1. Prijay Bakrania
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2.  Background
 Mechanism of action
 Structure-activity relationship
 Clinical information
 Current research
 Summary
 References
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3.  Discovered by Sir James Black in 1962
 Awarded the Nobel Prize for Medicine in 1988
 Propranolol and pronethalol were the first
clinically significant beta-blockers (van der Vring et
al., 1999)
 All beta-blockers end in ‘-lol’, e.g. labetalol,
timolol, bisoprolol, etc.
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Nobel Media,
2014

4.  β1- and β2-adrenoceptor inverse agonists
 Drugs vary in inverse agonist activity
 Selectivity vs. specificity
Panesar and
Guzman,
2009
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5.  Part of the sympathetic nervous system
 Metabotropic, G-protein-coupled receptors
 Linked to the Gs protein
 β1-adrenoceptors
◦ Heart, kidneys
 β2-adrenoceptors
◦ Bladder detrusor muscle, eye ciliary muscle, GI
tract, liver, pancreas, smooth muscle, skeletal
muscle (Lechat, 2008)
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6. Klabunde,
2013 6

7. Klabunde,
2013
7

8.  Essential for binding to receptors (Lechat, 2008)
◦ Oxymethylene
 Essential for activity (Gorre and Vanderkerckhove, 2010)
◦ Aromatic ring
◦ β-ethanolamine
Adapted from Mehvar and Brocks, 2001
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9.  Hypertension
 Angina pectoris
 Myocardial infarction
 Cardiac arrhythmias
 Congestive heart failure
 Anxiety
◦ Reduced adverse effects, e.g. tremor
 Glaucoma (Joint Formulary Committee, 2014)
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10.  Bradycardia
 Bronchospasm
 Dyspnoea
 Cold extremities
 Hypoglycaemia
 Hyponatraemia and hyperkalaemia
 Insomnia / vivid dreams and nightmares (Joint
Formulary Committee, 2014)
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11.  Second- or third-degree heart block
 Worsening unstable heart failure
 Renal impairment
◦ Dose reduction of water-soluble beta-blockers, e.g.
atenolol and sotalol
 Asthma or COPD
◦ Treatment should be initiated by a specialist
 Diabetes
◦ Cardioselective beta-blockers are preferred
◦ Avoid altogether if hypoglycaemia occurs frequently
(Joint Formulary Committee, 2014)
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12.  Adrenaline and noradrenaline
 Antihypertensives, e.g. ACE inhibitors,
angiotensin-II-receptor antagonists, alpha-blockers,
calcium-channel blockers, diuretics
 Anti-arrhythmics, e.g. amiodarone, flecainide
 Anti-psychotics
◦ Increased risk of arrhythmias with sotalol
 Insulins
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13.  Conflicting research on use of beta-blockers
in cancers
◦ Use of beta-blockers pre-mastectomy in breast
cancer patients was associated with improved
recurrence-free survival (Melhem-Bertrand et al., 2011)
◦ Increased survival time of patients with melanoma
receiving beta-blockers (Lemeshow et al., 2011)
◦ No association between exposure to beta-blockers
and improved survival for breast, lung, or colorectal
cancer in hypertensive patients (Musselman et al. 2014)
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14.  Beta-blockers reduce platelet aggregation
◦ Non-selective lipophilic beta-blockers cause a
greater reduction than selective hydrophilic beta-blockers
(Bonten et al., 2014)
 Beta-blockers reduced risk of fractures (Toulis et
al., 2014)
 Mortality reduced post-acute traumatic brain
injury by beta-blockers (Alali et al., 2014)
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15.  All beta-blocker drug names end in ‘-lol’
 β1- and β2-adrenoceptor inverse agonists
 Decrease cAMP concentration
 Different mechanisms of action in different
muscle types
 Importance of chemical structure
 Indications, adverse effects, cautions,
contraindications, drug interactions
 Current research
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16.  Alali AS, McCredie VA, Golan E, Shah PS, and Nathens AB. (2014) Beta Blockers for Acute
Traumatic Brain Injury: A Systematic Review and Meta-analysis. Neurocrit Care 20 (3):
514-523.
 Bonten TN, Plaizier CEI, Snoep JJD, Stijnen T, Dekkers OM, and van der Bom JG. (2014)
Effect of β-blockers on platelet aggregation: a systematic review and meta-analysis. Br J
Clin Pharmacol 78 (5): 940-949.
 Gorre F, Vanderkerckhove H. (2010) Beta-blockers: focus on mechanism of action. Which
beta-blocker, when and why? Acta Cardiol 65 (5):565–570.
 Joint Formulary Committee. (2014) Beta-adrenoceptor blocking drugs. In: Joint
Formulary Committee. British National Formulary. 68th ed. London: BMJ Group and
Pharmaceutical Press.
 Klabunde RE. (2013) Beta-Adrenoceptor Antagonists (Beta-Blockers). Available:
http://cvpharmacology.com/cardioinhibitory/beta-blockers.htm. Last accessed 24th Oct
2014.
 Lechat P. (2008) Clinical pharmacology of beta-blockers in cardiology: trial results and
clinical applications. Hot Topics in Cardiology 10 (7):7-44.
 Lemeshow S, Sørensen HT, Phillips G, Yang EV, Antonsen S, Riis AH, Lesinski GB, Jackson
R, and Glaser R. (2011) β-Blockers and survival among Danish patients with malignant
melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev 20 (10):
2273-2279.
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17.  Mehvar R, Brocks DR. (2001) Stereospecific Pharmacokinetics and Pharmacodynamics of
Beta-Adrenergic Blockers in Humans. J Pharm Pharmaceutical Sci 4 (2):185-200.
 Musselman RP, Li W, Gomes T, Mamdani M, Haggar F, Mollo H, Boushey RP, Al-Omran M,
Al-Obeed O, VanWalraven C, and Auer RC. (2014) Association Between Beta Blocker
Usage and Cancer Survival in a Large, Matched Population Study Among Hypertensive
Patients. J Surg Res 186 (2): 639-640.
 Nobel Media AB. (2014) Sir James W. Black – Facts. Available:
http://www.nobelprize.org/nobel_prizes/medicine/laureates/1988/black-facts.html.
Last accessed 10th Nov 2014.
 Toulis KA, Hemming S, Stergianos S, Nirantharakumar K, and Bilezikian JP. (2014) β-
adrenergic receptor antagonists and fracture risk: a meta-analysis of selectivity, gender,
and site-specific effects. Osteoporos Int 25 (1): 121-129.
 van der Vring JAFM, Daniëls MCG, Holwerda NJH, Withagen PJAM, Schelling A, Cleophas
TJ, Hendriks MGC. (1999) Combination of Calcium Channel Blockers and Beta Blockers
for Patients with Exercise-Induced Angina Pectoris: A Double-Blind Parallel-Group
Comparison of Different Classes of Calcium Channel Blockers. Angiology 50 (6):447-
454.
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