Drug Interactions between chlorothiazide / reserpine and Nalgest

MONITOR: The hypotensive effects of thiazide diuretics and alpha-adrenergic blockers may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Patients should be advised to take the alpha-blocker at bedtime and to notify their physician if they experience dizziness or syncope while awake.

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MONITOR: Sympathomimetic amines may decrease the hypotensive effect of postganglionic adrenergic blocking agents, while the latter may potentiate the pharmacologic effects of direct-acting sympathomimetic amines (e.g., dobutamine, epinephrine, methoxamine, norepinephrine) but inhibit those that are primarily indirect-acting (e.g., mephentermine). Postganglionic adrenergic blocking agents such as guanadrel, guanethidine, and rauwolfia alkaloids work by depleting catecholamine stores from adrenergic nerve endings. Therefore, they may sensitize adrenergic receptors to direct-acting sympathomimetics, but blunt the effects of indirect-acting agents whose activity is mediated through the release of catecholamines. Guanethidine and reserpine have been reported to attenuate the pharmacologic effects (mydriasis, pressor response) induced by ephedrine and dopamine, both of which exhibit direct and indirect sympathomimetic activities (i.e., mixed-acting). However, guanethidine intensified the mydriasis produced by phenylephrine, which is also thought to be mixed-acting. Conversely, ephedrine has been shown to partially reverse the hypotensive effect of guanethidine.

MANAGEMENT: Due to their pressor effect, sympathomimetic amines should be used cautiously in patients with hypertension. Alternatives to postganglionic adrenergic blocking agents should be considered if patients are treated with sympathomimetic amines, since effects of the latter may be intensified or diminished depending on whether they are direct- or indirect-acting. Most agents with indirect sympathomimetic activity are mixed-acting, thus it may be difficult to predict how they will be affected by postganglionic adrenergic blocking agents. If the combination is used, blood pressure and heart rate should be monitored.

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MONITOR: Sympathomimetic amines may decrease the hypotensive effect of postganglionic adrenergic blocking agents, while the latter may potentiate the pharmacologic effects of direct-acting sympathomimetic amines (e.g., dobutamine, epinephrine, methoxamine, norepinephrine) but inhibit those that are primarily indirect-acting (e.g., mephentermine). Postganglionic adrenergic blocking agents such as guanadrel, guanethidine, and rauwolfia alkaloids work by depleting catecholamine stores from adrenergic nerve endings. Therefore, they may sensitize adrenergic receptors to direct-acting sympathomimetics, but blunt the effects of indirect-acting agents whose activity is mediated through the release of catecholamines. Guanethidine and reserpine have been reported to attenuate the pharmacologic effects (mydriasis, pressor response) induced by ephedrine and dopamine, both of which exhibit direct and indirect sympathomimetic activities (i.e., mixed-acting). However, guanethidine intensified the mydriasis produced by phenylephrine, which is also thought to be mixed-acting. Conversely, ephedrine has been shown to partially reverse the hypotensive effect of guanethidine.

MANAGEMENT: Due to their pressor effect, sympathomimetic amines should be used cautiously in patients with hypertension. Alternatives to postganglionic adrenergic blocking agents should be considered if patients are treated with sympathomimetic amines, since effects of the latter may be intensified or diminished depending on whether they are direct- or indirect-acting. Most agents with indirect sympathomimetic activity are mixed-acting, thus it may be difficult to predict how they will be affected by postganglionic adrenergic blocking agents. If the combination is used, blood pressure and heart rate should be monitored.

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MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

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MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

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