Corticosteroids cardiovascular effects

There is a decreased effectiveness of ritodrine when the drug is administered with a -adrenergic blocking agent such as propranolol and an increased risk of pulmonary edema when administered with the corticosteroids. Co-administration of ritodrine with the sym-pathomimetics potentiates the effect of ritodrine. Cardiovascular effects (eg, arrhythmias or hypotension) of ritodrine may increase when the drug is administered with diazoxide, general anesthetics, magnesium sulfate, or meperidine... 

Taylor DR, Wilkins GT, Herbison GP, Flannery EM. Interaction between corticosteroid and beta-agonist drugs. Biochemical and cardiovascular effects in normal subjects. Chest 1992 102(2) 519-24. 

CARDIOVASCULAR SYSTEM The most striking cardiovascular effects of corticosteroids result from mineralocorticoid-induced changes in renal Na+ excretion, as is evident in primary aldosteronism. The resultant hypertension can lead to a diverse group of adverse effects on the cardiovascular system (see Chapter 32). Consistent with the known actions of mineralocorticoids in the kidney, restriction of dietary Na can lower the blood pressure considerably in mineralocorticoid excess. 

Although the prevention of the endotoxin-induced circulatory failure with the above agents appears to be an important approach for the therapy of a variety of diseases, it should be stressed that the beneficial effects of these agents—when administered in animal models of circulatory shock after the initiation of endotoxemia—are limited (Tracey etal., 1987 Mathison et al., 1988 Hinshaw et al., 1990 Silva et al., 1990). For example, inhibition of iNOS induction with corticosteroids (Radomski et al., 1990 Knowles et al., 1990b) prevents the cardiovascular failure caused by endotoxin, but does not exert beneficial cardiovascular effects once iNOS induction has occurred (Wright et al., 1992 Paya et al., 1993). 

The first point is that treatment with steroids is generally palliative rather than curative, and only in a very few diseases, such as leukemia and nephrotic syndrome, do corticosteroids alter prognosis. One must also consider which is worse, the disease to be treated or possible induced hypercortisolism. The patient s age can be an important factor, since such adverse effects as hypertension are more apt to occur in old and infirm individuals, especially in those with underlying cardiovascular disease. Glucocorticoids should be used with caution during pregnancy. If steroids are to be employed, prednisone or prednisolone should be used, since they cross the placenta poorly. 

Sholter DE and Armstrong PW. Adverse effects of corticosteroids on the cardiovascular system. Can J Cardiol 2000 16 505-511. 

Although they remain less effective than inhaled corticosteroids, a 5-LOX inhibitor (zileuton) and selective antagonists of the CysLTl receptor for leukotrienes (zafirlukast, montelukast, and pranlukast see Chapter 20) are used clinically in mild to moderate asthma. Growing evidence for a role of the leukotrienes in cardiovascular disease has expanded the potential clinical applications of leukotriene modifiers. Conflicting data have been reported in animal studies depending on the disease model used and the molecular target (5-LOX versus FLAP). Human genetic studies have demonstrated a link between cardiovascular disease and polymorphisms in the leukotriene biosynthetic enzymes, in particular FLAP, in some populations. 

The pharmacokinetics of morphine have been studied,201-203 as has its receptor binding,204-206 and its effects on hypothermia,207 on calcium uptake by synaptosomes208 and lysed synaptosomes,209 on metabolism of catecholamine in brain,210 on levels of corticosteroids and growth hormone in plasma,211 on leuteinising hormone,212 follicle-stimulating hormone,212 and prolactin,212-215 on neuroendocrine function,216 on brain function and biochemistry,217-226 on behaviour,227-240 on the gastrointestinal tract241 and on the cardiovascular... 

Corticosteroids should be used cautiously in the presence of congestive heart failure, myocardial infarction, hypertension, diabetes mellitus, epilepsy, glaucoma, hepatic disorders, osteoporosis, peptic ulceration, and renal impairment. Children are more susceptible to these adverse effects. To avoid cardiovascular collapse, steroids must be given slowly by intravenous injection. Large doses produce Cushing s syndrome (with moon face and sometimes hirsutism). 

Agents that inhibit steps in the steroidogenic pathway and thus alter the biosynthesis of adrenocortical steroids are discussed, as are synthetic steroids that inhibit glucocorticoid action. The effects of corticosteroids are numerous and widespread, and include alterations in carbohydrate, protein, and lipid metabolism maintenance of fluid and electrolyte balance and preservation of normal function of the cardiovascular system, the immune system, the kidney, skeletal muscle, the endocrine system, and the nervous system. 

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