Beta blockers

و في الرضِ
آياتٌ للموقنينَ *
و في أنفُسِكم
* أفل تُبْصِرونَ
الذاريات 20 و 21

HHooppee ddeessppiittee tthhee
““BBllaacckk”” yyeeaarr iinn
ccaarrddiioollooggyy
SSaayyeedd SSyylleeeemm,, MM..SScc..
Cardiologist
Kafr Saad central hospital
2010

Alpha 1 Receptors Alpha 2 receptors
Vasoconstriction (skin mucous m.)
Increase BP
Pupil dilation
Closure of urinary bladder sphincter
Thickened salivary secretions
Ejaculation
Decrease NE release
Decrease BP
Decrease GI motility
Beta 1 receptors Beta 2 receptors
Increase HR
Increase cardiac contraction
increase cardiac conduction
Lipolylis
Bronchodilation
Vasodilation (skeletal muscle)
Relaxation of uterus
Relaxation of GIT ↓GI secretions
Relaxation of urinary bladder
Increase blood sugar

Autonomic NS
PPaarraassyymmppaatthhoommiimmeettiiccss Direct Choline esters Acetyle choline
Cholinemimetic alkalo. Pilocarpine
Indirect Anti-choline esterase Physiostigmine
PPaarraassyymmppaatthhoollyyttiiccss Muscarinic receptor (-) Natural belladonna alk. Atropine
Synthetic atropine sups Ipratopium
Drugs affect ganglia Stimulants Nicotine
Blockers Tri-Metaphan
SSyymmppaatthhoommiimmeettiiccss Catecholamines Natural Dopamine- Adrenaline
Synthetic Dobutamine
Non-catecholamines  Ephidrine-Amphetam.
SSyymmppaatthhoollyyttiiccss Adrenergic blockers Alpha Prazocin
Beta    NNeexxtt
Alpha 2 stimulants  Alpha-Methyl dopa
Ganglion blockers  Tri-Metaphan
Neuron blockers  - NA release Bretylium
 Deplete NA stores Reserpine

Members
BB11BB22
AAcceebbuuttoollooll
AAtteennoollooll
Betaxolol
BBiissoopprroollooll
EEssmmoollooll
NNeebbiivvoollooll
MMeettoopprroollooll
BBeettaa bblloocckkeerrss wwiitthh iinnttrriinnssiicc ssyymmppaatthhoommiimmeettiicc aaccttiivviittyy ((IISSAA)) iinncclluuddee::
AAcceebbuuttoollooll
Carteolol
PPeennbbuuttoollooll
PPiinnddoollooll
BBeettaa bblloocckkeerrss tthhaatt aallssoo bblloocckk aallpphhaa bblloocckkeerrss iinncclluuddee::
CCaarrvveeddiillooll
LLaabbeettaallooll
BBeettaa bblloocckkeerrss tthhaatt aarree nnoonn--sseelleeccttiivvee,, ddoo nnoott hhaavvee IISSAA,, aanndd ddoo nnoott bblloocckk aallpphhaa rreecceeppttoorrss iinncclluuddee::
Levobunolol
Metipranolol
NNaaddoollooll
PPrroopprraannoollooll
SSoottaallooll
Timolol

UUsseess ooff BBeettaa bblloocckkeerrss
Preventing migraine headaches
Treating HTN
Reducing the risk of future heart attacks and heart-related
death in people who have had a heart attack
Treating CHF
Treating glaucoma
Treating certain arrhythmias, such as AF and AFlut
Treating angina
Treating HOCM.
Thyrotoxicosis
Portal HTN

BBuutt iinn 22000055
CCoonncclluussiioonnss:: Nonselective BBs are
ineffective in preventing varices in
unselected patients with cirrhosis
and portal HTN and are associated
with ↑↑ number of adverse events.
Groszmann, et al. (2005) Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.
New England Journal of Medicine , 353 (21) , pp. 2254-2261.

Side effects of Beta Blockers
Bradycardia
Hypotension
Fatigue
Cold hands and feet
Bronchospasm
Dizziness.
+ VLDL
Sudden stop Angina, MI, arrhythmia

Do Beta Blockers Cause
Sexual Side Effects?
Decreased libido.
Impotence (erectile dysfunction (ED))
Peyronie's disease

IIss iitt ttrruuee??
It is important to understand that BB are frequently used in oollddeerr and
hhyyppeerrtteennssiivvee individuals (who are more likely to have sexual problems). This
makes it difficult to know if the sexual side effects are actually caused by the
medication or other factors.
Researchers found that people who knew that impotence was a side effect of
BB were more likely to develop impotence. Their conclusion was that the
knowledge about side effects of BBs can produce anxiety that may cause
erectile dysfunction.“
This study also found that a placebo (a sugar pill that does not contain any
active ingredients) was just as effective as ssiillddeennaaffiill for reversing impotence in
these men taking a beta blocker.

PPrreeccaauuttiioonnss wwiitthh BBBB uussee
Heart failure
Bradycardia
Liver disease, such as liver failure, cirrhosis, or hepatitis
Kidney disease, such as renal failure
Diabetes
Had a CVA or TIA
Heart block
Sick sinus syndrome
Asthma
COPD
Hyperthyroidism
An upcoming surgery
Myasthenia gravis
PAD
Any allergies, including allergies to foods, dyes, or preservatives.
Pregnant or thinking of becoming pregnant
Breastfeeding.

AAnn oovveerrddoossee wwiitthh aa bbeettaa bblloocckkeerr mmaayy
ccaauussee tthhee ffoolllloowwiinngg pprroobblleemmss::
Bradycardia.
Constriction of the airway.
CHF
Cardiac arrest
Coma.
Hypotension.
Hypoglycemia.
TTrreeaattmmeenntt ffoorr aa BBeettaa BBlloocckkeerr OOvveerrddoossee
Medications to increase the heart rate
IV fluids and medications to increase blood pressure
Asthma medications to reverse airway constriction
IV glucose to reverse low blood sugar levels.

Pregnancy Category Ratings
The following beta blockers are Pregnancy Category B medications:
Acebutolol
Pindolol
Sotalol
The following beta blockers are Pregnancy Category C medications:
Betaxolol
Bisoprolol
Carteolol
Carvedilol
Esmolol
Labetalol
Levobunolol
Metipranolol
Metoprolol
Nadolol
Nebivolol
Penbutolol
Propranolol
Timolol
The following beta blockers are Pregnancy Category D medications:
Atenolol

Beta Blockers and Breast Milk
The following beta blockers ppaassss tthhrroouugghh bbrreeaasstt mmiillkk::
Acebutolol
Atenolol
Betaxolol
Levatol
Metoprolol
Nadolol
Pindolol
Propranolol
Sotalol
Timolol
TThhee mmeeddiiccaattiioonn ccoouulldd ppootteennttiiaallllyy ppaassss tthhrroouugghh bbrreeaasstt mmiillkk::
Bisoprolol
Carvedilol
Carteolol
Esmolol
Levobunolol
Metipranolol
Nebivolol
Penbutolol

There are many thousands of us
alive today thanks to the brilliant,
pioneering work of
JJaammeess WWhhyyttee
BBllaacckk..

He was born in 1924 in Uddingston, Lanarkshire.
His father was a Scottish mining engineer. He was
the 4th son of 5 .
Money was tight but he entered the St Andrews
University exam by his maths teacher and, at the
age of 15, won a residential scholarship there where
he studied medicine.

Black met Hilary Joan Vaughan (his age) at university in
1944.
He completed his medical degree in 1946, he committed
himself to physiological research.
In 1946 he married the fellow student Hilary Vaughan.
In 1947 they moved to Singapore, where he lectured at King
Edward VII College of Medicine, University of Malaya.

Returning to Britain in 1950, with what he said was
no home, no income of any kind and no prospects.
But a chance meeting with an old colleague on
Oxford Street led to a job (physiology lecturer) in the
University of Glasgow Veterinary School, where he
said he slowly learned, like a primitive painter, how
to be an effective experimenter.“ As he developed an
interest in the way adrenaline affects the human
heart, particularly in those suffering from angina.
The couple had a daughter, Stephanie, born in 1951.

He worked for ICI Pharmaceuticals from 1958 until
1964, during which time he developed propranolol
to treat high blood pressure and heart disease,
hailed as the greatest breakthrough in the
treatment of that killer disease since the discovery
of digitalis. Beta blockers, they became at one time
the world's best-selling drug, slowing down the
heart rate to treat and prevent heart attacks and
angina pectoris and reduce high blood pressure.

He was developing a similar method of treatment for
stomach ulcers, but ICI did not wish to pursue the idea so
Black resigned and joined Smith, Kline and French for
whom he worked for 9 years.
While there, he developed his second major drug,
cimetidine which was launched under the brand name
Tagamet in 1975. It outsold even his propranolol beta
blocker to become the world's largest-selling prescription
drug in 1988 and was the first prescription drug to sell over
a billion dollars-worth. Ranitidine followed, using similar
principles.
Prior to these drugs surgery was the most common way to
deal with stomach ulcers but this was often unsuccessful.
http://hosted.ap.org/photos/C/ccc684f9-0f18-4835-baec-cd953f98aff5-bi...

He was elected a Fellow of the Royal Society in 1976 and
the same year he was awarded the Lasker award.
In 1979, he was awarded the Artois-Baillet Latour Health
Prize.
He was made a Knight Bachelor on 10 February 1981 for
services to medical research, receiving the honour from the
Queen at Buckingham Palace,
In 1982 Black was awarded the Wolf Prize in Medicine.
In 1984 he became Professor of Analytical Pharmacology at
the Rayne Institute of the King's College London medical
school, where he remained until 1992.

Hilary died in 1986, aged 62.
He established the James Black Foundation in
1988 with funding from Johnson and Johnson and
led a team of 25 scientists in drugs research,
including gastrin inhibitors which may prevent
some stomach cancers.
He was awarded the 1988 Nobel Prize in Medicine.
On 26 May 2000 he was appointed to the Order of
Merit, of which there are only 24 members at any
one time, by Queen Elizabeth II.

Served as chancellor of the University of Dundee, Scotland,
from 1992 to 2006.
In 1994 he received the Ellison-Cliffe Medal from the Royal
Society of Medicine.
In 1994, he married Rona MacKie who survives him, as
does Stephanie, the daughter of his first marriage.
in 2004 was awarded the society's Royal Medal.
During this time, he pioneered a method of research of
intelligent drug design, now the foundation of the
development of most new developments in the world-wide
pharmaceutical industry.

His invention of pprroopprraannoollooll is considered to be one of the most
important contributions to clinical medicine and pharmacology of the
20th century.
It is estimated that medicines developed along the methodologies
established by Black represent 20% of the $825 billion annual turnover
of the world's top-selling drugs.
The success of beta blockers was a major contributor to reducing the
mortality rate from heart disease in the last few decades.
In the UK alone 255 of every 100,000 men died from coronary heart
disease in 1978. By 2007 that figure had plummeted to 65 per 100,000.
They have prolonged the lives of millions of people and improved the
quality of their lives as well.

Black was such a very
private man who
was averse to
publicity that he
was horrified to
discover he had
won the Nobel
Prize! He later
remarked dryly that
when he was told
he had won the
Nobel Prize he had
commented I wish
I had had my beta
blockers handy to
slow down my heart
rate!

أوضحت دراسة لباحثين في جامعة تكساس،
نشرت في مجلة نيوانجلند الطبية، أن إعطاء جرعات كبيرة
من عقار بروبرانولول تعجل في الستشفاء من
الحروق و تقلل من تلف العضلت الذي يصاحب عادة
الصابة بالحروق الشديدة.

يذكر أن فترة النقاهة التي تلي التعرض للحروق الشديدة تشهد ميل سلبيا للجسم يتمثل في محاولته
التخلص من البروتين وبالتالي ضمور وضعف
العضلت.
وتتبع رئيس الفريق العلمي الدكتور ديفيد هيرندون
25 أحوال طفل من ضحايا الحروق، تناول نصفهم
تقريبا عقار فيهم، فوجدوا www.بروبرانولول، وتم قياس هزال العضلت
أن مستويات بروتين العضلت
bbc.co.uk/doctorwho/dw

In March,22, 2010
after a long illness, Sir James died on
Monday aged 86.

In the days following the announcement of
his death, researchers revealed that beta
blockers had been found to be a potential
treatment for breast cancer, following trials
which showed that the drug produced
significant falls in both cancer spread and
local recurrence.

November 2006
USA study in Ohaio state university 
nore-adrenaline + tumor growth
and spread
“Ronald Glasser et al.”

March 2010
Germany-England study found that
patients with cancer who were taking
BBs  decreased the risk of dying

March 2010
Des Powe et al. (Nottingham university) (Queen’s medical
center) (UK)
The study looked at data on 466 patients over ten years. Three
groups were examined: those being treated for hypertension by
BBs, those whose HTN was treated by other medications, and
those who did not suffer from hypertension and were therefore
not taking any medication. 43 of the 466 patients were already
taking BBs and, in this group, there were significant falls in
both cancer spread and local recurrence. They also had a 71 %
lower risk of dying from breast cancer compared with the other
groups.

References
1. De biec, J. Ledoux, J. E. Neuroscience 129, 267 - 272 (2005).
2. Shalev, A. Y. Freedman, S. Am. J. Psychiatry 162, 1188 - 1191 (2005).
3. Verger, P. et al. Am. J. Psychiatry 161, 1384 - 1389 (2004).
4. Blanchard, E. B. et al. Behav. Res. Ther. 42, 191 - 205 (2004); 43, 143 - 150 (2005).
5. ^ Nobel Prize winning scientist dies stv.tv 22 March 2010 Link accessed 22 March 2010
6. ^ Tore Frängsmyr (1989). Sir James W. Black: The Nobel Prize in Physiology or Medicine. Les Prix Nobel. Nobel Foundation.
http://nobelprize.org/nobel_prizes/medicine/laureates/1988/black-autobio.html. Retrieved 2007-08-25.
7. ^ a b c d e f Black, Sir James W. Autobiography. The Nobel Foundation. http://nobelprize.org/nobel_prizes/medicine/laureates/1988/black-autobio.
html. Retrieved 23 March 2010.
8. ^ Scottish Nobel prize winner Sir James Black dies at age 85. The Daily Record. 23 March 2010.
http://www.dailyrecord.co.uk/news/scottish-news/2010/03/23/scottish-nobel-prize-winner-sir-james-black-dies-at-age-85-86908-22132778/.
Retrieved 25 March 2010.
9. ^ a b c d e f g h i j k l Sir James Black, OM. The Telegraph. 23 March 2010. http://www.telegraph.co.uk/news/obituaries/medicine-obituaries/
7507080/Sir-James-Black-OM.html. Retrieved 25 March 2010.
10. ^ a b Heart disease treatment pioneer James Black dies. Associated Press. 22 March 2010.
http://www.google.com/hostednews/ap/article/ALeqM5i2Ues0zJeT4AJpCxJoQTN4odqhCQD9EJUOF00. Retrieved 25 March 2010.
11. ^ a b c d e Led the way in heart drug find. The Age (Melbourne: Fairfax Digital). 25 March 2010. http://www.theage.com.au/world/led-the-way-
in-heart-drug-find-20100324-qwo8.html. Retrieved 25 March 2010.
12. ^ Sir James Black talks about his move from ICI to Smith Kline French (part of a series of in-depth videos of Sir James Black telling his life
story (http://webofstories.com). Web of Stories. http://www.webofstories.com/play/17232.
13. ^ Stapleton, Melanie P. (1997). Sir James Black and Propranolol. Texas Heart Institute Journal 24 (4): 336–342.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC325477/pdf/thij00027-0106.pdf.
14. ^ anTAGonist and ciMETidine. American Chemical Society. 2005. http://pubs.acs.org/cen/coverstory/83/8325/8325tagamet.html.
Retrieved December 25, 2005.
15. ^ Alan Taylor (25 January 2004). Or is this our national hero?. Sunday Herald.
http://findarticles.com/p/articles/mi_qn4156/is_20040125/ai_n9627859. Retrieved January 25, 2004.
16. ^ London Gazette: (Supplement) no. 48542, p. 3087, 3 March 1981. Retrieved 25 March 2010.
17. ^ London Gazette: no. 55859, p. 5821, 26 May 2000. Retrieved 26 March 2010.
18. ^ a b Diffin, Elizabeth (24 March 2010). What is the Order of Merit?. BBC News Magazine (BBC).
http://news.bbc.co.uk/1/hi/magazine/8584941.stm. Retrieved 25 March 2010.
19. ^ 1976 winners: Albert Lasker Award for Clinical Medical Research. Lasker Medical Research Network. 1976.
http://www.laskerfoundation.org/awards/library/1976clinical.shtml.
20. ^ 1988 Nobel Prize for Medicine. Karolinska Institute. 1988.
http://nobelprize.org/nobel_prizes/medicine/laureates/1988/.
21. ^ Deaths England and Wales 1984-2006
22. ^ Nobel Prize-winning scientist Sir James Black dies. BBC News (BBC). 22 March 2010.
http://news.bbc.co.uk/1/hi/scotland/glasgow_and_west/8580567.stm. Retrieved 25 March 2010.

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