Epinephrine cardiovascular effects

Adrenal medulla. On the one hand, release of epinephrine elicits cardiovascular effects, such as increases in heart rate und peripheral vascular resistance. On the other, it evokes metabolic responses, such as glycogenolysis and li-polysis, that generate energy-rich substrates. The sensation of hunger is suppressed. The metabolic state corresponds to that associated with physical exercise - silent stress . 

Cardiovascular Effects. Most studies of humans exposed to carbon tetrachloride by inhalation have not detected significant evidence of cardiovascular injury, even at exposure levels sufficient to markedly injure the liver and/or kidney. Changes in blood pressure, heart rate, or right- sided cardiac dilation have sometimes, but not always, been observed (Ashe and Sailer 1942 Guild et al. 1958 Kittleson and Borden 1956 Stewart et al. 1961 Umiker and Pearce 1953), and are probably secondary either to fluid and electrolyte retention resulting from renal toxicity, or to central nervous system effects on the heart or blood vessels. Carbon tetrachloride also may have the potential to induce cardiac arrhythmias by sensitizing the heart to epinephrine, as has been reported for various chlorinated hydrocarbon propellants (Reinhardt et al. 1971). 

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. 

The effects of sympathomimetic drugs on blood pressure can be explained on the basis of their effects on heart rate, myocardial function, peripheral vascular resistance, and venous return (see Figure 6-7 and Table 9-4). The endogenous catecholamines, norepinephrine and epinephrine have complex cardiovascular effects because they activate both and 13 receptors. It is easier to understand these actions by first describing the cardiovascular effect of sympathomimetics that are selective for a given adrenoreceptor. 

Intravenous administration of dopamine promotes vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels, via activation of Di receptors. Activation of the Di receptors in the renal vasculature may also induce natriuresis. The renal effects of dopamine have been used clinically to improve perfusion to the kidney in situations of oliguria (abnormally low urinary output). The activation of presynaptic D2 receptors suppresses norepinephrine release, but it is unclear if this contributes to cardiovascular effects of dopamine. In addition, dopamine activates Bj receptors in the heart. At low doses, peripheral resistance may decrease. At higher rates of infusion, dopamine activates vascular a. receptors, leading to vasoconstriction, including in the renal vascular bed. Consequently, high rates of infusion of dopamine may mimic the actions of epinephrine. 

Cardiovascular Effects. Thyroid hormones appear to increase heart rate and myocardial contractility, thus leading to an increase in cardiac output. It is unclear, however, if this occurrence is a direct effect of these hormones or if the thyroid hormones increase myocardial sensitivity to other hormones (norepinephrine and epinephrine). 

Interest in ephedrine in Western medicine was created by the classical investigations of Chen and Schmidt, which began in 1923 as a result of a Chinese druggist s assurance that ma huang was really a potent drug. These workers reported the cardiovascular effects of the alkaloid, its similarity to epinephrine, and its absorption from the intestinal tract. Numerous clinical and experimental studies soon followed, and the use of ephedrine spread so rapidly that several tons of the alkaloid are now consumed yearly. Synthetic ephedrine (racemic) was first prepared in 1927 and marketed under the name Ephetonin (Goodman and Gilman, 1955). 

Cardiovascular effects of intravenous infusion of low doses of epinephrine. 

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 highest NOAEL values and all reliable LOAEL values for cardiovascular effects in each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1. Cardiovascular effects reported in humans include sensitization of the heart to epinephrine and decreased blood pressure. Both effects were found only after brief exposure to high 1,1,1 -trichloroethane concentrations. 

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. 

The cardiovascular effects, although at times alarming, are usually of little clinical significance. Body temperature falls and orthostatic hypotension, at times of severe degree, may appear. Vasodilation may appear in the extremities. The effect of norepinephrine is reduced and the hypertensive effect of epinephrine is blocked, but not the hyperglycemic action. 

Inhibition of this enzyme allows intracellular concentrations of NE to increase to the point where reuptake mechanisms are no longer effective, and precipitate a leaching out of NE and an increase in tissue and blood concentrations. In addition, the metabolites of epinephrine and norepinephrine produced by the actions of COMT still have pharmacologic activity, until acted upon by MAO, so actual degradation is minimized severely. The increased levels of epinephrine, norepinephrine, and their metabolites (metanephrine and normetanephrine, respectively) result in tachycardia, increased cardiac output, increased blood sugar, and vasoconstriction. The cardiovascular effects may ultimately precipitate a hypertensive crisis. 

Cardiovascular System Following systemic absorption, local anesthetics decrease electrical excitabdity, conduction rate, and force of contraction. Most local anesthetics also cause arteriolar dilation. Untoward cardiovascular effects usually are seen only after high systemic concentrations are attained and effects on the CNS are produced. However, on rare occasions, lower doses of some local anesthetics wUl cause cardiovascular collapse and death, probably due to either an action on the pacemaker or the sudden onset of ventricular fibrillation. Ventricular tachycardia and fibrillation are relatively uncommon consequences of local anesthetics other than bupivacaine. The use of local anesthetics as antiarrhythmic drugs is discussed in Chapter 34. Untoward cardiovascular effects of local anesthetic agents may result from their inadvertent intravascular administration, especially if epinephrine also is present. 

Taken in proper doses, chloroquine is an extraordinarily safe drug however, its safety margin is narrow, and a single dose of 30 mg/kg may be fatal. Acute chloroquine toxicity is encountered most frequently with too rapid administration of parenteral doses. Cardiovascular effects include hypotension, vasodilation, depressed myocardial function, cardiac arrhythmias, and cardiac arrest. Confusion, convulsions, and coma denote central nervous system (CNS) dysfunction. Chloroquine doses of >5 g given parenterally usually are fatal. Prompt treatment with mechanical ventilation, epinephrine, and diazepam may be lifesaving. 

Adverse effects. Cardiovascular crises are a possible risk emotional stress of the patient may cause sympathoadrenal activation with epinephrine release. The resulting rise in blood pressure can be all the more marked because persistent depression of sympathetic nerve activity induces supersen-sitivily of effector organs to circulating catecholamines. 

The effects of nicotine on the cardiovascular system mimic those seen after activation of the sympathoadrenal system, and they are principally the result of a release of epinephrine and norepinephrine from the adrenal medulla and adrenergic nerve terminals. These effects include a positive inotropic and chronotropic effect on the myocardium as well as an increase in cardiac output. In addition, both systohc and diastolic blood pressures are increased secondary to stimulation of the sympathoadrenal system. These effects are the end result of a summation of adrenergic and chohnergic stimulation. 

Death from SNA Intoxication appears to Involve both cardiovascular and respiratory systems. 2 SNA Increases the effects of pentobarbital on both respiration and heart rate. The depressant effects of SNA on the myocardium and on the Purklnje system are antagonized effectively by epinephrine, but not by Metrazol (pentylenetetrazol) and caffeine. Artificial respiration restored cardiac stability and regularity. It was suggested that SNA Interferes with oxygen utilization In animals. The circulatory and respiratory responses to SNA were considered to be mediated through the medulla oblongata. 2... 

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