Adrenaline metabolic effects

Table 11.1 Some metabolic effects of insulin. These effects are generally countered by other hormones (glucagon and, in some cases, adrenaline). Hence, the overall effect noted often reflects the relative rates of these hormones present in the plasma...

While the inhibition of noradrenaline re-uptake exerts predominantly an a-adrenergic effect, a selective jS-adrenergic effect can not be obtained by such an indirect mechanism. All selective /3-sympathomi-metics activate the receptors, P -, P2- or both sub-types, directly. The first pure jS-sympathomimetic in clinical use was isoproterenol which is structurally identical to adrenaline except the methyl-moiety at the N-position in the side-chain is replaced by an isopropyl-group. All effects produced by isoproterenol are due to either P -or 62-adrenoceptor stimulation tachycardia, increased stroke volume, decreased vascular resistance, broncho dilatation and, in pregnancy, uterus relaxation. The metabolic effects of isoproterenol are less pronounced than those of adrenaline. 

Alpha blockers also produce certain metabolic effects such as inhibitory action of adrenaline on insulin secretion is blocked and adrenaline induced rise in blood potassium level is also blocked. 

Various hormonal and metabolic effects of aldesleukin are temporally related to hypotension. Transient serum rises in ACTH, cortisol, beta-endorphin, adrenaline and noradrenaline have been found, whereas there were no significant changes in the plasma concentrations of several other hormones (4). 

Sandor (SI) has investigated the effect of adrenaline on plasma proteins in the guinea pig. He found a rapid lowering of plasma albumin, with a frequent concomitant increase in -globulin levels. Although stimulation of ACTH may be involved he believes this to be largely a direct metabolic effect of the injected adrenaline. 

Table 43.1 Summary of main metabolic effects of insulin, glucagon and adrenaline...

Intravenous infusions of 0-3-2-0 /ig per 100 g body weight per minute of noradrenaline increased respiratory metabolism in rats (Hannon and Larson (1821). Ankermann 1822)) g uer and Lembeck found after subcutaneous injections of 30, 60, or 120 fig noradrenaline per 100 g body weight— metabolic increases of about the same degree as after adrenaline the effect of noradrenaline occurred more quickly, but that of adrenaline lasted longer. ... 

Our data do not permit us to know whether this metabolic effect of adrenalin is direct or mediated, for example by an induction of hyperfibrinolysis. 

Murmann, W., Rumore, G. and Gamba, A. (1967) Pharmacological properties of l-(4 -nitrophenyl)-2-isopropylamino-ethanol (INPEA), a new beta-adrenergic receptor antagonist. V. Effects of the optical isomers D(minus) and L(plus) INPEA on heart rate, oxygen consumption and body temperature and on the cardiac and metabolic effects of adrenaline and noradrenaline in urethane-anesthetized rats. Boll. Chim. Farm., 106, 251-268. 

In the ebb phase, there is increased activity of the sympathetic nervous system and increased plasma levels of adrenaline and glucocorticoids but a decreased level of insulin. This results in mobilisation of glycogen in the liver and triacylglycerol in adipose tissue, so that the levels of two major fuels in the blood, glucose and long-chain fatty acids, are increased. This is, effectively, the stress response to trauma. These changes continue and are extended into the flow phase as the immune cells are activated and secrete the proinflammatory cytokines that further stimulate the mobilisation of fuel stores (Table 18.2). Thus the sequence is trauma increased endocrine hormone levels increased immune response increased levels of cytokines metabolic responses. 

The hormones of adrenal glands, thyroid and pancreas exert various effects on the metabolism of drugs. Adrenalectomy of certain species e.g. rat impairs the metabolism of certain drugs, which can be reversed by administration of cortisone or prednisolone. Administration of ACTH, adrenaline or thyroxine impairs the hepatic microsomal metabolism of drugs. Thyroidectomy reduces the... 

Heart Direct effects on the heart are determined largely by receptors. Adrenaline increases the heart rate, force of myocardial contraction and cardiac output which is associated with increased metabolism by the myocardium, increased oxygen consumption and thus decreasing cardiac efficiency. 

Monoamine oxidase inhibitors (MAOIs), which were amongst the first antidepressant drugs to be used clinically. They affect one or both of the brain monoamine oxidase enzymes that play a role in the metabolism of serotonin, noradrenaline, dopamine and adrenaline. MAOIs inhibit breakdown of the neurotransmitters important in determining mood, which results in the antidepressant effect. 

LIDOCAINE BETA-BLOCKERS 1. Risk of bradycardia (occasionally severe), l BP and heart failure with intravenous lidocaine 2. Risk of lidocaine toxicity due to T plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. t plasma concentrations of propranolol and possibly some other beta-blockers 1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced 1 hepatic blood flow (due to 1 cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine 1. Monitor PR, BP and ECG closely watch for development of heart failure when intravenous lidocaine is administered to patients on beta-blockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Beta-blockers could cause dangerous hypertension due to stimulation of alpha-receptors if adrenaline is used with local anaesthetic... 

Catecholamines (adrenaline, noradrenaline, dopamine, dobutamine, isoprenaline) (plasma approx. 2 min) are metabolised by two enzymes, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). These enzymes are present in large amounts in the liver and kidney and account for most of the metabolism of injected catecholamines. MAO is also present in the intestinal mucosa (and in nerve endings, peripheral and central). Because of these enzymes catecholamines are ineffective when swallowed, but noncatecholamines, e.g. salbutamol, amphetamine, are effective orally. 

L-Tyrosine metabolism and catecholamine biosynthesis occur laigely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andUpid metabolism. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bile acids and the detoxification process of aromatic drugs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabolism related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Since adrenaline is so short acting, the metabolic and other adrenergic effects which it can produce are unlikely to be elicited unless a depot formulation is used in the latter event, hyperglycemia may occur. 

Ginsenoside Rgi had no effect on arachidonate metabolism, but it did reduce the elevation of cytosolic free calcium concentration [Ca2+]i shown in the second phase (Ca2+ influx) induced by adrenaline and thrombin "Fig. (37)". The results suggest that ginsenoside Rgl in red ginseng roots may be effective as a drug for the treatment of arteriosclerosis and thrombosis. 

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