A Project Report on

“PHARMACOTHERAPY OF HYPERTENSION”
is
Submitted in the partial fulfillment of the requirement for the degree of

BACHELOR OF PHARMACY
As per provision of ordinance of
RGPV, Bhopal (M.P.)

Academic Session 2020-21

Under the guidance of
Mrs. Reena Yadav
Assist / Assoc. Prof.

Submitted by:
Shivanand Prajapati
B. Pharm., VII Semester.
0155PY171054

RKDF School of Pharmaceutical Sciences

NH-12, Jatkhedi, Hoshangabad Road, Bhopal- 462026
Ph: (0755) 4017762, e-mail [email protected], [email protected]
RKDF School of Pharmaceutical Science Bhopal
Page | i
 RKDF SCHOOL OF PHARMACEUTICAL
SCIENCES
NH-12, Jatkhedi, Hoshangabad Road, Bhopal- 462026
Ph: (0755) 4017762, E-mail [email protected],
[email protected]

CERTIFICATE
This is certified that the project work report which is being submitted by
Shivanand Prajapati B. Pharm. VII semester Enrollment No 0155PY171054
to Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal for the degree of
bachelor of pharmacy, VII semester examination Nov.- 2021 is a record of his
Project work carried out by him under my supervision. The project work report is
his original work which he has submitted for partial fulfillment of degree of
bachelor of pharmacy as per the ordinance of Rajiv Gandhi Proudyogiki
Vishwavidyalaya, Bhopal.

Date: - Mrs. Reena Yadav

(Assist / Assoc. Prof.)

RKDF School of Pharmaceutical Science Bhopal

Page | ii
 RKDF SCHOOL OF PHARMACEUTICAL SCIENCES
NH-12, Jatkhedi, Hoshangabad Road, Bhopal- 462026
Ph: (0755) 4017762, E-mail [email protected],
[email protected]

CERTIFICATE
This is certified that the project work report which is being submitted by
Shivanand Prajapati B. Pharm. VII semester Enrollment No. 0155PY171054
to Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal for the degree of
bachelor of pharmacy, VII semester examination Jan- 2021. The partial
fulfillment of the requirement for the degree of bachelor of pharmacy as per
provision of ordinance of RGPV, Bhopal the project work carried out during a
period for the academic year 2020-21 as per curriculum.

Dr. (Prof.) Sailesh Kumar

Ghatuary
Date: - Principal

RKDF School of Pharmaceutical Science Bhopal

Page | iii
 DECLARATION

I hereby declare that the work incorporated in the major project work
report embodies my own work under the supervision & guidance of Mrs.Reena
yadav, Assoc. Prof., RKDF School of Pharmaceutical Sciences, Bhopal (M.P.)
for partial fulfillment of degree of bachelor of pharmacy as per the ordinance of
Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal.

Date: Shivanand Prajapati

B. Pharmacy VII Semester
Enrollment No. 0155PY171054

RKDF School of Pharmaceutical Science Bhopal

Page | iv
 Acknowledgement

First of all, I would like to express my profound thanks to respected Dr.

Sailesh Kumar Ghatuary, Principal, RKDF School of Pharmaceutical
Sciences, Bhopal for giving me warm encouragement and inspiration for my
task, his precious guidance cannot be expressed only with thanks.

I offer my humble gratitude to my guide Mrs. Reena Yadav Assistant

Professor, RKDF School of Pharmaceutical sciences, Bhopal, for fis valuable
faithful guidance, encouragement and suggestions till the completion of my
project. His personal attention brought the project expeditiously. Lastly, I wish
to express heart full thanks to all my faculty members loving parents and all my
friends who helped me directly and indirectly.

Name of Student

B. Pharm. VII Sem.

Roll Number

RKDF School of Pharmaceutical Science Bhopal

Page | v
Abstract

Background: Hypertension affects 29% of the adult U.S. population and is a leading
cause of heart disease, stroke, and kidney failure. Despite numerous effective treatments, only
53% of people with hypertension are at goal blood pressure. The chronic care model suggests
that blood pressure control can be achieved by improving how patients and physicians
address patient self-care.

Methods and design: This paper describes the protocol of a nested 2 × 2 randomized
controlled trial to test the separate and combined effects on systolic blood pressure of a
behavioral intervention for patients and a quality improvement-type intervention for
physicians. Primary care practices were randomly assigned to the physician intervention or to
the physician controlcondition. Physician randomization occurred at the clinic level. The
physician intervention include

training and performance monitoring. The training comprised 2 internet-based

modules detailingboth the JNC-7 hypertension guidelines and lifestyle modifications for
hypertension. Performancedata were collected for 18 months, and feedback was provided to
physicians every 3 months.Patient participants in both intervention and control clinics were
individually randomized to thepatient intervention or to usual care. The patient intervention
consisted of a 6-month behavioralintervention conducted by trained interventionists in 20
group sessions, followed by 12 monthlyphone contacts by community health advisors.
Follow-up measurements were performed at 6 and18 months. The primary outcome was the
mean change in systolic blood pressure at 6 months.

This is an Open Access article distributed under the terms of the Creative Commons
Attribution which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.Secondary outcomes were diastolic blood
pressure and the proportion of patients with adequateblood pressure control at 6 and 18
months.Discussion: Overall, 8 practices (4 per treatment group), 32 physicians (4 per
practice; 16 pertreatment group), and 574 patients (289 control and 285 intervention) were
enrolled. Baselincharacteristics of patients and providers and the challenges faced during
study implementation arepresented. The HIP interventions may improve blood pressure
control and lower cardiovasculardisease risk in a primary care practice setting by addressing
key components of the chronic caremodel. The study design allows an assessment of the
effectiveness and cost of physician and patientinterventions separately, so that health care
organizations can make informed decisions aboutimplementation of 1 or both interventions in
the context of local resources

RKDF School of Pharmaceutical Science Bhopal

Page | 1
INTRODUCTION

High blood pressure, termed "hypertension," is a condition that afflicts more than 50
million Americans and is a leading cause of morbidity and mortality. Hypertension is much
more than a "cardiovascular disease" because it affects other organ systems of the body such
as kidney, brain, and eye. Tens of millions of Americans are not even aware of being
hypertensive because it is usually asymptomatic until the damaging effects of hypertension
(such as stroke, myocardial infarction, renal dysfunction, etc.) are observed.
Hypertension is an intermittent or persistent elevation of the blood pressure (systolic
blood pressure above 140 mm Hg or diastolic blood pressure above 90 mm
Hg) or (a systolic and diastolic pressure of 20 mm Hg above the normal baseline
pressure). Hypertension has recently increased in incidence throughout the world. It is
thought that the stresses of everyday life with a change in the dietary habits and lack of
exercise has led to the increasing incidence of hypertension. Previously hypertension was
predominant only in industrialized and developed countries. However, of late there has been
a sudden increase in the number of cases in developing countries.
It is often asymptomatic, but even so, the detection rate has increased over the past
three decades. Untreated, hypertension can lead to devastating end organ damage. Therefore,
clinicians have the important responsibilities of first detection and then adequate treatment.

Revive of article
Hypertension is high blood pressure. Blood pressure is the force of blood pushing
against the walls of arteries as it flows through them. Arteries are the blood vessels that carry
oxygenated blood from the heart to the body's tissues.

WHY SHOULD PHARMACISTS BE INVOLVED IN HYPERTENSION

MANAGEMENT?
Advantages
More than 200 million people visit a pharmacy every day in Europe. A community
pharmacist is a highly trained professional who can be seen without appointment, in an
informal setting which is often considered to be part of an every day shopping experience.
Pharmacists are therefore the most highly accessible members of the primary health care
team. Community pharmacies are visited by both people who are sick and people who are in

RKDF School of Pharmaceutical Science Bhopal

Page | 2
good health. Therefore community pharmacies have a potential for health promotion and
disease prevention. Regular visits of a person with hypertension for prescribed drug therapy
puts the patient in a regular contact with the pharmacist and provides opportunities for
intervention. The pharmacist can complement the GP in hypertension management in various
ways (7-10). The following are examples of such opportunities where pharmacists participate
with other health care professionals in community based health promotion and disease
prevention and management programmes.
 Pharmacists have an extensive knowledge about the principles of drug therapy, use of

medicines and prevention.

 Pharmacy can verify and improve the patients' knowledge about necessary lifestyle

modifications and the use of medicines and improve compliance with therapy.
 Pharmacists can identify drug therapy related problems and recommend possible solutions

including referrals to the GP.

 Pharmacists can monitor therapeutic outcomes of hypertension management.

Adherence to long-term therapies

Pharmaceutical care is an effective approach in improving adherence to long-term
therapies.Advice, information and referral by community pharmacists have been
demonstrated to significantly improve adherence to antihypertensive therapy and improve
blood pressure control.
Pharmacists are also involved in giving information and service to patients with
hypertension. It has been shown that after having provided appropriate health education and
monitoring services to patients with hypertension, primary care pharmacists managed to get
patients to use less expensive antihypertensive medication. Parents with hypertension
received pharmaceutical care from community pharmacies comprehending education,
assistance to reach compliance and recommendations to their GPs regarding drug therapy. In
several studies the intervention group showed a significant decrease in mean blood pressure.
The involvement of pharmacists in hypertension management falls in line with the
Good Pharmacy Practice document developed and adopted in 1994 by the Pharmaceutical
Group of the European Union (PGEU). It represents the first set of standards for pharmacy
practice developed by the Profession and with the international standard for Good Pharmacy
Practice (GPP) in Community and Hospital Pharmacy Setting developed by WHO. The first
element of Good Pharmacy Practice is Health Promotion and Ill-health Prevention and
according to the document a number of national standards have to be elaborated within this
RKDF School of Pharmaceutical Science Bhopal
Page | 3
area. Currently, new programmes involving community pharmacies in Good Pharmacy
Practice programmes or pharmaceutical care programmes are being developed and
introduced. Some midterm results from Portugal, Spain and United Kingdom show that
community pharmacists are capable of providing pharmaceutical care leading to good results
with regards to optimizing the drug therapy and achieving more cost effective outputs.
Many patients with diabetes mellitus and hypertension were not treated according to
guidelines, with 47% of the patients meeting the 2003 guidelines definitions of hypertension
not being treated with antihypertensive medications. By reducing the cut points for defining
hypertension, the proportion of people affected increased substantially. Specific risk factors
determined may aid in identifying patients at high risk for inadequate treatment. Patient and
provider education, public health approaches, and health system changes are needed to
address these issues. Further work is needed to determine the reasons for lack of control,
approaches to improve control and long term patients outcomes, and the budget impact and
cost effectiveness of using the 2003 guidelines.
Hypertension is an additional risk factor in those with diabetes mellitus for
macrovascular and microvascular complications. The health and budgetary impacts of
addressing the treatment gap need to be further explored.
Disadvantages
 Fatique

 Dizziness

 Fainting spells (syncope)

 Swelling in the ankles or legs (edema)

 Bluish lips and skin (cyanosis)

 Chest pain

 Racing pulse

Palpitations (a strong feeling of a fast heartbeat)

RKDF School of Pharmaceutical Science Bhopal

Page | 4
DESCRIPTION
Blood flows through arteries it pushes against the inside of the artery walls. The more
pressure the blood exerts on the artery walls, the higher the blood pressure will be. The size
of small arteries also affects the blood pressure. When the muscular walls of arteries are
relaxed, or dilated, the pressure of the blood flowing through them is lower than when the
artery walls narrow, or constrict.
Blood pressure is highest when the heart beats to push blood out into the arteries.
When the heart relaxes to fill with blood again, the pressure is at its lowest point. Blood
pressure when the heart beats is called systolic pressure. Blood pressure when the heart is at
rest is called diastolic pressure.When blood pressure is measured, the systolic, pressure is
stated first and the diastolic pressure second. Blood pressure is measured in millimeters of
mercury (mm Hg). For example, if a person's systolic pressure is 120 and diastolic pressure is
80, it is written as 120/80 mm Hg. The American Heart Association considers blood pressure
less than 140 over 90 normal for adults.

Hypertension is serious because people with the condition have a higher risk for heart
disease and other medical problems than people with normal blood pressure. Serious
complications can be avoided by getting regular blood pressure checks and treating
hypertension as soon as it is diagnosed.
If left untreated, hypertension can lead to the following medical conditions;
 Arteriosclerosis, also called atherosclerosis
 Heart attack
 Stroke
 Enlarged heart
 Kidney damage
Arteriosclerosis is hardening of the arteries. The walls of arteries have a layer of
muscle and elastic tissue that makes them flexible and able to dilate and constrict as blood
flows through them. High blood pressure can make the artery walls thicken and harden.
When artery walls thicken, the inside of the blood vessel narrows. Cholesterol and fats are
more likely to build up on the walls of damaged arteries, making them even narrower. Blood
clots can also get trapped in narrowed arteries, blocking the flow of blood.

RKDF School of Pharmaceutical Science Bhopal

Page | 5
 Arteries narrowed by arteriosclerosis may not deliver enough blood to organs and
other tissues. Reduced or blocked blood flow to the heart can cause a heart attack. If an artery
to the brain is blocked, a stroke can result.
The kidneys remove the body's wastes from the blood. If hypertension thickens the
arteries to the kidneys, less waste can be filtered from the blood. As the condition worsens,
the kidneys fail and wastes build up in the blood. Dialysis or a kidney transplant are needed
when the kidneys fail. About 25% of people who receive kidney dialysis have kidney failure
caused by hypertension.

CLASSIFICATION
Table 1 : Classification of Hypertension
Category Systolic BPa (mm Hg) Diastolic BPa (mm Hg)
Normal <120 and <80
Pre-hypertension 120-139 or 80-89
Stage 1 hypertension 140-159 or 90-99
Stage 2 hypertension > 160 or > 100
a
BP = Blood pressure

Table 2: Classification of Hypertension

According to WHO/ISH*
Category Systolic BPa (mm Hg) Diastolic BPa (mm Hg)
Optimal < 120 < 80
Normal < 130 < 85
High Normal 130-139 85-89
Grade I (mild hypertension) 140-159 90-99
Sub group: borderline 140-149 90-94
Grade 2 (moderate hypertension) 160-179 100-109
Grade 3 (severe hypertension) > 180 > 110
Isolated Systolic Hypertension (ISH) > 140 < 90
Subgroup (borderline) 140-149 < 90
ISH = International Society of Hypertension.

RKDF School of Pharmaceutical Science Bhopal

Page | 6
CLASSIFICTION
Secondary Hypertension
A) Systolic hypertension with wide pulse pressure:
 Aortic regurgitation
 Thyrotoxicosis
 Patent ductus arteriosus

B) Systolic and diastolic hypertension with increased PVR

1. Renal
 Glomerulonephritis (acute or chronic)
 Pyelonephritis
 Polycystic kidneys
 Renal artery stenosis
2. Endocrine
 Cushing's syndrome (excessive glucocorticoids)
 Congential adrenal hyperplasia
 Conn's syndrome (primary hyperaldosteronism)
 Phaeochromocytoma
 Hypothyroidism
 Acromegaly

3. Neurogenic
 Raised intracranial pressure
 Psychological ("white coat hypertension")
 Acute porphyria
 Lead poisoning

4. Miscellaneous
 Coarctation of the aorta
 Polyarteritis Nodosa
 Hypercalcaemia
 Increased intravascular volume (PRV)
RKDF School of Pharmaceutical Science Bhopal
Page | 7
Method of Measuring Hypertension
Palpatory Method
Ausculatory Method (Instrument : Sphigmomanometre)

CLINICAL MANIFESTATIONS
The manifestations of hypertensive crises are those of end-organ dysfunction:
1. Hypertensive encephalopathy
2. Acute aortic dissection
3. Acute myocardial infarction
4. Acute cerebral vascular accident
5. Acute hypertensive renal injury
6. Acute congestive heart failure.
It is important to recognize that the absolute level of BP may not be as important as
the rate of increase. Patients with longstanding hypertension may tolerate systolic BPs of 200
mm Hg or diastolic BPs of up to 150 mm Hg without developing hypertensive
encephalopathy, while children or pregnant women may develop encephalopathy with
diastolic BPs 100 mm Hg.
Applications
DRUG USED IN THE TREATMENT OF HYPERTENSION
VASODILATORS
e.g.p.o. HYDRALAZINE and MINOXDIL or i.v. SODIUM NITROPRUSSIDE
Mechanisms of Action
Hydralazine acts predominantly on arterioles by a still unknown mechanism
(independent of Nitric Oxide). Minoxidil (or rather its sulphate metabolite) causes relaxation
of vascular smooth muscle by opening ATP-dependent K channels. Sodium nitroprusside is a
nitro-dilator directly activating guanylate cyclase.
Uses
Special indications are pregnancy-induced hypertension )Hydralazine) and severe
refractory hypertension (Minoxidil). Both hydralazine and minoxidil cause: (1) a reflex
tachycardia – that is often profound requiring beta-blockade (2) rebound Na retention – that
antagonizes their hypotensive action and especially in the case of minoxidil requires
aggressive use of a loop diuretic.

RKDF School of Pharmaceutical Science Bhopal

Page | 8
Centrally Acting Anti-Hypertensive Agents
These agents have historically enjoyed greater usage outside the UK (especially in the USA).
They cannot be considered first-line/alternative first/line agents due to:
1. Poor side effect profile
2. Conspicuous lack of outcome data.
NB: a-Methyl-DOPA is still widely prescribed for pregnancy-induced hypertension.
Mechanism
Act centrally to reduce sympathetic outflow. Target receptors (probably a2 and not 11)
are in the hind brain vasomotor nuclei that project to spinal sympathetic efferent cell bodies.
They all cause a degree of sedation and many worsen or precipitate depression.
Adverse Reactions
 Rebound hypertension – following missed doses
 Rebound hypertension – Risk greatest with CLONIDINE and least with MOXONIDINE
 Dry mouth –CLONIDINE >>MOXONIDINE
 Haemolytic anaemia 20% of patients on a Methyl DOPA develop a positive Coomb's Test
only 1% haemolyse.

Alpha-Blockers
e.g. doxazosin, prazosin (largely obselete)
Mechanism of Action
Competitive a 1-receptor antagonists resulting in arteriolar vasodilatation.
Adverse Effects
 Postural hypotension
 Nasal stuffiness – similar side effect to a –methyl-DOPA.
 Ejaculatory failure
 Detrusor relaxation – may alleviate outflow obstruction in men (with BPH) or precipitate
urinary incontinence in women.
NB: Phenoxybenzamine differs from other alpha blockers in acting as an irreversible
(and relatively non-selective) receptor antagonist. It is only used in patients with
PHAEOCHROMOCYTOMA where a competitive blockade can be overcome by the very
high circulating catecholamine levels.

RKDF School of Pharmaceutical Science Bhopal

Page | 9
Beta-Blockers
Vary with respect to:
 Relative selectivity for 1 compared to 2 receptors (cardioselectivity)
 Lipid solubility
 Intrinsic sympathiomimetic activity
 Membrane stabilizing activity
These properties are not important with the exception of the following:
 selective agents are less likely to worsen peripheral vascular disease or impair awareness
of hypoglycaemia in diabetic.
 Lipid soluble beta-blockers penetrate the CNS and are more commonly associated with
sleep disturbance/nightmares.
 Agents lacking ISA may be more effective in preventing angina and are effective in
preventing migraine attacks.

Mechanism of Action (Chronic dosing)

1. Inhibition of beta-receptor mediated rennin release
2. Increased baroreceptor sensitivity
3. Reduction of noradrenaline release by blockade of presynaptic –receptors

Adverse Effects
 Worsening bronchoconstriction – even with 1 selective agents
 Worsening of heart failure
 Cardiac conduction defects
 Worsening peripheral vascular disease
 Loss of awareness of hypoglycaemia
 Exercise related fatigue

Thiazide Diuretics
Thiazides are the cheapest agents and have the best long-term mortality data for
cardiovascular and cerebrovascular disease prevention. Recommended as first line therapy by
JNC-VII guidelines after ALLHAT trial success.

RKDF School of Pharmaceutical Science Bhopal

Page | 10
Mechanism of Action
1. Natriuretic but weakly compared to loop diuretics. On chronic dosing most patients show
little or no reduction in circulating volume.
2. Reduce responsiveness of resistance vessels to endogeneous vasconstrictors
Eg. Noradrenaline. This may be related to intracellular Na (and hence Ca) or due to an effect
on unidentified membrane ion channel.

Adverse Effects
 Impairment of glucose tolerance
 Adverse effect on lipid profile
 Raised blood urate and risk of gout
 Tendency to hypokalaemia
 Impotence
 Photosensitive rashes.

Angiotensin Converting Enzyme Inhibitors (ACEI)

e.g. LISINOPRIL and CAPTOPRIL with respectively long & short duration of action.
Mechanism of Action
1. Inhibit the enzyme responsible for conversion of biologically inert angiotensin I to active
angiotensin II (ATII)
2. ACEI also block degradation of kinnis (kininase II = ACE). Bradykinin a potent
vasodilator.
NB: The effects of ATII on BP (vasconstriction and aldosterone release) are mediated
by the type 1 ATII receptors (confusingly referred to as AT1 receptors). The type 2 receptor
(even more cvonfusingly dubbed AT@!!) may be important for regulating the matrix
response to elevated BP ie. ventricular hypertrophy and resistance vessel remodeling.

RKDF School of Pharmaceutical Science Bhopal

Page | 11
Adverse Effects
 Dry cough – affects upto 20% of patients; commoner in females and reflects elevated BK
levels in the vicinity of airway C fibres.
 Angioneurotic oedema – rare but can be fatal when larynx involved (commoner in Afro
Caribbeans).
 Altered taste – only with older agents containing – SH groups eg CAPTOPRIL.
 Risk of hyperkalaemia.
 Deterioration in renal function in patients with renal artery stenosis – glomerular
perfusion dependent on ATII.
 First-dose hypotension – only if plasma rennin elevated (eg following DS loop diuretic)
hence usually a problem of CCF not hypertension.
NB: Angiotensin receptor antagonists (eg. LOSARTAN, IRBESARTAN) also act on
the rennin-angiotensin axis but block AT1 receptors. They may eventually replace ACEI in
both hypertension and heart failure BUT.
 There exists no outcome data with AT 1 receptor antagonists for either indication.
 They are licensed currently only for use in hypertension NOT heart failure.
 They are better tolerated than ACEI – they do not cause cough.
 They may be superior to ACEIs in causing regression of LVH due to stimulation of
antiproliferative AT2 receptors.

Calcium Channel Blockers

Classification
 Dihydropyridines (DHPs) – Nifedipine, Amlodipine
 Non-dihydropyridines (non-DHPs) – Diltiazem, Verapamil.

Mechanism of Action
Inhibit passage of calcium through the voltage gated L-type (for large/long-lasting
current) calcium channel on vascular smooth muscle cells and cardiac myocytes, reducing
calcium availability for muscle contraction. Note that an inhibitor of the T-type (Transient
current) cardiac calcium channel, MIBEFRADIL, has recently been terminated due to
unacceptable drug interactions. Ion channel blockade explains the observed.
 Peripheral vasodilatation
 Negative inotropic and negative chronotropic effects.

RKDF School of Pharmaceutical Science Bhopal

Page | 12
Adverse Effects
 Flushing*
 Headache*
 Palpitations* - reflecting the reflex tachycardia in response to vasodilatation.
 Pedal oedema – dilatation of the precapillary 'sphincters' NOT generally a reflection of
worsening heart failure!.
 May worsen heart failure due to their negative inotropic effect**.
* These effects are most commonly reported when absorption is rapid causing a
prompt vasomotor response; particularly with early 'instantaneous' release formulations of
nifedipine. Agents with a slow onset of action (eg. AMLODIPINE) or reformulation as a
'sustained' release preparation markedly reduces these problems.
** Most agents are negatively inotropic – non-DHP CCBs more so than DHPs.
AMLODIPINE is exceptional in having a 'neutral' inotropic effect and is well tolerated in
heart failure (PRAISE study).
NB: Non-DHPs also have AV nodal blocking properties (verapami>diltiazem) that
preent any reflex tachycardia. They may also interact with other agents affecting
conduction: beta-blockers should be combined with verapamil cautiously.

EPIDEMIOLOGY
Population-based cost-effective hypertension control strategies should be developed.
2020. Hypertension is directly responsible for 57% of all stroke deaths and 24% of all
coronary heart disease deaths in India. Indian urban population studies in the mid 1950s used
older WHO guidelines for diagnosis (BP > or + 160 and/or 95 mmHG) and reported
hypertension prevalence of 1.2-4.0%. Subsequent studies report steadily increasing
prevalence from 5% in 1960s to 12-15% in 1990s. Hypertension prevalence is lower in the
rural Indian population, although there has been a steady increase over time here as well.
Recent studies using revised criteria (BP > or = 140 and /or 90 mmHg) have shown a high
prevalence of hypertension among urban adults: men 30% women 44% in Jaipur (1995), men
44% in Mumbai (1999), men 31%, women 36% in Thiruvananthapuram (2000).Among the
rural populations, hypertension prevalence is men 24%, women 17% in Rajasthan (1994).
Hypertension diagnosed by multiple examinations has been reported in 27% male and 28%
female executives in Mumbai (2000) and 4.5% rural subjects in Haryana (1999). There is a
strong correlation between changing lifestyle factors and increase in hypertension in India.
RKDF School of Pharmaceutical Science Bhopal
Page | 13
The nature of genetic contribution and gene environment interaction in accelerating the
hypertension epidemic in India needs more studies. Pooling of epidemiological studies shows
that hypertension is present in 25% urban and 10% rural subjects in India. At an
underestimate, there are 31.5 million hypertensives in rural and 34 million in urban
populations. A total of 70% of these would be Stage I hypertension (systolic BP 140-159
and/or diastolic BP 90-99mmHg). Recent reports show that borderline hypertension *systolic
BP 130-139 and/or diastolic BP 85-89 mmHg) and Stage I hypertension carry a significant
cardiovascular risk and there is a need to reduce this blood pressure
The epidemiology of hypertension, in terms both of its importance as a risk factor for
cardiovascular and other diseases and of its own etiology, continues to be a major field of
investigation with an enormous peer reviewed literature each year. As stated by Paul Elliot in
the opening sentence of this book, "Raised blood pressure is one of the most important
underlying risk factors for morbidity and mortality in the world today, ranking alongside
tobacco in estimates of the worldwide attributable burden of mortality."
Interest in the pressure level in the circulation dates from 1733, when Hales placed a
glass tube in a horse's artery, about 100 years after Harvey demonstrated the circulation of
blood. Such direct measurements of arterial pressure were clearly impractical in clinical
practice, and efforts to develop devices for indirect measurement persisted throughout the
19th century, culminating in Riva-Rocci's description in 1896 of a cuff inflated by a pump to
occlude the palpated pulse. The occlusion pressure was recorded by a mercury manometer.
By 1901, it was appreciated that Riva-Cocci's cuff, which was 5 cm wide, gave erroneously
high occlusion pressures, and larger cuffs were introduced. In 1905, Korotkiff published his
paper reporting the use of a stethoscope to auscultate the diastolic and systolic blood
pressures. This technique became widely accepted within a few years and, along with
relatively inexpensive sphygmomanometers, opened the way for routine collection of blood
pressure data in large numbers of people. Sources of measurement artifact other than cuff size
and the need to standardize measurement methods to reduce these artifacts were well
appreciated prior to World War I. Acturial studies soon showed increased risk of mortality
among those at the higher end of the blood pressure distribution. The emergence after World
War II of chronic disease epidemiology, and particularly of cardiovascular epidemiology,
was followed by the development of effective pharmacologic treatments in the 1950s, and
their testing in randomized trials starting in the 1960s. The fields of hypertension
epidemiology, treatment, and control in populations began to take their modern forms.

RKDF School of Pharmaceutical Science Bhopal

Page | 14
 The Handbook of Hypertension is a multi volume series that encompasses these fields
as well as experimental, pathophysiologic, and genetic aspects. The present volume is an
updated version of the 1985 edition of the Epidemiology of Hypertension and includes 41
chapters by different authors on various aspects of the epidemiology of hypertension. The
uniformity very high quality of these chapters is evidence of a strong editorial hand, both in
the selection of authors and oversight of the work. There are sections on hypertension in
populations; blood pressure measurement; blood pressure and the environment; blood
pressure and nutrition; secondary forms of hypertension; genetics and clustering of risk
factors; blood pressure, hormone replacement, and oral contraceptives; community control of
hypertension; community control of hypertension in different countries and problems in
community control. This last section has two chapters, both exemplary, the first issues of
clinical labeling (effects of telling people they are hypertensive), and the second on the
pervasive role of the pharmaceutical industry in influencing prescribing decisions. A strength
throughout this book is the directness of the authors in articulating the limitations of data, the
controversies that remain unresolved, and the conflicting views of experts in the field.
Another strength, for a US reader, is the largely European author list and the consistent
citation of European publications. The literature cited is highly international and is generally
very up to date through 1998. Some of the chapters that I thought were particularly excellent
included Safar and Smulyan's chapter on systolic versus diastolic blood pressure, Prineas'
chapter on blood pressure in children and adolescents, Sever and Poulter's chapter on blood
pressure and migration, Simpson's chapter on sodium intake, Robertsons's comprehensive
review of the rennin-angiotensin system, and Alderman's chapter on work site hypertension
treatment programs. A number of others could be included in this list.
ETIOLOGY OF ESSENTIAL HYPERTENSION
Environment
A number of environmental factors have been implicated in the development of
hypertension, including salt intake, obesity, occupation, alcohol intake, family size, 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.

RKDF School of Pharmaceutical Science Bhopal

Page | 15
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 rennin activities observed
in hypertensive subjects in broader than in normotensive individuals. In consequences, some
hypertensive patients have been defined as having low rennin and others as having high
rennin 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. The 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 common complex genetic disorders, with genetic
heritability averaging 30%.Data supporting this view emerge from animal studies as well as
in population studies in humans. Most of these studies support the concept that the
inheritance is probably multifactorial or that a number of different 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.

RKDF School of Pharmaceutical Science Bhopal

Page | 16
Renal Hypertension
Hypertension produced by diseases of the kidney. A simple explanation for renal
vascular hypertension is that decreased perfusion of renal tissue due to stenosis of a main or
branch renal artery activates the rennin angiotensin system.
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 catecholamines such as
epinephrine and norepinephrine by a tumor (most often located in the adrenal medulla)
causes excessive stimulation of (adrenergic receptors), which results in peripheral
vasoconstriction and cardiac stimulation. This diagnosis is confirmed by demonstrating
increased urinary excretion of epinephrine and norepinephrine and/or their metabolites
(vanillylmandelic acid).
Coarctation of the Aorta
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, the number of collagen fibres 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.

PATHOPHYSIOLOGY
1. Abrupt increases in systemic vascular resistance likely related to humoral
vasoconstrictors.
2. Endothelial injury
3. Fibrinoid recrosis of the arterioles
4. Deposition of platelets and fibrin
5. Breakdown of the normal autoregulatory function
6. The resulting ischemia prompts further release of vasoactive substances completing a
vicious cycle.

RKDF School of Pharmaceutical Science Bhopal

Page | 17
 There is still much uncertainty about the pathophysiology of hypertension. A small
number of patients (between2% and 5) have anunderlying renal or adrenal disease as the
cause for their raised blood pressure. In the remainder, however, no clear single identifiable
cause is found and their condition is labeled "essential hypertension". A number of
physiological mechanisms are involved in the maintenance of normal blood pressure, and
their derangement may play a part in the development of essential hypertension.
It is probable that a great many interrelated factors contribute to the raised blood
pressure in hypertensive patients, and their relative roles may differ between individuals.
Among the factors that have been intensively studied are salt intake, obesity and insulin
resistance, the rennin-angiotensin system, and the sympathetic nervous system. In the past
few years, other factors have been evaluated, including genetics, endothelial dysfunction (as
manifested by changes in endothelin and nitric oxide), low birth weight and intrauterine
nutrition, and neurovascular anomalies.

SIGNS AND SYMPTOMS

Most people with high blood pressure have no signs of symptoms, even if blood
pressure readings reach dangerously high levels.
Although a few people with early stage high blood pressure may have dull headaches
dizzy spells or a few more nosebleeds than normal, these signs and symptoms typically don't
occur until high blood pressure has reached an advanced – possibly life-threatening--stage.
What are the Signs and Symptoms of Pulmonary Arterial Hypertension?
Difficulty breathing or shortness of breath (dyspnea) is the main symptom of
pulmonary arterial hypertension (PAH). If you have PAH, you may feel that it is difficult to
get enough air.
As the disease advances are:
 The pumping action of your heart grows weaker.
 Your energy decreases
In the more advanced stages, you:
 Are able to perform very little activity
 Have symptoms even when resting
 May become completely bedridden.

RKDF School of Pharmaceutical Science Bhopal

Page | 18
Conclusion
Hypertension is a very important disorder in aged people and is associated with higher
risk of cardiovascular morbidity and mortality. The fact of reducing blood pressure values
decreases the risk for cardiac death as well as neurological, metabolic, and musculoskeletal
system sequelae in aged people. Therefore, the aim of the antihypertensive treatment must be
to reduce cardiovascular risks and to maintain an adequate quality of life and good functional
capacity in these patients.

BIBLIOGRAPHY
1. Joseph T. Dipiro, Robert L. Talbert, Gury, C. Yee, Gary R. Matzke, Barbara
G. Wells, L. Michael Posey (editors). Pharmacotherapy a Pathophysiologic
Approach. 5th ed. McGraw Hill; 2002.
2. Roger Walker, Clive Edwards, editors. Clinical Pharmacy and
Terapeutics. 3rd ed. Churchill Livingston: 2003.
3. Joel G. Hardman, Lee E. Limbird, Alfred Goodman Gilman (editors). The
Pharmacological Basis of Therapeutics. 10th ed. McGraw Hill; 2001.
4. Robinson, Clinical Pathology.
5. R.s. Satoskar, S.D., Bhandarkar, Nirmala N. Rege. Pharmacology and
Pharmacotherapeutics. 19th ed. Mumabi: Popular Prakashan; 2005.
6. K.D. Tripathi, Pharmacology, 2005.
7. Current Pharmaceutical Biotechnology, Volume 7, Number 2, April 2006.
8. http/www.spring link.com.
9. http/www.medscape.com.
10. http/www.Aldrich.com.

RKDF School of Pharmaceutical Science Bhopal

Page | 19