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Pain can be due to chronic illness, acute injury, or because of surgery or manipulation. Although it is unlikely, but not impossible, that health care professionals would be administering general anaesthetics, they are included here for the sake of completeness and because it is possible that overdose of local anaesthetics can cause general anaesthesia.

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Many drugs are bound to plasma proteins and this can limit their distribution and action because only the free drug can have an effect. Eventually, whether metabolized or not, a drug is eliminated from the body.

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