Tolerance sympathomimetics

In rats, we know that tolerance does not occur to parasympathomimetic effects of LSD at a time when sympathomimetically mediated and behavioral effects show tolerance. Apart from the postreserpine LSD-induced pupillary changes, such differential effects in man are not known. We know also that the bradycardia in unrestrained rats (19) converts readily to a tachycardia, and assertions that LSD elevates blood pressure or pulse in man should be viewed as reactivity rather than a direct effect. 

Khat produces sympathomimetic effects, increasing heart rate and blood pressure. When khat is chewed, the increases are gradual, maximizing at about 2 hours and lasting for 4 hours. However, tolerance develops to blood pressure and heart rate effects in habitual users. Mydriasis and increases in respiration also occur. Cathinone induces thermogenesis in brown adipose tissue, which is mediated by jS-adrenergic receptors (Tariq et al. 1989). 

Tolerance Tolerance may occur with prolonged use of sympathomimetic agents, but temporary cessation of the drug restores its original effectiveness. 

Despite impressions to the contrary, MAOIs are generally well tolerated if patients observe the restricted diet and avoid medications that contain sympathomimetic amines. Adverse effects are rarely a treatment-limiting problem with the exception of hypotension. MAOIs also fall between TCAs and SSRIs in terms of overdose risk. Major toxic reactions to MAOIs are uncommon but require immediate discontinuation and symptomatic treatment. 

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). 

Sympathomimetics can be physically addictive and should not be prescribed to people with a history of drug abuse. A person may develop a tolerance to the drug and attempt to increase the dosage. The person may develop intoxication symptoms such as insomnia and severe skin diseases. 

Tachycardia, dysrhythmias, and a rise in blood pressure have been described after the administration of centrally acting sympathomimetic amines. Amfetamine acutely administered to men with a history of amfetamine abuse enhanced the pressor effects of tyramine and noradrenaline, while continuous amfetamine led to tolerance of the pressor response to tyramine. As with intravenous amphetamines, cardiomyopathy, cardiomegaly, and pulmonary edema have been reported with smoking of crystal metamfetamine (15-17). 

Case Conclusion HP began methimazole therapy for her Graves hyperthyroidism. She also began propranolol to help control her tachycardia and tremor. During this time HP should avoid excessive exercise or other sympathomimetic drugs until her symptoms of tachycardia have subsided. HP will return to the clinic for follow-up in 4 weeks. At that time, methimazole dose, tolerability, compliance, and thyroid function tests will be reassessed. 

The goal of treatment of patients with HCM is primarily to reduce their symptoms of dyspnea and exercise intolerance. Either /3-blockers or CCBs may be used. If a /3-blocker is chosen, it is best to use an agent that does not have intrinsic sympathomimetic activity. The dose should be maximized. If the patient does not tolerate a -blocker or has a contraindication to the use of a /3-blocker, then verapamil may be tried. Patients should be monitored for resolution of symptoms and an increase in exercise tolerance. Resolution of symptoms may take months to occur. In addition, both 8-bIockers and CCBs may cause hypotension and conduction abnormalities. -Blockers may worsen pulmonary function. If dyspnea continues with maximal doses of a /3-blocker or CCB, a diuretic agent or a nitrate may be added with caution. Patients who are at high risk for sudden cardiac death should be considered candidates for an ICD. 

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