Catecholamine crisis

Two important pathways for catecholamine metaboHsm are 0-methylation by COMT, which is cytoplasmicaHy localized, and oxidative deamination by the mitochondrial localized enzyme MAO. There are large amounts of MAO in tissues such as the fiver and the heart which are responsible for the removal of most of the circulating monoamine, including some taken in from the diet. Tyramine is found in high concentrations in certain foods such as cheese, and in wine. Normally, this tyramine is deaminated in the fiver. However, if MAO is inhibited, the tyramine may then be converted into octopamine [104-14-37] which may indirecdy cause release of NE from nerve terminals to cause hypertensive crisis. Thus MAO, which is relatively nonspecific, plays an important role in the detoxification of pharmacologically active amines ingested from the diet. 

The answer is b. (Hardmanr p 444.) This patient ate tyramine-rich foods while taking an MAOI and went into hypertensive crisis. Tyramine causes release of stored catecholamines from presynaptic terminals, which can cause hypertension, headache, tachycardia, cardiac arrhythmias, nausea, and stroke. In patients who do not take MAOls, tyramine is inactivated in the gut by MAO, and patients taking MAOls must be warned about the dangers of eating tyramine-rich foods. 

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). 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

Correct answer = D. MAO inhibitors and aspirin can be taken concurrently. Hypertensive crisis may result from use (concurrently or within 2 weeks) of MAO inhibitors and indirect sympathomimetic amines, such as ephedrine. Concomitant use of MAO inhibitors and tricyclic antidepressants may result in mutual enhancement of effects with the possibility of hyperpyrexia, hypertension, seizures and death. Tyramine-containing foods, such as aged cheeses and beer, may precipitate a hypertensive crisis because of the accumulation and release of stored catecholamines from nerve endings. MAO inhibitors may lead to an exaggerated response to dopamine. 

Hansson L, Hunyor SN, Julius S, Hoobler SW. Blood pressure crisis following withdrawal of clonidine (Catapres, Catapresan), with special reference to arterial and urinary catecholamine levels, and suggestions for acute management. Am Heart J 1973 85(5) 605-10. 

E.A.M. Gerlo and C. Sevens, Urinary and plasma catecholamines and urinary catecholamine metabolites in pheochromocytoma diagnostic value in 19 cases, Clin. Chem.. 40, 250-256 (1994). T. Jan, B.E. Metzger and G. Baumann, Epinephrine-producing pheochromocytoma with hypertensive crisis after corticotrophin injection. Am. J. Med.. 89, 824-825 (1990). 

The antihypertensive effects of guanethidine may be partially or totally reversed by the mixed-acting sympathomi-metics. Halogenated hydrocarbon anesthetics may sensitize the myocardium to the effects of catecholamines. Use of vasopressors may lead to serious arrhythmias. MAO inhibitors, such as tranylcypromine, increase the pressor response to mixed-acting vasopressors. Possible hypertensive crisis and intracranial hemorrhage may occur. This interaction may also occur with furazolidone, an antimicrobial with MAO inhibitor activity. In obstetrics, if vasopressor drugs are used either to correct hypotension or are added to the local anesthetic solution, some oxytocics may cause severe persistent hypertension in the presence of mephenteramine. The pressor response of mephenteramine may be attenuated by tricyclic antidepressants, which block the uptake of norepinephrine. 

Use of tricyclics in the presence of catecholamine-secreting tumors of the adrenal medulla (e.g., pheochromocytoma, neuroblastoma), may precipitate a hypertensive crisis, due to the increase in catecholamine production in the face of decreased adrenergic reuptake. 

Administration of a catechol-O-methyltransferase (COMT) inhibitor in conjunction with a drug that increases catecholamine levels would dramatically increase levels of catecholamines, leading to a hypertensive crisis, cardiac insufficiency, and possibly death. 

The decrease in circulating catecholamines due to prolonged clonidine administration mediates a supersensitivity of receptors. When clonidine therapy is abruptly withdrawn, catecholamine levels rebound, reflex activity overcompensates, and this, combined with the supersensitivity of receptors, produces an exaggerated response to stimulation and a dramatic increase in blood pressure. A hypertensive crisis may ensue within 12 to 24 hours after drug withdrawal. 

The most significant drug interaction limiting the efficacy of the nonselective MAOIs is with certain foods that have the potential to cause hypertensive crisis because of the release and potentiation of catecholamines. The severity and consequences of such interactions vary among individuals from only minor increases in blood pressure to substantial and rapid increases in blood pressure within 20 minutes. These patients may experience symptoms associated with brain hemorrhage or cardiac failure. 

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