Transcript Beta-blockers

PHM142 Fall 2014
Instructor: Dr. Jeffrey Henderson
β blockers
Arpit Chhabra
Stephanie Rankin
Victor Lam
Natalie Ternamian
PHM 142
Dec 2, 2014
overview
β-adrenergic receptors
- subtypes
- distribution
β-blockers
- introduction and classification
propranolol
- indications and uses
- special use cases
summary
G-protein Coupled
Receptors (GPCRs)
distribution of β-adrenergic receptors
β1 receptors
- cardiac muscle
- kidney
β2 receptors
- smooth muscle cells
- vascular, bronchiolar, uterine,
detrusor muscle etc.
β3 receptors
- adipose tissues
what is a β blocker?
Agent which competitively inhibits βagonists (epinephrine, norepinephrine)
from binding to receptors.
classification of β blockers
Adrenergic Receptor Antagonists
Alpha Blockers
α1
selective
α2
selective
Nonselective
(Irrev/Rev)
Beta Blockers
Nonselective
β1
selective
β2
selective
all the LOLs
non-selective:
Timolol
Carvedilol
Sotalol
Pindolol
β1 selective:
Atenolol
Bisoprolol
Metoprolol
Nebivolol
β2/β3 selective not clinically
significant
propranolol
Inderal (propranolol)
•
•
•
•
non-selective
short t1/2
hospital use
lipid-soluble
propranolol: β1-antagonism
β1-adrenoceptor agonist effect
location
propranolol effect
indications
cardiac muscle
increased C.O.
(chronotropy,
inotropy)
decreased C.O.
• hypertension
• post-MI (cardioprotective)
• angina pectoris (reduced O2
demand)
cardiac muscle
Proarrhythmic
antiarrhytmic via
membrane
stabilization
• tachyarrhythmias
• tremors
propranolol: BP pathways
propranolol: β1-antagonism
β1-adrenoceptor agonist effect
location
propranolol effect
indications
cardiac muscle
increased C.O.
(chronotropy,
inotropy)
decreased C.O.
• hypertension
• post-MI (cardioprotective)
• angina pectoris (reduced O2
demand)
cardiac muscle
Proarrhythmic
antiarrhytmic via
membrane
stabilization
• tachyarrhythmias
• tremors
kidneys
renin release
upregulates A II,
increasing
vasoconstriction
and blood volume
decreased renin
secretion (RLS of the
renin-angiotensin
system)
hypertension; perhaps more so in
patients with high PRA
propranolol: β2-antagonism
β2-adrenoceptor
location
agonist effect
propranolol effect
clinical notes
peripheral
vasculature
vasodilation
little, if any (NE has very
low affinity vs α1)
cranial and cortex
vasculature
vasodilation
vasoconstriction
proposed mechanism of antimigraine effects
bronchial smooth
muscle
bronchodilation
possible
bronchoconstriction
contraindicated in asthma
eye
aqueous humour
production
decreased aqueous
humour production
useful in reducing intraocular
pressure in glaucoma
*timolol
propranolol: first-line treatment for IH
Infantile Hemangioma
• vascular tumours characterized by rapid
proliferation and subsequently slower
involution.
• Most regress, but some can cause
disfigurement and systematic
complications.
propranolol: first-line treatment for IH
propranolol treatment results in
inhibition of
• angiogenesis
• stimulation of vasoconstriction
• triggering of apoptosis
• increase of GJIC
• prevention of cell proliferation
propranolol: diverse uses
• musicians
• athletes (pistol shooting, archery.. )
• surgeons
Summary
•
•
•
β-adrenoceptors: A Gs-type GPCR. Primary effects are downstream of activated PKA.
β-blockers: competitively inhibit β-agonists (E, NE) from binding to β-receptors.
•
classified into: non-selective, β1-selective and β2-selective.
propranolol: A non-selective, lipophilic β-blocker with a short half life.
β1-adrenoceptor location
agonist effect
propranolol effect
indications
cardiac muscle
increased C.O. (chronotropy,
inotropy)
decreased C.O.
•
•
•
hypertension
post-MI (cardioprotective)
angina pectoris (reduced O2 demand)
cardiac muscle
Proarrhythmic
antiarrhytmic via membrane
stabilization
•
•
tachyarrhythmias
tremors
kidneys
renin release upregulates A II,
increasing vasoconstriction and
blood volume
decreased renin secretion (RLS of
the renin-angiotensin system)
hypertension; perhaps more so in patients with high PRA
•
•
•
β2 effects of propranolol:
•
vasoconstriction – useful in migraine prophylaxis
•
bronchioconstriction – counter-indication for asthmatics
•
inhibiting aqueous humour production – topical use in glaucoma (*timolol preferred)
novel use of propranolol: treatment of Infantile Hemangiomas by inhibition of angiogenesis, cell proliferation and improved intercellular
communication and triggering apoptosis.
diverse uses of propranolol: reduces performance anxiety (sports, musicians)
references

Wang, D. W., Mistry, A. M., Kahlig, K. M., Kearney, J. A., Xiang, J., & George Jr, A. L. (2010). Propranolol blocks cardiac and neuronal voltage-gated sodium channels. Frontiers in
pharmacology, 1.

Mueller, H. S., AYRES, S. M., RELIGA, A., & EVANS, R. G. (1974). Propranolol in the Treatment of Acute Myocardial Infarction Effect on Myocardial Oxygenation and
Hemodynamics. Circulation, 49(6), 1078-1087.

Blanke, K., Dähnert, I., & Salameh, A. (2013). Role of connexins in infantile hemangiomas. Frontiers in pharmacology, 4.

Joyce, Jeffrey N., Nedra Lexow, Soo Jin Kim, Roman Artymyshyn, Shari Senzon, David Lawerence, Manuel F. Cassanova, Joel E. Kleinman, Edward D. Bird, and Andrew Winokur.
"Distribution of beta‐adrenergic receptor subtypes in human post‐mortem brain: Alterations in limbic regions of schizophrenics."Synapse 10, no. 3 (1992): 228-246.

Lockwood, A.H. Medical Problems of Musicians. N Engl J Med 1989; 320:221-227
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Fishbein, M. et al. Medical Problems Among ICSOM Musicians: Overview of a National Survey. Med Probl Perform Artist 1988; 3:1–8.
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Nubé, J. Beta-blockers: Effects on performing musicians. Medical Problems of Performing Artists 1991, 6(2):61-68.
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Oransky, I. (2008, August 15). Why would an Olympics shooter take propranolol? Retrieved November 24, 2014, from http://www.scientificamerican.com/article/olympicsshooter-doping-propranolol/
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Elman, M.J. The Effect of Propranolol Versus Placebo on Resident Surgical Performance. Tr Am Ophth Soc 1998, 96:283-294
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http://www.patient.co.uk/medicine/propranolol-a-beta-blocker
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http://medschool.swmed.edu/resources/drugs/list-001/drug-009.php
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http://www.bhsoc.org/pdfs/therapeutics/Beta-adrenoceptor%20Antagonists%20(Beta-Blockers).pdf
images
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http://www.frontiersin.org/files/Articles/47366/fphar-04-00041-HTML/image_m/fphar-04-00041-g001.jpg
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http://www.onlinedermclinic.com/dz_images/8/9/8957919314e47100f6c0c2.jpg
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http://www.herballove.com/sites/default/files/images/guide/men/penis_curvature/hypertension_drugs_b.gif
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http://image.slidesharecdn.com/betablockersdrwanazizi-130731201402-phpapp01/95/beta-blockers-dr-wan-azizi-21-638.jpg?cb=1375319693
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http://cmapspublic2.ihmc.us/rid=1H4CT1Y3D-T7YJB6-1CK8/propranolol.png
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http://medimoon.com/wp-content/uploads/2013/04/propranolol_80x56s.gif