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# Beta Blockers ## Overview Beta-adrenergic blockers reduce heart rate, myocardial contractility, and renin release. Selectivity varies: - **β1-selective:** metoprolol, atenolol, bisoprolol, esmolol, nebivolol - **Nonselective:** propranolol, nadolol, timolol, sotalol - **β- and α1-blocking:** carvedilol, labetalol Dosing and maximum doses depend substantially on the specific agent and indication. The doses below are commonly used adult doses; verify local protocols and product labeling. ## Primary Indications - Hypertension - Angina and ischemic heart disease - Rate control in atrial fibrillation/flutter and some supraventricular tachycardias - Heart failure with reduced ejection fraction: **carvedilol, metoprolol succinate, or bisoprolol** - Acute myocardial infarction and secondary prevention - Migraine prevention - Essential tremor - Hyperthyroid symptoms - Aortic dissection or selected tachyarrhythmias - Portal hypertension: propranolol or nadolol - Infantile hemangioma: propranolol - Glaucoma: topical timolol or related agents ## Adult Dosing ### Hypertension - **Metoprolol tartrate:** 25–100 mg orally twice daily; usual maximum 400 mg/day. - **Metoprolol succinate extended release:** 25–100 mg orally once daily; usual maximum 400 mg/day. - **Atenolol:** 25–50 mg orally once daily; maximum 100 mg/day. - **Bisoprolol:** 2.5–5 mg orally once daily; maximum 20 mg/day. - **Carvedilol:** 6.25 mg orally twice daily; titrate as needed. Maximum 25 mg twice daily. - **Labetalol:** 100 mg orally twice daily, titrate every 2–3 days; maximum 2,400 mg/day. - **Propranolol immediate release:** 40 mg orally twice daily; maximum commonly 640 mg/day, depending on indication and formulation. - **Nebivolol:** 5 mg orally once daily; maximum 40 mg/day. Beta blockers are generally not preferred as initial monotherapy for uncomplicated hypertension unless there is a compelling indication. ### Heart Failure With Reduced Ejection Fraction Use only when clinically stable and initiate at low doses. - **Carvedilol:** 3.125 mg orally twice daily; double approximately every 2 weeks as tolerated. - Target: 25 mg twice daily if weight is ≤85 kg; 50 mg twice daily if weight is >85 kg. - **Metoprolol succinate extended release:** 12.5–25 mg orally once daily; double every 2 weeks or longer. - Target: 200 mg once daily. - **Bisoprolol:** 1.25 mg orally once daily; titrate gradually. - Target: 10 mg once daily. Do not initiate or up-titrate during cardiogenic shock, marked fluid overload, symptomatic bradycardia, or acute decompensated heart failure. ### Rate Control or Supraventricular Tachycardia - **Metoprolol tartrate:** 2.5–5 mg IV over 2 minutes, repeated every 5 minutes as needed; commonly maximum 15 mg IV initially. Oral dosing often 25–100 mg twice daily. - **Esmolol:** 500 micrograms/kg IV loading dose over 1 minute, then 50 micrograms/kg/min infusion; titrate every 4–5 minutes. Usual maximum is 200 micrograms/kg/min for many indications; local protocols may permit higher rates. - **Propranolol:** 10–40 mg orally three to four times daily, or IV dosing under specialist monitoring. For atrial fibrillation with pre-excitation/Wolff–Parkinson–White syndrome, avoid AV-nodal blockers, including beta blockers. ### Angina or Post-Myocardial Infarction - **Metoprolol tartrate:** commonly 25–50 mg orally twice daily, titrated to heart rate and symptoms. - **Atenolol:** 50 mg orally once daily, may increase to 100 mg/day. - **Carvedilol:** 6.25–25 mg orally twice daily depending on clinical status. ### Migraine Prevention - **Propranolol:** 40 mg orally twice daily, titrate to 80–160 mg/day; some patients require up to 240 mg/day. - **Metoprolol:** 50–100 mg orally twice daily; maximum commonly 200 mg/day. - **Atenolol:** 25–50 mg orally once daily; maximum commonly 100 mg/day. ### Essential Tremor - **Propranolol:** 10–40 mg orally two to three times daily; titrate to response. Typical total dose 60–320 mg/day. Use the lowest effective dose. ### Portal Hypertension - **Propranolol:** start 20 mg orally twice daily; titrate to a resting heart rate approximately 55–60 beats/minute if tolerated. - **Nadolol:** start 20–40 mg orally once daily; titrate similarly. Dose targets and titration should follow hepatology or local protocol. ## Pediatric Dosing Pediatric use is indication- and age-specific. Many doses are off-label and require specialist oversight. ### Hypertension - **Atenolol:** 0.5–1 mg/kg orally once daily; may titrate to 2 mg/kg/day. Maximum commonly 100 mg/day. - **Propranolol:** 1–2 mg/kg/day orally divided two to three times daily; may titrate to 4 mg/kg/day, with a usual maximum of 640 mg/day. Specialist supervision is recommended. ### Infantile Hemangioma - **Propranolol:** typically initiate at 0.5 mg/kg/dose orally twice daily, then increase to 1 mg/kg/dose twice daily and, if tolerated, to a total of approximately 2–3 mg/kg/day divided twice daily. Give during or immediately after feeding. Monitor for hypoglycemia, bradycardia, hypotension, and bronchospasm. Hold during poor oral intake, vomiting, or significant respiratory illness according to the treating protocol. ### Pediatric Heart Failure or Arrhythmias - **Carvedilol:** specialist-directed, commonly initiated around 0.01–0.05 mg/kg/dose twice daily and titrated slowly. Pediatric maximums vary by protocol and are not firmly standardized. - **Metoprolol:** commonly initiated around 0.5–1 mg/kg/day divided once or twice daily and titrated by a pediatric cardiologist. Maximum dosing is indication- and formulation-specific. - **Propranolol:** dosing varies widely by arrhythmia and age; use pediatric cardiology protocols. ## Dose Adjustments - **Renal impairment** - Reduce or lengthen the dosing interval for **atenolol, nadolol, sotalol, and acebutolol**, which rely substantially on renal elimination. - Metoprolol and carvedilol generally do not require routine renal adjustment. - Sotalol requires creatinine-clearance-based dosing and QT monitoring; avoid empiric dosing without a protocol. - **Hepatic impairment** - Use lower initial doses and slower titration for **metoprolol, propranolol, carvedilol, labetalol, and nebivolol**. - Severe hepatic impairment may require substantial dose reduction. - **Older adults or frail patients** - Start at the lowest dose and titrate slowly because of increased risk of bradycardia, hypotension, and falls. - **Acute illness** - Consider temporarily holding therapy for severe hypotension, shock, symptomatic bradycardia, or cardiogenic shock. - Do not abruptly discontinue chronic therapy; taper when clinically appropriate to reduce rebound angina, hypertension, or tachycardia. ## Contraindications ### Generally contraindicated or requiring specialist assessment - Severe bradycardia - Second- or third-degree AV block without a functioning pacemaker - Sick sinus syndrome without a functioning pacemaker - Cardiogenic shock - Decompensated heart failure with hypoperfusion - Severe hypotension - Known serious hypersensitivity ### Relative or agent-specific concerns - **Asthma or bronchospastic disease:** avoid nonselective agents; even β1-selective agents may cause bronchospasm at higher doses. - Severe peripheral arterial disease or vasospastic disease - Diabetes mellitus: may mask adrenergic symptoms of hypoglycemia and delay recovery from hypoglycemia. - Prinzmetal or vasospastic angina: avoid nonselective beta blockers. - Pheochromocytoma: establish adequate α-blockade before beta blockade. - Acute cocaine-associated coronary vasospasm: use requires specialist judgment; pure beta blockade is generally avoided acutely. - Sotalol: avoid with prolonged QT, significant bradycardia, uncompensated heart failure, hypokalemia/hypomagnesemia, or markedly reduced renal function. ## Adverse Effects - Bradycardia, hypotension, dizziness, fatigue - Exercise intolerance and reduced libido - Cold extremities - Depression or sleep disturbance, more often reported with lipophilic agents - Bronchospasm - Worsening peripheral circulation or Raynaud symptoms - Erectile dysfunction - Masking of hypoglycemia symptoms and possible prolonged hypoglycemia - Conduction abnormalities or heart block - Worsening heart failure during rapid initiation or dose escalation - Nausea or diarrhea - **Sotalol:** QT prolongation and torsades de pointes - **Abrupt withdrawal:** rebound tachycardia, hypertension, angina, myocardial infarction, or arrhythmia Topical ophthalmic beta blockers can still cause systemic bradycardia, hypotension, bronchospasm, and fatigue. ## Key Drug Interactions - **Verapamil or diltiazem:** additive bradycardia, hypotension, AV block, and reduced contractility; avoid IV combinations unless closely monitored. - **Digoxin:** additive bradycardia and AV block. - **Amiodarone:** additive bradycardia, conduction delay, and hypotension. - **Clonidine:** withdrawal can cause severe rebound hypertension; if stopping both, generally taper the beta blocker only after appropriate clonidine management. - **CYP2D6 inhibitors** such as paroxetine, fluoxetine, bupropion, and quinidine may increase metoprolol concentrations. - **Insulin and sulfonylureas:** beta blockers may mask hypoglycemia and, in some cases, prolong it. - **NSAIDs:** may reduce antihypertensive effects and promote fluid retention. - **Other QT-prolonging drugs:** clinically important with sotalol. - **Anesthetics and other negative inotropes:** increased risk of hypotension, bradycardia, or myocardial depression. - **Epinephrine and other sympathomimetics:** may cause unopposed α-mediated vasoconstriction, particularly with nonselective beta blockade. ## Monitoring - Blood pressure and apical pulse at baseline and after dose changes - Symptoms of dizziness, syncope, fatigue, dyspnea, wheezing, or exercise intolerance - ECG when there is bradycardia, conduction disease, arrhythmia treatment, or use of sotalol - Renal function and electrolytes for renally cleared agents, especially sotalol - Hepatic function when clinically indicated - Signs of worsening heart failure: weight gain, edema, orthopnea, and increasing dyspnea - Blood glucose and patient education regarding masked hypoglycemia in diabetes - Heart rate, blood pressure, and feeding status in infants receiving propranolol - QTc and inpatient initiation requirements for sotalol, according to local protocol ## Clinical Pearls - Select the agent based on the indication, comorbidities, renal/hepatic function, and dosing frequency. - Prefer evidence-based agents for HFrEF: **carvedilol, metoprolol succinate, or bisoprolol**. - β1-selective agents may be better tolerated in patients with reactive airway disease, but are not risk-free. - Do not stop chronic beta-blocker therapy abruptly. - In atrial fibrillation with decompensated heart failure or significant hypotension, seek specialist guidance before using a beta blocker. - In patients with diabetes, teach patients to recognize atypical hypoglycemia symptoms such as sweating, dizziness, or confusion. - Sotalol initiation and dose changes often require ECG, electrolyte, renal-function assessment, and sometimes inpatient monitoring. - For topical ophthalmic beta blockers, consider systemic exposure and review the patient’s cardiac and pulmonary history. - If resting heart rate is persistently below approximately 50–55 beats/minute, or the patient has symptomatic hypotension or bradycardia, reassess therapy before further titration. *Educational information only; not a substitute for patient-specific clinical judgment. Verify current prescribing information, contraindications, renal/hepatic dosing, pediatric protocols, and local institutional guidance before prescribing or administering any beta blocker.*