Isoproterenol, positive inotropic

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]. 

PHARMACOLOGICAL ACTIONS The major cardiovascular effects of isoproterenol (compared with Epi and NE) are illustrated in Eigure 10-2. Intravenous infusion of isoproterenol lowers peripheral vascular resistance, primarily in skeletal muscle but also in renal and mesenteric vascular beds. Diastolic pressure falls. Systolic blood pressure may remain unchanged or rise mean arterial pressure typically falls. Cardiac output increases due to the positive inotropic and chronotropic effects of the drug in the face of diminished peripheral vascular resistance. The cardiac effects of isoproterenol may lead to palpitations, sinus tachycardia, and more serious arrhythmias. 

Dopamine and dobutamine are the positive inotropic agents most often used for the shortterm support of the circulation in advanced heart failure. These drugs act via stimulation of the cardiac myocyte dopamine Dj and adrenergic receptors, leading to stimulation of the G -adenylyl cyclase-cyclic AMP-PKA pathway. Isoproterenol, epinephrine, and norepinephrine, although useful in specific circumstances, have little role in the treatment of heart failure see Chapter 10). 

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. 

Isoproterenol (isoprenaline) is a very potent 3-receptor agonist and has little effect on receptors. The drug has positive chronotropic and inotropic actions because isoproterenol activates 3 receptors almost exclusively, it is a potent vasodilator. These actions lead to a marked increase in cardiac output associated with a fall in diastolic and mean arterial pressure and a lesser decrease or a slight increase in systolic pressure (Table 9-4 Figure 9-6). 

P effects, nonselective (i.e. pj + Pj) isoprenaline (isoproterenol). Its uses as bronchodilator (P2), for positive cardiac inotropic effect and to enhance conduction in heart block (p, pp have been largely superseded by agents with a more appropriately selective profile of effects. Other agents with nonselective P effects, ephedrine, orciprenaline, are also obsolete for asthma. 

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