Epinephrine metabolic effects

TABLE 23-6 Physiological and Metabolic Effects of Epinephrine Preparation for Action... 

Kidney decreases glomerular filtration rate Lung, intestine, genital system inhibited Metabolic effects, weak epinephrine effect... 

Adrenal medulla Epinephrine, Norepinephrine Vascular and metabolic effects that facilitate increased physical activity... 

The metabolic effects of epinephrine are important during injury. Epinephrine can activate purine metabolism and may contribute to the increased excretion of nitrogen after injury (G9). Epinephrine and norepinephrine promote chemical thermogenesis after injury and thus will contribute to the increased metabolic expenditure of the injury period (S7). Epinephrine will also cause an acute lowering of the plasma albumin with a rise in the a-globulin fraction probably due to the effect on ACTH secretion. 

Epinephrine Tyr Adrenal medulla Minor Cardiovascular and metabolic effects (via a- and /3-adrenergic receptors). 

Unlike glucagon, the catecholamines have short-lived metabolic effects. Epinephrine action on skeletal and heart muscle cells is a crucial part of the "fight or flight" response. 

The actions of epinephrine and norepinephrine in the liver, the adipocyte, the skeletal muscle cell, and the a and 3 cells of the pancreas direcdy influence fuel metabolism (Fig. 43.6). These catecholamines are counterregulatory hormones that have metabolic effects directed toward mobilization of fuels from their storage sites for oxidation by cells to meet the increased energy requirements of acute and chronic stress. They simultaneously suppress insulin secretion, which ensures that fuel fluxes will continue in the direction of fuel utilization rather than storage as long as the stressful stimulus persists. 

D. Monoamine oxidase inhibitors may enhance pressor effects because of decreased neuronal epinephrine metabolism. 

BENEDETTI, A. and KOLB, F. 0. (1966) Metabolic effects of glucagon and epinephrine in four adults vith type I glycogen storage disease. Diabetes, 15, 529. 

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

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. 

Vasopressin is a potent vasoconstrictor that increases blood pressure and systemic vascular resistance. It may have several advantages over epinephrine. First, the metabolic acidosis that frequently accompanies cardiopulmonary arrest can blunt the vasoconstrictive effect of epinephrine this does not occur with vasopressin. Second, stimulation of P receptors by epinephrine can increase myocardial oxygen demand and complicate the postresuscitative phase of CPR. Vasopressin can also have a beneficial effect on renal blood flow in the kidney, causing vasodilation and increased water reabsorption. 

Sutherland, E.W. (1952). The effects of epinephrine and the hyperglycemic factor on liver and muscle metabolism in vitro. In Phosphorus Metabolism. (McElroy, W.D. Glass, B., Eds.), Vol. 2, pp. 577-593. The Johns Hopkins Press, Baltimore. 

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 . 

Procaine hydrochloride Novocain) is readily hydrolyzed by plasma cholinesterase, although hepatic metabolism also occurs. It is not effective topically but is employed for infiltration, nerve block, and spinal anesthesia. It has a relatively slow onset and short (1 hour) duration of action. All concentrations can be combined with epinephrine. It is available in dental cartridges with phenylephrine as the vasoconstrictor. 

Corticosteroids also affect adrenomeduUary function by increasing epinephrine production the mechanism is exertion of a stimulatory action on two of the enzymes that regulate catecholamine synthesis, tyrosine hydroxylase, the rate-Umiting enzyme, and phenyl-ethanolamine Af-methyltransferase, which catalyzes the conversion of norepinephrine to epinephrine. Steroids also influence the metabolism of circulating catecholamines by inhibiting their uptake from the circulation by noimeuronal tissues (i.e., extraneuronal uptake see Chapter 9). This effect of corticoids may explain their permissive action in potentiating the hemodynamic effects of circulating catecholamines. 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

Local anesthetics are frequently coadministered with vasoconstrictor molecules such as epinephrine. Normally, they are applied or injected locally and then taken up by local blood vessels into the systemic circulation, ultimately leading to their metabolic breakdown. The co-administration of a vasoconstrictor decreases the systemic absorption of the local anesthetic, thereby increasing its effective half-life in the area of administration and decreasing the probability of systemic toxicity (i.e., cardiac toxicity) secondary to systemic distribution. 

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