Which would a nurse identify as a contraindication for the use of a beta 1 selective blocker?

Continuing Education Activity

Bisoprolol is a medication used in the management and treatment of hypertension and congestive heart failure. It is in the selective beta-blocker class of drugs. This activity illustrates the indications, action, and contraindications for bisoprolol as a valuable agent in managing hypertension and other disorders when applicable. Further, the training will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for interprofessional team members in the treatment of patients with hypertension and related conditions.

Objectives:

• Identify the mechanism of action of bisoprolol.
• Describe the adverse effects of bisoprolol.
• Explain the appropriate monitoring of patients using bisoprolol.
• Review interprofessional team strategies for improving care coordination and communication to advance bisoprolol use and improve outcomes.

Indications

Bisoprolol is a cardioselective Beta1-blocker (B1-blocker). Selective B1-blockers are used to treat multiple heart diseases such as congestive heart failure without having the unwanted effect of the B2 receptor blocking, which can affect various systems in the body.[1]

• It is FDA approved for treating hypertension, post, or recent myocardial infarction (MI). It correlates with decreased morbidity and mortality post-MI.[2]
• Bisoprolol is used in the treatment plan of compensated heart failure. It reduces the risk of stroke and coronary artery diseases in patients with heart diseases.[3]
• Selective B1- blockers are used as the first-line treatment for chronic stable angina.[4]
• Other non-FDA-approved uses of bisoprolol include the treatment of migraine, tremor, arrhythmia, and use as an anxiolytic for some athletes and musicians.[5][6]

Mechanism of Action

Selective B1 blocker drugs have a negative inotropic and chronotropic effect; they decrease the heart contractions and heart rate. As a net result, bisoprolol reduces the oxygen consumption of myocardial cells. B1 receptors are also present in the juxtaglomerular cells. By blocking these receptors, bisoprolol leads to a decrease in the release of renin; as a result, it blocks the activation of the renin-angiotensin system.[7]

B1 adrenergic receptors are present in cardiac myocyte cells and juxtaglomerular cells. They couple with the G-stimulatory protein receptor (Gs receptor) and become stimulated by either norepinephrine or circulating catecholamine. Activation of B1 receptors in cardiac myocytes leads to positive chronotropic and inotropic effects; therefore, the net result will be increased heart rate, contraction, and the strength of myocyte contraction by activating Gs receptors (by the exchange of GTP to GDP). Eventually, it increases intracellular calcium concentration and promotes heart cell contraction.[8][9][10]

Activation of B1 receptors on juxtaglomerular cells leads to the activation of the renin-angiotensin system. Renin's release, therefore, increases the production of angiotensin I, which is eventually converted by angiotensin-converting enzyme (ACE) to angiotensin II.

B2 receptors occur in multiple organs of the body and are activated by epinephrine, leading to different manifestations according to the location involved. In peripheral vessels, it causes vasodilation and decreases peripheral resistance, opposing the effect of alpha-1 receptors, which cause vasoconstriction on the peripheral vessels. On the bronchioles, it leads to extensive bronchodilation. In addition, B2 receptor activation in the liver and the muscles activates glycogenolysis and increases glucagon release, increasing the blood sugar level.

Non-selective beta-blocker drugs block both the B1 receptor and B2 receptors, decreasing cardiac output and decreasing renin release from the kidney. And B2 receptor blockage leads to additional manifestations—vasoconstriction of the peripheral vessels. It causes bronchial muscles contraction in the lung, leading to bronchospasm in patients with COPD or asthma. It also leads to decrease glycogenolysis and glucagon release, which may lead to hypoglycemia.[6][11]

Administration

Cardioselective agents are either administered orally or intravenously. Bisoprolol fumarate is administered only orally as 5 or 10 mg tablets once daily. Bisoprolol has low lipophilicity, so it does not cross the blood-brain barrier with a high amount. Bisoprolol fumarate has a long half-life that extends from 9 to 12 hours. It also has high bioavailability, reaching 80 % compared to most beta-blockers with lower bioavailability since they have high first-pass metabolism in the liver.  

The dose of bisoprolol fumarate should be tailored to the patient's individualized needs. The usual starting dose is 5 mg once daily. If the 5 mg dose does not produce a desired antihypertensive effect,  the dose should be gradually increased to 10 mg and then, if needed, to 20 mg once daily.[12]

Specific Population

Hepatic Impairment: According to the manufacturer's prescribing information in patients with hepatitis or cirrhosis, the initial daily dose should be 2.5 mg and, if needed, should be titrated upward slowly.

Renal Impairment: According to the manufacturer's prescribing information in patients with creatinine clearance, less than 40 ml/min starting dose should be 2.5 mg per day and titrate upwards slowly. Since limited data suggest that bisoprolol fumarate is not dialyzable, dose adjustment is unnecessary for dialysis patients.

Geriatric Patients: The dose needs to be adjusted in the elderly only if there is significant hepatic or renal dysfunction.

Pediatric Patients: Product labeling has no information on pediatric experience with bisoprolol fumarate.

Pregnant Women: Bisoprolol is a pregnancy category c medicine and should be used only if there are no other alternatives to its therapy. Other beta-blockers might be preferred over bisoprolol to treat maternal cardiovascular complications.[13] 

Breastfeeding Women: There is limited experience of bisoprolol during breastfeeding; other agents are preferred, especially if nursing a newborn or preterm infant.[14]

Adverse Effects

A common side effect of cardiovascular blockers is bradycardia, decreasing heart rate and strength of contraction due to its negative chronotropic and inotropic effect. It also decreases cardiac output; therefore, it decreases exercise capacity. Blocking beta receptors on the SA and AV node always carries a risk of heart block. It correlates less frequently with exacerbation of peripheral diseases such as the Raynaud phenomenon, bronchoconstriction, and hypoglycemia than non-selective beta-blockers.[15]

Other commonly encountered side effects include nausea, vomiting, and constipation. Hypoglycemia is a dangerous side effect that happens in people with diabetes mellitus using beta-blockers. The drug blocks the typical signs of hypoglycemia, such as tachycardia; therefore, it delays the body's normal response to hypoglycemia, which may lead to fear of complications.[16] Among all adverse events, bradycardia, fatigue, asthenia, diarrhea, and sinusitis are dose-related.

Contraindications

Cardioselective beta-blockers are contraindicated in patients with marked sinus bradycardia, cardiogenic shock, complete heart block and should be monitored carefully in patients with second or third-degree heart block.

In addition, patients with a history of recent fluid retention should not use beta-blockers without concomitant use of diuretics.[17]

New studies suggest that cardioselective beta-blockers are contraindicated in patients with severe asthma or COPD, while it is entirely safe in patients with mild to moderate diseases.[18] 

In patients with diabetes mellitus, it may lead to masked hypoglycemia, so careful monitoring is necessary.[19]

Bisoprolol should not be abruptly withdrawn as it can cause rebound hypertension and tachycardia. In addition, some patients have developed or exacerbated existing angina pectoris, myocardial infarction, or ventricular arrhythmia when cessed therapy abruptly.

Monitoring

The essential components to monitor in patients on the cardioselective beta-blocker are blood pressure and heart rate to prevent bradycardia and hypotension. Therefore, it should be obtained with each visit while taking the vital signs.

The cardiac electricity level should be monitored to prevent any degree of heart block. Renal function tests and complete blood count are not indicated for regular monitoring but are necessary when there is a suspicion of toxicity or the physician is concerned about the therapeutic level of the medicine.[15] 

The blood sugar level is regularly monitored in diabetic patients to prevent masked hypoglycemic episodes.

Monitoring of lactate level is mandatory in a patient suspected to ingest a high dose of beta-blockers due to the chance of having mesenteric ischemia.

In case of maternal exposure to bisoprolol, then monitor the newborn baby for HR, Blood glucose, and respiratory rate for initial 48 hours after birth.[13]

Toxicity

The toxicity of cardio-selective beta-blockers occurs after the ingestion of a high dose of the drug, either intentionally or unintentionally. It can be asymptomatic in some patients, but treatment is always required. Patients in such cases usually present with bradycardia and hypotension. In addition, selective beta-blockers in high doses lose their selectivity so that patients may demonstrate signs of respiratory distress, congestive heart failure, neurological manifestations, such as confusion and mental retardation, hypoglycemia, and hyperkalemia.

The beta-blocker overdose treatment protocol includes several medicines based on the signs and symptoms of clinical toxicity.[20][21]

• Sympathomimetic agents ( IV atropine or isoproterenol ) are used in patients who experience bradycardia.
• To antagonize beta-blocker-induced hypotension, the clinician should administer intravenous glucagon and fluid. Glucagon stimulates heart contraction by glucagon receptors, which are not blocked by beta-blockers.
• To reverse the bronchospasm induced by beta-blockers, isoproterenol and/or aminophylline can be used.
• Hypoglycemia can be addressed by administering glucose orally or IV, depending on the patient's hemodynamic stability.
• The patient needs to be monitored carefully in case of a heart block and should be treated with isoproterenol infusion or transvenous cardiac pacemaker insertion.
• If a patient experiences CHF, then digitalis, diuretics, inotropic agents, vasodilating agents should be used.

Enhancing Healthcare Team Outcomes

Beta-1 selective blockers are used to treat hypertension and many other heart diseases worldwide. In addition, Bisoprolol is indicated in patients with compensated heart failure along with metoprolol and carvedilol. Therefore, interprofessional healthcare team members, including physicians, nurses, and pharmacists, should be cautious when withdrawing bisoprolol as it can cause life-threatening tachycardia, rebound hypertension, and in some cases, angina. With careful monitoring of the patient's heart rate, blood pressure, temperature, and renal function, the clinician must know the possible side effects and the means to address them.

Bisoprolol masks hypoglycemia in a patient with diabetes, so health care staff should be aware of all the side effects of the drug. Bisoprolol toxicity from accidental overdose is also possible in a patient with hypertension, so it is essential to know how to antagonize the drug's effect. Pharmacists must be aware of the required doses of the drug to each patient and perform medication reconciliation. Nurses can counsel the patients regarding administration and, along with the pharmacist, counsel the patient on potential adverse effects. Pharmacists and nurses need to report any issues with the therapy regimen to the prescribing clinician for corrective action. With this type of interprofessional collaboration, bisoprolol can achieve its therapy goals with minimal adverse events. [Level 5]