Beta Blockers

Mechanism of Action

• Blocks beta-receptors of the sympathetic nervous system
• Some agents act primarily on beta receptors in the heart
  • these are called cardioselective
• Beta- blockage results in decreased heart rate, blood pressure, and contractility of the heart
  • thereby reducing the demand for oxygen by the heart

Treatment

• High blood pressure (hypertension)
• Chest pain (angina pectoris)
• Abnormal heart rhythms (arrhythmias)
  • Fast heart rates called tachycardia
  • Irregular rhythms like atrial fibrillation
• Migraine headaches
• Previous MI patients
  • Reduce the risk of death after a heart attack
• Glaucoma, Ocular hypertension
  • Eg: Carteolol, Timolol, Betaxolol
• Anxiety (off-label)

Non-selective Beta Blockers

• Carteolol (Cartrol, Ocupress, Teoptic, Arteolol, Arteoptic, Calte, Cartéabak, Carteol, Cartéol, Cartrol, Elebloc, Endak, Glauteolol, Mikelan, Poenglaucol, Singlauc)
  • Used to treat glaucoma
  • Also a serotonin 5-HT1A and 5-HT1B receptor antagonist
• Carvedilol (Coreg)
  • Also decreases peripheral vascular resistance through alpha-1 blockade
• Labetalol (Normodyne, Trandate)
  • Also decreases peripheral vascular resistance through alpha-1 blockade
• Nadolol (Norpramin)
• Oxprenolol (Trasacor, Trasicor, Coretal, Laracor, Slow-Pren, Captol, Corbeton, Slow-Trasicor, Tevacor, Trasitensin, Trasidex)
  • Also exhibits intrinsic sympathomimetic activity
  • Lipophilic beta blocker which more easily passes the blood–brain barrier associated with higher incidence of CNS-related side effects
• Penbutolol (Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin)
  • Also exhibits intrinsic sympathomimetic activity
• Pindolol (Visken)
  • Also exhibits intrinsic sympathomimetic activity
• Propranolol (Inderal)
• Sotalol (Betapace, Sotalex, Sotacor, Sotylize)
  • Prescribed only for serious arrhythmias
  • Prolongs QT Interval
• Timolol (Betimol)
  • Also used to treat glaucoma and ocular hypertension

β1-selective Beta Blockers

• Acebutolol (Sectral, Prent)
  • Also exhibits intrinsic sympathomimetic activity
  • Lipophilic beta blocker which more easily passes the blood–brain barrier
  • No HDL decrease, unlike most beta blockers
• Atenolol (Tenormin, Norpramin)
  • Higher risk of type 2 diabetes
• Betaxolol (Betoptic, Lokren, Kerlone)
  • Also used to treat glaucoma
• Bisoprolol (Zebeta, Concor)
• Celiprolol (Cardem, Selectol, Celipres, Celipro, Celol, Cordiax, Dilanorm)
  • Also exhibits intrinsic sympathomimetic activity
• Metoprolol Succinate (Lopressor, Metolar XR)
  • Long-acting beta-blocker
• Nebivolol (Bystolic, Nebilet)
  • Decrease peripheral vascular resistance through promoting nitric oxide (NO) release
  • Significantly increases stroke volume while maintaining cardiac output

Effect on Weight

• Lowered resting metabolic rate (RMR) (Bélanger & Boulay 2005)
• Weight gain usually occurs in the first few months of treatment (Bélanger & Boulay 2005)
• Limits the increase in RMR normally observed following aerobic exercise (Bélanger & Boulay 2005)
• Beta blockers such as Carvedilol don't increase weight gain.

Effect During Rest

• Decreased resting heart rate (ACSM 2013, Gladson 2011, Niedfeldt 2002)
  • 30-35% reduction (Tesch 1985)
  • Less decrease by intrinsic sympathomimetic activity (ISA) and Beta Blocker (ACSM 2013)
• Decreased blood pressure (ACSM 2013)
  • Decreased systolic blood pressure (Gladson 2011)
  • Decreased rate pressure product (Gladson 2011)
• Decreased arrhythmias (ACSM 2013)
  • Decreased ST depression (Gladson 2011)
• Increased diastolic function (Gladson 2011)
  • Increased myocardial efficiency (Gladson 2011)
• Increased myocardial oxygen consumption (MVO2) (Gladson 2011)
• Decreased coronary blood flow (Gladson 2011)
• Increased diastolic filling time (Gladson 2011)

Effect on Exercise

• Decreased heart rate during exercise (ACSM 2013, Gladson 2011)
  • Less decrease by cardioselective Beta Blocker (ACSM 2013)
  • 20 to 30% decrease in maximum heart rate (Gladson 2011)
• Decreased blood pressure (ACSM 2013)
• Impairment of cardiac output
  • Decrease in cardiac output (Niedfeldt 2002)
  • Decrease or no change in cardiac output (ACSM 2013)
  • 5 to 23% decrease in cardiac output (Gladson 2011)
• Possible increased stroke volume (Tesch 1985)
  • No effect on stroke volume (Niedfeldt 2002)
  • Increased stroke volume during moderate exercise (Gladson 2011)
• Impairment of maximum oxygen uptake (Niedfeldt 2002)
  • Decreased acute (single dose) VO2max (ACSM 2013)
    • Decrease of 5-15% (Tesch 1985)
  • Increased chronic VO2max (ACSM 2013, Gladson 2011)
• Decreased exercise ischemia (ACSM 2013)
  • Decreased ischemic threshold (Gladson 2011)
• Increase in vascular resistance (Niedfeldt 2002)
• No effect on plasma volume (Niedfeldt 2002)
• No effect on muscular strength and power
• No effect on psychomotor performance
• Potentially greater ability to perform athletic events requiring high levels of motor control under emotional stress (Tesch 1985)
• Exercise / Work Capacity
  • Increased exercise capacity (Gladson 2011)
  • Increased exercise capacity
    • Patients with angina (Dreeben-Irimia 2008)
    • Patients with cardiovascular disease (Gladson 2011)
      • Selective β-blockers more than non-selective β-blockers
  • Decreased exercise capacity
    • Patients without angina (Dreeben-Irimia 2008)
    • Patients with hypertension but no cardiovascular disease (Gladson 2011)
  • Impaired work capacity as reflected by the ability to perform intense short term or more prolonged steady-state exercise. (Tesch 1985)
    • Significant decrease in training (Niedfeldt 2002)
    • Exercise performance ability is more greatly impair following a beta 1- and beta 2 receptors (non-selective than beta 1-selective) blockade as opposed to only a beta 1-receptors (beta 1-selective blockers) blockade at equal reductions in heart rate. (Tesch 1985)
• Increased total exercise time (Gladson 2011)
• Earlier fatigue and lactate threshold (Niedfeldt 2002)
  • Increase in perceived exertion levels (Niedfeldt 2002)
  • Increase acute (single dose) RPE during exercise.
    • This effect partially subsides with long term treatment (Tesch 1985)
• Possible exacerbation of exercise-induced bronchospasm or asthma (Niedfeldt 2002)

Metabolic Effects

• Both selective and non-selective β-blockers disrupt the utilization of fat, glucose, and triglycerides during exercise
  • However, non-selective β-blockers have greater disruptions
    • However, benefits of selective β-blockers are lost at higher doses
• Greater metabolic disruptions and fatigue occurs at peak plasma concentrations
  • Generally 90 minutes after administration

Nonselective β-blockers

• Some Nonselective β-blockers may cause adverse effects to the CNS (Gladson 2011)
  • Fatigue
  • Depression
  • Nightmares
• Thermoregulatory effects during exercise (Gladson 2011)
  • 10% accelerated sweating response
    • Increased risk of dehydration
  • Decreased skin blood flow
    • Peripheral constriction
    • Reduce cardiac output
  • Fluid replacement is important to prevent drop in blood pressure
• Metabolic effects during exercise (Gladson 2011)
  • Increased fatigue
  • Decreased adipose and intramuscular lipolysis
  • Decreased glycogen breakdown
  • Decreased blood glycogen levels
    • Decreased hepatic glycogenolysis
    • Decreased hepatic gluconeogenesis
    • Possible decrease of glucose utilization by working muscles

Recommendations

• Exercise same time each day to avoid variations in plasma concentration of β-blockers
• Take appropriate actions when experiencing any adverse effects of exercise.
• Patients on Beta-blockers who achieved 65% age-predicted maximal heart rate had a similar adjusted mortality rate as those not on Beta-blockers who achieved 85% age-predicted maximal heart rate (p >0.05) (Hung 2016)

Recommended Populations

• Recommended to those with coronary artery disease

Populations Not Recommend

• Not recommended to those with asthma, endurance athletes, collegiate athletes
• Caution when prescribing some beta-blockers to patients with asthma or bronchospasm

Banned Status

• Banned in precision sports (ie: shooting, archery, diving, ice skating

References

American College of Sports Medicine (2013). Guidelines for Exercise Testing and Prescription, William & Wilkins, 9, 401

Bélanger M, Boulay P (2005). Effect of an aerobic exercise training program on resting metabolic rate in chronically beta-adrenergic blocked hypertensive patients. J Cardiopulm Rehabil. 25(6):354-60.

Dreeben-Irimia O (2008). Physical Therapy Clinical Handbook for PTAs. Jones and Bartlett Publishers, 373.

Gladson B (2011). Pharmacology for Rehabilitation Professionals, Elsevier Saunders (2) 486-490.

Hung RK, Al-Mallah MH, Whelton SP, Michos ED, Blumenthal RS, Ehrman JK, Brawner CA, Keteyian SJ, Blaha MJ (2016). Effect of Beta-Blocker Therapy, Maximal Heart Rate, and Exercise Capacity During Stress Testing on Long-Term Survival (from The Henry Ford Exercise Testing Project). Am J Cardiol. 2016 Dec 1;118(11):1751-1757.

Tesch PA (1985). Exercise performance and beta-blockade. Sports Med. 1985 Nov-Dec;2(6):389-412.

Niedfeldt MW (2002). Managing Hypertension in Athletes and Physically Active Patients. Am Fam Physician. 1;66(3):445-453.