Alterations of drug toxicity in cardiovascular disease

The past ten years have seen a rapid expansion in the field of cardiovascular pharmacology. New indications for old agents have appeared and new powerful drugs have been introduced, including entirely new classes of compounds. The availability of so many agents has considerably expanded the risk of life-threatening adverse reactions due to overdosage or to inappropriate drug associations. The liability to encounter severe side effects is often enhanced in patients with underlying cardiovascular diseases, which may change the usual drug action either by inducing modifications of the drug pharmacolinetic or by altering the receptor sensitivity. In most cases these kind of reactions are predictable on the ground of the knowledge of both the drug mechanism of action and the functional alterations induced by the disease. However entirely unexpected adverse reactions may also occur in cases in which unrecognized alterations exist, whose pathophysiology has not been fully elucidated. Recent demonstrations that some physiopathological influences, as well as prolonged drug treatment, can modulate the number of adrenergic receptors in the cardiovascular system has offered a clue to a better understanding of at least some episodes of altered responsiveness to cardiovascular drugs, previously considered of unknown origin. The possibility of obtaining some indications of the adrenoceptor status in man, by the assessment of the receptor density in circulating blood cells, seems to represent a promising diagnostic approach to the problem of disease induced adrenergic regulation and its possible consequences in terms of altered drug responsiveness.