Urine epinephrine

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. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

Tyrosine (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

The initial report of sustained, lower urinary cortisol levels in PTSD highlighted the disassociation between cortisol and catecholamine levels in PTSD. Norepinephrine and epinephrine levels assayed from the same urine specimens revealed elevations in both of these catecholamines, while cortisol levels in PTSD fell within the normal range of 20-90 pg/day, indicating that the alteration was not in the hypoadrenal or endocrinopathologic range (Mason et al. 1986). This finding established the expectation that alterations in basal levels of cortisol might be subtle, and not easily differentiated from normal values (Mason et al. 1986). 

Although either COMT or MAO may act first on circulating norepinephrine or epinephrine, COMT is the more rapidly acting enzyme, and therefore more molecules are 0-methylated and then deaminated than the reverse. Some norepinephrine and epinephrine appear unchanged in the urine. The larger portion, however, is metabolized and the products of metabolism excreted in the urine, often as conjugates. 

Measurements of norepinephrine, epinephrine, and their metabolites in the urine constitute valuable diagnostic aids, particularly in the detection of tumors that synthesize and secrete norepinephrine and epinephrine (e.g., pheochromocytoma). 

The detrusor muscle (which contains (32-adrenoceptors) in the body of the urinary bladder is relaxed by epinephrine and isoproterenol. On the other hand, the trigone and sphincter (which contain aj-receptors) are contracted by norepinephrine and epinephrine this action inhibits the voiding of urine. 

Norepinephrine and epinephrine can be metabolized by several enzymes, as shown in Figure 6-6. Because of the high activity of monoamine oxidase in the mitochondria of the nerve terminal, there is significant turnover of norepinephrine even in the resting terminal. Since the metabolic products are excreted in the urine, an estimate of catecholamine turnover can be obtained from laboratory analysis of total metabolites (sometimes... 

Lei et al. and Nie et al. [110, 111] have reported two assays for indapamide and indomethacin, respectively, also based on luminol as chemiluminescent reagent. Again MAA and EGDMA were used as monomers and acetonitrile as porogen. Excellent detection limits were achieved 10 x M for indapamide and indomethacin in urine and 10-9 M for epinephrine in serum. The authors describe the crossreactivity for other contaminants potentially present in urine such as antibiotics (norfloxacin), ions (Fe2+, Ca2+, K+), or glucose. 

Four substances have been described as having pressor effects, which are probably amines or aminelike. Urosympathin, described by Holtz, Credner, and Kronberg (34), is a substance found in normal urine in amounts per day, giving a pressor response equal to 2 to 3 mg. of hydroxytyramine or 100 to 150 micrograms of epinephrine or arterenol. In cases of essential hypertension the amount is said to be increased three- to fourfold. Because its action was intensified by cocaine and lessened by ergotoxin and yohimbine, they believed that it represented a mixture of hydroxytyramine, epinephrine, and arterenol. The material was recovered by lead acetate precipitation of urine with subsequent acid hydrolysis. 

Ephedrine is readily and completely absorbed after oral or parenteral administration. As it is less active than epinephrine, it does not produce enough local vasoconstriction to hinder absorption after subcutaneous or intramuscular injection. As has been indicated, ephedrine is resistant to amine oxidase, but it is deaminated to some extent in the liver, probably by the ascorbic-dehydroascorbic acid system. Conjugation also occurs. In addition, up to 40% of the ephedrine administered may be excreted unchanged in the urine. Inactivation and excretion are so slow that the action of ephedrine may persist for several hours. 

The metabolism of epinephrine has received special attention lately. Older experiments had indicated that a large part of dexZro-epinephrine is excreted in a combined form after a large dose, and, since the ester sulfate fraction of the urine was elevated, it was assumed that this indicated sulfate conjugation of otherwise-unchanged epinephrine.234 Deichmann236 claimed that the only conjugate of Zero-epinephrine excreted by the rabbit is a sulfate, since he found that Zero-epinephrine increases the ratio of... 

Schayer236 has recently studied the metabolism of epinephrine containing isotopic carbon. di-i8-Epinephrine-C14 fed to rats gave rise to the excretion of a conjugated, ether-soluble product containing radioactivity, but, after subcutaneous injection of methyl-di-epinephrine-C14, no activity was found in the ether-soluble fraction of urine. 

Biotransformations Epinephrine, like the other catecholamines, is metabolized by two enzymatic pathways COMT, which has S-adenosylmethionine as a cofactor, and MAO (see Figure 6.3). The final metabolites found in the urine are metanephrine and vanillylmandelic acid. [Note Urine also contains normeta-nephrine, a product of norepinephrine metabolism.]... 

Pharmacokinetics Epinephrine has a rapid onset but brief duration of action. In emergency situations epinephrine is given intravenously for the most rapid onset of action it may also be given subcutaneously, by endotracheal tube, by inhalation, or topically to the eye. Oral administration is ineffective, since epinephrine and the other catecholamines are inactivated by intestinal enzymes. Only metabolites are excreted in the urine. 

Four catecholamines have been found in increased amounts in the urine after injury (W2), metanephrine, normetanephrine, iV-methyl-metanephrine, and 3-methoxytyramine. The JV-methylmetanephrine probably indicates an increased production of epinephrine (Cll). The increase in norepinephrine production is relatively greater than that of epinephrine, suggesting an active release of hormone from sympathetic nerve tissue as well as from the adrenal medulla. 

Benzoyl peroxide, the active ingredient in some shampoos for dogs, is almost completely metabolized to benzoic acid in the epidermis. Benzoic acid undergoes conjugation with glycine, primarily in the liver, and is excreted in urine as hippuric acid. Methylation of norepinephrine to epinephrine, an A-transferase-mediated conjugation reaction, in human and animal skin preparations has been reported. ... 

I, fluorescence intensity of 1.5 ml of treated urine to which 0.25 /ig of epinephrine standard had been added... 

Quinuronium sulfate is a bitter, white to yellow, crystalline powder that is usually available as a stable 5% aqueous solution. This compound is effective in the treatment of B. caballi infections but is associated with relapses, making it more effective for premunition than for the elimination of infection. One treatment consists of two doses of a 5% solution of quinuronium sulfate, administered s.c. at 0.3mg/kg, 6h apart. Quinuronium sulfate has a narrow margin of safety and overdosing produces parasympathomimetic effects including tremors, salivation, urination and defecation. These signs usually respond to treatment with atropine, epinephrine (adrenaline) and calcium gluconate. The interval between treatments should not be shorter than 2 weeks and should preferably be 3 months because sensitization occurs, which results in shock, with a profound drop in blood pressure, and death. 

In the non-exercising horse, increased blood lactate concentrations are sufficient evidence of a metabolic disturbance to initiate fluid therapy. They are an indication of poor tissue perfusion or increased circulating epinephrine (adrenaline) concentrations (James et al 1999). Hypovolemia and endotoxemia are common causes of increased lactate concentrations in the horse. Endotoxemia increases tissue lactate production both through circulatory changes, which reduce blood flow to the tissues and inappropriate anaerobic metabolism (Fink 1997). Whereas lactate is a good indicator of the need to start fluid therapy, continued high lactate concentrations should be assessed in the context of cardiovascular parameters, such as pulse rate, urine output and blood pressure, because decreases in plasma lactate concentration... 

The primary metabolites of dopamine are homovanillic acid and dihydroxyphenylacetic acid (75%) and norepinephrine (25%). The primary metabolites of epinephrine and norepinephrine are vanilylmandelic acid and 3-methoxy-4-hydroxy-phenethyleneglycol. Catecholamine metabolites and their conjugates are excreted in urine. 

Peripheral Dopaminergic System Dopamine is usually thought of as a neurotransmitter in the brain or as an intermediate in the production of norepinephrine and epinephrine in the periphery. It has been presumed tliat these sources account for the large amounts of dopamine and dopamine metabolites excreted in urine. The contribution of the brain to circulating levels and urinary excretion of dopamine metabolites is, however, now known to be relatively minor. Also, in sympathetic nerves and the adrenal medulla most dopamine is converted to norepinephrine. Therefore other sources and functions of dopamine in the periphery must be considered. Emerging evidence suggests the presence of a third peripheral catecholamine system, in which dopamine functions not as a neurotransmitter or circulating hormone, but as an autocrine or paracrine substance. ... 

Earlier fluorometric methods for analysis of urinary free catecholamines have been replaced by HPLC methods that allow selective quantitation of epinephrine, norepinephrine, and dopamine. Preliminary extraction of urine is stid required and numerous preanalytical cleanup techniques are available. An alumina extraction procedure is typically coupled with ion-exchange or adsorption chromatography. Alumina pretreatment usually involves a batch extraction technique in which catechols are first adsorbed at pH 8.6 and then eluted with boric acid, which forms a complex with cis-diol groups. Purification on boric acid affinity gels provides an alternative procedure for selective adsorption of catecholamines. 

Normetanephrine andmetanephrine are metabolic products of norepinephrine and epinephrine, respectively, and are formed by the action of catechol-0-methyltransferase without deamination. As a result of active neuronal reuptake and deamination of norepinephrine, normetanephrine normally represents <5% of the total norepinephrine excretion products in urine. Metanephrine, however, even with its lower urinary concentration relative to normetanephrine, represents a major excretion product of epinephrine. The metanephrines are excreted in both conjugated and unconjugated forms. Unlike the catecholamines, total metanephrine excretion is not significantly influenced by diet. As a result, the total metanephrines are routinely measured after acid hydrolysis or sulfatase pretreatment. 

Vanillylmandehc Acid (VMAj is a major catecholamine metabolite formed by the actions of catechol-0-methyl-transferase and MAO. It is excreted by the kidney and represents an average of 40% to 50% of the urinary excretion production of norepinephrine and epinephrine. Norepinephrine is the major source of VMA, with metabolism through MHPG as the major pathway. VA4A is not significantly conjugated and therefore is measured without a hydrolysis step. VMA was first isolated and identified in the urine of a patient with a pheochromocytoma, and its analysis is commonly performed to detect the presence of pheochromocytomas and neuroblastomas. 

Using the mouse ear epidermis in vitro as an assay system and counting mitoses arrested by Colcemid in the medium over a 4-hour period, the same workers showed that the epidermal chalone is not species specific, but is tissue specific (B49, B52) that it requires epinephrine for effect (B48), and perhaps glucocorticoids (B50) and that it is most likely a glycoprotein with a molecular weight of about 30,000 (B25). This work has been recently reviewed and the additional comment made that epidermal chalone is present in active form in human urine (B45). 

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