Ans. is 'b' i.e., Need to cross the cell membrane to produce the block Penetration of axonal membrane by L.A. o Local anaesthetics are weak bases and are used in the form of acid salts (usually HCL). o They penetrate the axoplasmic membrane in unionized form (unionize molecules are lipid soluble and diffusible). o Inside axon they becomes ionized and act from inside of Na+ channel. Sodium bicarbonate speeds the onset of action of LAs by increasing the unionized form (weak bases are unionized at alkaline pH). About other option Stimulated fibers are blocked rapidly (not resting fibers) Smaller fibers are more sensitive than larger o LA does not effect resting membrane potential as it does not block the Na+ channel in resting state (see above explanantion). LA inhibits depolarization as it prolonges the inactive state and prolongs the refractory period.