Tolerance and Tachyphylaxis

Tolerance refers to decreased responses following the long-term administration of drugs. For example, after repeated morphine use, tolerance to all of its effects, except for miosis and constipation, occurs, and respiratory depression is also reduced. 

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Even before administering the first dose of a drug, the prescriber should consider factors that may help in predicting the direction and extent of possible variations in responsiveness. These include the propensity of a particular drug to produce tolerance or tachyphylaxis as well as the effects of age, sex, body size, disease state, genetic factors, and simultaneous administration of other drugs. 

Sources of bias in this study design arise from the exposure of patients to lower doses first. Patients obligatorily must tolerate, and fail to respond to, lower doses before being exposed to higher doses. Any degree of treatment familiarization, tachyphylaxis, or patient withdrawal rate biases dose-... 

Continuous infusions of nitroglycerin should be initiated at a dose of 5 to 10 mcg/minute and increased every 5 to 10 minutes until symptomatic or hemodynamic improvement. Effective doses range from 35 to 200 mcg/minute. The most common adverse events reported are headache, dose-related hypotension, and tachycardia. A limitation to nitroglycerin s use is the development of tachyphylaxis, or tolerance to its effects,... 

Decreased sensitivity to a drug, or tolerance, is seen with some drugs such as opiates and usually requires repeated administration of the drug. Tachyphylaxis, in contrast, is tolerance that develops rapidly, often after a single injection of a drug. In some cases, this may be due to what is termed as the dawn regulation of a drug receptor, in which the number of receptors becomes decreased. 

Tolerance Following 12 days of dronabinol, tolerance to the cardiovascular and subjective effects developed at doses 210 mg/day or less. An initial tachycardia induced by dronabinol was replaced successively by normal sinus rhythm and then bradycardia. A fall in supine blood pressure, made worse by standing, was also observed initially. Within days, these effects disappeared, indicating development of tolerance. Tachyphylaxis and tolerance did not, however, appear to develop to the appetite stimulant effect. 

With continuous exposure to nitrates, isolated smooth muscle may develop complete tolerance (tachyphylaxis), and the intact human becomes progressively more tolerant when long-acting preparations (oral, transdermal) or continuous intravenous infusions are used for more than a few hours without interruption. 

Tachyphylaxis refers to a quickly developing tolerance brought about by the rapid and repeated administration of drugs. For example, indirect-acting sympathomimetic agents such as tyramine, which exert their effects through the release of norepinephrine, are able to cause tachyphylaxis. If norepinephrine is not present, tyramine fails to act until the supply of norepinephrine in nerve terminals has been replenished (Figure 3.3). 

The desirability of continuous sustained levels of drug in the plasma is questionable. Tachyphylaxis and/or tolerance cannot be predicted from the physicochemical properties. Neither can the occurrence of irritant or allergic responses although recent studies have investigated the relationship between chemical structure and irritancy [34]. 

The main reason MDMA has little abuse potential is that it exhibits tachyphylaxis —a rapid buildup of tolerance so that repeated usage within a short space of time leads to the loss of desired effects. In contrast to its "heart-opening" and stress-reducing qualities, this substance, if taken within a few days of a prior ingestion, tends paradoxically to produce an increase in stress and many of the least desirable characteristics of amphetamine overdosage. Very few people are attracted to such effects, and even those who are could achieve them more cheaply via other substances. 

Tachyphylaxis the progressive reduction in response due to repeated agonist stimulation (see Desensitization and Fade). The maximal response to the agonist is reduced in tachyphylaxis (whereas the sensitivity is reduced with tolerance). 

One must keep in mind that older patients with uric acid kidney stones also may have hypertension, congestive heart failure, or renal insufficiency, and obviously should not be exposed to overload with aUcalinizing sodium salts or unlimited fluid intake. Acetazolamide, a carbonic anhydrase inhibitor, produces rapid and effective urinary alkalinization and sometimes is used in conjunction with alkali therapy. When a 250-mg dose of acetazolamide is given at bedtime, the excretion of an acidic urine in the early morning hours is avoided. The usual tachyphylaxis (rapid tolerance) to this drug is obviated by a daily repletion dose of bicarbonate. 

When a drug is given over time, the effects may decrease accordingly. This may be the consequence of, for example, desensitization of receptors or depletion of neurotransmitter stores. This effect is termed tolerance. If a drug is administered and produces a response that diminishes with subsequent doses, the effect is termed tachyphylaxis. This phenomenon is a rapid decrease in drug effect with subsequent dosing. 

Tachyphylaxis. The patient builds a tolerance to the drug due to the frequency in which the drug is administered. This occurs with narcotics, barbiturates, laxatives, and psychotropic agents. The patient may eventually need more of the dmg to reach the desired effect. 

Acute tolerance (tachyphylaxis) to vasoconstriction and antimitotic effects of and suppression of epidermal DNA synthesis by topical corticoids have been demonstrated [15, 16]. This suggests that the resistance clinically observed after prolonged use might be prevented by less intensive therapy, such as daily application with short resting periods between treatment courses [5, 67]. Another study examining corticoid tachyphylaxis used fluocinolone acetonide under occlusion to the forearm and induced wheal and flare to histamine with the prick technique [80]. By the eighth day, the wheal was nonexistent, adding now a third tachyphylaxis phenomena. 

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