Isoproterenol cardiovascular effects

The cardiovascular effects of norepinephrine, epinephrine, and isoproterenol are shown in Table 10.1. Differences in the action of these three catecholamines on various vascular beds are due both to the different... 

Cardiovascular effects of Infusion of norepinephrine, epinephrine, Isoproterenol, and dopamine in humans. Infusions were made intravenously during the time indicated by the broken lines. Heart rate is given in beats per minute, blood pressure in millimeters of mercury, and peripheral resistance in arterial blood pressure. (Reprinted with permission from Allwood MJ, Cobbald AF, and Ginsburg J. Peripheral vascular effects of noradrenaline, isopropyl-noradrenaline, and dopamine. Br Med Bull 19 132, 1963. Reproduced by permission of the Medical Department, The British Council. 

Isoproterenol Bi and B2 agonist Bronchodilation plus powerful cardiovascular effects Asthma, but 32-selective agents preferred Aerosol, nebulizer, or parenteral see Chapter 9... 

The first adrenergic receptor types to be distinguished from each other were the adrenergic a- and (3-receptors. Initially based on the different cardiovascular effects of epinephrine and norepinephrine, this distinction was borne out more clearly with the synthetic (3-selective agent isoproterenol. Furthermore, subtypes of both a- and (3-receptors can be distinguished by selective agonists (Figure 10.5). 

Fig. 22.1 Cardiovascular effects of noradrenaline (norepinephrine), adrenaline (epinephrine) and isoprenaline (isoproterenol) pulse rate/min, blood pressure in mmHg (dotted line is mean pressure), peripheral resistance in arbitrary units.The differences are due to the differential a and p agonist selectivities of these agents (see text). (By permission,after GinsburgJ,Cobbold A F I960 ln Vane J R et al (eds) Adrenergic mechanism. Churchill, London)...

The major dired-ading adrenoceptor agonist drugs are described. The alpha agonist phenylephrine increases mean BP, has no effed on pulse pressure, and elicits a reflex bradycardia. Isoproterenol, a beta agonist, decreases mean BP, increases pulse pressure, and causes marked tachycardia. Cardiovascular effects of norepinephrine (NE) are similar to phenylephrine, but it is also a cardiac (i, adrenoceptor j activator. The cardiovascular effects of epinephrine (E) are betalike at low doses and alphalike at high j doses. 

PHARMACOLOGICAL PROPERTIES The pharmacological actions of NE and Epi have been extensively compared in vivo and in vitro (Table 10-2). They are approximately equipotent in stimulating /3j receptors they differ mainly in their effectiveness in stimulating a and receptors. NE is a potent a agonist and has relatively little action on fi receptors however, it is somewhat less potent than Epi on the a receptors of most organs. Isoproterenol stimulates all /3 receptors but not a receptors. Eigure 10-2 compares the cardiovascular effects of infusions of NE, Epi, and isoproterenol. 

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. 

The cardiovascular effects of racemic dobutamine are a composite of the pharmacological properties of the (—) and (-V) stereoisomers. Dobutamine has relatively more prominent inotropic than chronotropic effects, compared to isoproterenol. This useful selectivity may arise because peripheral resistance is relatively unchanged due to a counterbalancing ofa receptor-mediated vasoconstriction and receptor-mediated vasodilation. Alternatively, cardiac receptors may contribute to the inotropic effect. At equivalent inotropic doses, dobutamine enfumces automatic-ity of the sinus node to a lesser extent than does isoproterenol however, enhancement of AV and intraventricular conduction is similar for both drugs. 

Albuterol (ventoun, proventil, others) is a selective P2 agonist with pharmacological properties and therapeutic indications similar to those of terbutaline. It is administered by inhalation or orally for the symptomatic relief of bronchospasm. When administered by inhalation, terbutaline produces significant bronchodilation within 15 minutes effects persist for 3-4 hours. Cardiovascular effects of albuterol are considerably weaker than those of isoproterenol that produce comparable bronchodilation when administered by inhalation. Oral albuterol may delay preterm labor. Rare CNS and respiratory side effects are sometimes observed. 

Albuterol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects. 

The pharmacology and clinical effectiveness of fenoterol (34) has been recently reviewed with comparisons made to isoproterenol (35). orclprenallne (26) and salbutamol (22) Clinical experience has shown that fenoterol, a highly selective 2 agonist, is an effective bronchodilator with negligable effects on the cardiovascular system following... 

The p agonist isoproterenol effectively decreases pulmonary artery pressure when administered intravenously in acute studies. Long-term studies with sublingual isoproterenol appear to show beneficial effects, but only in a limited number of patients. Since isoproterenol is not a selective pulmonary vasodilator, however, cardiovascular side effects are common. 

For further evaluation, selected compounds are submitted to a dog assay (117,118) in which the prostaglandin is administered by aerosol to an anesthetized pilocarpine bronchoconstricted dog (n=3 to 6) and the decrease in airway resistance is recorded at the same time effects on the cardiovascular system (femoral pressure, pulmonary pressure, heart rate) are noted. This experiment is allowed to proceed for one hour, which also permits an assessment of the compound s ability to produce a prolonged bronchodilation. In this assay salbutamol maintains its effect for the entire hour, whereas isoproterenol and 1-PGEi lose theirs within the first twenty minutes. At the conclusion of the study a standard dose of isoproterenol is administered to determine the animal s maximum capacity to respond. 

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