All nerve libres are sensitive lo local anaesthetics but in general, small-diameter libres are more sensitive than large fibres. Thus, a differential block can be achieved where the smaller pain and autonomic fibres are blocked, while coarse touch and movement fibres are spared. Local anaesthetics vary widely in their potency, duration of action, toxicity and ability to penetrate mucous membranes.
Local anaesthetics depress other excitable tissues (e.g. myocardium) if the concentration in the blood is sufficiently high, but their main systemic effects involve the central nervous system. Synthetic agents buy accutane sedation and lightheadedness, although anxiety and restlessness sometimes occur, presumably because central inhibitory synapses arc depressed. Higher toxic doses cause twitching and visual disturbances, while severe toxicity causes convulsions and coma, with respiratory and cardiac depression resulting from medullary depression.
In general, high potency and long duration are related to high lipid solubility because this results in much of the locally applied drug entering the cells. Vasoconstriction also lends to prolong online accutane effect by reducing systemic distribution of the agent, and this can be achieved by the addition of a vasoconstrictor such as epinephrine (adrenaline) or less often, norepinephrine (noradrenaline). Vasoconstrictors must not be used for producing ring-block of an extremity (e.g. finger or toe) because they may cause prolonged ischaemia and gangrene.
Amides are dealkylated in the liver and esters (not cocaine) are hydrolysed by plasma pseudocholinesterase, but drug metabolism has little effect on the duration of action of agents actually in the tissues.