Of epinephrine

Division of the receptors in the adrenergic nervous system into two classes (a and P) was proposed in 1948 (39) when a difference in the rank order of potency of epinephrine (1, R = CH ), norephinephrine (1, R = H), and isoproterenol [7683-59-2], C H yNO, (1, R = CH(CH3)2) was noted to depend on the organ examined. Eurther subdivision into groups P2 proposed in 1967 (40). Both types of P-adrenoceptors are found throughout the... 

The action of epinephrine and related agents forms the basis of therapeutic control of smooth muscle contraction. Breathing disorders, including asthma and various allergies, can result from excessive contraction of bronchial smooth muscle tissue. Treatment with epinephrine, whether by tablets or aerosol inhalation, inhibits MLCK and relaxes bronchial muscle tissue. More specific bronchodilators, such as albuterol (see figure), act more selec-... 

Stimulation of glycogen breakdown involves consumption of molecules of ATP at three different steps in the hormone-sensitive adenylyl cyclase cascade (Figure 15.19). Note that the cascade mechanism is a means of chemical amplification, because the binding of just a few molecules of epinephrine or glucagon results in the synthesis of many molecules of cyclic / MP, which, through the action of c/ MP-dependent protein kinase, can activate many more molecules of phosphorylase kinase and even more molecules of phosphorylase. For example, an extracellular level of 10 to 10 M epinephrine prompts the for-... 

Epinephrine itself does find some use in clinical medicine. The drug is used in order to increase blood pressure in cases of circulatory collapse, and to relax the bronchial muscle in acute asthma and in anaphylactic reactions. These activities follow directly from the agent s physiologic role. The biogenetic precursor of epinephrine, norepinephrine, has activity in its own right as a mediator of sympathetic nerve action. (An apocryphal story has it that the term nor is derived from a label seen on a bottle of a key primary amine in a laboratory in Germany N ohne... 

The homolog of epinephrine in this series is a potent vasoconstrictor. Reaction of 3,4-dimethoxypropiophenone with butyl nitrite leads to nitrosation at the a position (36). Stepwise reduction of the nitrosoketone leads to the amino alcohol (37). Removal of the methyl ether affords racemic 38. Resolution of this last followed by separation of the (-) isomer gives levonor-defrine (38). ... 

Adrenergic blocking agent. A drug that blocks the effects of epinephrine and/or norepinephrine. 

Figure 11.16 The biosynthesis of epinephrine from norepinephrine occurs by an Sjyj2 reaction with S-acfenosylmethionine.

Intravenous infusion of epinephrin 0.1-0.5 mg epinephrin dissolved in plasma replacement, this can be repeated after 5 min. 

The adrenergic dragp are important in the care and treatment of patients in shock. Shock is defined as a life-threatening condition of inadequate perfusion. In shock, there is an inadequate supply of arterial blood flow and oxygen delivery to the cells and tissues. The body initiates compensatory mechanisms to counteract the symptoms of shock (eg, the release of epinephrine and norepinephrine), hi some situations, the body is able to compensate and blood pressure is maintained. However, if shock is untreated and compensatory mechanisms of the body fail, irreversible shock occurs and... 

As a protective mechanism, the corticosteroids are released during periods of stress (eg, injury or surgery). The release of epinephrine or norepinephrine by the adrenal medulla during stress has a synergistic effect along with the corticosteroids. 

An elemental analysis of epinephrine resulted in the following composition 59.0% carbon, 26.2% oxygen, 7.15% hydrogen, and 7.65% nitrogen by mass. When 0.64 g of epinephrine was dissolved in 36.0 g of benzene, the freezing point decreased by 0.50°C. (a) Determine the empirical formula of epinephrine, (b) What is the molar mass of epinephrine ... 

Effects of topically applied liposomes on disposition of epinephrine and inulin in the albino rabbit eye, Int. J. Pharm., n, 263-272. 

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]. 

The initial dose of epinephrine which is generally recommended is 0.01 mg/ kg, possibly increased to a maximum of 0.5 mg in adults and 0.3 mg in children. 

A major progress in the field is the availability of epinephrine autoinjectors which can be used by the patient him-/herself as a self-medication. Different devices are available which either trigger the injection needle just by pressure on the thigh or which have to be triggered by pressing on a button (like a pencil). The handling of these devices has to be explained and practiced with the patients (see Management, Education) [37-40]. 

Brown SG, Blackman KE, Stenlake V, Heddle RJ Insect sting anaphylaxis prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emerg Med J 2004 21 149-154. Lieberman P Use of epinephrine in the treatment of anaphylaxis. Curr Opin Allergy Clin Immunol 2003 3 313-318. 

For nearly a century, epinephrine (adrenaline) has been the cornerstone of the acute management of anaphylaxis [1-6], a sudden-onset multi-systemic allergic reaction that can cause death. The World Health Organization lists epinephrine as an essential medication for anaphylaxis [7], Where national guidelines are available for the acute management of anaphylaxis, they universally recommend injection of epinephrine as the initial medication of choice [8]. 

In this review, we will describe the pharmacologic activity of epinephrine in anaphylaxis, the evidence base for its use, epinephrine dosing and routes of administration, epinephrine autoinjector use in first-aid treatment, reasons for failure to inject epinephrine promptly, reasons for occasional apparent lack of response, and future directions in epinephrine research. 

Table 1. Pharmacologic activities of epinephrine relevant to anaphylaxis... 

Epinephrine has a narrow benefit-to-risk ratio. Along with its therapeutic effects, when administered in recommended doses by any route, it potentially causes transient anxiety, fear, restlessness, palpitations, pallor, tremor, and headache. Although usually perceived as adverse effects, such symptoms indicate that a pharmacologically active dose of the medication has been absorbed. The desirable pharmacologic effects of epinephrine cannot be separated from the undesirable pharmacologic effects [10]. 

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]. 

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