Intravenous epinephrine , effect

In healthcare settings, the risk of harmful effects is higher with intravenous epinephrine than with epinephrine administered through other routes of injection [2, 6]. Dosing errors have been attributed to the common practice of using ratios such as 1 10,000 to express the epinephrine concentrations therefore, use of mass concentration such as 0.1 mg in 1 ml is recommended [23]. 

Its most important adverse effects are nephrotoxicity and ototoxicity. The risks for nephrotoxicity can be limited by adequate hydration. Marked nausea and vomiting are frequent. Only mild-to-moderate myelosuppression is seen. Pseudo-allergic reactions may occur which respond to intravenous epinephrine and corticosteroids or antihistamines. 

The cornerstone of therapy for ventricular fibrillation is electrical deflbrillation. In the acute setting, defibrination is first-line therapy. Intravenous bretylium can occasionally contribute to conversion, but this is infrequent. In the management of out-of-hospital cardiac arrest, high-dose epinephrine (5 mg intravenously) improves the rate of successful resuscitation in patients with asystole, but not in those with ventricular fibrillation, when compared with the standard dose of 1 mg. Vasopressin (40 U intravenously) may more effective than 1 mg intravenous epinephrine in out-of-hospital patients with ventricular fibrillation that is resistant to electrical defibrillation. The OPTIC smdy (see Connolly et al., 2006) showed that amiodarone plus jS-blocker is superior than sotalol or jS-blocker alone for reducing ICD shocks in patients with reduced left ventricular function and history of sustained VT, VF, or cardiac arrest. 

In a third study the time course of the effects of intravenous and intracoronary injections of cysteinyl leukotrienes on metabolic parameters and systemic and coronary hemodynamics was examined in patients with normal coronary arteries [32]. LTD4 (3 nmol, injected into the left coronary artery) induced an early (20 s), transient fall in mean arterial pressure paralleled by rises in heart rate and plasma levels of epinephrine and norepinephrine, all of which had returned to baseline by 10 min. CVR rose at 10 and 15 min and myocardial oxygen extraction at 15 min. Thus, small doses of cysteinyl leukotrienes may induce both an early, transient fall in mean arterial pressure, with secondary sympathoadrenergic activation, and a later increase in small coronary arteriolar resistance. 

While epinephrine is usually well tolerated in young and healthy individuals, there may be problems in elderly patients with cardiac arrhythmia or previous myocardial infarction episodes [31-33]. Pharmacological effects of epinephrine include rapid rise in blood pressure, pallor, anxiety, tachycardia, headache and tremor as well as vertigo. Most commonly these effects occur after intravenous injection or after overdosing epinephrine. Cardiac arrhythmia or pulmonary edema may develop in serious cases [33, 34]. 

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Norepinephrine is the primary neurotransmitter produced and released by adrenergic neurons, and in literature it is also described as and called (-) noradrenaline or levarterenol. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating a-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of )3i-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of jSj-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine. 

Veltman DJ, van Zijderveld GA, van Dyck R (1996) Epinephrine infusions in panic disorder a double-blind placebo-controlled study. J Affect Disord 39 133-140 Westenberg HGM, Den Boer JA (1989) Serotonin fimction in panic disorder effect of L-5-hydroxytryptophan in patients and controls. Psychopharmacology (Berl) 98 283-285 Wetzler S, Asnis GM, DeLecuona JM (1996) Serotonin function in panic disorder intravenous administration of meta-chlorophenylpiperazine. Psychiatry Res 62 77-82 Wiedemann K, Jahn H, Yassom-idis A, Kellner M (2001) Anxiolyticlike effects of atrial natrim-etic peptide on cholecystokinin tetrapeptide-induced panic attacks. Arch Gen Psychiatry 58 371-377... 

A small dose of epinephrine causes a fall in mean and diastolic pressure with little or no effect on systolic pressure. This is due to the net decrease in total peripheral resistance that results from the predominance of vasodilation in the skeletal muscle vascular bed. The intravenous infusion or subcutaneous administration of epinephrine in the range of doses used in humans generally increases the systolic pressure, but the diastolic pressure is decreased. Therefore, the mean pressure may decrease, remain unchanged, or increase slightly, depending on the balance between the rise in systolic and fall in diastolic blood pressures (Rg. 10.4). 

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. 

D. A small dose of epinephrine (0.1 Jig/kg) given by intravenous route may cause the blood pressure to fall, decreasing peripheral resistance. The depressor effect of small doses is due to greater sensitivity to epinephrine of vasodilator [Sj-adrenoceptors than of constrictor a-adrenoceptors and a dominant action on Pz-adrenoceptors of vessels in skeletal muscle. Consequently, diastolic blood pressure usually falls. The mean blood pressure in general, however, is not greatly elevated. The compensatory barore-ceptor reflexes do not appreciably antagonize the direct cardiac actions. 

A dose of 1 at 30 mg/kg increased the effects of intravenous doses of epinephrine at 5 g/kg and of dl-noreplnephrine at 10 ug/kg on both blood flow and blood pressure. Intravenous phenoxybenzamine at 15 mg/kg plus tolazollne at 2 mg/kg prevented almost completely the actions of I on blood pressure and blood flow Intravenous reserpine at 2 mg/kg increased markedly the effects of I at 30 mg/kg on blood pressure and peripheral resistance, but converted the usual immediate, small, temporary increase in blood flow into an immediate, small, temporary decrease. These various responses would be expected from either a mild sympathomimetic amine or an inhibitor of the breakdown of endogenous catecholamines Indeed, I at 10 M, was found to inhibit the monoamlneoxldase of the rat s liver. If the dose of I used in these experiments were distributed into the same fraction of the body water as that estimated for the human body,the concentration in the plasma would be about 9 times that stated above as the effective concentration for inhibiting the mono amine oxIdase. It is possible that inhibition of monoamlneoxldase by I plays a part in inducing the effects of the oxime on blood vessels and blood pressure. It is possible also that I interferes with reuptake of catecholamines by nerve endings this possibility seems not to have been explored. 

Effects of an -selective (phenylephrine), 13-selective (isoproterenol), and nonselective (epinephrine) sympathomimetic, given as an intravenous bolus injection to a dog. Reflexes are blunted but not eliminated in this anesthetized animal. BP, blood pressure HR, heart rate. 

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. 

Top Effects of phentolamine, an a-receptor-blocking drug, on blood pressure in an anesthetized dog. Epinephrine reversal is demonstrated by tracings showing the response to epinephrine before (middle) and after (bottom) phentolamine. All drugs given intravenously. BP, blood pressure HR, heart rate. 

Presumably, vasoactive substances act upon smooth muscle cells by intimate association with them, and are destroyed in the process of stimulation or depression. Epinephrine, when injected intravenously, can be recovered in much larger amounts from arterial than from venous blood minute doses given intraarterially may affect only the local circulation. If amines formed from the incomplete catabolism of amino acids are active in hypertension, one must postulate their formation by ischemic organs in direct venous connection with the heart (kidneys, brain, liver, adrenals, etc.) or in direct arterial connection with the arteriolar bed (heart and lungs). If the former, they must not be destroyed in large amounts by the lungs. Furthermore, arterial blood could be expected to contain larger quantities than venous. Absorption from or formation in the intestinal tract or spleen of amines would not produce vascular effects, as these substances probably would be metabolized by the liver. 

Figure 11. Effect of Intravenously Injected Phenylserine, p-Hydroxyphenylserine, and /-Epinephrine on Blood Pressure of Anesthetized Dog...

Figure 12. Effect of Intravenously Injected /-Epinephrine, Dihydroxyphenylserine,...

In experimental animals the effect of ephedrine administered intravenously is similar to that of epinephrine. The arterial pressure — systolic, diastolic, and mean pressure — rises and vagal slowing occurs. Compared with epinephrine, the pressor response to ephedrine occurs somewhat more slowly and lasts about ten times longer. Furthermore, it requires more ephedrine than epinephrine to obtain an equivalent pressor response. How much more depends on the species tested, type and degree of anesthesia, dose level, and individual variability of the test animal. It is, therefore, almost impossible to give a definite figure for the relative potency of ephedrine and epinephrine. It is commonly accepted that it requires about 250 times more ephedrine than epinephrine to achieve equipressor responses. 

The effects of ephedrine are similar to those of epinephrine. However, ephedrine is much less potent, and with routes of administration other than intravenous, the glandular responses do not always occur. Ephedrine does produce hyperglycemia and eosinopenia. 

The treatment of acute attacks of asthma in patients reporting to the hospital requires more continuous assessment and repeated objective measurement of lung function. For patients with mild attacks, inhalation of a -receptor agonist is as effective as subcutaneous injection of epinephrine. Both of these treatments are more effective than intravenous administration of aminophylline. 

---