeatedly.* Degree of blockade is frequency dependent - greater blockade at higher frequency of stimulation.* Exposure to higher concentration of Ca+2 reduces inactivation of Na+ channels and lessens the block.Sequence of events* Order of blockade of fibers B > C > Ad > Ag, b > Aa (i.e., Type B fibers are most susceptible).* Accordingly order of block is autonomic (Preganglionic sympathetic) > Sensory > motor. Order of recovery is in reverse order.* Among sensory afferents, order of block is Temperature (cold before heat) > Pain > touch > deep pressure > proprioception.* When applied to tongue, bitter taste is lost first followed by sweet and sour, and salty taste last of all.* Myelinated nerves are blocked earlier than nonmyelinated.* Smaller fibers are more sensitive than larger fibers.