Beta Blocker

blockers are used for a number of

cardiovascular conditions, including ischemic
heart disease, hypertension, heart failure, and
tachyarrhytmias.
blockers decrease inotropy, slow heart rate, and
decrease conduction velocity.
1-adrenergic receptors are primarily located on
the surface of the myocardium
2-adrenergic receptors are primarily located on
the vascular and bronchial smooth muscle

Pathophysiology of the heart

Lionel Opie, Drugs for the heart
1. Ischemic Heart Disease
 Blockade is usually started early
Blockers are often combined with nitrate
vasodilators and calcium channel blockers (CCBs)
in the therapy of angina
Chronic Il-blockade increases B-receptor density.
When P-blockers are suddenly withdrawn, angina
may be exacerbated, sometimes resulting in
myocardial infarction.
Printzmetals variant angina B blocker is
ineffective and even harmful
 STEMI
Early STEMI
American Heart Association (AHA) guidelines
recommend starting half-dose oral b-blockade
on day 2 (assuming hemodynamic stability)
followed by dose increase to the full or the
maximum tolerated dose, followed by long-
term postinfarct b-blockade
Postinfarction

Administer b-blockade for all postinfarct

patients with an ejection fraction (EF) of 40%
or less unless contraindicated,
Administer b-blockade for 3 years in patients
with normal LV function after AMI or ACS.
 the Thrombolysis in Myocardial Infarction (TIMI)-II-
B trial, patients with ACS treated with fibrinolysis
were randomized to receive immediate treatment
with -blockers (metoprolol 5 mg IV) or deferred
treatment. After 6 weeks of follow-up, there was
no difference in the primary outcome of mortality
between the 2 groups. There was, however, a
lower incidence of recurrent chest pain (18.8 vs.
24.1%) and recurrent infarction (2.7 vs. 5.1%) in
the patients that received immediate treatment
with -blockade
 These findings were reproduced with atenolol in a
post hoc analysis of the Global Utilization of
Streptokinase and Tissue Plasminogen Activator
for Occluded Coronary Arteries-1 (GUSTO-1)
database. It is important to note that this trial
demonstrated a slightly increased risk of heart
failure.
 The most recent randomized trial evaluating the
use of intravenous metoprolol for ACS included
45,852 patients in Asia [Clopidogrel and
Metoprolol in Myocardial Infarction Trial
(COMMIT)]. The majority of this population
presented with ECG evidence of STEMI (93%) and
were randomized to receive immediate treatment
with intravenous -blockers (metoprolol 5 mg IV)
followed by oral metoprolol (200 mg daily) or
placebo.
 The primary combined composite end-point of
death, reinfarction, or cardiac arrest was
equivalent between the 2 groups (9.4 vs. 9.9%).
Treatment with -blockers did result, however, in
a reduction in the rate of reinfarction (2.0 vs.
2.5%) as well as an increase in the rate of
cardiogenic shock (5.0 vs. 3.9%). Based on this
data, greater caution is now suggested in the
routine use of intravenous -blockers for ACS. In
particular, these agents should be avoided in
patients with clinical evidence of heart failure or
hemodynamic instability
 In the last 10 years, the U.S. carvedilol trials,
Carvedilol Prospective Randomized Cumulative
Survival (COPERNICUS), and Effect of Carvedilol on
Outcome After Myocardial Infarction in Patients with
Left Ventricular Dysfunction (CAPRICORN), all
explored the benefits of the selective beta-blocker,
carvedilol, in the polypharmacy environment of
patients with heart failure. The former two studies
were in heart failure populations with reduced left
ventricular ejection fraction (LVEF); the CAPRICORN
trial studied a post-AMI population with low LVEF
(40%).
 The SAVE trial showed that ACE
inhibitors and blockade are additive in
reducing postinfarct mortality, at least
in patients wilh reduced ejection
fractions. The benefit of blockade when
added to cotherapy wilh ACE inhibitors
is a mortality reduction of 23% to 40%
2. Hypertension
B-Blockers are no longer recommended as first-line
treatment for hypertension.
JNC7 lists the following as 'compelling indications
for the use of B-blockers in hypertension: heart
failure, post-MI hypertension, high coronary risk,
and diabetes
Hypertension plus effort angina : risk of new
diabetes.
Older patient : B Blockade reduces the central
aortic pressure
 INVEST study, in 6391 patients with
hypertension and coronary artery
disease followed for more than 2 years,
the b-blocker atenolol gave similar
major cardiovascular outcomes to the
nondihydropyridine CCB verapamil, and
yet the b-blocker group had more
anginal episodes, new diabetes, and
psychological depression
3. Heart failure
3. Heart failure
Trials in patients with all classes of clinically stable
heart failure have actually shown a survival benefit
with chronic B-blocker administration using
carvedilol, metoprolol, or bisoprolol.
The mechanism may relate to blunting of
cardiotoxic effects of excesive circulating
cathecolamines.
The therapy should be started at low dosage,
augmented slowly, and carefully monitored
 The first large, prospective, comparative trial of a
beta-blocker vs an angiotensin-converting enzyme
(ACE) inhibitor as initial therapy in patients with
congestive heart failure (CHF), the Cardiac
Insufficiency Bisoprolol Study III (CIBIS III), has
shown that initiating treatment with the selective
beta-1 receptor blocker bisoprolol is as effective
and well tolerated as beginning treatment with the
ACE inhibitor enalapril. Results of CIBIS III,
presented at the European Society of Cardiology
(ESC) Congress 2005[1]and published
simultaneously inCirculation,also suggest that
starting treatment with bisoprolol may reduce the
risk of death, especially in the first year of
treatment.
 the COMET trial; carvedilol reduced
mortality more than metoprolol. Thus far
there is no evidence that diastolic heart
failure improves.
For every heart rate reduction of 5
beats/min with b-blockade, there is an
18% reduction (cardiac index, 6%-29%)
in the risk for death as occurred in the
23 b-blocker trials in 19,209 patients, of
whom more than 95% had systolic
dysfunction
4. Antiarrhytmias
B-blocker decreased slope of phase 4
depolarization reduce automaticity
B-blocker increase the effective refractory periode
of the AV node reduce reentry
b-blockade may help in the prophylaxis of SVTs by
inhibiting the initiating atrial ectopic beats and in
the treatment of SVT by slowing the AV node and
lessening the ventricular response rate
In patients with atrial fibrillation, current
management practices often aim at control of
ventricular rate (rate control)
a retrospective analysis of data from the CAST
study shows that B-blockade reduced all cause
mortality and arrhythmia deaths
Other cardiac indication
Hypertrophic obstructive cardiomyopathy
high dose propanolol
Mitral stenosis with sinus rhythm
decreasing resting and exercise heart rates
Mitral valve prolapse for control of
associated arrhythmias
Dissecting aneurysms propanonol IV, but
could be replaced by esmolol.
TOF 2mg/kg twice daily effective against
cyanotic spells
Adverse Effects
1. B-blocker non selective agents (or large doses of
B1 selective blockers) can exacerbate
bronchospasm
2. The impairment of AV nodal conduction by B-
blockade can cause conduction blocks.
3. B-blocker can precipitate arterial vasospasm
worsening PAD
4. Abrubt withdrawal of a B-blocker after chronic
use could precipitate myocardial ischemia in
patients with CAD.
5. Reduce HDL and increase triglyseride
6. B2 blockade may impair recovery from
hypoglycemia in diabetics suffering in insulin
reaction.
Calcium
Channel
Blocker
 Calcium channel blockers (CCBs; calcium
antagonists) act chiefly by vasodilation and
reduction of the peripheral vascular resistance
CCBs have ability to impede the influx of calcium
through membrane channels in cardiac and
smooth muscle.
CCBs reduce myocardial contractility resulting in
a reduction in myocardial oxygen demand.
CCBs also dilate the epicardial coronary arteries
resulting in an increase in myocardial oxygen
supply
CCBs are particularly effective in elderly patients.
Major indications
Stable effort angina
Unstable angina verapamil
Coronary spasm
Hypertensionbest for older and black
patients
SVT inhibit the AV node
Postinfact protection verapamil
Verapamil
Oral verapamil takes 2 hours to act and
peaks at 3 hours
The elimination half-life is usually 3 to 7
hours
Dose is 180-360 mg daily
Side effects of verapamil causing
headaches, facial flushing, and
dizziness.
 Diltiazem
The onset of action of short-acting diltiazem is
within 15 to 30 minutes (oral), with a peak at 1
to 2 hours. The elimination half-life is 4 to 7
hours.
The dose of diltiazem is 120 to 360 mg, given in
four daily doses of the short-acting formulation
or once or twice a day with slow-release
preparations.
Normally side effects of the standard
preparation are few and limited to headaches,
dizziness, and ankle edema
Amlodipin
Peak blood levels are reached after 6 to
12 hours, the elimination half-life is 35
to 48 hours
In women there is more edema (15%)
than in men (6%). Next in significance
are dizziness (3% to 4%) and flushing
(2% to 3%).
Clinical Trial
The Multicenter Diltiazem Postinfarction
Trial (MDPIT) randomized 2,466 patients
to diltiazem (240 mg daily) or placebo
315 days after presenting with a
myocardial infarction. After over 2 years
of follow-up, the mortality between the
2 groups was identical (13.5%) with a
nonsignificant trend toward fewer
recurrent events in patients treated with
diltiazem (16.4 vs. 18.3%)
 The Danish Study Group on Verapamil in
Myocardial Infarction II (DAVIT II) randomized
almost 1,800 patients to verapamil (360 mg
daily) or placebo in the second week after
admission for ACS. Treatment with verapamil had
a nonsignificant reduction in mortality (11.1 vs.
13.8%). A meta-analysis including 19,000
patients derived from 28 independent trials
assessing the utility of calcium channel blockers
has confirmed these findings
 In the aforementioned MDPIT, patients with
impaired left ventricular ejection fraction (<40%)
with evidence of pulmonary congestion on chest
radiograph, who were treated with diltiazem, had
an increased number of cardiac events and
worsened mortality. Because of this, CCBs should
be avoided in patients presenting with ACS with
concomitant left ventricular systolic dysfunction
 Terima Kasih
InACTION,a large placebo-controlled trial long-
acting nifedipine in SCAD proved to be safe and
reduced the need for coronary angiography and
cardiovascular interventions