ANTI HYPERTENSIVE DRUGS

Hypertension is a clinical syndrome, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood
pressure ≥ 90 mmHg. Hypertension should be considered a major risk factor for an array of cardiovascular and
related disease as well as diseases leading to a marked increase in cardiovascular risk. Evaluation for
hypertension includes accurate assessment of blood pressure, cardiovascular risk stratification, and identification
and treatment of secondary causes of hypertension. In primary hypertensive patients, the primary goal of
treatment is to achieve maximum reduction in the long-term total risk of cardiovascular disease.

1. ETIOLOGY OF HYPERTENSION

Genetic factors play an important role. Environmental factors also are significant, such as increased salt intake.

2. PATHOGENESIS

The pathogenesis of essential hypertension is multifactorial, including sympathetic nervous system hyperactivity,
renin-angiotensin system (RAS) hyperactivity, Defect of natriuresis and so on.

3. PATHOLOGY

Heart: left ventricular hypertrophy, congestive heart failure, ventricular arrhythmias, myocardial ischemia, and
sudden death.

Brain: stroke, such as intracerebral hemorrhage and cerebral infarction.

Kidney: nephrosclerosis.

4. CLINICAL FINDINGS

Symptoms: elevations in pressure are often intermittent early. Mild to moderated essential hypertension is
usually associated with normal health for many years. Suboccipital pulsating headaches, but any type of
headache, may occur.

Signs ： blood pressure is high, and other physical findings depend upon the duration and severity of
hypertension, and the degree of blood pressure effect on target organs.

5. INITIAL EVALUATION FOR HYPERTENSION

Goal 1: accurate assessment of blood pressure

Goal 2: cardiovascular risk stratification
Goal 3: identification of secondary causes of hypertension

6. MANAGEMENT

Goals of treatment: In hypertensive patients, the primary goal of treatment is to achieve maximum reduction in
the long-term total risk of cardiovascular disease.

Lifestyle Modification
Weight Loss
Sodium Restriction
Potassium Supplementation
High-Fiber, Low-Fat Diet
Alcohol Moderation
Smoking cessation
Exercise

WHEN TO INITIATE ANTIHYPERTENSIVE TREATMENT

Based on two criteria:
-The level of systolic and diastolic blood pressure
-The level of total cardiovascular risk

CHOICE OF ANTIHYPERTENSIVE DRUGS

Five major classes of antihypertensive agents – thiazide diuretics, calcium antagonists, ACE inhibitors,
angiotensin receptor antagonists and β-blockers – are suitable for the initiation and maintenance of
antihypertensive treatment, alone or in combination.

Monotherapy could be the initial treatment for a mild BP elevation with a low or moderate total cardiovascular
risk.

A combination of two drugs at low doses should be preferred as first step treatment when initial BP is in the
grade 2 or 3 range or total cardiovascular risk is high or very high.

In several patients BP control is not achieved by two drugs, and a combination of three of more drugs is required.

ACE INHIBITORS

ACE (Angiotensin converting enzyme) INHIBITORS - medications that inhibit the activity of the enzyme
angiotensin converting enzyme (ACE), which is important for controlling blood pressure.
medications that inhibit the activity of ACE which decreases the production of angiotensin II. As
a result, these medications cause the blood vessels to enlarge or dilate, and this reduces blood
pressure. This lower blood pressure makes it easier for the heart to pump blood and can
improve the function of a failing heart. Angiotensin is a hormone in the body that causes blood
vessels to narrow. The angiotensin-converting enzyme (ACE) inhibitors decrease the
production of angiotensin and, in turn, that helps lower blood pressure. Examples of ACE
inhibitors include:

Benazepril hydrochloride (Lotensin)

Captopril (Capoten)
enalapril (Vasotec)
Enalapril Maleate (Vasotec)
Fosinopril sodium (Monopril)
Lisinopril (Prinivil, Zestril)
Moexipril (Univasc)
Perindopril (Aceon)
Quinapril hydrochloride (Accupril)
Ramipril (Altace)
Trandolapril (Mavik)

ARBS
ARBS (Angiotensin receptor blockers) - are medications used to treat elevated blood pressure; these
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 pressure is 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 due to high blood pressure or diabetes is slowed.

losartan (Cozaar)
irbesartan (Avapro)
valsartan (Diovan)
candesartan (Atacand)
olmesartan (Benicar)
telmisartan (Micardis)
eprosartan (Teveten)
azilsartan (Edarbi)

DIURETICS

Diuretics increase urination which reduces sodium and fluid in the body. That can help lower blood
pressure because it lowers blood volume. Mild hypertension can sometimes be treated using diuretics
alone, although they are more commonly used in combination with other high blood pressure
medications. Examples of diuretics include:

Bumetanide (Bumex)
Chlorthalidone (Hygroton)
Chlorothiazide (Diuril)
Ethacrynate (Edecrin)
Furosemide (Lasix)
Hydrochlorothiazide HCTZ (Esidrix, Hydrodiuril, Microzide)
Indapamide (Lozol)
Methyclothiazide (Enduron)
Metolazone (Mykroz, Zaroxolyn)
Torsemide (Demadex)

BETA BLOCKERS

These are medications that block norepinephrine and epinephrine (adrenaline) from binding to both
beta 1 and beta 2 receptors on organs and muscles, including the muscles surrounding blood vessels
that cause the blood vessels to narrow and the heart to beat. By blocking the effect of norepinephrine
and epinephrine, beta blockers reduce blood pressure by dilating blood vessels and reducing heart rate.
They also may constrict air passages because stimulation of beta receptors in the lung cause the
muscles that surround the air passages to contract. Beta blockers lower blood pressure by acting
directly on the heart. These high blood pressure medications reduce heart rate and force of pumping,
as well as reduce blood volume. Beta blockers include:
Acebutolol (Sectral)
Atenolol (Tenormin)
betaxolol (Kerlone has been discontinued)
Bisoprolol fumarate (Zebeta)
carteolol (Cartrol, discontinued)
Carvedilol (Coreg) -- Combined alpha/beta blocker
Esmilol (Brevibloc)
HCTZ and bisoprolol (Ziac) is a beta blocker plus diuretic
Labetalol (Trandate, Normodyne) -- Combined alpha/beta blocker; discontinued
Metoprolol tartrate (Lopressor) and metoprolol succinate (Toprol-XL)
Nadolol (Corgard)
Nebivolol (Bystolic)
Penbutolol sulfate (Levatol has been discontinued)
pindolol (Visken, discontinued)
propranolol (Hemangeol, Inderal LA Inderal XL, InnoPran XL)
Sotalol (Betapace)
timolol (Blocadren, discontinued)

ANGIOTENSIN II RECEPTOR BLOCKERS

The hormone angiotensin narrows blood vessels, but to do its job it needs a place to bind. That's where
angiotensin II receptor blockers come in. They prevent angiotensin from binding to receptors on the
blood vessels and that helps lower blood pressure. Angiotensin II receptor blockers include:

Azilsartan (Edarbi)
Candesartan (Atacand)
Eprosartan mesylate (Teveten)
Irbesarten (Avapro)
Losartin Potassium or Lozartan (Cozaar)
Olmesartan (Benicar)
Telmisartan (Micardis)
Valsartan (Diovan)

CALCIUM CHANNEL BLOCKERS

Calcium increases the strength and force of contractions in the heart and blood vessels. Blocking its
entry into smooth muscle tissue reduces this effect. Calcium channel blockers lower blood pressure by
relaxing blood vessels and reducing heart rate. Examples of calcium channel blockers include:

Amlodipine besylate (Norvasc, Lotrel)

Clevidipine (Cleviprex)
Diltiazem hydrochloride (Cardizem CD, Cardizem SR, Dilacor XR, Tiazac)
Felodipine (Plendil)
Isradipine (DynaCirc, DynaCirc CR)
Nicardipine (Cardene SR)
Nifedipine (Adalat CC, Procardia XL)
Nimodipine (Nimotop, Nymalize)
Nisoldipine (Sular)
Verapamil hydrochloride (Calan SR, Isoptin SR, Verelan, Covera HS)

ALPHA BLOCKERS

Alpha blockers cause blood vessels to dilate, thereby lowering blood pressure. These medications are
also used to treat prostate enlargement in men. Alpha blockers include doxazosin mesylate (Cardura),
prazosin hydrochloride (Minipress), and terazosin hydrochloride (Hytrin).

ALPHA-2 RECEPTOR AGONIST

Methyldopa, formerly known under the brand name Aldomet, is one of the oldest blood pressure
medications still in use. It was first introduced more than 50 years ago. Methyldopa works in the central
nervous system to lower blood pressure. While its general use has declined over the years, methyldopa
is considered the first-line of treatment for high blood pressure that develops during pregnancy.

CENTRAL AGONISTS

Some hypertension medications work in the central nervous system rather than directly on the
cardiovascular system. Central agonists thus tend to cause drowsiness. Drugs in this class include
clonidine hydrochloride (Catapres) and guanfacine hydrochloride (Tenex).

PERIPHERAL ADRENERGIC INHIBITORS

The peripheral adrenergic inhibitors work in the brain to block signals that tell blood vessels to
constrict. They are mostly used when other high blood pressure medications fail to solve the problem.
Guanadrel (Hylorel), guanethidine monosulfate (Ismelin), and reserpine (Serpasil) are peripheral
adrenergic inhibitors.

VASODILATORS

Vasodilators relax artery wall muscles, and that causes blood pressure to drop. These drugs are usually
not used alone -- and, in the case of Minoxidil (Loniten) -- used only in severe hypertension.
Hydralazine (Apresoline) and minoxidil (Loniten) are vasodilators.

WHAT ARE THE MOST COMMON BLOOD PRESSURE MEDICATIONS?

In terms of dollar sales, recent statistics put the angiotensin II receptor blocker valsartan (Diovan) in the
lead for high blood pressure medications, followed by the beta blocker metoprolol, the generic
combination of valsartan and HCTZ, olmesartan (Benicar), and olmesartan and HCTZ (Benicar HCT).

In terms of prescriptions written, the ACE inhibitor lisinopril (Prinivil, Zestril) tops the list, followed by
amlodipine besylate (Norvasc), a calcium channel blocker, and generic hydrochlorothiazide (HCTZ).

WHAT IS THE BEST HIGH BLOOD PRESSURE MEDICATION?

Selecting the "best" high blood pressure medication depends on several things, including the general
health of the patient, his or her age, ethnicity, and whether or not they have any co-existing medical
issues or drug sensitivities.

For example, in a hypertensive patient with asthma, it may be inadvisable to prescribe a beta blocker,
as these drugs can aggravate that respiratory condition. Similarly, in patients prone to constipation (the
elderly, for example) use of certain calcium channel blockers might best be avoided -- along with
diuretics -- as both these classes of drugs can inhibit proper bowel function.

Certain groups of patients require use of a specific class of high blood pressure medication. These
include:

Pregnant Women

The drug of choice for hypertensive, pregnant women is one of the oldest high blood pressure
medications on the market. Methyldopa, which works to lower blood pressure through the central
nervous system, has the lowest risk of harming the mother and developing fetus. Other possible safe
options include labetalol, beta blockers, and diuretics. Two classes of drugs which should never be used
during pregnancy include the ACE inhibitors and the angiotensin II receptor blockers.

Elderly Patients

With age, comes an increased risk for systolic hypertension which can be aggravated by severe
atherosclerosis. According to one study, the diuretic chlorthalidone (Hygroton) had significant benefit in
elderly patients with systolic hypertension. Along with a diuretic, some calcium channel blockers, ACE
inhibitors and angiotensin II receptor blockers may also be good choices. However, beta blockers may
not be as effective for hypertension in those over 60; though they may be good choices if co-
existing heart disease is present. It also may be preferable in elderly patients to give two high blood
pressure medications at a low dose versus one at a higher dose.

WHAT ARE COMMON HIGH BLOOD PRESSURE SIDE EFFECTS?

Different classes of blood pressure medications have different side effects.

Diuretics

Diuretics can lead to an increase in potassium loss, known as hypokalemia, which, in turn can affect
muscular function -- including the muscles of the heart. There is also an increased risk for gout with
diuretics -- as well as the possibility of weakness, thirst, dehydration, and increased urination. Changes
in blood sugar levels are also possible. Skin reactions, some severe, are possible with thiazide diuretics
(such as hydrochlorothiazide). Potassium-sparing diuretics, such as spironolactone (Aldactone) may
cause breast enlargement in males.
Beta blockers

Beta-blockers cause the heart to slow down and so some of their side effects can be traced to that
mechanism of action. Dizziness, weakness, fatigue, and fainting are possible. Beta-blockers also affect
the respiratory system, so other side effects include shortness of breath, difficulty breathing, and chest
pain. Beta-blockers should not be withdrawn suddenly, as that could result in a heart attack or sudden
death.

ACE inhibitors

The most common side effect from ACE Inhibitors is also an unusual one -- a dry cough. Usually it goes
away with continued use of the drug, but that could take weeks. ACE Inhibitors could reduce blood
pressure too much, resulting in hypotension which could, in turn lead to headache, dizziness, fainting,
and reduced kidney function.

Angiotensin II receptor blockers

The most common side effect from the angiotensin receptor blockers (ARBs) is an increased potassium
level in the blood, known as hyperkalemia. Dizziness is also common, along with fatigue. Upper
respiratory tract infections have also been reported -- along with gastrointestinal issues such as upset
stomach and diarrhea.

Calcium channel blockers

Up to a third of patients may experience the following side effects with calcium channel blockers:
Swelling of the ankles and other extremities, flushing, and dizziness. Other common side effects include
heartburn and nausea.

Alpha blockers

A common, transient, but distressing initial side effect of the alpha blockers is postural hypotension.
This is a sudden drop in blood pressure when standing up. It can be severe enough to cause dizziness or
even fainting. In addition, the alpha blockers can result in increased heart rate, headache, nausea, and
weakness.

Methyldopa

Methyldopa is mostly well tolerated, but some patients may experience dizziness, drowsiness,
weakness, headache, and dry mouth.

Central agonists

Up to 40% of patients taking clonidine (Catapres) will experience dry mouth and about a third will have
drowsiness, headache, and sleepiness. Other common side effects include constipation, dizziness, and
local skin reactions with use of the Catapres-TTS skin patch. Reserpine use is linked with possible side
effects including nightmares, stuffy nose, depression, and an inability to fall asleep. Diarrhea and
heartburn are also possible. Guanadrel and guanethidine can cause diarrhea and other gastrointestinal
issues – as well as dizziness and drowsiness.

Vasodilators

Taking minoxidil might result in excessive body hair growth, as well as weight gain and dizziness.
Hydralazine is linked to headaches, heart palpitations, swelling around the eyes, and aches and pains in
the joints.

IS IT SAFE TO TAKE HIGH BLOOD PRESSURE MEDICATION DURING PREGNANCY?

Some high blood pressure medications should absolutely NOT be used during pregnancy as they may
harm the mother and developing fetus. These medications include the ACE inhibitors and the
angiotensin II receptor blockers. Reserpine may also be harmful during pregnancy and should only be
used when no other alternatives exist.

Safe medications to use include methyldopa and potentially some diuretics and beta blockers, including
labetalol.

IS IT SAFE TO DRINK ALCOHOL WHILE TAKING HIGH BLOOD PRESSURE MEDICATIONS?

Some high blood pressure medications initially cause drowsiness, dizziness, and lightheadedness. Some
even cause fainting on the first dose. The body usually adjusts to the effects of these medications and
the side effects disappear. Consuming alcohol during the early phase of antihypertensive treatment
could be risky because alcohol can also cause dizziness, drowsiness, and lightheadedness.

Also, alcohol consumption causes a transient rise in blood pressure that could persist if the drinking is
beyond the level of "moderation."

DOES HIGH BLOOD PRESSURE LEAD TO WEIGHT GAIN?

Some high blood pressure medications can, in fact, lead to weight gain. Common offenders include
older beta blockers such as propranolol (Inderal) and atenolol (Tenormin). There could be several
reasons for this -- including the fact that the medications can make patients feel tired and thus less
likely to exercise. Minoxidil tablets (Loniten) -- used only when other antihypertensive medications have
failed -- can also cause weight gain. Weight gain is also listed as a common side effect of doxazosin
(Cardura). Diuretics are more likely to cause weight loss.