THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 1

Introduction
Hypertension
Hypertension (high blood pressure) is one of the major risk factors for cardiovascular
diseases. There is overwhelming evidence that elevated blood pressure (systolic, diastolic or
both) increases the probability of ischemic heart disease, stroke, coronary hem disease and
overall mortality. In the general population, hypertension is more common in males, in
smokers and in older age groups
[1]



Arterial Pressure

Arterial blood pressure is generated by the left ventricle ejecting blood into the systemic
vasculature, which acts as a resistance to cardiac output. With each ejection of blood during
ventricular systole, the aortic blood volume increases, which stretches the wall of the aorta.
As the heart relaxes (ventricular diastole), blood flows from the aorta into distributing arteries
that transport the blood to the various organs. Within the organs, the arterial vasculature
undergoes extensive branching and the vessel diameters decrease. The smaller arteries and
arterioles serve as the chief resistance vessels, and through changes in their diameter, serve to
regulate systemic vascular resistance and organ blood flow.
In hemodynamic terms, the mean arterial pressure (MAP) can be described by

Equation 1: MAP = (CO x SVR) + CVP

where CO = cardiac output, SVR = systemic vascular resistance, and CVP = central venous
pressure. Therefore, increases in CO, SVR or CVP will lead to increases in MAP.
Hypertension Categories
According to the latest U.S. national guidelines (JNC 7 Report), the following categories of
hypertension have been defined:
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 2

Classification
Systolic
(mmHg)
Diastolic
(mmHg)
Normal* <120 <80
Prehypertension 120-139 80-89
Stage 1 140-159 90-99
Stage 2 >160 >100
Table 1. Category of Hypertension
*Arterial pressures less than 90/60 mmHg are considered hypotension, and therefore not
normal.
It is important to note that a hypertensive state may defined as an abnormal elevation of either
systolic or diastolic pressure. In past years, the diastolic value was emphasized in determining
whether or not a person was hypertensive. However, elevations in systolic pressure ("systolic
hypertension") are also associated with increased incidence of coronary and cerebrovascular
disease (e.g., stroke). Therefore, we now recognize that both systolic and diastolic pressure
values are important to note.
Causes of Hypertension

Fig 1. Causes of Hypertension
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 3


There are two basic types of hypertension: primary (essential) hypertension and secondary
hypertension. The vast majority of patients (90-95%) have essential hypertension, which is a
form with no identifiable underlying cause. This form of hypertension is commonly treated
with drugs in addition to lifestyle changes (e.g., exercise, proper nutrition, weight reduction,
stress reduction).
A smaller number of patients (5-10%) have secondary hypertension that is caused by an
identifiable underlying condition such as renal artery disease, thyroid disease, primary
hyperaldosteronism, pregnancy, etc.

BP = blood pressure; CKD = chronic kidney disease; CV = cardiovascular; CVD =
cardiovascular disease; DBP = diastolic blood pressure;HT = hypertension; OD = organ
damage; RF = risk factor; SBP = systolic blood pressure.
Table 2. Stratification of total CV risk in categories of low, moderate, high and very high risk
according to SBP and DBP






THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 4

Some causes of secondary hypertension are listed below:
Renal artery stenosis
Chronic renal disease
Primary hyperaldosteronism
Stress
Sleep apnea
Hyper- or hypothyroidism
Pheochromocytoma
Preeclampsia
Aortic coarctation



Fig 2 Some causes of secondary hypertension

The Pharmacologic Treatment of Systemic Hypertension - Antihypertensive Drugs
Rationale for Pharmacologic Treatment of Hypertension
Patients with primary hypertension are generally treated with drugs that
1) reduce blood volume (which reduces central venous pressure and cardiac output),
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 5

2) reduce systemic vascular resistance, or
3) reduce cardiac output by depressing heart rate and stroke volume. Patients with secondary
hypertension are best treated by controlling or removing the underlying disease or
pathology, although they may still require antihypertensive drugs.
Rationale for Reducing Arterial Pressure
Reduce Cardiac Output
Reduce blood volume
Reduce heart rate
Reduce stroke volume
Reduce Systemic Vascular Resistance
Dilate systemic vasculature
Arterial pressure can be reduced by decreasing cardiac output systemic vascular resistance,
or central venous pressure. An effective and inexpensive way of reducing venous pressure
and cardiac output is by using drugs that reduce blood volume. These drugs (diuretics) act on
the kidney to enhance sodium and water excretion. Reducing blood volume not only reduces
central venous pressure, but even more importantly, reduces cardiac output by the Frank-
Starling mechanism due to the reduction in ventricular preload. An added benefit of these
drugs is that they reduce systemic vascular resistance with long-term use.
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 6


Fig. 3 Areas of everyday life influenced by hypertension
Many antihypertensive drugs have their primary action on systemic vascular resistance. Some
of these drugs produce vasodilation by interfering with sympathetic adrenergic vascular tone
(sympatholytics) or by blocking the formation of angiotensin II or its vascular receptors.
Other drugs are direct arterial dilators, and some are mixed arterial and venous dilators.
Although less commonly used because of a high incidence of side effects, there are drugs that
act on regions in the brain that control sympathetic autonomic outflow. By reducing
sympathetic efferent activity, centrally acting drugs decrease arterial pressure by decreasing
systemic vascular resistance and cardiac output.
Some antihypertensive drugs, most notably beta-blockers, depress heart rate and contractility
(this decreases stroke volume) by blocking the influence of sympathetic nerves on the heart.
Calcium-channel blockers, especially those that are more cardioselective, also reduce cardiac
output by decreasing heart rate and contractility. Some calcium-channel blockers (most
notably the dihydropyridines) are more selective for the systemic vasculature and therefore
reduce systemic vascular resistance.
[2][3]


THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 7


Fig. 4 Methods for controlling Hypertension




THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 8

Drugs Used to Treat Hypertension
Classes of drugs used in the treatment of hypertension are listed below. Clicking on the drug
class will link you to the page describing the pharmacology of that drug class.

Diuretics
- thiazide diuretics
- loop diuretics
- potassium-sparing diuretics

Vasodilators
- alpha-adrenoceptor antagonists (alpha-blockers)
- angiotensin converting enzyme inhibitors (ACE inhibitors)
- angiotensin receptor blockers (ARBs)
- calcium-channel blockers
- direct acting arterial dilators
- ganglionic blockers
- nitrodilators
- potassium-channel openers
- renin inhibitors

Cardioinhibitory drugs
- beta-blockers
- calcium-channel blockers

Centrally acting sympatholytics







THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 9





Table 3. Blood Pressure Levels and Treatment Guidance










THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 10


Oral Antihypertensive Drugs


Table 4. Oral Antihypertensive Drugs



Beta-Adrenoceptor Antagonists (Beta-Blockers)

THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 11

Beta blockers (-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic
antagonists, beta-adrenoreceptor antagonists, or beta adrenergic receptor antagonists) are a
class of drugs that target the beta receptor. Beta receptors are found on cells of the heart
muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the
sympathetic nervous system and lead to stress responses, especially when they are stimulated
by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of
epinephrine and other stress hormones, and weaken the effects of stress hormones.
They are particularly used for the management of cardiac arrhythmias, protecting the heart
from a second heart attack (myocardial infarction) after a first heart attack (secondary
prevention),
[4]
and hypertension.
[5]

In 1962, Sir James W. Black found the first clinically significant beta blockerspropranolol
and pronethalol; it revolutionized the medical management of angina pectoris
[6]
and is
considered by many to be one of the most important contributions to clinical medicine and
pharmacology of the 20th century.
[7]

Beta blockers block the action of endogenous catecholamines epinephrine (adrenaline) and
norepinephrine (noradrenaline) in particular, on -adrenergic receptors, part of the
sympathetic nervous system, which mediates the fight-or-flight response.
[8][9]
Three types of
beta receptors are known, designated
1
,
2
and
3
receptors.
[10]

1
-adrenergic receptors are
located mainly in the heart and in the kidneys.
2
-adrenergic receptors are located mainly in
the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle.
[9]

3
-adrenergic receptors are located in fat cells.
[11]

General Pharmacology
Beta-blockers are drugs that bind to beta-adrenoceptors and thereby block the binding
of norepinephrine and epinephrine to these receptors. This inhibits normal sympathetic
effects that act through these receptors. Therefore, beta-blockers are sympatholytic drugs.
Some beta-blockers, when they bind to the beta-adrenoceptor, partially activate the receptor
while preventing norepinephrine from binding to the receptor. These partial
agonists therefore provide some "background" of sympathetic activity while preventing
normal and enhanced sympathetic activity. These particular beta-blockers (partial agonists)
are said to possess intrinsic sympathomimetic activity (ISA). Some beta-blockers also possess
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 12

what is referred to as membrane stabilizing activity (MSA). This effect is similar to the
membrane stabilizing activity ofsodium-channels blockers that represent Class I
antiarrhythmics.
The first generation of beta-blockers were non-selective, meaning that they blocked both
beta-1 (
1
) and beta-1 (
2
) adrenoceptors. Second generation beta-blockers are more
cardioselective in that they are relatively selective for
1
adrenoceptors. Note that this relative
selectivity can be lost at higher drug doses. Finally, the third generation beta-blockers are
drugs that also possess vasodilator actions through blockade of vascular alpha-adrenoceptors.

Fig. 5. General Mechanism of Action of beta blockers
Heart
Beta-blockers bind to beta-adrenoceptors located in cardiac nodal tissue, the conducting
system, and contracting myocytes. The heart has both
1
and
2
adrenoceptors, although the
predominant receptor type in number and function is
1
. These receptors primarily bind
norepinephrine that is released from sympathetic adrenergic nerves. Additionally, they bind
norepinephrine and epinephrine that circulate in the blood. Beta-blockers prevent the normal
ligand (norepinephrine or epinephrine) from binding to the beta-adrenoceptor by competing
for the binding site.
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 13

Beta-adrenoceptors are coupled to a Gs-proteins, which activate adenylyl cyclase to
form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A)
that phosphorylates L-type calcium channels, which causes increased calcium entry into the
cell. Increased calcium entry during action potentials leads to enhanced release of calcium by
the sarcoplasmic reticulum in the heart; these actions increase inotropy (contractility). Gs-
protein activation also increases heart rate (chronotropy). PK-A also phosphorylates sites on
the sarcoplasmic reticulum, which lead to enhanced release of calcium through the ryanodine
receptors (ryanodine-sensitive, calcium-release channels) associated with the sarcoplasmic
reticulum. This provides more calcium for binding thetroponin-C, which enhances inotropy.
Finally, PK-A can phosphorylate myosin light chains. which may contribute to the positive
inotropic effect of beta-adrenoceptor stimulation.
Because there is generally some level of sympathetic tone on the heart, beta-blockers are able
to reduce sympathetic influences that normally stimulate chronotropy (heart rate), inotropy
(contractility), dromotropy (electrical conduction) and lusitropy (relaxation). Therefore, beta-
blockers cause decreases in heart rate, contractility, conduction velocity, and relaxation rate.
These drugs have an even greater effect when there is elevated sympathetic activity.

Fig. 5. Mechanism of Action of beta blockers


THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 14

Blood vessels
Vascular smooth muscle has
2
-adrenoceptors that are normally activated by norepinephrine
released by sympathetic adrenergic nerves or by circulating epinephrine. These receptors, like
those in the heart, are coupled to a Gs-protein, which stimulates the formation of cAMP.
Although increased cAMP enhances cardiac myocyte contraction (see above), in vascular
smooth muscle an increase in cAMP leads to smooth muscle relaxation. The reason for this is
that cAMP inhibitsmyosin light chain kinase that is responsible for phosphorylating smooth
muscle myosin. Therefore, increases in intracellular cAMP caused by
2
-agonists inhibits
myosin light chain kinase thereby producing less contractile force (i.e., promoting
relaxation).
Compared to their effects in the heart, beta-blockers have relatively little vascular effect
because
2
-adrenoceptors have only a small modulatory role on basal vascular tone.
Nevertheless, blockade of
2
-adrenoceptors is associated with a small degree of
vasoconstriction in many vascular beds. This occurs because beta-blockers remove a small

2
-adrenoceptor vasodilator influence that is normally opposing the more dominant alpha-
adrenoceptor mediated vasoconstrictor influence.

Therapeutic Indications
Beta-Blockers
Cardiac Effects
Decrease contractility
(negative intropy)
Decrease relaxation rate
(negative lusitropy)
Decrease heart rate
(negative chronotropy)
Decrease conduction velocity
(negative dromotropy)
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 15

Vascular Effects
Smooth muscle contraction
(mild vasoconstriction)

Beta-blockers are used for treating hypertension, angina, myocardial infarction, arrhythmias
and heart failure.
Hypertension
Beta-blockers decrease arterial blood pressure by reducing cardiac output. Many forms of
hypertension are associated with an increase in blood volume and cardiac output. Therefore,
reducing cardiac output by beta-blockade can be an effective treatment for hypertension,
especially when used in conjunction with adiuretic. Acute treatment with a beta-blocker is not
very effective in reducing arterial pressure because of a compensatory increase in systemic
vascular resistance. This may occur because of baroreceptor reflexes working in conjunction
with the removal of
2
vasodilatory influences that normally offset, to a small degree, alpha-
adrenergic mediated vascular tone. Chronic treatment with beta-blockers lowers arterial
pressure more than acute treatment possibly because of reduced renin release and effects of
beta-blockade on central and peripheral nervous systems. Beta-blockers have an additional
benefit as a treatment for hypertension in that they inhibit the release of renin by the kidneys
(the release of which is partly regulated by
1
-adrenoceptors in the kidney). Decreasing
circulating plasma renin leads to a decrease in angiotensin II and aldosterone, which enhances
renal loss of sodium and water and further diminishes arterial pressure.
Hypertension in some patients is caused by emotional stress, which causes enhanced
sympathetic activity. Beta-blockers can be very effective in these patients.
Beta-blockers are used in the preoperative management of hypertension caused by a
pheochromocytoma, which results in elevated circulating catecholamines. When used for this
condition, the blood pressure is first controlled using an alpha-blocker such
as phenoxybenzamine, and then a beta-blocker can be carefully administered to reduce the
excessive cardiac stimulation by the catecholamines. It is important that a beta-blocker is
administered only after adequate blockade of vascular alpha-adrenoceptors so that a
hypertensive crisis does not occur as a result of unopposed alpha-adrenoceptor stimulation.
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 16


A-V, atrio-ventricular; eGFR, estimated glomerular filtration rate; LV, left ventricular.
Table 5. Compelling and possible contra-indications to the use of antihypertensive
drugs

Theraputic Use of Beta-Blockers
Hypertension
Angina
Myocardial infarction
Arrhythmias
Heart failure
The antianginal effects of beta-blockers are attributed to their cardiodepressant and
hypotensive actions. By reducing heart rate, contractility, and arterial pressure, beta-blockers
reduce the work of the heart and the oxygen demand of the heart. Reducing oxygen demand
improves the oxygen supply/demand ratio, which can relieve a patient of anginal pain that is
caused by a reduction in the oxygen supply/demand ratio due to coronary artery disease.
Furthermore, beta-blockers have been found to be very important in the treatment of
myocardial infarction in that they have been shown to decrease mortality. Their benefit is
derived not only from improving the oxygen supply/demand ratio and reducing arrhythmias,
but also from their ability to inhibit subsequent cardiac remodeling.
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 17

Arrhythmias
The antiarrhythmic properties beta-blockers (Class II antiarrhythmic) are related to their
ability to inhibit sympathetic influences on cardiac electrical activity. Sympathetic nerves
increase sinoatrial node automaticity by increasing the pacemaker currents, which increases
sinus rate. Sympathetic activation also increases conduction velocity (particularly at the
atrioventricular node), and stimulates aberrant pacemaker activity (ectopic foci). These
sympathetic influences are mediated primarily through
1
-adrenoceptors. Therefore, beta-
blockers can attenuate these sympathetic effects and thereby decrease sinus rate, decrease
conduction velocity (which can block reentry mechanisms), and inhibit aberrant pacemaker
activity. Beta-blockers also affect non-pacemaker action potentials by increasing action
potential duration and the effective refractory period. This effect can play a major role in
blocking arrhythmias caused by reentry.
Heart failure
The majority of patients in heart failure have a form that is called systolic dysfunction, which
means that the contractile function of the heart is depressed (loss of inotropy). Although it
seems counterintuitive that cardioinhibitory drugs such as beta-blockers would be used in
cases of systolic dysfunction, clinical studies have shown quite conclusively that some
specific beta-blockers actually improve cardiac function and reduce mortality. Furthermore,
they have been shown to reduce deleterious cardiac remodeling that occurs in chronic heart
failure. Although the exact mechanism by which beta-blockers confer their benefit to heart
failure patients is poorly understood, it may be related to blockade of excessive, chronic
sympathetic influences on the heart, which are known to be harmful to the failing heart.
Different Classes of Beta-Blockers and Specific Drugs
Beta-blockers that are used clinically can be divided into two classes: 1) non-selective
blockers (block both
1
and
2
receptors), or 2) relatively selective

1
blockers ("cardioselective" beta-blockers). Some beta-blockers have additional
mechanisms besides beta-blockade that contribute to their unique pharmacologic profile. The
two classes of beta-blockers along with specific compounds are listed in the following table.
Additional details for each drug may be found at www.rxlist.com. The clinical uses indicated
in the table represent both on and off-label uses of beta-blockers. For example, a given beta-
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 18

blocker may only be approved by the FDA for treatment of hypertension; however,
physicians sometimes elect to prescribe the drug for angina because of the class-action
benefit that beta-blockers have for angina.


Clinical Uses

Class/Drug HTN Angina Arrhy MI CHF Comments
Non-selective

1
/
2


carteolol X

ISA; long acting; also used for glaucoma
carvedilol X

X -blocking activity
labetalol X X

ISA; -blocking activity
Nadolol X X X X

long acting
penbutolol X X

ISA
pindolol X X

ISA; MSA
propranolol X X X X

MSA; prototypical beta-blocker
Sotalol

X

several other significant mechanisms
Timolol X X X X

primarily used for glaucoma

1
-selective

acebutolol X X X

ISA
Atenolol X X X X

betaxolol X X X

MSA
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 19

bisoprolol X X X

Esmolol X

X

ultra short acting; intra or postoperative HTN
metoprolol X X X X X MSA
nebivolol X
relatively selective in most patients;
vasodilating (NO release)

Abbreviations: HTN, hypertension; Arrhy, arrhythmias; MI, myocardial infarction; CHF,
congestive heart failure; ISA, intrinsic sympathomimetic activity.
Table 6. Clinical uses of different class of beta blockers


Side Effects and Contraindications
Cardiovascular side effects
Many of the side effects of beta-blockers are related to their cardiac mechanisms and include
bradycardia, reduced exercise capacity, heart failure, hypotension, and atrioventicular (AV)
nodal conduction block. Beta-blockers are therefore contraindicated in patients with sinus
bradycardia and partial AV block. The side effects listed above result from excessive
blockade of normal sympathetic influences on the heart. Considerable care needs to be
exercised if a beta-blocker is given in conjunction with cardiac selective calcium-channel
blockers (e.g., verapamil) because of their additive effects in producing electrical and
mechanical depression. Although this may change with future clinical trials on safety and
efficacy of beta-blockers in heart failure, at present only carvedilol and metoprolol have been
approved by the FDA for this indication.
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 20

Other side effects
Bronchoconstriction can occur, especially when non-selective beta-blockers are administered
to asthmatic patients. Therefore, non-selective beta-blockers are contraindicated in patients
with asthma or chronic obstructive pulmonary disease. Bronchoconstriction occurs because
sympathetic nerves innervating the bronchioles normally activate
2
-adrenoceptors that
promote bronchodilation. Beta-blockers can also mask the tachycardia that serves as a
warning sign for insulin-induced hypoglycemia in diabetic patients; therefore, beta-blockers
should be used cautiously in diabetics.














THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 21

Review of Literature

Should beta blockers remain first-line drugs for hypertension?-Maros Elsik et
al.,
Hypertension is an important risk factor for stroke and other cardiovascular events.
National and international guidelines recognise five classes of drugs for the first-line
treatment of hypertension, but the effectiveness of beta blockers has recently been
questioned, especially in the elderly. However, achieving a lower blood pressure is
more important than the choice of drug used in treatment. Many patients will need
more than one drug to treat their hypertension. Beta blockers remain important and
effective drugs, but age and comorbidities need to be considered when selecting a
first-line drug.
[12]


Beta-Blockers in the Treatment of Hypertension: Latest Data and Opinions-
Danai Tsalta et al.,
Beta-adrenergic blockers have been widely used as first-line drugs in the treatment of
idiopathic arterial hypertension for around 40 years. Recent meta-analyses, however,
suggest that they are significantly inferior to other categories of drugs (thiazide
diuretics, calcium channel blockers, angiotensin converting enzyme [ACE] inhibitors,
angiotensin II receptor blockers). This observation has led to the demotion of beta-
blockers to fourth-line drugs in the latest guidelines of the British Hypertension
Society.3 The aim of this review is to illuminate the historical course of the use of
beta-blockers in the treatment of hypertension up to the present day, to present the
most recent data from meta-analyses that have downgraded them from
antihypertensive drugs of first choice, and to discuss the different views expressed in
the most recent guidelines for the treatment of hypertension issued by the European
Society of Hypertension and the European Society of Cardiology.
[13]


Current and Future Status of Beta-blockers in the Treatment of Hypertension-
Steven G. Chrysant- et al.,
Beta-adrenergic receptor blockers (beta-blockers) are effective and safe
antihypertensive drugs, and have been recommended as first-line therapy for
hypertension by all Joint National Committees (JNCs) for the prevention, detection,
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 22

evaluation, and treatment of high blood pressure (BP) from the first to the last (JNC-
7) in 2003. However, recently questions have been raised by several investigators
regarding the antihypertensive effectiveness and safety of these drugs. The Medline
literature on this subject was searched and pertinent studies were retrieved. Other
pertinent references from existing publications were retrieved and analyzed up to
2007. Additionally, a historical perspective on the discovery of beta-blockers and
their mechanism of action is given. Most of the reviewed short-term and long-term
clinical trials demonstrate an effective and safe antihypertensive pattern for the beta-
blockers. The weaknesses identified include the adverse effect of older beta-blockers
on glucose control and stroke protection, especially in older persons. These adverse
effects are attributed to their mechanism of action and BP effectiveness. On the basis
of the evidence presented, beta-blockers are effective and safe antihypertensive drugs
and should still be recommended as first-line therapy in most uncomplicated
hypertensive patients, either alone or in combination with other drugs. There are
reservations regarding their administration to diabetic and older hypertensive patients.
However, when compelling indications for their use exist, they should not be
withheld.
[14]


Beta blockers and their combinations in the management of hypertension-Ker
JA,

Beta blockers should not be used as first-line monotherapy for the treatment of
hypertension, but can be added at a later stage as a fourth-line drug to control
pressure. There are still compelling indications for the use of beta blockers.
[15]


Beta-blockers as Single-Agent Therapy for Hypertension and the Risk of
Mortality among Patients with Chronic Obstructive Pulmonary Disease-David
H. Au et al.,
Compared with calcium channel blockers, betablockers were associated with a
decrease in mortality from any cause after adjusting for propensity for having been
prescribed a beta-blocker (hazard ratio _ 0.57; 95% confidence interval: 0.33 to 0.89).
The association was similar when beta-blockers were compared with all other
antihypertensive medications, and the decreased risk of mortality was apparent among
THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 23

patients with pre-existing cardiac disease. Restriction of analyses to long-acting
calcium channel blockers or to patients who used beta-agonists did not affect the point
estimates. Exposure to the remaining classes of antihypertensive agents was not
associated with mortality.
[16]


Effect of Obesity on the Traditional and Emerging Cardiovascular Disease Risk
Factors in African American Women-Queen Obiageli Henry-Okafor
Obesity is a growing health care concern with cardiovascular disease (CVD)
implications. African American women (AAW) have the highest prevalence rate of
obesity and highest CVD morbidity and mortality rate of all ethnic groups. The
traditional CVD risk factors have not been sufficient to explain this disparity in
disease prevalence and outcomes. Current knowledge is limited regarding the
interaction between various levels of adiposity and both traditional and emerging
CVD risk factors, particularly in AAW. This study sought to explore these
interactions.
[17]



Atenolol & Beta-blockers for primary hypertension: Do they perform under
pressure?- G Michael Allan & Christina Korownyk
Atenolol is an inferior choice for blood pressure treatment. Beta-blockers in general
should not be considered first line in age 60 and some have suggested they should
not be first line in any patient with uncomplicated hypertension.
[18]


Assessment of Clinical Pharmacist Management of Lipid-Lowering Therapy in a
Primary Care Setting- Traywick Till et. al.,
Pharmacists have been shown to positively impact the outcomes of care for treatment
of many different kinds of disease states. In particular, pharmacist-run lipid clinics
have enjoyed varying degrees of success, depending on the outcome assessed. At our
hospital, when a patient is transferred to the pharmacist coordinated lipid clinic, the
primary care pharmacist is responsible for ordering and interpreting labs and
prescribing and monitoring lipid-altering therapy.
[19]


THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 24

How strong is the evidence for use of beta-blockers as first-line therapy for
hypertension? Systematic review and meta-analysis- Hazel A. Bradley

Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several
important hard end points. Compared with diuretics, they had similar outcomes, but
were less well tolerated. Hence beta-blockers are generally suboptimal first-line
antihypertensive drugs.
[20]

Why -Blockers Should Not Be Used as First Choice in Uncomplicated
Hypertension-Alberto Ranieri De Caterina, and Antonio Maria Leone

In the past 4 decades, _ blockers (BBs) have been widely used in the treatment of
uncomplicated hypertension and are still recommended as first-line agents in national
and international guidelines. Their putative cardioprotective properties, however,
derive from the extrapolation into primary prevention of data relative to the reduction
of mortality observed in the 1970s in patients with previous myocardial infarctions.
In the past 5 years, a critical reanalysis of older trials, together with several meta-
analyses, has shown that in patients with uncomplicated hypertension BBs exert a
relatively weak effect in reducing stroke compared to placebo or no treatment, do not
have any protective effect with regard to coronary artery disease and, compared to
other drugs, such as calcium channel blockers, renin-angiotensin-aldosterone system
inhibitors or thiazide diuretics, show evidence of worse outcomes, particularly with
regard to stroke. Several reasons can explain their reduced cardioprotection: their
suboptimal effect in lowering blood pressure compared to other drugs; their pseudo
antihypertensive efficacy (failure to lower central aortic pressure); their undesirable
adverse effects, which reduce patients compliance; their unfavourable metabolic
effects; their lack of an effect on regression of left ventricular hypertrophy and
endothelial dysfunction. In conclusion, the available evidence does not support the
use of BBs as first-line drugs in the treatment of hypertension. Whether newer BBs,
such as nebivolol and carvedilol, which show vasodilatory properties and a more
favorable hemodynamic and metabolic profile, will be more efficacious in reducing
morbidity and mortality remains to be determined.
[21]

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Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 25

Hypertension Guidelines-Jeffery Martin
An estimated 73 million people in the United States live with hypertension. As many
as 55,000 deaths are directly attributed to hypertension each year, and it is considered
an underlying or contributing factor in at least another 300,000. In 2003, the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC) issued its seventh report, which provided guidelines for the
diagnosis and management of this disease. Included in the guidelines were: a new
classifi cation system for hypertension; recommendations for lifestyle modifi cations;
and recommendations for pharmacologic therapy. New JNC guidelines are expected
in 2009, but until then, and to understand the forthcoming changes in
recommendations, it is important to revisit and review those of JNC 7.
[22]
-Adrenergic Receptor Blockers and Weight Gain-A Systematic Analysis- Arya
M. Sharma et. al.,
One of the arguments put forward against the primary use of b-blockers has been
concern about adverse metabolic effects, such as unfavorable effects on lipids or
insulin sensitivity. Another less-appreciated potential drawback is their propensity to
cause weight gain in some patients. In 8 evaluable prospective randomized controlled
trials that lasted $6 months, body weight was higher in the b-blocker than in the
control group at the end of the study. The median difference in body weight was 1.2
kg (range 20.4 to 3.5 kg). A regression analysis suggested that b-blockers were
associated with an initial weight gain during the first few months. Thereafter, no
further weight gain compared with controls was apparent. There was no relationship
between demographic characteristics and changes in body weight. Based on these
observations, the first-line use of b-blockers in obese hypertensive patients should be
reviewed. Obesity management in overweight hypertensive patients may be more
difficult in the face of b-blocker treatment.
[23]


How strong is the evidence for use of beta-blockers as first-line therapy for
hypertension? Systematic review and meta-analysis-Hazel A. Bradley
Beta-blockers are inferior to Calcium Channel Blocker (CCBs) and to Renin
Angiotensin System (RAS) inhibitors for reducing several important hard end points.
Compared with diuretics, they had similar outcomes, but were less well tolerated.
Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.
[24]
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Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 26

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