II. History: Sir James Black and Propranolol

  1. Sir James Black won 1988 Nobel Prize for Propranolol
  2. Synthesized Propranolol first in the 1960's
  3. Revolutionized cardiovascular medicine

III. Indications

  1. Hypertension
  2. Atrial Fibrillation Rate Control
  3. Coronary Artery Disease without prior Myocardial Infarction
    1. Consider to reduce Anginal symptoms and improve Exercise tolerance
  4. Myocardial Infarction without Congestive Heart Failure
    1. Continue for at least 2-3 years after Myocardial Infarction
  5. Stable Congestive Heart Failure (Carvedilol, Metoprolol, Bisoprolol)
    1. Continue Beta Blocker indefinately
  6. Arrhythmia refractory to other modality
    1. Recurrent Ventricular Tachycardia
    2. Recurrent Ventricular Fibrillation
  7. Migraine Prophylaxis

IV. Contraindications

  1. Reactive Airway Disease (Asthma, COPD)
    1. Cardioselective Beta Blockers are not contraindicated
    2. See Bronchospasm under adverse effects below
  2. Acute Congestive Heart Failure exascerbation
  3. Concurrent Calcium Channel Blocker use

V. Precautions

  1. Abrupt discontinuation is associated with exacerbation of Angina and risk of MI (FDA black box warning)
  2. Taper over one to two weeks

VI. Mechanism: General

  1. Beta Adrenergic Receptor Antagonist
  2. Inhibits effects of circulating Catecholamines
  3. Blocks Beta Adrenergic Receptors
    1. Beta-1 Adrenergic Receptors
      1. Cardiac muscle (primarily contraction)
      2. Allow calcium entry into cells (cAMP mediated)
      3. Inotropic and chronotropic effects
    2. Beta-2 Adrenergic Receptors
      1. Smooth muscle and Bronchioles
    3. Beta-3 Adrenergic Receptors
      1. Lipolysis

VII. Mechanism: Cardiovascular Specific (Beta-1 Adrenergic Receptor blockade)

  1. General Cardiac Effects
    1. Negative Inotrope
      1. Reduces Myocardial Contractility
    2. Negative Chronotrope
      1. Reduces Heart Rate
    3. Reduces Blood Pressure
    4. Reduces Myocardial Oxygen Demand
  2. Antiarrhythmic effects
    1. Seen with non-selective Beta Blockers (Propranolol)
    2. Controls Catecholamine stimulated arrhythmias
      1. Recurrent Ventricular Tachycardia
      2. Recurrent Ventricular Fibrillation
    3. Controls Myocardial Ischemia related arrhythmias
    4. Reduces AV Nodal Conduction
      1. Slows ventricular response
        1. Atrial Fibrillation
        2. Atrial Flutter
        3. Paroxysmal Supraventricular Tachycardia
      2. Quinidine-like effect on action potential
        1. Seen with Propranolol
  3. Myocardial protection
    1. Reduces Myocardial Infarction size
    2. Prevents re-infarction after Thrombolytic

VIII. Mechanism: Non-Selective effects (non-cardiovascular effects)

  1. Beta 2 Adrenergic Receptor blockade
    1. Results in bronchoconstriction
      1. Beta 2 Adrenergic Receptors affect Bronchiole and smooth muscles
    2. Non-Selective Beta Blockers (e.g. Propranolol)
    3. Selective Beta Blockers lose selectivity at high dose and in Overdose
      1. High dose Metoprolol (over 200 mg/day)
      2. High dose Esmolol (over 300 ug/kg/min)
  2. Beta 3 Adrenergic Receptor blockade
    1. Lipolysis inhibited

IX. Adverse Effects

  1. SA and AV nodal blockade
    1. Avoid in over age 75 unless secondary indication
    2. Do not use with Calcium Channel Blockers
  2. Hypotension or Orthostasis
  3. Congestive Heart Failure
    1. Treat with vasodilators and Diuretics with inotropes
  4. Bradycardia
    1. Treat with Atropine, Transcutaneous pacing, Dopamine
  5. Bronchospasm
    1. Treat with Sympathomimetics and Aminophylline
    2. Unlikely to occur in cardioselective Beta Blockers at standard doses
      1. Study looked at Atenolol, Metoprolol, bisoprolol
      2. First dose may lower FEV1 (responds to Albuterol)
      3. Continuous use does not impair lung function
      4. Salpeter (2002) Ann Intern Med 137:715-25 [PubMed]
  6. Major Depression exacerbation
  7. Fatigue

X. Drug Interactions: Decreased Heart Rate and AV Conduction

XI. Preparations: Cardioselective (Beta-1 Selective Adrenergic Blockade)

  1. Acebutolol
  2. Atenolol (Tenormin)
    1. Despite daily dosing, duration of activity is not a a full 24 hours
      1. Consider dividing dosing into twice daily (e.g. 50 mg twice daily)
    2. Not as effective as other Beta Blockers in cardiovascular disease prevention (especially with Hypertension present)
      1. Consider Metoprolol, Bisoprolol, Carvedilol or Nadolol instead
      2. Carlberg (2004) Lancet 364:1684-9 [PubMed]
    3. Dosing
      1. Regular: 50 mg PO daily (MAX: 100 mg/day)
      2. IV (Acute MI): 5 mg IV over 5 min, repeat in 10 min
  3. Betaxolol
  4. Bisoprolol
    1. Most cardioselective of Beta Blockers
  5. Metoprolol (Lopressor)
  6. Esmolol Hydrochloride (Brevibloc)
  7. Nebivolol (Bystolic)
    1. Third generation Beta Blocker with vasodilatory properties (nitric oxide release)

XII. Preparations: Nonselective (Beta-1 and Beta-2 Adrenergic Blockade)

  1. Carteolol
  2. Timolol (Blocadren)
    1. Dose: 10 mg PO bid (MAX 60 mg/day)
  3. Nadolol (Corgard)
    1. Dose: 40 mg PO qd (MAX 320 mg/day)
  4. Oxprenolol
  5. Penbutolol
  6. Propranolol (Inderal)
  7. Sotalol
  8. Timolol

XIII. Preparations: Combined Alpha-1, Beta-1 and Beta-2 Adrenergic Blockade

  1. Carvedilol (Coreg)
    1. Third generation Beta Blocker with vasodilatory properties (alpha blocker)
  2. Labetalol

XIV. References

  1. (2012) Presc Lett 19(12): 67-8
  2. Yen (2015) Crit Dec Emerg Med 29(10): 18-23

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Cost: Medications

Atenolol (on 6/18/2017 at Walmart.com)
Atenolol 100mg #30 tablets for $4.00 $0.13 each
Atenolol 100mg #90 tablets for $10.00 $0.11 each
Atenolol 25mg #30 tablets for $4.00 $0.13 each
Atenolol 25mg #90 tablets for $10.00 $0.11 each
Atenolol 50mg #30 tablets for $4.00 $0.13 each
Atenolol 50mg #90 tablets for $10.00 $0.11 each
Timolol Maleate (on 6/18/2017 at Walmart.com)
Timolol Maleate 0.25% op. soln (5ml) #1 bottle for $4.00 $4.00 each
Timolol Maleate 0.25% op. soln (5ml) #3 bottles for $10.00 $3.33 each
Timolol Maleate 0.5% op soln (5ml) #1 bottle for $4.00 $4.00 each
Timolol Maleate 0.5% op soln (5ml) #3 bottles for $10.00 $3.33 each
atenolol (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ATENOLOL 100 MG TABLET Generic $0.03 each
ATENOLOL 25 MG TABLET Generic $0.01 each
ATENOLOL 50 MG TABLET Generic $0.02 each
ATENOLOL-CHLORTHALIDONE 100-25 Generic $0.49 each
ATENOLOL-CHLORTHALIDONE 50-25 Generic $0.35 each
timolol (on 9/21/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
TIMOLOL 0.25% EYE DROPS Generic $0.49 per ml
TIMOLOL 0.25% GEL-SOLUTION Generic $19.36 per ml
TIMOLOL 0.25% GFS GEL-SOLUTION Generic $19.36 per ml
TIMOLOL 0.5% EYE DROPS Generic $0.78 per ml
TIMOLOL 0.5% GEL-SOLUTION Generic $16.83 per ml
TIMOLOL 0.5% GFS GEL-SOLUTION Generic $16.83 per ml
TIMOLOL MALEATE 10 MG TABLET Generic $1.41 each
TIMOLOL MALEATE 5 MG TABLET Generic $1.09 each
nadolol (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
NADOLOL 20 MG TABLET Generic $1.57 each
NADOLOL 40 MG TABLET Generic $1.90 each
NADOLOL 80 MG TABLET Generic $3.19 each

Ontology: Adrenergic beta-Antagonists (C0001645)

Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (CHV) a type of drug used for hypertension, migraine, cardiac infarction, etc
Definition (NCI) Natural or synthetic beta adrenergic antagonists selectively or non-selectively blocking or diminishing physiologic beta-adrenergic agonist actions on the sympathetic system. This group of antagonists are generally used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Definition (NCI_CDISC) Natural or synthetic beta adrenergic antagonists selectively or non-selectively blocking or diminishing physiologic beta-adrenergic agonist actions on the sympathetic system. This group of antagonists are generally used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Definition (MSH) Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Concepts Pharmacologic Substance (T121)
MSH D000319
SnomedCT 318350007, 33252009, 373254001
LNC LP18062-7, MTHU003324
English beta Adrenergic Blocking Agents, beta Adrenergic Receptor Blockaders, beta Blockers, Adrenergic, Adrenergic beta Antagonists, Adrenergic beta Receptor Blockaders, Adrenergic beta-Blockers, Adrenergic beta-Receptor Blockaders, Agents, beta-Adrenergic Blocking, Blockaders, Adrenergic beta-Receptor, Blockaders, beta-Adrenergic Receptor, Blockers, beta-Adrenergic, Blocking Agents, beta-Adrenergic, Receptor Blockaders, beta-Adrenergic, beta Adrenergic Blockers, beta-Adrenergic Blockers, beta-Adrenergic Blocking Agents, beta-Adrenergic Receptor Blockaders, beta-Antagonists, Adrenergic, beta-Blockers, Adrenergic, beta-Receptor Blockaders, Adrenergic, Beta-adrenoceptor blocker, BETA BLOCKERS ADREN, ADREN BETA RECEPT BLOCK, BETA ADREN RECEPT BLOCK, BETA ADREN BLOCK, ADREN BETA ANTAG, ADRENERGIC ANTAGONISTS BETA, ADRENERGIC RECEPTOR BLOCKADERS BETA, BETA ADREN BLOCK AGENTS, beta adrenergic blocking agents (medication), adrenergic beta receptor blockaders, beta adrenergic blocking agents, Adrenergic beta-Antagonists, Beta-Blockers, Beta Blocker, beta-adrenergic receptor blockaders, beta-adrenergic blocking agents, beta adrenergic blockers, beta blocker, beta blockers, beta-adrenergic blocking agent, beta-blocking agent, beta adrenergic antagonist, beta adrenergic blocker, beta-blocker, beta-adrenergic blockers, BETA BLOCKING AGENTS, Beta-adrenoceptor blocking drug (substance), Beta blockers, Adrenergic beta blockers, Beta-adrenoceptor blocking drug, Beta-blocker, beta-Adrenergic blocking agent, beta-Blocking agent (product), beta-Blocking agent (substance), beta-Blocking agent, Beta-adrenoceptor blocking agent, beta-Adrenergic blocking agent, NOS, beta-Blocking agent, NOS, Beta Blockers, Beta-Adrenergic Antagonist, Beta-Adrenergic Blocking Agent, Beta-adrenergic Blocking Agents
French Bêta-bloquants adrénergiques, Antagonistes des adrénorécepteurs bêta, Agents bloquants bêta-adrénergiques, Bêta-adrénolytiques, Bêta-bloquants, Adrénolytiques bêta, Antagonistes bêta-adrénergiques, Antagonistes des récepteurs adrénergiques bêta, Bêta-bloqueurs
Swedish Adrenerga betablockerare
Spanish bloqueantes beta, Antagonistas Adrenérgicos beta, Agentes Bloqueadores Adrenérgicos beta, Bloqueadores Adrenérgicos beta, Bloqueadores de los Receptores Adrenérgicos beta, Bloqueadores beta Adrenérgicos, beta-Antagonistas Adrenérgicos, Agentes Bloqueadores beta-Adrenérgicos, Bloqueadores de los Receptores beta Adrenérgicos, Bloqueadores de los Receptores beta-Adrenérgicos, agente betabloqueante (producto), agente betabloqueante (sustancia), agente betabloqueante, antiadrenérgicos beta, betabloqueantes, bloqueantes beta (producto), bloqueantes beta (sustancia)
Czech beta-adrenergní blokátory, betablokátory, receptory adrenergní beta - blokátory, beta-blokátory, antagonisté beta-adrenergních receptorů, blokátory adrenergních beta-receptorů, blokátory betaadrenergních receptorů
Finnish Beetasalpaajat
Italian Bloccanti dei recettori adrenergici, Agenti bloccanti beta-adrenergici, Bloccanti beta-adrenergici, Beta-antagonisti adrenergici
Russian ADRENERGICHESKIE BETA-ANTAGONISTY, ADRENERGICHESKIKH BETA-RETSEPTOROV BLOKATORY, BETA-ADRENERGICHESKIKH RETSEPTOROV BLOKATORY, BETA-ADRENOLITICHESKIE SREDSTVA, BETA-ADRENOLITIKI, BETA-BLOKATORY ADRENERGICHESKIE, АДРЕНЕРГИЧЕСКИЕ БЕТА-АНТАГОНИСТЫ, АДРЕНЕРГИЧЕСКИХ БЕТА-РЕЦЕПТОРОВ БЛОКАТОРЫ, БЕТА-АДРЕНЕРГИЧЕСКИХ РЕЦЕПТОРОВ БЛОКАТОРЫ, БЕТА-АДРЕНОЛИТИКИ, БЕТА-АДРЕНОЛИТИЧЕСКИЕ СРЕДСТВА, БЕТА-БЛОКАТОРЫ АДРЕНЕРГИЧЕСКИЕ
German ADRENERGE REZEPTORENBLOCKER BETA, ADRENERGE ANTAGONISTEN BETA, Adrenerge Beta-Antagonisten, Adrenerge Beta-Rezeptorenblocker, Beta-Blocker, adrenerge, Beta-adrenerge Blocker, Beta-adrenerge Rezeptorenblocker
Croatian ADRENERGIČKI BETA-ANTAGONISTI
Polish Środki blokujące receptory adrenergiczne beta, Leki blokujące receptory beta-adrenergiczne, Beta-adrenolityki, Blokery beta, Antagoniści adrenergiczni beta
Japanese β-アドレナリン作動性受容体遮断薬, β-遮断剤, β-ブロッカー, β-受容体遮断薬, β-遮断薬, アドレナリンベータきっ抗剤, アドレナリン作用性ベータ受容体遮断剤, アドレナリン作用性ベータ受容体遮断薬, アドレナリン作用性ベータ拮抗薬, アドレナリン作用性ベータ遮断薬, ベータアドレナリン作用性受容体遮断薬, ベータアドレナリン作用性遮断薬, β-アドレナリン受容体遮断薬, β-アドレナリン遮断薬, β受容体遮断薬, β遮断薬, アドレナリンベータアンタゴニスト, アドレナリンベータブロッカー, アドレナリン作用性ベータ受容器遮断薬, ベータ遮断剤
Portuguese Antagonistas Adrenérgicos beta, Bloqueadores dos Receptores Adrenérgicos beta, Agentes Bloqueadores Adrenérgicos beta, Bloqueadores Adrenérgicos beta, Bloqueadores beta Adrenérgicos, Agentes Bloqueadores beta-Adrenérgicos, Bloqueadores dos Receptores beta-Adrenérgicos, beta-Antagonistas Adrenérgicos, Bloqueadores dos Receptores beta Adrenérgicos

Ontology: Atenolol (C0004147)

Definition (MSH) A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.
Definition (CHV) a drug that treats rapid heart rate and high blood pressure
Definition (NCI) A synthetic isopropylamino-propanol derivative used as an antihypertensive, hypotensive and antiarrhythmic Atenolol acts as a peripheral, cardioselective beta blocker specific for beta-1 adrenergic receptors, without intrinsic sympathomimetic effects. It reduces exercise heart rates and delays atrioventricular conduction, with overall oxygen requirements decreasing. (NCI04)
Definition (CSP) l-p-carbamoylmethylphenoxy-3-isopropylamino -2-propanol, is a peripheral beta blocker used as an antihypertensive; propranolol, by contrast, also has CNS effects.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D001262
SnomedCT 391790005, 387506000, 87652004
LNC LP16037-1, MTHU015491
English Atenolol, Benzeneacetamide, 4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)-, atenolol, ATENOLOL, atenolol (medication), Atenolol [Chemical/Ingredient], Atenolol - chemical (substance), Atenolol - chemical, Atenolol (product), Atenolol (substance)
Swedish Atenolol
Czech atenolol
Finnish Atenololi
Russian ATENOLOL, ICI 66082, АТЕНОЛОЛ
Japanese アテノロール
Croatian ATENOLOL
Polish Atenolol
Spanish atenolol (producto), atenolol (sustancia), atenolol, Atenolol
French Aténolol
German Atenolol
Italian Atenololo
Portuguese Atenolol

Ontology: Nadolol (C0027302)

Definition (NCI) A non-selective beta-adrenergic antagonist with antihypertensive and antiarrhythmic activities. Nadolol competitively blocks beta-1 adrenergic receptors located in the heart and vascular smooth muscle, inhibiting the activities of the catecholamines epinephrine and norepinephrine and producing negative inotropic and chronotropic effects. This agent exhibits antiarrhythmic activity via the impairment of atrioventricular (AV) node conduction and a corresponding reduction in sinus rate. In the kidney, inhibition of the beta-2 receptor within the juxtaglomerular apparatus results in the inhibition of renin production and a subsequent reduction in angiotensin II and aldosterone levels, thus inhibiting angiotensin II-dependent vasoconstriction and aldosterone-dependent water retention.
Definition (MSH) A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for MIGRAINE DISORDERS and for tremor.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D009248
SnomedCT 387482003, 82896009
LNC LP16211-2, MTHU003377
English Nadolol, 2,3-Naphthalenediol, 5-(3-((1,1-dimethylethyl)amino)-2-hydroxypropoxy)-1,2,3,4-tetrahydro-, nadolol, nadolol (medication), NADOLOL, Nadolol [Chemical/Ingredient], Nadolol (product), Nadolol (substance)
Swedish Nadolol
Czech nadolol
Finnish Nadololi
Russian NADOLOL, НАДОЛОЛ
Japanese ナドロール
Polish Nadolol
Spanish nadolol (producto), nadolol (sustancia), nadolol, Nadolol
French Nadolol
German Nadolol
Italian Nadololo
Portuguese Nadolol

Ontology: Timolol (C0040233)

Definition (NCI) A propanolamine derivative and a non-selective beta-adrenergic antagonist with antihypertensive property. Timolol competitively binds to beta-1-adrenergic receptors in the heart and vascular smooth muscle and beta-2-receptors in the bronchial and vascular smooth muscle, resulting in a decrease in beta-adrenergic stimulation. Beta-1-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta-2-blockade results in an increase in peripheral vascular resistance. The ultimate results include vasodilation, and negative chronotropic and inotropic cardiac effects. In addition, timolol reduces intra-ocular pressure possibly by decreasing aqueous humor production by reduction of blood flow to the ciliary processes and cAMP synthesis.
Definition (MSH) A beta-adrenergic antagonist similar in action to PROPRANOLOL. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D013999
SnomedCT 372880004, 85591001
LNC LP16293-0, MTHU018379, LA14716-7
English Timolol, (S)-1-((1,1-Dimethylethyl)amino)-3-((4-(4-morpholinyl)-1,2,5-thiadazol-3-yl)oxy)-2-propanol, 2-Propanol, 1-((1,1-dimethylethyl)amino)-3-((4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl)oxy)-, (S)-, (S)-1-(tert-Butylamino)-3-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)propan-2-ol, timolol (ophthalmic) (medication), timolol (medication), timolol (ophthalmic), Timolol, Ophthalmic, timolol ophthalmic, timolol, Timolol [Chemical/Ingredient], TIMOLOL, Timolol (product), Timolol (substance)
Swedish Timolol
Czech timolol
Finnish Timololi
Russian TIMOLOL, ТИМОЛОЛ
Japanese チモレート, チマバック, ファルチモ, ブルンネ, チモプトール, マレイン酸チモロール, リズモン, チアブート, チモロールT, チモロール
Polish Timolol
Spanish timolol (producto), timolol (sustancia), timolol, Timolol
French Timolol
German Timolol
Italian Timololo
Portuguese Timolol