Chapter 3 :Drugs acting on

Cardiovascular System
Lecture 1 : Antihypertensives

COURSE NO AND TITLE: PHARM 417 T

PHARMACOLOGY & THERAPEUTICS-IB [Theory]
BY DR. AISHA AZIZ, DEPARTMENT OF PHARMACOLOGY , JINNAH
UNIVERSITY FOR WOMEN
Learning Objectives
In this lecture we will discuss hypertension, its types,
and classification of drugs used in management of
hypertension
 Hypertension
Hypertension, also known as high or raised blood pressure, is a condition in which the

blood vessels have persistently raised pressure. Blood is carried from the heart to all parts

of the body in the vessels. Each time the heart beats, it pumps blood into the vessels.

Blood pressure is created by the force of blood pushing against the walls of blood vessels

(arteries) as it is pumped by the heart. The higher the pressure, the harder the heart has to

pump.

Hypertension is a serious medical condition and can increase the risk of heart, brain,

kidney and other diseases. It is a major cause of premature death worldwide, with upwards

of 1 in 4 men and 1 in 5 women – over a billion people ­– having the condition.

Classification of Hypertension according to The Seventh
Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood
Pressure (JNC 7)
 Types of Hypertension
There are two types of primary hypertension . For 95
percent of people with high blood pressure, the cause of
their hypertension is unknown — this is called essential,
or primary, hypertension. When a cause can be found, the
condition is called secondary hypertension.
Essential/ Primary hypertension.
 This type of hypertension is diagnosed after a doctor notices
that your blood pressure is high on three or more visits and
eliminates all other causes of hypertension. Usually people
with essential hypertension have no symptoms, but you may
experience frequent headaches, tiredness, dizziness, or nose
bleeds. Although the cause is unknown, researchers do know
that obesity, smoking, alcohol, diet, and heredity all play a role
in essential hypertension.
Secondary hypertension.
 The most common cause of secondary hypertension is an
abnormality in the arteries supplying blood to the kidneys.
Other causes include airway obstruction during sleep,
diseases and tumors of the adrenal glands, hormone
abnormalities, thyroid disease, and too much salt or
alcohol in the diet. Drugs can cause secondary
hypertension, including over-the-counter medications
such as ibuprofen and pseudoephedrine
Additional Hypertension Types:
 Additional Hypertension Types: Isolated Systolic,
Malignant, and Resistant
 Isolated systolic hypertension, malignant hypertension, and
resistant hypertension are all recognized hypertension types
with specific diagnostic criteria.
Isolated systolic hypertension
Blood pressure is recorded in two numbers: The upper, or
first, number is the systolic pressure, which is the pressure
exerted during the heartbeat; the lower, or second, number is
the diastolic pressure, which is the pressure as the heart is
resting between beats. Normal blood pressure is considered
under 120/80. With isolated systolic hypertension, the systolic
pressure rises above 140, while the lower number stays near
the normal range, below 90. This type of hypertension is most
common in people over the age of 65 and is caused by the
loss of elasticity in the arteries. The systolic pressure is much
more important than the diastolic pressure when it comes to
the risk of cardiovascular disease for an older person.
Malignant hypertension.
This hypertension type occurs in only about 1 percent of people with
hypertension. It is more common in younger adults, African-American men,
and women who have pregnancy toxemia. Malignant hypertension occurs
when your blood pressure rises extremely quickly. If your diastolic pressure
goes over 130, you may have malignant hypertension. This is a medical
emergency and should be treated in a hospital. Symptoms include numbness
in the arms and legs, blurred vision, confusion, chest pain, and headache.
Resistant hypertension. If your doctor has prescribed three different
types of antihypertensive medications and your blood pressure is still too
high, you may have resistant hypertension. Resistant hypertension may
occur in 20 to 30 percent of high blood pressure cases. Resistant
hypertension may have a genetic component and is more common in people
who are older, obese, female, African American, or have an underlying
illness, such as diabetes or kidney disease.
What Defines Hypertensive
Urgency/Emergency?
•
Hypertensive urgency is defined as a diastolic blood pressure of 110 mm Hg
or greater without the acute signs of end-organ damage.Some sources suggest that a
patient must also have certain risk factors (eg, heart disease, renal disease) to be
given this diagnosis.The presence of acute and rapidly evolving end-organ damage
with an elevated diastolic blood pressure, usually greater than 120 mm Hg,
establishes a diagnosis of hypertensive emergency.
No specific blood pressure measurement indicates a hypertensive emergency,
however; rather, the defining feature of this diagnosis is the presence of progressive
target end-organ damage. This is most commonly manifested in cardiopulmonary,
central nervous system, and/or renal findings; for the specific forms of end-organ
damage, Preeclampsia and eclampsia are also considered manifestations of
hypertensive end-organ damage but are beyond the scope of this article.
The most common form of organ damage associated with hypertension is ischemic
heart disease, in the form of either heart failure or acute coronary syndrome
Normal Regulation of Blood Pressure

According to the hydraulic equation, arterial blood

pressure (BP) is directly proportionate to the product
of the blood flow (cardiac output, CO) and the
resistance to passage of blood through precapillary
arterioles (peripheral vascular resistance, PVR):
BP = CO × PVR
Cont….
Physiologically, in both normal and hypertensive individuals, blood
pressure is maintained by moment-to-moment regulation of cardiac
output and peripheral vascular resistance, exerted at three anatomic
sites : arterioles, postcapillary venules (capacitance vessels), and
heart. A fourth anatomic control site, the kidney, contributes to
maintenance of blood pressure by regulating the volume of
intravascular fluid.
Baroreflexes, mediated by autonomic nerves, act in combination with
humoral mechanisms, including the renin-angiotensin-aldosterone
system, to coordinate function at these four control sites and to
maintain normal blood pressure. Finally, local release of vasoactive
substances from vascular endothelium may also be involved in the
regulation of vascular resistance. For example, endothelin-1 constricts
and nitric oxide dilates blood vessels.
A. Postural Baroreflex

Baroreflexes are responsible for rapid, moment-to-moment adjustments in

blood pressure, such as in transition from a reclining to an upright posture
When there is increase in arterial blood pressure, Carotid baroreceptors
are stimulated by the stretch of the vessel walls , Baroreceptor activation
inhibits central sympathetic discharge which normalizes the blood pressure
Conversely, reduction in blood pressure causes reduction in stretch results
in a reduction in baroreceptor activity. Thus, in the case of a transition to
upright posture, baroreceptors sense the reduction in arterial pressure that
results from pooling of blood in the veins below the level of the heart as
reduced wall stretch, and sympathetic discharge is increases. The reflex
increase in sympathetic outflow acts through nerve endings to increase
peripheral vascular resistance (constriction of arterioles) and cardiac output
(direct stimulation of the heart and constriction of capacitance vessels, which
increases venous return to the heart), thereby restoring normal blood
pressure.
B. Renal Response to Decreased Blood Pressure
By controlling blood volume, the kidney is primarily responsible
for long-term blood pressure control. A reduction in renal
perfusion pressure causes intrarenal redistribution of blood flow
and increased reabsorption of salt and water. In addition,
decreased pressure in renal arterioles as well as sympathetic neural
activity (via β adrenoceptors) stimulates production of renin,
which increases production of angiotensin II Angiotensin II
causes (1) direct constriction of resistance vessels and (2)
stimulation of aldosterone synthesis in the adrenal cortex, which
increases renal sodium absorption and intravascular blood volume.
Vasopressin released from the posterior pituitary gland also plays a
role in maintenance of blood pressure through its ability to
regulate water reabsorption by the kidney
Anatomic Sites of blood pressure control
BASIC PHARMACOLOGY OF
ANTIHYPERTENSIVE AGENTS
1. Diuretics, which lower blood pressure by depleting the concentration
of sodium and reducing blood volume and perhaps by other
mechanisms.
2. Sympathoplegic agents, which lower blood pressure by reducing
peripheral vascular resistance, inhibiting cardiac function, and
increasing venous pooling in capacitance vessels. (The latter two effects
reduce cardiac output.) These agents are further subdivided according to
their putative sites of action in the sympathetic reflex arc (see below).
3. Direct vasodilators, which reduce pressure by relaxing vascular
smooth muscle, thus dilating resistance vessels and—to varying degrees
—increasing capacitance as well.
4. Agents that block production or action of angiotensin and thereby
reduce peripheral
 Site of action of
the major classes
of
antihypertensives
JNC 8 Guidelines for the Management of Hypertension in Adults

Key Points for Practice

• In the general population, pharmacologic treatment should be initiated when
blood pressure is 150/90 mm Hg or higher in adults 60 years and older, or
140/90 mm Hg or higher in adults younger than 60 years.
• In patients with hypertension and diabetes, pharmacologic treatment should be
initiated when blood pressure is 140/90 mm Hg or higher, regardless of age.
• Initial antihypertensive treatment should include a thiazide diuretic, calcium
channel blocker, ACE inhibitor, or ARB in the general nonblack population or a
thiazide diuretic or calcium channel blocker in the general black population.
• If the target blood pressure is not reached within one month after initiating
therapy, the dosage of the initial medication should be increased, or a second
medication should be added.
From the AFP Editors
Summary
In this lecture we have discussed
 Definitions and types of Hypertension.
Treatment and management of different types of
Hypertension
Classification of Antihypertensives
References
 Basic & Clinical Pharmacology by Katzung BG, 15th Edition , 2020”.
 Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth
Edition 12th Edition.
 Hawary MBEL, etal.Handbook of pharmacology.The scientific book centre,
Volume 1 & 2
https://www.drugs.com/cg/pulmonary-arterial-hypertension.html
https://www.who.int/health-topics/hypertension/#tab=tab_1
https://www.nhlbi.nih.gov/health-topics/seventh-report-of-joint-national-
committee-on-prevention-detection-evaluation-and-treatment-high-
blood-pressure
https://www.nhs.uk/conditions/pulmonary-hypertension/treatment/#:~:
text=Treatments%20include%3A,concentration%20of%20oxygen%20th
an%20normal
https://www.wikidoc.org/index.php/Chronic_hypertension_classification