Cardiovascular system introduction

Compounds which act as antagonists at the receptors for beta sympathetic transmitters (beta blockers) have gained very wide acceptance as antihypertensive agents. It was found subsequent to their introduction that there are two populations of beta receptors the beta-1 receptors are richest in the cardiovascular system whereas beta-2 receptors are mostly found in the bronchi. Lack of receptor-type specificity led to bronchial spasm in some asthmatic individuals on ingestion of the earlier beta blockers. Much of the work outlined below had as its goal the preparation of agents which showed selectivity for beta-1 receptors. 

Introduction of )3-adrenoblockers into medicine was one of the main advancements of pharmacology of the cardiovascular system. Initially these drags were used only in treating essential hypertension. Currently, they are used in treating angina, arrhythmia, migraines, myocardial infarctions, and glaucoma. 

This book is a self-contained introduction to, and exposition of, the field of biophar-maceutical cardiovascular safety. While drugs for cardiovascular diseases or conditions of clinical concern are expected to affect the cardiovascular system, drugs for other indications are not. However, there is always the possibility that a noncardio-vascular drug can exert a deleterious influence on one or more parts of the cardiovascular system, and, while rare, some drug-induced cardiac adverse events can be fatal. The field of cardiovascular safety, of which proarrhythmic cardiac safety is an important component, has therefore assumed considerable importance in contemporary drug development and therapeutic use. Not everyone needs to be an expert in cardiovascular safety (and this book by itself does not presume to make anyone an expert), but everyone can benefit from a fundamental knowledge of the field. 

Compounds available in the United States are Hsted in Table 1. Whereas they vary in degree, all of them share similar HabiUties of cardiovascular side effects, the potential for central nervous system (CNS) stimulation, the development of tolerance, and abuse potential. AH, with the exception of ma2indol, are derivatives of phenethylamine. The introduction of an oxygen atom on the -carbon of the side chain tends to reduce CNS stimulant properties without decreasing the anorectic activity. Following the Federal Controlled Dmg Act of 1970, dmgs were classified into one of five schedules according to medical utiUty and abuse potential. 

Before the introduction of neuromuscular blocking drugs, profound skeletal muscle relaxation for intracavitary operations could be achieved only by producing levels of volatile (inhaled) anesthesia deep enough to produce profound depressant effects on the cardiovascular and respiratory systems. The adjunctive use of neuromuscular blocking drugs makes it possible to achieve adequate muscle relaxation for all types of surgical procedures without the cardiorespiratory depressant effects produced by deep anesthesia. 

The introduction of an extra nitrogen into the xanthine system to give 8-azaxanthines had been reported to reduce cardiovascular effects ( ) and we found that 8-azatheophylline (III) was 10 times more active than the corresponding theophylline or 6-thiotheophylline in inhibiting the rat PCA reaction whereas the other pharmacological properties were reduced in magnitude. A series of 8-azaxanthines (IT) were prepared and the best of these compounds was found to be the p-nitrobenzyl derivative (V) which was equiactive witti DSG in the rat PCA test ( ),... 

Documented effects The biological activity is due to the presence of saponins, and removal of the saponins from the tincture leads to complete loss of the pharmacological properties (Ivanova 1963). The sedative effect of this species is nearly twice as strong as that of Valeriana (Tolmachev 1976). The roots of this species reduce excitability of the nervous system. Clinical tests showed that application of an alcohol infusion stopped or noticeably reduced chest pain as well as nervous and cardiovascular excitation caused by hypodermic introduction of caffeine (Akopov 1990). 

Cardiovascular Paradoxical severe hypertension occurred in three patients with advanced chronic kidney disease and bilateral renal artery stenosis. After the introduction of ramipril, an initial fall in blood pressure was followed by a paradoxical increase in blood pressure. This was postulated to be caused by activation of the renin-angiotensin-aldosterone system, as a result of renal artery stenosis and renal dysfunction [55 ]. 

---