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Local anaesthetics preferentially bind to channels in the inactive state and prevent them from opening again. This is similar to the mechanism of action of some antiepileptic drugs. Moreover, like antiepileptic drugs, local anaesthetics show use dependence in that they preferentially block neurons that are transmitting impulses at high frequency (as pain sensory neurons do). open closed inactivated sodium ion channels local anaesthetic ionized local anaesthetic neuronal membrane diffusion Figure Local anaesthetics are weak bases and at the slightly alkaline pH of body fluids, they exist in both ionized and unionized forms in equilibrium. Only the unionized form can reach its site of action, which is inside the neuron. This is because the drug has to be in a lipid soluble form to diffuse through the myelin sheath and neuronal membrane.

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