indication

For management of heart failure, angina pectoris, and mild to moderate hypertension and for secondary prevention of myocardial infarction (MI).

pharmacology

Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist. Activation of β1-receptors (located mainly in the heart) by epinephrine increases heart rate and the blood pressure causing the heart to consume more oxygen. β1-adrenergic blocking agents such as bisopolol lower the heart rate and blood pressure and may be used to reduce workload on the heart and hence oxygen demands. They are routinely prescribed in patients with ischemic heart disease. In addition, β1-selective blockers prevent the release of renin, a hormone produced by the kidneys causes constriction of blood vessels. Bisoprolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane-stabilizing activity.

mechanism of action

Bisoprolol selectively blocks catecholamine stimulation of β1-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. At higher doses (e.g. 20 mg and greater) bisoprolol may competitively block β2-adrenergic receptors in bronchial and vascular smooth muscle causing bronchospasm and vasodilation.

toxicity

Oral, mouse: LD₅₀ = 100 mg/kg; Skin, rabbit: LD₅₀ = 200 mg/kg; Skin, rat: LD₅₀ = 500 mg/kg. Symptoms of overdose include congestive heart failure (marked by sudden weight gain, swelling of the legs, feet, and ankles, fatigue, and shortness of breath), difficult or labored breathing, low blood pressure, low blood sugar, and slow heartbeat.

biotransformation

Approximately 50% of the dose is metabolized primarily metabolized by CYP3A4 to inactive metabolites. In vitro studies have shown that bisoprolol is also metabolized by CYP2D6 though this does not appear to be clinically significant. Approximately half the administered dose is excreted in unchanged in urine.

absorption

Well absorbed. Bioavailability > 80%. Absorption is not affected by food. Peak plasma concentrations occur within 2-4 hours.

half life

9-12 hours; prolonged in the elderly and those with decreased renal function

route of elimination

Eliminated equally by renal and non-renal pathways. Approximately 50% of the total orally administered dose is excreted unchanged in urine with the remainder appearing as inactive metabolites. Less than 2% of the dose is excreted in the feces.

drug interactions

Acetohexamide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Chlorpropamide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene

Dihydroergotoxine: Ischemia with risk of gangrene

Disopyramide: The beta-blocker, bisoprolol, may increase the toxicity of disopyramide.

Epinephrine: Hypertension, then bradycardia

Ergonovine: Ischemia with risk of gangrene

Ergotamine: Ischemia with risk of gangrene

Fenoterol: Antagonism

Formoterol: Antagonism

Gliclazide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Glipizide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Glisoxepide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Glycodiazine: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Ibuprofen: Risk of inhibition of renal prostaglandins

Indomethacin: Risk of inhibition of renal prostaglandins

Insulin Aspart: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Insulin Detemir: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Insulin Glargine: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Insulin Glulisine: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Insulin Lispro: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Isoproterenol: Antagonism

Lidocaine: The beta-blocker, bisoprolol, may increase the effect and toxicity of lidocaine.

Methysergide: Ischemia with risk of gangrene

Orciprenaline: Antagonism

Pipobroman: Antagonism

Pirbuterol: Antagonism

Piroxicam: Risk of inhibition of renal prostaglandins

Prazosin: Risk of hypotension at the beginning of therapy

Procaterol: Antagonism

Repaglinide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Rifampin: Rifampin may decrease the serum concentration of bisprolol by increasing its metabolism.

Salbutamol: Antagonism

Salmeterol: Antagonism

Telithromycin: Telithromycin may reduce clearance of Bisoprolol. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Bisoprolol if Telithromycin is initiated, discontinued or dose changed.

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbutaline: Antagonism

Tolazamide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Tolbutamide: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Verapamil: Increased effect of both drugs

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of bisoprolol by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bisoprolol if voriconazole is initiated, discontinued or dose changed.