27/11/2019

1. BETA BLOCKERS
PRESENTED BY:
DR RAJESH KUMAR SHAH
RESIDENT, PHARMACOLOGY
KUSMS, DHULIKHEL, NEPAL.

2. Brief introduction
 These drugs block the actions of
catecholamines by acting selectively and
competitively on the beta(β) adrenoceptors.
 The first β-adrenergic blocker drug to be used
clinically was propranolol (Inderal). Earlier β-
adrenoceptor blocking compound, Dichloro
isoprenaline (dichloroisoproterenol) had low
potency and was a partial agonist, and could
never be clinically used.
 All β-blockers are competitive antagonists.

3. Classification of β-blockers
A) Non-selective BBs:
1) PROPRANOLOL
2) PENBUTOLOL
3) CARTEOLOL
4) PINDOLOL
5) OXPRENOLOL
6) TIMOLOL
7) NADOLOL
8) SOTALOL
9) LABETALOL (α1+ non-selective β-blocker; +LA+IS)
10) CARVEDILOL (α1+ non-selective β-blocker; -LA-IS)
With additional LA/MS axn only
With additional partial
agonist/IS axn only
With both LA/MS as well
as PA/IS properties
With neither LA/MS nor
PA/IS properties
LA/MS: Local anaesthetic/Membrane
Stabilizing
PA/IS: Partial Agonist/Intrinsic

4. B) β1-Selective (Cardioselective) BBs:
1) METOPROLOL
2) ATENOLOL
3) ACEBUTOLOL
4) BISOPROLOL
5) BETAXOLOL
6) CELIPROLOL
7) ESMOLOL
8) NEBIVOLOL
C) β2-Selective BBs (not used clinically)
1) BUTOXAMINE

5. CLINICAL USES
 Mostly prophylactic, but also therapeutic
purpose.
 Used in following conditions:
1) Chronic prophylaxis of Angina of effort
2) Secondary prevention of Myocardial
infarction (MI)
3) Treatment of Acute MI (unless
contraindicated)
4) Heart failure (clinically stable chronic cases
only)
5) Hypertension
6) Cardiac arrhythmias
7) Hypertrophic obstructive cardiomyopathy

6. Clinical uses/…
8) Dissecting aortic aneurysm
9) Prevention of adverse cardiovascular
outcomes resulting from a non-cardiac
surgery (in selected at-risk patients)
10) Phaeochromocytoma
11) Thyrotoxicosis
12) Glaucoma
13) Migraine
14) Oesophageal variceal bleeding
associated with portal HTN and cirrhosis
of liver

7. 15) Essential tremor
16) Anxiety states
17) Withdrawal symptoms in alcohol
addicts
Novel uses (under trials)
1) Retinopathy of premature born
infants
2) PTSD (post traumatic stress
disorder)

8. A) In Angina Pectoris
 are used as chronic prophylaxis against
angina of effort.
 Due to negative chronotropic and inotropic
effect- decreases myocardial contraction and
C.O.
 Long term use has shown decreased
frequency of anginal episodes.

9. B) In MIs
 In 2 conditions:
1) In acute phase of MI- by
suppressing arrhythmias.
2) As a secondary prophylaxis to MI
– by decreasing myocardial oxygen
demand, prevent development of
infarct
 Prolongs survival with long-term use.

10. C) In Heart Failures
 Decrease in mortality in patients with
chronic heart failure.
◦ Decreased CO- decreased work load
◦ Decreases Renin secretion – finally leads to
decreased TPR
 By preventing overactive sympathetic
stimulation of myocardium by
catecholamines occurs in chronic cases
of heart failure, which may lead to
myocyte apoptosis.

11. D) In Cardiac Arrhythmias
 BBs slows down AV conduction, increases
refractory period .
 are Class II Antiarrhythmic drugs.
 SOTALOL is a Class III Antiarrhythmic drug
which additionally blocks K+ channels.
 Used in
1) Treatment of Supraventricular and
Ventricular arrhythmias
2) Supression of ventricular ectopic beat
precipitated by CA-mediated sympathetic
overactivity as during exercise, emotion and
anaesthesia.

12. E) In Hypertension(HTN)
 Decreases BP by:
a) Reducing C.O.
b) Inhibition in release of renin from
JG cells of kidney
c) reducing central sympathetic
outflow
d) by decreasing t.p.r after prolonged use.
 no longer a single drug for first-line therapy
against HTN.
 Are relatively milder antihypertensives when
compared to others like CCBs.

13. F) In Hypertrophic Obstructive
Cardiomyopathy
 Idiopathic hypertrophic subaortic
stenosis
 Decreases stroke volume by slowing
ventricular ejection and decreasing
outflow resistance.
Suppresses symptoms like palpitation,
angina; Propranolol 60 to 100mg per

14. G) Dissecting aortic aneurysm
 An aneurysm (an excessive localized
swelling of the wall of an artery) in
which the wall of an artery rips
(dissects) longitudinally.
 has beneficial effect by reducing
cardiac contractile force and systolic
pressure.

15. H) Phaeochromocytoma
 To control tachycardia and arrhythmia,
and cardiomyopathy associated with
excess CA release.
 Should never be used without a prior
α-blocker administration, otherwise a
serious rise in BP ensues.

16. I) Thyrotoxicosis
 BBs like PROPRANOLOL is used to
control symptoms like supraventricular
tachycardia which develops during
thyrotoxicosis and which may lead to
heart failure.

17. J) Glaucoma
 Timolol 0.25 to 0.5 % ophthalmic
drops used in chronic open-angle
glaucoma.
 by blocking β2-receptor on ciliary
epithelium, hence reducing secretion
of aqueous humor, thus decreasing
i.o.p.
 Comparable efficacy and often better
tolerated than pilocarpine or Adr.

18. K) Migraine
 PROPRANOLOL is the most effective
drug for chronic prophylaxis of
migraine headaches.
 Decreases the frequency and intensity
of migraine headaches.
 Mechanism unknown.

19. L) Oesophageal variceal
bleeding associated with portal
HTN and cirrhosis of liver
 by lowering BP in portal circulation.

20. M) Essential tremor
 Nonselective BBs used.
 Since sympathetic activity enhances
skeletal muscle tremor, sympatholytics
like BBs useful in such cases.
However, no benefit in Parkinsonian
tremors.

21. N) Anxiety states
 reduces performance anxiety by
suppressing symptoms like palpitation,
tremor, etc. associated with
sympathetic activity

22. O) Withdrawal symptoms in
alcohol addicts
 by suppressing symptoms like
anxiety, tremor, tachycardia etc.

23. Adverse effects
1) Bronchoconstriction :
due to β2-blockade; can be
lifethreatening in patients with asthma
and worsen obstructive lung diseases
like COPD.
2) Bradycardia:
can be lifethreatening in patients with
partial or complete AV conduction
defects as it would lead to
bradyarrhthmias.

24. 3) High risk of developing rebound
HTN, MI and sudden death, if BB-
therapy discontinued abruptly after
prolonged use (2 or more years) as a
chronic prophylaxis against angina
of effort:
(?due to upregulation of β2-receptors
or incresed sensitivity to it’s natural
laigands, the CAs?)

25. 4) Risk of heart failure in patients with
cardiac damage (severe,
uncompensated cases of CHF)
5) Hypoglycaemia unawareness:
BB (esp. non-selective BBs) will prevent
the appreciation of symptoms like
palpitation which are warning sign
when there is hypoglycaemia

26. Also, BB prevents CA-mediated
glycogenolysis inn hepatocytes in severe
hypoglycaemia.
6) Fatigue:
due to reduced C.O. by heart,
reduced skeletal muscle
perfusion,
reduced FFA (free fatty acid)
released in blood which could be used
as an alternative fuel.

27. 7) Cold extremities in winter:
cold hands and feet that
accompany chronic therapy are
probably due chiefly to reduced C.O.
with reduced peripheral blood flow,
rather than to the blocking of
peripheral skeletal muscles’ (β2)
vasodilator receptors.

28. 8) Total TGL (triglyceride) tend to
increase while HDL-cholesterol level
of blood decreases with long-term
use, which may increase
cardiovascular risks.
9) Exacerbates variant (vasospastic)
angina due to unopposed α-mediated
coronary vasoconstriction.

29. 10) Side effects not overtly related to β-
blockade include-
GI upset
Loss of libido in men
Forgetfulness
Mental depression (propranolol
may block some Serotonin receptors
in brain)

30. Contraindications
1) Severe bradicardia
2) Pre-existing heart block
3) Left ventricular heart failure (untreated
cases)
4) Cardiogenic shock
5) Active airway diseases like asthma
(absolute C/I), COPD (relative C/I)
6) Mental depression
7) Raynaud’s phenomenon
8) Prinzmetal’s angina
9) Diabetes mellitus
10) Concomitant use of CCBs or Digoxin.

31. references
1) Katzung
2) KD tripathi
3) Satoskar
4) Rang and Dale
5) Gillman and Goodman

32. THANK YOU!