PHARMACOLOGY

 TOLERANCE ::

On repeated dosage if more drug is required by the patient than the usual amount the patient is then said to have acquired tolerance to the drug In other words tolerance is a state of decreased responsiveness to a drug brought about by prolong usage consequently demanding larger dosage of drug 

        Tolerance can be natural (inborn) or acquired There is also species tolerance Rabbits for example are highly tolerant to belladonna Similarly little mice can withsteand comparatively large doses of digitalis In human beings there is racial and familial tolerance Acquired tolerance occurs with continued usage An alcoholic is more tolerant partly because his absorption is decreased due to the gastroenteritis which he develops and partly because his cells become less responsive to alcohol 

        Acquired tolerance may be of three types ::

(a) Metabolic or pharmacokinetic tolerance ::

Certain drugs increase the metabolism of own or other drugs e.g. barbiturates As a result tolerance develops due to increase metabolism of drug This is metabolism or pharmacokinetic tolerance 

(b) Physiological tolerance ::

Here tolerance develops due to certain physiological homeostatic mechanisms e.g. tolerance develops with hydralazine due to reflex tachycardia and activation of sympathetic nervous system 

(c) Pharmacodynamic tolerance ::

This type of tolerance is common with morphine barbiturates etc This is due to adaptation of cells to the environment 

    Tolerance may be true or pseudo In true tolerance receptiveness of the cell to the drug is decreased True tolerance can be acute or chronic it can also be tissue tolerance which is localised to particular type of tissue 

            Pseudotolerance is not working at the target cell level it results by a decrease in rate of absorption or an increase in rate of excretion