Norepinephrine 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. 

Cardiovascular effect. [6]-shogaol, administered intravenously to rats at a dose of 0.5 mg/kg, produced a rapid fall in blood pressure, bradycardia, and apnea. There was a marked pressure pressor response in blood pressure that occurred after the rapid fall. A dose of 3.6 pM produced inotropic and chronotropic actions on isolated atria in rats. The effect disappeared by repeated injections or pretreatment of 100 mg/kg administered subcutaneously ° k Intravenous doses of 0.1 to 0.5 pg produced a pressor response in a dose dependent manner. The response was markedly reduced by spinal destruction at the sacral cord level. Norepinephrine (10 pg/kg, intravenously) induced pressor response that was not affected by spinal destruction. In rats in which the spinal cord was destroyed at the thoracic cord level, [6]-shogaol-induced pressor response was reduced by hexamethonium (10 mg/kg, intravenously) and phentolamine (10 mg/ kg, intravenously). When the spinal cord was destroyed at the sacral level, the pressor response was not affected by these blockades. In the hindquarters of rats that were perfused with rat s blood, [6]-shogaol produced two pressor responses on the perfusion pressure. The first was accompanied by a rise in systemic blood pressure, was re-... 

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. 

Dopamine is the immediate precursor in the synthesis of norepinephrine (see Figure 6-5). Its cardiovascular effects were described above. Endogenous dopamine may have more important effects in regulating sodium excretion and renal function. It is an important neurotransmitter in the central nervous system and is involved in the reward stimulus relevant to addiction. Its deficiency in the basal ganglia leads to Parkinson s disease, which is treated with its precursor levodopa. Dopamine receptors are also targets for antipsychotic drugs. 

Atomoxetine is a selective inhibitor of the norepinephrine reuptake transporter. Its actions, therefore, are mediated by potentiation of norepinephrine levels in noradrenergic synapses. It is used in the treatment of attention deficit disorders (see below). Atomoxetine has surprisingly little cardiovascular effect because it has a clonidine-like effect in the central nervous system to decrease sympathetic outflow while at the same time potentiating the effects of norepinephrine in the periphery. However, it may increase blood pressure in some patients. Norepinephrine reuptake is particularly important in the heart, particularly during sympathetic stimulation, and this... 

Cocaine differs from the other local anesthetics with respect to its cardiovascular effects. Cocaine s blockade of norepinephrine reuptake results in vasoconstriction and hypertension, as well as cardiac arrhythmias. The vasoconstriction produced by cocaine can lead to local ischemia and, in chronic abusers who use the nasal route, ulceration of the mucous membrane and damage to the nasal septum have been reported. The vasoconstrictor properties of cocaine can be used clinically to decrease bleeding from mucosal damage or surgical trauma in the nasopharyneal region. 

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). 

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). 

Theoretically, other agents with norepinephrine reuptake blocking properties, such as venlafaxine, duloxetine, atomoxetine, milnacipran, and reboxetine, could also add to amphetamine s CNS and cardiovascular effects... 

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)...

Pancuronium can be administered i.v. during general anesthesia at a dose rate of 0.08 mg/kg (Muir Hubbell 1989). If used appropriately, adverse effects are rare. Pancuronium and vecuronium produce minimal cardiovascular effects, although pancuronium can potentially stimulate the release of norepinephrine (noradrenaline), resulting in increased heart rate and blood pressure. Horses with pre-existing cardiovascular disease may develop hypotension. Atracurium... 

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. 

SSRIs have less sedative, anticholinergic, and cardiovascular effects than do the tricyclic antidepressants, due to dramatically decreased binding to receptors of histamine, acetylcholine, and norepinephrine. 

Cardiovascular effects are primarily due to increased production of norepinephrine, and include atrial and ventricular arrhythmias, ventricular tachycardia, and atrial fibrillation. These effects are markedly reduced with concurrent administration of an inhibitor of peripheral LAAD. 

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. 

Originally tested in cardiovascular disease, trivastal (x, ET U95) has been proposed as a dopamine receptor stimulant with better oral absorption and longer duration of action than apomorphine. In addition to its direct effect on the receptors the data suggested a weak dopamine and norepinephrine releasing effect. Trivastal blocked caudate EEG spindles as did apomorphine and reduced tremor in monkeys with midbrain lesions . Others have reported its drug dynamics and pharmacological actions . 

Methyldopa, through its metaboHte, CX-methyInorepinephrine formed in the brain, acts on the postsynaptic tt2-adrenoceptor in the central nervous system. It reduces the adrenergic outflow to the cardiovascular system, thereby decreasing arterial blood pressure. If the conversion of methyldopa to CX-methyl norepinephrine in the brain is prevented by a dopamine -hydroxylase inhibitor capable of penetrating into the brain, it loses its antihypertensive effects. 

Autonomic Cocaine has stong sympathomimetic effects due to inhibition of norepinephrine reuptake, and perhaps central mechanisms as well. Effects include those typical of sympathetic autonomic activation. Cardiovascular and cerebrovascular effects are prominent. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

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