Drug Interactions between bisoprolol / hydrochlorothiazide and Simuc-HD

MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting diuretics.

MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is recommended during coadministration. Patients should be advised to seek medical assistance if they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control.

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MONITOR: A case report suggests that beta-blockers may enhance the pressor response to phenylephrine. The proposed mechanism involves blockade of beta-2 adrenergic receptors in the peripheral vasculature, resulting in unopposed alpha-adrenergic effect of phenylephrine that is responsible for vasoconstriction. Additionally, beta-blockers may desensitize baroreceptors that normally modulate heart rate in response to blood pressure elevations by increasing vagal activity on the sinoauricular node. In the case report, a woman with a history of hypertension treated with hydrochlorothiazide (50 mg twice a day) and propranolol (40 mg four times a day) developed sudden bitemporal pain and became unconscious shortly after she was given one drop of a 10% phenylephrine solution in each eye during an ophthalmic examination. She subsequently died of intracerebral hemorrhage due to rupture of a berry aneurysm. The authors noted that the patient had received the same eye drop without incident on two previous occasions when she was not receiving blood pressure or other medications. Nevertheless, an interaction between phenylephrine and beta-blockers is not well established. Phenylephrine acts predominantly on alpha-adrenergic receptors and has little or no direct effect on beta-2 adrenergic receptors, although it may affect them indirectly by enhancing release of norepinephrine from adrenergic nerve terminals. In a study of 12 patients with hypertension, mean phenylephrine doses required to increase systolic blood pressure by 25 mmHg were not significantly different following 2 weeks on propranolol, metoprolol, and placebo (4.8 mcg/kg, 4.7 mcg/kg, and 5.3 mcg/kg, respectively). Baroreceptor-mediated decreases in heart rate during phenylephrine infusion were also in the same range on propranolol, metoprolol, and placebo over baseline heart rate values. In another study, no changes in blood pressure or heart rate were observed in hypertensive patients treated with metoprolol who were given 0.5 to 4 mg doses of phenylephrine intranasally every hour up to a total of 7.5 to 15 mg, or 4 to 30 times the usual recommended dose, compared to placebo or baseline values. These results support the lack of a significant interaction between beta-blockers and phenylephrine.

MANAGEMENT: Until more information is available, caution should be exercised when phenylephrine is used in combination with beta-blockers including ophthalmic formulations, which may be systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels. Monitoring of blood pressure should be considered, particularly when phenylephrine is administered intravenously or intraocularly. Although an interaction is not likely to occur with cardioselective beta-blockers, caution may be advisable when high dosages are used, since cardioselectivity is not absolute and may be lost with larger doses. A beta-blocker such as propranolol may be used to treat cardiac arrhythmias that occur during administration of phenylephrine.

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MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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