Pheochromocytoma catecholamines

G. Eisenhofer, J.W.M. Lenders, D.S. Goldstein, M. Mannelli, G. Csako, M.M. Walther, F.M. Brouwers and K. Pacak, Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines, Clin. Chem., 51, 735-744 (2005). 

The regulation of phosphorylation of tyrosine hydroxylase is affected by stimuli that increase Ca2+ or cAMP concentrations in neurons, including nerve impulse conduction and certain neurotransmitters in well-defined regions of the nervous system, in the adrenal medulla and in cultured pheochromocytoma cells. In addition, tyrosine hydroxylase phosphorylation is stimulated by nerve growth factor in certain cell types, possibly via the activation of ERKs. These changes in the phosphorylation of tyrosine hydroxylase have been shown to correlate with changes in the catalytic activity of the enzyme and in the rate of catecholamine biosynthesis. 

Recent studies have shown that cyanide releases catecholamines from rat pheochromocytoma cells and brain slices (Kanthasamy et al. 1991b), from isolated bovine adrenal glands (Borowitz et al. 1988), and from the adrenals of mice following subcutaneous injection of high doses of potassium cyanide (Kanthasamy et al. 1991b). Thus, it was proposed that the cardiac and peripheral autonomic responses to cyanide are partially mediated by an elevation of plasma catecholamines (Kanthasamy et al. 1991b). 

Colorimetric assays used in endocrinological procedures are also often subject to drug interference. We have observed an interesting interference in a patient with carcinoid. The patient excreted 400 mg of 5-hydroxyindoleacetic acid (5-HIAA) and when a vanillylmandclic acid (VMA) determination was performed by a nonspecific diazo method, the value was reported to be 375 mg. The catecholamines were just above normal. There was an immediate suggestion that the patient also had a pheochromocytoma. However, when a specific chromatographic VMA method was used, the value was found to be within normal limits. Subse-... 

It is used for treating patients with pheochromocytoma, in cases where a rise in the level of catecholamines is observed. A synonym of this dmg is demser. 

Drug/Lab test interactions Methyidopa may interfere with tests for Urinary uric acid by phosphotungstate method serum creatinine by alkaline picrate method AST by colorimetric methods. Because methyidopa causes fluorescence in urine samples at the same wavelengths as catecholamines, falsely high levels of urinary catecholamines may occur and will interfere with the diagnosis of pheochromocytoma. 

Hypersensitivity to any component of the product pheochromocytoma (because the drug may stimulate secretion of catecholamines from the tumor through its antihypertensive action) acute Ml dissecting aortic aneurysm. 

When stimulation of Gl motility might be dangerous (eg, in the presence of Gl hemorrhage, mechanical obstruction, or perforation) pheochromocytoma (the drug may cause a hypertensive crisis, probably because of release of catecholamines from the tumor control such crises with phentolamine) sensitivity or intolerance to metoclopramide epileptics or patients receiving drugs likely to cause extrapyramidal reactions (the frequency and severity of seizures or extrapyramidal reactions may be increased). 

Therapeutic uses Conditions of catecholamine excess such as pheochromocytoma Peripheral vascular disease Benign prostatic hypertrophy Same as phenoxybenzamine Primary hypertension Benign prostatic hypertrophy... 

For pharmacologic research, - and K2-adrenoceptor antagonist drugs have been very useful in the experimental exploration of autonomic nervous system function. In clinical therapeutics, nonselective antagonists are used in the treatment of pheochromocytoma (tumors that secrete catecholamines), and -selective antagonists are used in primary hypertension and... 

Pheochromocytoma is a tumor of the adrenal medulla or sympathetic ganglion cells. The tumor secretes catecholamines, especially norepinephrine and epinephrine. The patient in the case study at the beginning of the chapter had a left adrenal pheochromocytoma that was identified by imaging. In addition, she had elevated plasma and urinary norepinephrine, epinephrine, and their metabolites, normetanephrine and metanephrine. 

The major clinical use of phenoxybenzamine is in the management of pheochromocytoma. Patients have many symptoms and signs of catecholamine excess, including intermittent or sustained hypertension, headaches, palpitations, and increased sweating. 

Release of stored catecholamines from pheochromocytomas may occur in response to physical pressure, chemical stimulation, or spontaneously. When it occurs during operative manipulation of pheochromocytoma, the resulting hypertension may be controlled with cx-receptor blockade or nitroprusside. Nitroprusside is preferred because its effects can be more readily titrated... 

Phenoxybenzamine Irreversibly blocks a and Lowers blood pressure (BP) but heart rate (HR) rises due to baroreflex activation Pheochromocytoma high catecholamine states Irreversible blocker half-life > 1 day Toxicity Orthostatic hypotension tachycardia myocardial ischemia... 

The nonselective agents, phentolamine and phenoxybenzamine, are useful in diagnosis and treatment of pheochromocytoma and in other clinical situations associated with exaggerated release of catecholamines (eg, phentolamine may be combined with propranolol to treat the clonidinewithdrawal syndrome, described previously). Their pharmacology is described in Chapter 10. 

Metyrosine (Demser). Metyrosine inhibits the enzyme initiating catecholamine synthesis (epinephrine, norepinephrine) this drug is used to diminish catecholamine stores prior to removal of a catecholamine-producing tumor (pheochromocytoma). 

In contrast to phenoxybenzamine, phentolamine [fen TOLE a meen] produces a competitive block of ai and a2 receptors. The drug s action lasts for approximately 4 hours after a single administration. Like phenoxybenzamine, it produces postural hypotension and causes epinephrine reversal. Phentolamine had been used in the diagnosis of pheochromocytoma and in other clinical situations associated with excess release of catecholamines. Phentolamine-induced reflex cardiac stimulation and tachycardia are mediated by the baroreceptor reflex and by blocking the a2 receptors of the cardiac sympathetic nerves. The drug can also trigger arrhythmias and anginal pain and is contraindicated in patients with decreased coronary perfusion. 

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