20 percent and reduces the likelihood of dementia, heart failure, and

mortality from vascular disease.

The aim of treatment should be blood pressure control to <140/90

mmHg for most patients, and lower in certain contexts such as diabetes
or kidney disease ( some medical professionals recommend keeping
levels below 120/80 mmHg). Each added drug may reduce the systolic
blood pressure by 5-10 mmHg, so often multiple drugs are necessary to
achieve blood pressure control. (Shaw 2003)

The commonly used drugs for hypertension are the Calcium

channel blockers, such as Amlodipine, diltiazem and verapamil, and
angiotensin II receptor antagonists like losartan, valsartan and
candesartan.

Amlodipine is a long-acting calcium channel blocker. It is indicated

for the treatment of hypertension and can be used as the sole agent to
control blood pressure in the majority of patients.

Losartan potassium is an angiotensin receptor blocker (ARB) and

works by relaxing blood vessels so that blood can flow more easily.
Hydrochlorothiazide is a "water pill" (diuretic) that causes you to make
more urine, which helps your body get rid of extra salt and water.

REVIEW OF RELATED LITERATURE AND STUDIES

A. Related Literature

Hypertension

Hypertension, commonly referred to as “high blood pressure”, is a

medical condition where the blood pressure is chronically elevated.
While it is formally called arterial hypertension, the word “hypertension”
without a qualifier usually refers to arterial hypertension. Hypertension
gives the highest risk of heart attack or stroke than any other disease.
Persistent hypertension is one of the risk factors for strokes, heart
attacks, heart failure and arterial aneurysm, and is a leading cause of
chronic renal failure.

Hypertension can be classified as either essential or secondary.

Essential hypertension is the term used when no specific medical
cause can be found to explain a patient’s condition. Secondary
hypertension means that the high blood pressure is a result of (i.e.
secondary to another condition, such as kidney disease

Recently, the JNC 7 ( The seventh Report of the Joint National

Committee on Prevention, Detection,Evaluation, and Treatment of
High Blood Pressure) has defined blood pressure 120/80 mmHg to
139/89 mmHg as “prehypertension”. Prehypertension is not a disease
category; rather, it is a designation chosen to identify individuals at
risk of developing hypertension .”

The Mayo Clinic website indicates that your blood pressure is

“normal if its below 120/180” but that “some data indicate that
115/75mmHg should be the gold standard.”

In patients with diabetes mellitus or kidney disease studies have

shown that blood pressure over 130/80 mmHg should be considered
a risk factor and warrants treatment. Even lower numbers are
considered diagnostic using home blood pressure monitoring devices.

Etiology of Essential Hypertension

Environment

A number of environmental factors have been implicated in the

development of hypertension, including salt intake, obesity,
occupation, and alcohol intake family size, stimulant intake, excessive
noise exposure, and crowding.

Salt Sensitivity

Sodium is the environmental factor that has received the greatest

attention. It is to be noted that approximately 60% of the essential
hypertension population is responsive to sodium intake.

Role of Renin

Renin is an enzyme secreted by the juxtaglomerular cells of the

kidney and linked with aldosterone in a negative feedback loop. The
range of plasma renin activities observed in hypertensive subjects is
broader than in normotensive individuals. In consequence, some
hypertensive patients have been defined as having low- renin and
others as having high- renin essential hypertension.

Insulin Resistance

Insulin is a polypeptide hormone secreted by the pancreas. Its

main purpose is to regulate the levels of glucose in the body, it also
has some other effects. Insulin resistance and/or hyperinsulinemia
have been suggested as being responsible for the increased arterial
pressure in some patients with hypertension. This feature is now
widely recognized as part of syndrome X, or the metabolic syndrome.

Sleep Apnea

Sleep apnea is a common, under recognized cause of

hypertension. It is best treated with weight loss and nocturnal nasal
positive airway pressure.

Genetics
 Hypertension is one of the most complex genetic disorders, from
animal studies as well as in population studies in humans. Most of
these studies support the genetic defects each have an elevated
blood pressure as one of their phenotypic expressions.

More than 50 genes have been examined in association studies

with hypertension, and the number is constantly growing.

Other Etiologies

There are some anecdotal or transient causes of high blood pressure.

These are not to be confused with the disease called hypertension in
which there is an intrinsic physiopathological mechanism as
described above.

Etiology of Secondary Hypertension

Only in a small minority of patients with elevated arterial pressure

can a specific cause be identified. These individuals will probably
have an endocrine or renal defect that if corrected would bring blood
pressure back to normal values.

Adrenal Hypertension

Hypertension is a feature of a variety of adrenal cortical

abnormalities. In primary aldosteronism there is a clear relationship
between the aldosterone-induced sodium retention and the
hypertension.

In patients with pheochromocytoma increased secretion of

canocholamines such as epinephrine and norepinephrine by a tumor
(most often located in the adrenal medulla) causes excessive
stimulation of { adrenergic receptors which}, which results in
peripheral vasoconstriction and cardiac stimulation. This diagnosis is
confirmed by demonstrating increased urinary excretion of
epinephrine and norepinephrine and/or their meracholies
remilymandelic acid).

Hypercalcemia is a condition in which the calcium level in your blood

is above normal. Too much calcium in your blood can weaken your
bones, create kidney stones, and interfere with the way your heart
and brain works. Hypercalcemia most commonly results from
overactive parathyroid glands.

Diet

Certain medications, especially NSAIDS (Motrin/Ibupofen) and

steroids can cause hypertension. Ingestion of imported licorice (
Glycyrrhiza glabra) can cause secondary hypoaldosteronism, which
itself is a cause of hypertension.

Age

Over time, a number of collagen fibers in artery and arteriole walls

increases, making blood vessels stiffer. With the reduced elasticity
comes a smaller cross –sectional area in systole, and so a raised
mean arterial blood pressure.

Signs and Symptoms

Hypertension is usually found incidentally- “case finding” – by

healthcare professionals. It normally produces no symptoms.

Malignant hypertension (or accelerated hypertension) is distinct as

a late phase in the condition, and may present with headaches,
blurred vision and end-organ damage.
 It is determined that stressful situations can increase the blood
pressure.

Hypertension is often confused with mental tension, stress and

anxiety. While chronic anxiety is associated with poor outcomes in
people with hypertension.

Hypertensive urgencies and emergencies

Hypertension is rarely severe enough to cause symptoms. These

typically only surface with a systolic blood pressure over 240 mmHg
and/or a diastolic blood pressure over 120mmHg. These pressures
without signs of end- organ damage (such as renal failure) are termed
“accelerated” hypertension. When end-organ damage is possible or
already ongoing, but in absence of raised intracranial pressure, it is
called hypertensive emergency. Hypertension under this
circumstance needs to be controlled, but prolonged hospitalization is
not necessarily required. When hypertension causes increased
intracranial pressure, it is called malignant hypertension. Increased
intracranial pressure causes papilledema, which is visible on
opthalmoscopic examination of the retina.

Complications

While elevated blood pressure alone is not an illness, it often

requires treatment due to its short-and long term effects on many
organs. The risk is increased for cerebrovascular accident (CVAs or
strokes). Myocardial infarction (heart attack), hypertensive
cardiomyopathy (heart failure due to chronically high blood pressure),
hypertensive retinopathy-damage to the retina, hypertensive
nephropathy-chronic renal failure due to chronically high blood
pressure.
Pregnancy

Although few women of childbearing age have high blood

pressure, up to 10% develop hypertension of pregnancy. While
generally benign, it has three complications of pregnancy: pre-
eclampsia, HELLP syndrome and eclampsia. Follow-up and control
with medication is therefore often necessary.

Measuring Blood Pressure

Diagnosis of hypertension is generally on the basis of a

persistently high blood pressure. Usually this requires three separate
measurements at least one week apart. Exceptionally, if the elevation
is extreme, or end organ damage is present then the diagnosis may
be applied and treatment commenced immediately.

Obtaining reliable blood pressure measurements relies on the

following several rules and understanding the many factors that
influence blood pressure reading.

For instance, measurements in control of hypertension should be

at least 1 hour after caffeine, 30 minutes after smoking and without
any stress, Cuff size is also important. The bladder should encircle
and cover two-thirds of the length of the arm. The patient should be
sitting for a minimum of five minutes. The patient should not be on
any adrenergic stimulants, such as those found in many cold
medications.

When taking manual measurements, the person taking the

measurement should be careful to inflate the cuff suitably above
anticipated systolic pressure. A stethoscope should be placed lightly
 over the branchial artery. The cuff should be at the level of the heart
and the cuff should be deflated at a rate of 2 to 3 mmHg/s. Systolic
pressure is the pressure reading at the onset of the sounds described
by Korotkoff (Phase one). Diastolic pressure is then recorded as the
pressure at which the sounds disappear (K5) or sometimes the K4
point, where the sound is abruptly muffled. Two measurements
should be made at least 5 minutes apart, and, if there is discrepancy
of more than 5mmHg, a third reading should be done. The readings
should then be averaged. An initial measurement should include both
arms. The BP should at some time have been measured in each arm,
and the higher pressure arm preferred for subsequent
measurements.

BP varies with time of day, as may the effectiveness of treatment,

and archetypes used to record the data should include the time taken.
Automated machines are commonly used and reduce the variability in
manually collected readings. Routine measurements done in medical
offices of patients with known hypertension may incorrectly diagnose
20% of patients with uncontrolled hypertension.

Distinguishing primary vs. secondary hypertension

Once the diagnosis of hypertension has been made it is important

to attempt to exclude or identify reversible (secondary) causes.

Primary Hypertension

The vast majority of high blood pressure diagnoses fall into the
category of “primary hypertension” also called “essential hypertension.”
This classification means that your doctor or health care team is not able
to locate a single cause which explains the elevated blood pressure.

Another medical term used to describe illness without obvious

underlying cause is “idiopathic,” and you may hear your doctor use this
term. High blood pressure is a complicated disease, with complex and
often interrelated genetic and environmental factors, it is usually not
possible to say for sure which elements combined to produce it.

Secondary Hypertension

A modest number of high blood pressure diagnoses are classified

as “secondary hypertension.” The classification differs from a diagnosis
of primary hypertension because, in this case, a clearly identifiable
cause of the high blood pressure is determined. A wide variety of
underlying problems can cause high blood pressure. Some important
conditions include Obstructive sleep apnea, Kidney problems, Adrenal
gland tumors, Thyroid problems, Certain defects in blood vessels you're
born with (congenital), Certain medications, such as birth control pills,
cold remedies, decongestants, over-the-counter pain relievers and some
prescription drugs, Illegal drugs, such as cocaine and amphetamines,
Alcohol abuse or chronic alcohol use.

The ALLHAT (Antihypertensive and Lipid-Lowering Treatment

to Prevent Heart Attack Trial ) study showed a slightly better
outcome and cost-effectiveness for the thiazide diuretic
chlortalidone compared to anti-hypertensives. Whilst a subsequent
smaller study (ANBP2) did not show this small difference in outcome
and actually showed a slightly better outcome for ACE- inhibitors in
older male patients.

Whilst thiazides are cheap, effective, and recommended as

the best first-line drug for hypertension by many experts, they are
not prescribed as often as some newer drugs. Arguably, this is
because they are off-patent and thus rarely promoted by the drug
industry. Although physicians may start with non-thiazide
antihypertensive medications if there is a compelling reasons to do
so. An example is the use of ACE-inhibitors in diabetic patients who
have evidence of kidney disease, as they have been shown to both
reduce blood pressure and slow the progression of diabetic
nephropathy. In patients with coronary artery disease or a history of
a hypertension.

Specific Angiotensin-II Receptor Antagonists

“ARB” stands for “angiotensin II receptor blocker” or “angiotensin II

receptor inhibitor.” ARBs are typically used to treat high blood
pressure, congestive heart failure, kidney damage caused by
diabetes, chronic kidney disease, and even scleroderma (a skin
condition).
 ARBs are alternatives to ACE inhibitors. They work by blocking
angiotensin II receptors, allowing blood vessels to dilate and blood
pressure to decrease. Basically, angiotensin is a chemical that causes
arteries to constrict. To perform this action, angiotensin must find a
specific receptor. ARBs make it impossible for angiotensin to constrict
blood vessels by blocking this receptor. This means that ARBs don’t
actively cause blood vessels to relax. Rather, they prevent the uptake of
a chemical which would cause blood vessels to tense.

Relaxed blood vessels help supply adequate blood and oxygen to the
heart, which helps it to work efficiently. When arteries are constricted or
narrowed, blood is under more pressure because it’s being forced to
move through a smaller space than it normally would be.

Common ARBs include:

candesartan (Atacand),eprosartan mesylate (Teveten),irbesarten

(Avapro),losartin potassium (Cozaar),telmisartan (Micardis),valsartan
(Diovan)
ARBs are usually prescribed in once-daily doses. However, more
frequent dosing schedules are recommended for some specific ARBs,
including losartan, candesartan, and eprosartan.

Who Needs Them

You may be prescribed ARBs if you: have had a heart attack, have
coronary artery disease, have high blood pressure that hasn’t responded
well to ACE inhibitors,have had many side effects from ACE
inhibitors,Many patients experience a chronic cough when using ACE
inhibitors. ARBs were specifically developed to avoid this side effect.
Consequently, chronic cough is a much less common side effect of
ARBs.
Benefits
ARBs can decrease risk of heart attack, stroke, or death from a cardiac
event. Most physicians will ask you to try an ACE inhibitor first. If it isn’t
suitable for you, doesn’t decrease your symptoms, or has many side
effects, they may recommend an ARB. Studies have shown that taking
both ACE inhibitors and ARBs provides no additional benefit over taking
just one medication.

Side Effects and Risks

Side effects of ARBs include:headache,faintingdizzinessnasal
congestiondiarrheaback painleg pain

In rare cases, some people taking an ARB have experienced allergic

reactions, liver failure, kidney failure, angioedema (tissue swelling), and
decreased white blood cell counts. Another, less common side effect is
arrhythmia, which is caused by elevated blood-potassium levels that
affect how the heart beats.

These medications aren’t recommended for pregnant women or women

who plan to become pregnant. Talk to your doctor if side effects are
particularly troublesome or if you’re not sure whether the medication is
improving your condition.

Angiotensin II is a very potent chemical formed in the blood that

causes muscles surrounding blood vessels to contract, thereby
narrowing the vessels. This narrowing increases the pressure
within the vessels and can cause high blood
pressure (hypertension). Angiotensin II receptor blockers (ARBs)
are medications that block the action of angiotensin II by
preventing angiotensin II from binding to angiotensin II receptors
on the muscles surrounding blood vessels. As a result, blood
vessels enlarge (dilate) and blood pressureis reduced. Reduced
 blood pressure makes it easier for the heart to pump blood and
can improve heart failure. In addition, the progression of kidney
disease caused by the high blood pressure or diabetes is slowed.
ARBs have effects that are similar to angiotensin converting
enzyme (ACE) inhibitors, but ACE inhibitors act by preventing the
formation of angiotensin II rather than by blocking the binding of
angiotensin II to muscles on blood vessels.

The FDA has labeled losartan, valsartan, irbesartan,

cardesartan and telmisartan for use in the treatment of
hypertension. Controlled trials have demonstrated the efficacy of
these agents in patients with hypertension.

The antihypertensive effects of these drugs should become

apparent within two to four weeks after the initiation of theraphy.
Greater blood pressure lowering effect is achieved by adding a
low-dose diuretic such as hydrochlorothiazide than by increasing
the angiotensin-II receptor antagonist dosage. Hydrochlorithiazide
provides blood pressure reduction through mechanisms such as
mild natriuresis and vasodilation of blood vessels.

Statement of the Problem

The researcher aimed to determine on the efficacy and tolerability of

hypertensive agents; amlodipine and losartan.

Specifically, this study sought answers to the following questions:

1. What is the demographic profile of the respondents of this study

to characterize the perceptual responses obtained for the
categories under investigation?
2. What is the profile of the blood pressure measurements of the
respondents treated with Losartan and Amlodipine on the first,
second and third visits?
3. Is there a significant decrease in the blood pressure recordings
of the respondents in this study, basing on their recorded
systolic and diastolic readings treated with Losartan and
Amlodipine respectively?
 4. Do the following variables such as age and sex have a
significant implication on the blood pressure readings recorded
among the respondents of this study treated with Losartan and
Amlodipine?

Evidence suggests that reduction of the blood pressure by 5-6

mmHg can decrease the risk of stroke by 40%, of coronary heart disease
by 15-20%, and reduces the likelihood of dementia, heart failure, and
mortality from vascular disease. (Shaw 2013).

The aim of treatment should be blood pressure control to <140/90

mmHg fot most patients, and lower in certain contexts such as diabetes
or kidney disease ( some medical professionals recommend keeping
levels below 120/80 mmHg). Each added drug may reduce the systolic
blood pressure by 5-10mmHg, so often multiple drugs are necessary to
achieve blood pressure control. (Shaw 2003)

Conceptual framework

In this research, the antihypertensive drugs, losartan and

amlodipine, is the independent variable. Whereas the effect of the above
mentioned antihypertensive drugs on systolic blood pressure and diastolic
Conceptual framework

In this research, the antihypertensive drugs, losartan and

amlodipine, is the independent variable. Whereas the effect of the above
mentioned antihypertensive drugs on systolic blood pressure and diastolic
blood pressure in mmHg is the dependent variable. Furthermore, age, sex
and weight are the intervening variables in this study.