Isoproterenol cardiac stimulant effect

The most severe side effect of Isoproterenol is its cardiac stimulant effect. 

Terbutaline and albuterol are relatively selective Pj-adrenoceptor agonists. Both have a longer duration of action than isoproterenol because they are not metabolized by COMT. Like isoproterenol, they are not metabolized by MAO and are not transported into adrenergic neurons. Terbutaline and albuterol are effectively administered either orally or subcutaneously. Because of their selectivity for Pj-adrenoceptors, they produce less cardiac stimulation than does isoproterenol but are not completely without effects on the heart. 

Beta Adrenoceptor Agonists - Beta adrenoceptors have been divided into subclasses based on the relative activities of various sympathomimetic amines on different target tissues. For example, beta-1 receptors are found in the heart and beta-2 receptors are found in bronchlolar and other smooth muscle. The potent beta adrenoceptor stimulant Isoproterenol, a common agent for the treatment of asthma, is nonselectlve and may cause undesirable cardiac stimulation at doses which relax bronchlolar smooth muscle. Besides direct effects on bronchial smooth muscle, these compounds inhibit mediator release from skln or passively sensitized human lung and also inhibit antigen-stimulated histamine synthesis in human leucocytes. ... 

FIGURE 2.18 Inotropic and lusitropic responses of guinea pig left atria to (3-adrenoceptor stimulation. Panels A to C isometric tension waveforms of cardiac contraction (ordinates are mg tension abscissae are msec), (a) Effect of 0.3 nM isoproterenol on the waveform. The wave is shortened due to an increase in the rate of diastolic relaxation, whereas no inotropic response (change in peak tension) is observed at this concentration, (b) A further shortening of waveform duration (lusitropic response) is observed with 3 nM isoproterenol. This is concomitant with positive inotropic response (increase maximal tension), (c) This trend continues with 100 nM isoproterenol, (d) Dose-response curves for ino tropy (filled circles) and lusitropy (open circles) in guinea pig atria for isoproterenol, (e) Dose-response curves for inotropy (filled circles) and lusitropy (open circles) in guinea pig atria for the P-adrenoceptor partial agonist prenalterol. Data redrawn from [6]. 

Similarly, De Mello [1989] reported on an improvement in intercellular coupling by the P-adrenoceptor agonist isoproterenol in cardiac cell pairs. Thus, stimulation of P-adrenoceptors can be assumed to result in enhancement of intercellular coupling, at least in some preparations. However, on the basis of the hndings of Kwak and Jongsma [1996] on a lack of the effect of PKA to alter gap junction conductance in rat cardiomyocytes, caution seems necessary and species variability or tissue variability seems to play an important role. 

One effect that theophylline, nitroglycerin, isoproterenol, and histamine have in common is (A) Direct stimulation of cardiac contractile force Tachycardia... 

I. Pharmacology. Isoproterenol is a catecholamine-like drug that stimulates beta-adrenergic receptors (beta-1 and -2). Pharmacologic properties include positive inotropic and chronotropic cardiac effects, periphery vasodilation, and bron-chodilation. Isoproterenol is not absorbed orally and shows variable and erratic absorption from sublingual and rectal sites. The effects of the drug are rapidly terminated by tissue uptake and metabolism effects persist only a few minutes after intravenous injection. 

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