Continuous or repeated or administration of a drug is often accompanied by a gradual diminution of the effect it produces. Tolerance is said to have been acquired when it becomes necessary to increase the dose of a drug to get an effect previously obtained with a smaller dose, i.e. reduced sensitivity. By contrast, the term tachyphylaxis describes the phenomenon of progressive lessening of effect (refractoriness) in response to frequently administered doses (see Receptors, p. 91); it tends to develop more rapidly than tolerance.

Tolerance is readily observed with opioids, as witness the huge doses of morphine that may necessary to maintain pain relief in terminal care; the effect is due to reduced pharmacological efficacy (p. 94) at receptor sites or to down-regulation of receptors. Tolerance is acquired rapidly with nitrates used to prevent angina, possibly mediated by the generation of oxygen free radicals from nitric oxide; it can be avoided by removing transdermal nitrate patches for 4—8 h, e.g. at night, to allow the plasma concentration to fall.

Increased metabolism as a result of enzyme induction (see p. 113) also leads to tolerance, as experience shows with alcohol, taken regularly as opposed to sporadically. There is commonly cross-tolerance between drugs of similar structure.

Failure of certain individuals to respond to normal doses of a drug, e.g. resistance to warfarin, vitamin D, may be said to constitute a form of natural tolerance (see Pharmacogenetics p. 122).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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