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Hypertension
• The heart is a cone-shaped, muscular organ located
between the lungs behind the sternum.
• The heart muscle forms the myocardium, with
tightly interconnect cells of cardiac muscle tissue.
• The pericardium is the outer sac with lubricating
fluid membranous
The Heart
External heart anatomy
Coronary artery circulation
Passage of Blood Through the Heart
• Blood follows this sequence through the heart:
superior and inferior vena cava → right atrium →
tricuspid valve → right ventricle → pulmonary
semilunar valve → pulmonary trunk and arteries to
the lungs → pulmonary veins leaving the lungs →
left atrium → bicuspid valve → left ventricle →
aortic semilunarvalve → aorta → to the body.
Internal view of the heart
Path of blood through the heart
• Heart is relatively small, roughly the same size as your closed fist.
• Heart rest on the diaphragm, near the midline of the thoracic cavity.
• It lies in the mediastinum, a mass of tissue that extends from the sternum to the
vertebral column between the lungs.
• Human heart is covered by double walled covering called pericardium. The
membrane that surrounds and protects the heart is the pericardium.
• It confines the heart to its position in the mediastinum, while allowing sufficient
freedom of movement for vigorous and rapid contraction.
• The pericardiums consist of two parts; the fibrous pericardium and the serous
pericardium.
• The superficial fibrous pericardium is composed of tough, inelastic dense
irregular connective tissue. The fibrous pericardiums prevent overstretching of
heart, provide protection
• Hypertension or high blood pressure, is a very common and
serious condition that can lead to or complicate many health
problems.
• The risk of cardiovascular morbidity and mortality is
directly correlated with blood pressure.
• Risks of stroke, MI, angina, heart failure, kidney failure or
early death from a cardiovascular cause are directly
correlated with BP.
• Hypertension is often called "the silent killer" because it
generally has no symptoms until serious complications
develop.
• Essential or primary hypertension occurs when the condition
has no known cause.
• This form of hypertension cannot be cured, but it can be
controlled. More than 90% of individuals with hypertension
have essential hypertension.
• Genetic factor may play an important role in the development of
essential hypertension.
• When hypertension is caused by another condition or
disease process, it is called secondary hypertension.
• Fewer than 10% of patients have secondary hypertension;
where either a co-morbid disease or drug is responsible for
elevating BP.
• In most of these cases renal dysfunction resulting from sever chronic
kidney disease or renovascular disease is the most common secondary
cause.
• Hypertension has a variety of causes. Blood pressure generally tends
to rise with age.
• Hypertension can also be caused by other medical conditions, such
as thyroid disease or chronic kidney disease.
• Hypertension may also be a side effect of certain medications, such
as over-the-counter cold medications and oral contraceptives and
other hormone drugs.
• Obesity, heredity and life style also play a role in the development
of hypertension.
• Systolic blood pressure is a stronger predictor of cardiovascular diseases than
diastolic blood pressure in adults’ ≥ 50 year of age and is the most important clinical
blood pressure parameter for most patients.
• Patient with diastolic blood pressure value less than 90 mmHg and systolic blood
pressure value ≥140 mmHg have isolated systolic hypertension.
• Many people think of a reading of 120/80mmHg as "normal". In fact there are
many variations of normal that are dependent on a variety of factors.
• As a very general guide, adults should keep their blood pressure below
140/90mmHg.
• In addition, current guidelines consider consistent readings over 120/80mmHg as a
condition called pre-hypertension, which should be monitored and addressed to
ensure that blood pressure does not rise higher over time.
• It is very possible that a diagnosis of hypertension can be missed or delayed
because there are generally no symptoms in the early stages.
BLOOD PRESSURE (BP)
• Blood pressure (BP) is defined as lateral pressure exerted by the
blood on the walls of the blood vessels while flowing through them.
• Blood pressure in a blood vessel depends upon two things.
1) Distance from the heart and 2) Nature of the blood vessel.
• Blood pressure is more in blood vessels close to the heart. Blood
pressure is more in arterial system than in the venous system.
• This is because walls of arteries are thicker and less elastic; the walls
of the veins are thinner and more elastic.
• Normal blood pressure is 120/80 mmHg, Systolic BP (SBP) is the
maximum BP during the ventricular systole- 120 mmHg. Range:
110-130 mmHg. Diastolic BP (DBP) is the minimum pressure during
the ventricular diastole. It is 80 mmHg. Range: 70-90 mmHg
 Physiological Variations
Age: BP more in adult than in children.
Sex: BP more in male than females.
Pregnancy: During the later stages of pregnancy BP usually increase.
Altitude: BP is higher in people living at higher altitude.
Exercise: Systolic BP increases during exercise.
Emotion: BP rises during emotional expressions.
Sleep: BP falls during sleep
 Factor Effecting Blood Pressure
1)Volume of blood.
2)Force of contraction of the heart.
3)Heart rate and BP are inversely proportional.
4)Viscosity of blood.
5)Nature of the blood.
6)Elasticity of blood vessel
REGULATION OF BLOOD PRESSURE
• It means maintaining a constant blood pressure within a narrow variation.
• Both increase in blood pressure (hypertension) and decrease in blood
pressure (hypotension) are harmful in the body.
• The mechanism of regulation of BP is divided in to two groups.
1) Rapidly acting mechanism 2) Slow acting mechanism
 Rapidly acting mechanism
This includes both nervous regulations as well as endocrine or
hormonal regulation.
a) Nervous Regulation of BP
• The smooth muscles of blood vessels will always remain in a state of
contraction. Because of this the blood vessels remain in a state of
constriction- vasoconstriction.
• The degree of vasoconstriction depends upon the sympathetic tone.
• When sympathetic tone increase the degree of vasoconstriction will also
increase.
• When vasoconstriction increases total peripheral resistance (TPR) wills
increases which will in turn increase BP.
• Suppose the BP increases that will be detected by the baroreceptors situated at
the aortic arch and carotid sinus. These baroreceptors will send impulses to the
medulla oblongata.
• In the medulla oblongata there is a group of nervous concerned with control of
BP. It is known as vasomotor centre.
• There are two different area, Pressor area and Depressor area.
• These impulses coming from baroreceptors will inhibit the pressor area; this
will decrease the sympathetic tone.
• This will increase vasodilatation. TPR decreases so BP decreases to normal
level. This mechanism operated very fast. It corrects BP within few second.
Baroreceptors and the sympathetic nervous system
• Baroreflexes involving the sympathetic nervous system are responsible for the rapid
moment to moment regulation of blood pressure.
• A fall in blood pressure causes pressure-sensitive neurons (baro-receptors in the aortic
arch and carotid sinuses) to send fewer impulses to cardiovascular centers in the spinal
cord.
• This prompts a reflex response of increased sympathetic and decreased
parasympathetic output to the heart and vasculature, resulting in vasoconstriction
and increased cardiac output. These changes result in a compensatory rise in blood
pressure.
b)Endocrine or Hormonal Regulation of BP
There are three important hormones taking part in regulation of BP.
1)Renin- Angiotensin- Aldosterone mechanism or system.
2)Regulation of BP by Vasopressin or ADH.
3)Adrenalin (Epinephrine) and noradrenalin (nor epinephrine).
1) Renin- Angiotensin- Aldosterone mechanism or system
• Suppose BP falls, it will stimulate the kidney. The juxta glomerular apparatus of
the kidney will secrete renin.
• Renin acts as an enzyme. It acts on a plasma protein, angiotensin substrate and
converts in to angiotensin I.
• The angiotensin I is converted in to angiotensin II by the action of converting
enzyme. Angiotensin II is a vasoconstrictor in action.
• It acts on the walls of blood vessels and increases the degree of vasoconstriction. TPR
will increase; this will in turn increase the BP to normal level.
• In addition to that angiotensin II stimulates adrenal cortex. This will increase
the secretion of the hormone aldosterone.
• Aldosterone acts as kidneys. It increases the reabsorption of sodium and water.
This will increase blood volume. When blood volume increases that will in turn
increase BP
 Regulation of BP by Vasopressin or ADH
• Suppose BP falls, that wills stimuli hypothalamus.
• Hypothalamus in turn stimulate posterior pituitary. Posterior pituitary secrete
vasopressin.
• It acts on the wall of blood vessels. It increases vasoconstriction. TPR increases and
BP will increases to the normal level.
• In addition to this, ADH acts at the kidneys. It increases the reabsorption of water. That
will increase blood volume, so BP increases to the normal level
 Adrenaline (Epinephrine) and noradrenaline (nor epinephrine)
• Suppose BP falls that will stimulate hypothalamus.
• Hypothalamus in turn stimulates sympathetic nervous system. This will in turn
stimulate adrenal medulla. It secretes more adrenaline.
• Adrenaline acts at the wall of the blood vessels. It increases vasoconstriction. This will
increase TPR, this will in turn increase BP to normal level.
HYPERTENSION
• Hypertension is defined as abnormally high blood pressure (more
than 120/80 mm Hg) in the arteries.
• Persistent increase in systemic arterial blood pressure is known as
hypertension.
• Usually a mean arterial pressure greater than in 110mm Hg
under resting conditions is considered to be hypertensive.
• This level normally occurs when the diastolic blood pressure is
greater than 90 mm Hg and the systolic pressure is greater than
about 135-140 mm Hg.
• Hypertension is generally symptom less, but increases the risk of
various other cardiovascular diseases like stroke, heart attack
and non-cardiovascular diseases like renal damage, end stage of
renal failure, etc.
THE COMMON DETERMINANTS
Age and sex: BP generally rises with age in both male and female. The rise is more steep in
the middle age and thereafter. At initial phase, pressure is more in men while in later phase
rise is more in women.
Weight: the rise in BP with respect to weight is found to be directly proportional.
Alcohol consumption: it is also reported that alcohol intake than positively increase the BP,
but the reason is not clear
Geographic variation: geographical variation can affect BP via variable contributing factors
like TPR, hypoxia, primitive condition, etc.
Smoking: tobacco combustion results in nicotine and carbon monoxide production, a potent
vasoconstrictor leading to development of hypertension.
Salt consumption: Salt intake can promote rigidity to vascular smooth muscle and therefore
excessive salt intake (more than 8 -10 gm per day) may result in hypertension.
Genetic predisposition: Based upon survey it is now believed that hypertension may be the
result of typical genetic makeup.
TYPES OF HYPERTENSION
Category pressure Systolic pressure mm Hg Diastolic pressure mm Hg
Normal 90–119 60-79
Pre-hypertension 120–139 80–89
Stage 1 140–159 90–99
Stage 2 ≥160 ≥100
Isolated systolic
Hypertension
≥140 <90
It is divided into two types
1) Primary hypertension (Essential hypertension)
2) Secondary hypertension (Non-essential hypertension)
PRIMARY HYPERTENSION
It results when arterial blood pressure is increased due to increased peripheral resistance. It is
further divided in to two types namely: benign and malignant hypertension
a) Benign hypertension
Here, there is a moderate increase in blood pressure with systolic pressure of 200 mm Hg and
the diastolic pressure of above 100 mm Hg. However, in resting condition and sleep, the
blood pressure returns to normal level.
b) Malignant hypertension
• Here, the blood pressure elevated to a great extends of about 250 mm Hg of systolic
pressure and 150 mm Hg of diastolic pressure. It produces severe symptoms like renal
disease, retinal disease, and being a fatal disease, it causes death within few years.
• Some of the characteristics of primary or essential hypertension are, the mean arterial
pressure is increased 40-60 %.
• The renal blood flow in the later stages is decreased about one half of normal.
• The resistance to blood flow through the kidney is increased 2-4 fold. The kidneys will not
excrete adequate amounts of salt and water unless the arterial pressure is high.
SECONDARY HYPERTENSION
The different forms of secondary hypertension are
 Cardiovascular hypertension-
a. It is produced due to Atherosclerosis- hardening and narrowing of blood vessels
b. Coarctation of aorta- narrowing of aorta.
 Renal hypertension
a. It is produced due to Stenosis renal arteries- narrowing of one or both renal arteries,
so that the renal function is impaired.
b. Glomerulonephritis- nephritis with inflammation of the capillary loops in the renal
glomeruli.
 Endocrine hypertension
a. It occurs due to Pheochromocytoma- tumer in adrenal medulla
b. Hyperaldosteronism- excess secretion of aldosterone from adrenal cortex Conn’s
syndrome.
c. Cushing’s syndrome- excess secretion of cortisone.
d. Gigantism or Acromegaly- excess secretion of growth hormone.
 Neurogenic hypertension
Acute hypertension can be caused by strong stimulation of the sympathetic nervous
system.
a. Section of the baroreceptors nerves.
b. Lesions in tractus solitarius.
c. Increased intracranial pressure.
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 % of high blood
pressure cases.
• At least four medications may be necessary to treat resistant
hypertension.
• 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.
ETIOLOGY OF HYPERTENSION
• Although hypertension may occur secondary to other disease processes,
more than 90% of patients have essential hypertension, a disorder of
unknown origin affecting blood pressure regulating mechanism.
• A family history of hypertension is increases the likelihood that an
individual will develop hypertensive disease.
• Essential hypertension occurs four times more frequently amoung
blacks than amoung whites, and it occur more often amoung middle-
aged males than amoung middle-aged females.
• Environmental factors such as stressful lifestyle, high dietary intake
of sodium, obesity, and smoking all further predispose an individual
to the occurrence of hypertension.
Epidemiology
• Overall, approximately 20% of the world’s adults are
estimated to have hypertension.
• Worldwide, approx. 1 billion people have hypertension, contributing to
more than 7.1 million deaths per year.
• The age-specific prevalence was
• 3.3% in group aged 18-29 yr
• 13.2% in group aged 30-39 yr
• 22% in group aged 40-49 yr
• 37.5% in group aged 50-59 yr
• 51% in group aged 60-74 yr
PATHOGENESIS OF HYPERTENSION
• The multiple mechanism of hypertension constitutes aberrations of
the normal physiologic regulation of blood pressure.
• Regulation of normal blood pressure: The blood pressure level is a
complex trait that is determined by the interaction of multiple
genetic, environmental, and demographic factors that influence to
hemodynamic variables: cardiac output and total peripheral
resistance.
• Cardiac output affected by the blood volume, itself greatly
dependent on body sodium homeostasis.
• Total peripheral resistance is predominantly determined at the level
of the arterioles and depends on the effect of neutral and hormonal
influence.
• Normal vascular tone reflects the balance between humoral
vasoconstriction influences (including angiotensin II and
catecholamine) and vasodilators (including kinins, prostagladins, and
nitric oxide).
• Resistance vessels also exhibit autoregulation, whereby increased
blood flow induced vasoconstriction to protect against tissue hyper
perfusion.
• Other local factors such as pH and hypoxia, as well as neuronal
interactions (α- and β- adrenergic systems), May important
• The kidneys play an important role in blood pressure regulation, as
follows:
• Through the renin-angiotensin system, the kidney influences both
peripheral resistance and sodium homeostasis.
• Renin elaborated by the juxta glomerular cells of kidney transforms
plasma angiotensinogen to angiotensin I, which is then converted to
angiotensin II by angiotensin converting enzyme (ACE).
• Angiotensin II raises blood pressure by increasing both peripheral
resistance (direct action on vascular SMCs) and blood volume (stimulation
of aldosterone secretion, increase in distal tubular reabsorption of sodium).
• The kidney also produced a variety of vasodepressor or
antihypertensive substances (including prostaglandins and nitric oxide)
that presumably counterbalance the vasopressor effects of angiotensin.
• When blood volume is reduced, the glomerular filtration rate falls,
leading to increased reabsorption of sodium and water by proximal
tubules and thereby conserving sodium and expanding blood volume.
• Glomerular filtration rate- independent natriuretic factors including atrial
natriuretic peptide, secreted by heart atria in response to volume
expansion, inhibit sodium reabsorption in distal tubules and cause
vasodilation
• When renal excretory function is impaired, increased atrial pressure is
a compensatory mechanism that helps restore fluid and electrolyte
balance.
CAUSES
1. Essential Hypertension
2. Renal
a) Acute nephritis
b) Interstitial nephritis and pyelonephritis
c) Polycystic kidneys
d) Renal artery stenosis
3. Vascular: Arteriosclerosis, coaractation of aorta.
4. Endocrine: Pheochromocytoma, Cushing’s syndrome, thyrotoxicosis,
myxedema.
5. Neurological: Raised intracranial tension, lead encephalopathy, etc.
6. Miscellaneous: Polycythemia, aortic incompetence, toxaemia of
pregnancy, gout, etc.
Measurement of Blood Pressure
• Regulation of Normal Blood Pressure is carried out by :
• Systemic Vascular Resistance is an index of arteriolar compliance or
constriction throughout the body. It is the resistance that left ventricle
must overcome to pump blood through the systemic circulation.
• Cardiac Output is the amount of blood pumped by the heart per min.
The cardiac output is usually expressed in lit/min. A normal adult has
a cardiac output of around 5 liters of blood per minute.
Blood Pressure =
Cardiac Output
(CO) ×
Systemic
Vascular Resistance
• Cardiac output can be calculated by following :
• Heart rate is the speed of the heartbeat measured by the number of
contractions of the heart per minute (bpm). A normal resting heart
rate for adults ranges from 60 to 90 beats in a minute. But ideally it is 72
beat/ min.
• Stroke volume (SV) is the volume of blood pumped from the left
ventricle per beat. The stroke volumes for each ventricle are generally
being approximately 70 ml/ beat in a healthy man.
• Hence, cardiac output = 72 * 70 = 5040 ml/min
• A normal adult has a cardiac output of around 5 liters of blood per
minute.
Cardiac Output
(CO) =
Heart Rate
(HR)
×
Stroke Volume
(SV)
Signs & Symptoms
• Severe headache
• Fatigue /confusion /dizziness
• Vision problems
• Chestpain
• Difficulty breathing
• Irregular heartbeat
• Blood in the urine
• Pounding in neck orears
• It is often called Silent Killer
• because it is frequently
• asymptomatic until it has becomesevere.
Diagnosis
• Manometer : Mercury, anaeroid or electronic devices is used in
measurement of blood pressure. It should be calibrated frequently
and routinely against standards (typically every 6 months) to assure
accuracy.
• Electrocardiogram : A test that measures the electrical activity,
rate, and rhythm of your heartbeat via electrodes attached to
your arms, legs, and chest. The results are recorded on graph paper.
• Echocardiogram : This is a test that uses ultrasound waves to
provide pictures of the heart's valves and chambers so the
pumping action of the heart can be studied and measurement of
the chambers and wall thickness of the heart can be made.
Complication
• Heart attack or stroke : High blood pressure can cause hardening and
thickening of the arteries (atherosclerosis), which can lead to a heart
attack, stroke or other complications.
• Heart failure : To pump blood against the higher pressure in your vessels,
your heart muscle thickens. Eventually, the thickened muscle may have
a hard time pumping enough blood to meet your body's needs, which
can lead to heart failure.
• Aneurysm : Increased blood pressure can cause your blood vessels to
weaken and bulge, forming an aneurysm. If an aneurysm ruptures, it
can be life-threatening.
• Renal Failure : Weakened and narrowed blood vessels in the kidneys
can prevent these organs from functioning normally.
• Retinopathy : Thickened, narrowed or torn blood vessels in the eyes
can result in vision loss.
• Metabolic syndrome. This syndrome is a cluster of disorders of the
body's metabolism, including increased waist circumference; high
triglycerides; low high-density lipoprotein (HDL) cholesterol, the
"good" cholesterol; high blood pressure; and high insulin levels.
These conditions make the person more likely to develop diabetes,
heart disease and stroke.
• Trouble with memory or understanding. Uncontrolled high blood
pressure may also affect the ability to think, remember and learn.
Trouble with memory or understanding concepts is more common in
people with high blood pressure.
Management
Non-Clinical Management
Non-pharmacological management plays an important role
in improving
1.
in the management of hypertension and
overall cardiovascular health.
Lifestyle Modification
• Weight reduction : Weight-reducing diets in overweight
hypertensive persons can result in modest weight loss in
the range of 3-9% of body weight and are associated with
blood pressure reduction of about 3-6 mmHg. It is
advisable for overweight hypertensive patients to lose at
least 5% of theirweight.
• Quit smoking : Tobacco abuse in any form is found to
increase blood pressureacutely.
• Avoidance of alcohol intake : Moderation of alcohol consumption is
advised. Alcohol consumption elevates BP acutely. Meta analyses have
shown that, interventions to reduce alcohol consumption caused a small
but significant reduction (3.3/2 mmHg) in both systolic and diastolic
blood respectively.
• Physical exercise : Aerobic physical exercise for 20–30 minutes per day
for at least 5 days per week improves blood pressure and reduces
cardiovascular morbidity.
2. Dietary Modification
• A diet rich in fruits, vegetables and low fat dairy products with
reduced saturated and total fat can substantially lower BP due to high
potassium content. More recently, diet high in L-Arginine has been
shown to be able to reduce BP by 5.4/2.3 mmHg.
• Low sodium diet : High salt intake is associated with significantly
increased risk of stroke and total cardiovascular disease.
• Typical Indian food provides 4–5 gm of sodium per day. Pickles, salted
vegetables and canned fish are rich in sodium and should be avoided.
• Intake of 2-3 gm of sodium or less is recommended as per dietary
approaches to stop hypertension.
• Evidence from published systematic review and meta analyses showed that
restricting sodium intake in people with elevated blood pressure in the
short term leads to reductions in blood pressure of up to 10.5 mmHg
systolic and 2 mmHg diastolic.
Clinical Treatment
• There are following class of drugs useful for the treatment of
Hypertension :
• Angiotensin Converting Enzyme (ACE) Inhibitors
• Angiotensin Receptor Blockers
• Diuretics
• Calcium Channel Blockers
• β blockers
• α blockers
• Centrally acting agents
• Direct Vasodilators
Overall Mechanismof Drug
Angiotensin Converting Enzyme (ACE) Inhibitors
• These agents reduce blood
pressure by blocking the
renin-angiotensin system.
• They do this by preventing
conversion of angiotensin I to
the blood pressure raising
hormone angiotensin II.
• They also increase availability
of the vasodilator bradykinin
by blocking its breakdown
• Use : These drugs have established clinical outcome benefits in patients
with heart failure, post–myocardial infarction, left ventricular systolic
dysfunction, and diabetic and non- diabetic chronic kidney disease.
• Side Effects : They are well tolerated. Their main side effect is cough.
Angioedema is an uncommon but potentially serious complication that
can threaten airway function.
• These drugs can increase serum creatinine by 30% due to reduce pressure
within the renal glomerulus which is not harmful.
• These drugs must not be used in pregnancy.
• Egs., Ramipril
• Captopril
• Enalapril
• Perindopril
Angiotensin Receptor Blockers
• Angiotensin receptor blockers antagonize
the renin angiotensin system. They reduce
blood pressure by blocking the action of
angiotensin II on its AT1 receptor and thus
prevent the vasoconstrictor effects of this
receptor.
• Egs., Losartan
• Valsartan
• Telmisartan
• Candesartan
• Use : These drugs have the same benefits on cardiovascular and renal
outcomes as angiotensin-converting enzyme inhibitors like heart failure,
post–myocardial infarction, left ventricular systolic dysfunction, and
diabetic and non- diabetic chronic kidney disease.
• Side Effect : They are well tolerated because they do not cause cough and
only rarely cause angioedema and have effects similar to ACE inhibitors,
they are generally preferred over ACE inhibitors if they are available and
affordable. They also can increase serum creatinine which is not harmful.
• These drugs must not be used in pregnancy.
Diuretics
• These agents work by increasing
excretion of sodium by the
kidneys and additionally may
have some vasodilator effects.
• 2 types of diuretics are used in
the treatment of Hypertension :
• Thiazide diuretic
• Loop diuretic
• Clinical outcome benefits have been best established with chlorthalidone,
indapamide, and hydrochlorothiazide.
• Chlorthalidone has more powerful effects on blood pressure than
hydrochlorothiazide and has a longer duration of action.
• Side Effect : The main side effects of these drugs are metabolic
(hypokalemia, hyperglycemia, hyperuricemia). The likelihood of these
problems can be reduced by using low doses or by combining with ACE
inhibitors or angiotensin receptor blockers, which have been shown to
reduce these metabolic changes. Diuretics are most effective with these
two combinations. Combining diuretics with potassium-sparing agents
also helps to prevent hypokalemia and with calcium channel blockers
are also effective.
Calcium Channel Blockers
These agents reduce blood pressure by
blocking the inward flow of calcium ions
through the L channels of arterial smooth
musclecells.
• Ex.
Non dihydropyridines :
Diltiazem
Verapamil
Dihydropyridines :
Nifedipine Amlodipine
• There are 2 main types of calcium channel blockers: dihydropyridines,
such as amlodipine and nifedipine, which work by dilating arteries;
and nondihydropyridines, such as diltiazem and verapamil, which
dilate arteries somewhat less but also reduce heart rate and
contractility. Hence Nondihydropyridine are not recommended in
patients with heart failure.
• Side Effect : The main side effect of calcium channel blockers is
peripheral edema, which is most prominent at high doses.
• They have powerful blood pressure reducing effects, when
combined with ACE inhibitors or angiotensin receptor blockers.
βAdrenoreceptor Blockers
β blockers reduce Cardiac output
and decrease the also release of
renin from the kidney.
Egs., Propranolol
Atenolol Metoprolol Carvediol
Acebtalol
• Use : They have strong clinical outcome benefits in patients with histories of myocardial
infarction and heart failure and are effective in the management of angina pectoris.
• Side Effect : The main side effects associated with b-blockers are reduced sexual function,
fatigue, and reduced exercise tolerance.
• Many of these agents have adverse effects on glucose metabolism and therefore are not
recommended in patients at risk of diabetes, especially in combination with diuretics.
They may sometimes also be associated with heart block.
• The combined α and β blocker, LABETALOL, is widely used intravenously for
hypertensive emergencies and is also used orally for treating hypertension in pregnant
and breastfeeding women.
αAdrenergic Blockers
α Blockers reduce blood
pressure by blocking arterial α
Receptors adrenergic and thus
preventing the vasoconstrictor
actions of these receptors.
Ex., Prazosin
Terazosin
Doxazosin
• Use : These drugs are less widely used as first-step agents than other
classes because clinical outcome benefits have not been well
established. However, they can be useful in treating resistant
hypertension when used in combination with agents diuretics, β
blockers, and ACE inhibitors.
• To be maximally effective, they should usually be combined with a
diuretic. Since α blockers can have somewhat beneficial effects on
blood glucose and lipid levels, they can potentially neutralize some
of the adverse metabolic effects of diuretics.
• The α blockers are effective in treating benign prostatic
hypertrophy and so can be a valuable part of hypertension
treatment regimens in older men who have this condition.
Centrally Acting Agents
• These drugs, the most well- known of
which are clonidine and methyldopa
work primarily by reducing
sympathetic outflow from the central
nervous system.
• Egs., Methyldopa
• Clonidine
• Clonidine patch
• Side Effect : such as drowsiness and dry mouth have reduced their
popularity.
• Treatment with a clonidine skin patch causes fewer side effects than
the oral agent, but the patch is not always available and can be more
costly than the tablets.
• In certain countries, including the United States, α methyldopa is
widely employed for treating hypertension in pregnancy.
Direct Vasodilators
• Because these agents often cause
fluid retention and tachycardia,
they are most effective in reducing
blood pressure when combined
with diuretics and β blockers or
sympatholytic agents. For this
reason, they are now usually used
only as fourth-line or later
additions to treatment regimens.
• Egs., Hydralazine
• Minoxidil
• Hydralazine is the more widely used of these agents. The powerful
drug minoxidil is sometimes used by specialists in patients whose
blood pressures are difficult to control. Fluid retention and
tachycardia are frequent problems with minoxidil, as well as
unwanted hair growth (particularly in women). Furosemide is often
required to cope with the fluid retention.
Thank you

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Hypertension.pptx

  • 2. • The heart is a cone-shaped, muscular organ located between the lungs behind the sternum. • The heart muscle forms the myocardium, with tightly interconnect cells of cardiac muscle tissue. • The pericardium is the outer sac with lubricating fluid membranous The Heart
  • 5. Passage of Blood Through the Heart • Blood follows this sequence through the heart: superior and inferior vena cava → right atrium → tricuspid valve → right ventricle → pulmonary semilunar valve → pulmonary trunk and arteries to the lungs → pulmonary veins leaving the lungs → left atrium → bicuspid valve → left ventricle → aortic semilunarvalve → aorta → to the body.
  • 6. Internal view of the heart
  • 7. Path of blood through the heart
  • 8. • Heart is relatively small, roughly the same size as your closed fist. • Heart rest on the diaphragm, near the midline of the thoracic cavity. • It lies in the mediastinum, a mass of tissue that extends from the sternum to the vertebral column between the lungs. • Human heart is covered by double walled covering called pericardium. The membrane that surrounds and protects the heart is the pericardium. • It confines the heart to its position in the mediastinum, while allowing sufficient freedom of movement for vigorous and rapid contraction. • The pericardiums consist of two parts; the fibrous pericardium and the serous pericardium. • The superficial fibrous pericardium is composed of tough, inelastic dense irregular connective tissue. The fibrous pericardiums prevent overstretching of heart, provide protection
  • 9. • Hypertension or high blood pressure, is a very common and serious condition that can lead to or complicate many health problems. • The risk of cardiovascular morbidity and mortality is directly correlated with blood pressure. • Risks of stroke, MI, angina, heart failure, kidney failure or early death from a cardiovascular cause are directly correlated with BP. • Hypertension is often called "the silent killer" because it generally has no symptoms until serious complications develop.
  • 10. • Essential or primary hypertension occurs when the condition has no known cause. • This form of hypertension cannot be cured, but it can be controlled. More than 90% of individuals with hypertension have essential hypertension. • Genetic factor may play an important role in the development of essential hypertension. • When hypertension is caused by another condition or disease process, it is called secondary hypertension. • Fewer than 10% of patients have secondary hypertension; where either a co-morbid disease or drug is responsible for elevating BP.
  • 11. • In most of these cases renal dysfunction resulting from sever chronic kidney disease or renovascular disease is the most common secondary cause. • Hypertension has a variety of causes. Blood pressure generally tends to rise with age. • Hypertension can also be caused by other medical conditions, such as thyroid disease or chronic kidney disease. • Hypertension may also be a side effect of certain medications, such as over-the-counter cold medications and oral contraceptives and other hormone drugs. • Obesity, heredity and life style also play a role in the development of hypertension.
  • 12. • Systolic blood pressure is a stronger predictor of cardiovascular diseases than diastolic blood pressure in adults’ ≥ 50 year of age and is the most important clinical blood pressure parameter for most patients. • Patient with diastolic blood pressure value less than 90 mmHg and systolic blood pressure value ≥140 mmHg have isolated systolic hypertension. • Many people think of a reading of 120/80mmHg as "normal". In fact there are many variations of normal that are dependent on a variety of factors. • As a very general guide, adults should keep their blood pressure below 140/90mmHg. • In addition, current guidelines consider consistent readings over 120/80mmHg as a condition called pre-hypertension, which should be monitored and addressed to ensure that blood pressure does not rise higher over time. • It is very possible that a diagnosis of hypertension can be missed or delayed because there are generally no symptoms in the early stages.
  • 13. BLOOD PRESSURE (BP) • Blood pressure (BP) is defined as lateral pressure exerted by the blood on the walls of the blood vessels while flowing through them. • Blood pressure in a blood vessel depends upon two things. 1) Distance from the heart and 2) Nature of the blood vessel. • Blood pressure is more in blood vessels close to the heart. Blood pressure is more in arterial system than in the venous system. • This is because walls of arteries are thicker and less elastic; the walls of the veins are thinner and more elastic. • Normal blood pressure is 120/80 mmHg, Systolic BP (SBP) is the maximum BP during the ventricular systole- 120 mmHg. Range: 110-130 mmHg. Diastolic BP (DBP) is the minimum pressure during the ventricular diastole. It is 80 mmHg. Range: 70-90 mmHg
  • 14.  Physiological Variations Age: BP more in adult than in children. Sex: BP more in male than females. Pregnancy: During the later stages of pregnancy BP usually increase. Altitude: BP is higher in people living at higher altitude. Exercise: Systolic BP increases during exercise. Emotion: BP rises during emotional expressions. Sleep: BP falls during sleep  Factor Effecting Blood Pressure 1)Volume of blood. 2)Force of contraction of the heart. 3)Heart rate and BP are inversely proportional. 4)Viscosity of blood. 5)Nature of the blood. 6)Elasticity of blood vessel
  • 15. REGULATION OF BLOOD PRESSURE • It means maintaining a constant blood pressure within a narrow variation. • Both increase in blood pressure (hypertension) and decrease in blood pressure (hypotension) are harmful in the body. • The mechanism of regulation of BP is divided in to two groups. 1) Rapidly acting mechanism 2) Slow acting mechanism  Rapidly acting mechanism This includes both nervous regulations as well as endocrine or hormonal regulation. a) Nervous Regulation of BP • The smooth muscles of blood vessels will always remain in a state of contraction. Because of this the blood vessels remain in a state of constriction- vasoconstriction.
  • 16. • The degree of vasoconstriction depends upon the sympathetic tone. • When sympathetic tone increase the degree of vasoconstriction will also increase. • When vasoconstriction increases total peripheral resistance (TPR) wills increases which will in turn increase BP. • Suppose the BP increases that will be detected by the baroreceptors situated at the aortic arch and carotid sinus. These baroreceptors will send impulses to the medulla oblongata. • In the medulla oblongata there is a group of nervous concerned with control of BP. It is known as vasomotor centre. • There are two different area, Pressor area and Depressor area. • These impulses coming from baroreceptors will inhibit the pressor area; this will decrease the sympathetic tone. • This will increase vasodilatation. TPR decreases so BP decreases to normal level. This mechanism operated very fast. It corrects BP within few second.
  • 17. Baroreceptors and the sympathetic nervous system • Baroreflexes involving the sympathetic nervous system are responsible for the rapid moment to moment regulation of blood pressure. • A fall in blood pressure causes pressure-sensitive neurons (baro-receptors in the aortic arch and carotid sinuses) to send fewer impulses to cardiovascular centers in the spinal cord. • This prompts a reflex response of increased sympathetic and decreased parasympathetic output to the heart and vasculature, resulting in vasoconstriction and increased cardiac output. These changes result in a compensatory rise in blood pressure. b)Endocrine or Hormonal Regulation of BP There are three important hormones taking part in regulation of BP. 1)Renin- Angiotensin- Aldosterone mechanism or system. 2)Regulation of BP by Vasopressin or ADH. 3)Adrenalin (Epinephrine) and noradrenalin (nor epinephrine).
  • 18. 1) Renin- Angiotensin- Aldosterone mechanism or system • Suppose BP falls, it will stimulate the kidney. The juxta glomerular apparatus of the kidney will secrete renin. • Renin acts as an enzyme. It acts on a plasma protein, angiotensin substrate and converts in to angiotensin I. • The angiotensin I is converted in to angiotensin II by the action of converting enzyme. Angiotensin II is a vasoconstrictor in action. • It acts on the walls of blood vessels and increases the degree of vasoconstriction. TPR will increase; this will in turn increase the BP to normal level. • In addition to that angiotensin II stimulates adrenal cortex. This will increase the secretion of the hormone aldosterone. • Aldosterone acts as kidneys. It increases the reabsorption of sodium and water. This will increase blood volume. When blood volume increases that will in turn increase BP
  • 19.
  • 20.  Regulation of BP by Vasopressin or ADH • Suppose BP falls, that wills stimuli hypothalamus. • Hypothalamus in turn stimulate posterior pituitary. Posterior pituitary secrete vasopressin. • It acts on the wall of blood vessels. It increases vasoconstriction. TPR increases and BP will increases to the normal level. • In addition to this, ADH acts at the kidneys. It increases the reabsorption of water. That will increase blood volume, so BP increases to the normal level  Adrenaline (Epinephrine) and noradrenaline (nor epinephrine) • Suppose BP falls that will stimulate hypothalamus. • Hypothalamus in turn stimulates sympathetic nervous system. This will in turn stimulate adrenal medulla. It secretes more adrenaline. • Adrenaline acts at the wall of the blood vessels. It increases vasoconstriction. This will increase TPR, this will in turn increase BP to normal level.
  • 21. HYPERTENSION • Hypertension is defined as abnormally high blood pressure (more than 120/80 mm Hg) in the arteries. • Persistent increase in systemic arterial blood pressure is known as hypertension. • Usually a mean arterial pressure greater than in 110mm Hg under resting conditions is considered to be hypertensive. • This level normally occurs when the diastolic blood pressure is greater than 90 mm Hg and the systolic pressure is greater than about 135-140 mm Hg. • Hypertension is generally symptom less, but increases the risk of various other cardiovascular diseases like stroke, heart attack and non-cardiovascular diseases like renal damage, end stage of renal failure, etc.
  • 22. THE COMMON DETERMINANTS Age and sex: BP generally rises with age in both male and female. The rise is more steep in the middle age and thereafter. At initial phase, pressure is more in men while in later phase rise is more in women. Weight: the rise in BP with respect to weight is found to be directly proportional. Alcohol consumption: it is also reported that alcohol intake than positively increase the BP, but the reason is not clear Geographic variation: geographical variation can affect BP via variable contributing factors like TPR, hypoxia, primitive condition, etc. Smoking: tobacco combustion results in nicotine and carbon monoxide production, a potent vasoconstrictor leading to development of hypertension. Salt consumption: Salt intake can promote rigidity to vascular smooth muscle and therefore excessive salt intake (more than 8 -10 gm per day) may result in hypertension. Genetic predisposition: Based upon survey it is now believed that hypertension may be the result of typical genetic makeup.
  • 23. TYPES OF HYPERTENSION Category pressure Systolic pressure mm Hg Diastolic pressure mm Hg Normal 90–119 60-79 Pre-hypertension 120–139 80–89 Stage 1 140–159 90–99 Stage 2 ≥160 ≥100 Isolated systolic Hypertension ≥140 <90
  • 24. It is divided into two types 1) Primary hypertension (Essential hypertension) 2) Secondary hypertension (Non-essential hypertension)
  • 25. PRIMARY HYPERTENSION It results when arterial blood pressure is increased due to increased peripheral resistance. It is further divided in to two types namely: benign and malignant hypertension a) Benign hypertension Here, there is a moderate increase in blood pressure with systolic pressure of 200 mm Hg and the diastolic pressure of above 100 mm Hg. However, in resting condition and sleep, the blood pressure returns to normal level. b) Malignant hypertension • Here, the blood pressure elevated to a great extends of about 250 mm Hg of systolic pressure and 150 mm Hg of diastolic pressure. It produces severe symptoms like renal disease, retinal disease, and being a fatal disease, it causes death within few years. • Some of the characteristics of primary or essential hypertension are, the mean arterial pressure is increased 40-60 %. • The renal blood flow in the later stages is decreased about one half of normal. • The resistance to blood flow through the kidney is increased 2-4 fold. The kidneys will not excrete adequate amounts of salt and water unless the arterial pressure is high.
  • 26. SECONDARY HYPERTENSION The different forms of secondary hypertension are  Cardiovascular hypertension- a. It is produced due to Atherosclerosis- hardening and narrowing of blood vessels b. Coarctation of aorta- narrowing of aorta.  Renal hypertension a. It is produced due to Stenosis renal arteries- narrowing of one or both renal arteries, so that the renal function is impaired. b. Glomerulonephritis- nephritis with inflammation of the capillary loops in the renal glomeruli.
  • 27.  Endocrine hypertension a. It occurs due to Pheochromocytoma- tumer in adrenal medulla b. Hyperaldosteronism- excess secretion of aldosterone from adrenal cortex Conn’s syndrome. c. Cushing’s syndrome- excess secretion of cortisone. d. Gigantism or Acromegaly- excess secretion of growth hormone.  Neurogenic hypertension Acute hypertension can be caused by strong stimulation of the sympathetic nervous system. a. Section of the baroreceptors nerves. b. Lesions in tractus solitarius. c. Increased intracranial pressure.
  • 28. 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 % of high blood pressure cases. • At least four medications may be necessary to treat resistant hypertension. • 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.
  • 29. ETIOLOGY OF HYPERTENSION • Although hypertension may occur secondary to other disease processes, more than 90% of patients have essential hypertension, a disorder of unknown origin affecting blood pressure regulating mechanism. • A family history of hypertension is increases the likelihood that an individual will develop hypertensive disease. • Essential hypertension occurs four times more frequently amoung blacks than amoung whites, and it occur more often amoung middle- aged males than amoung middle-aged females. • Environmental factors such as stressful lifestyle, high dietary intake of sodium, obesity, and smoking all further predispose an individual to the occurrence of hypertension.
  • 30. Epidemiology • Overall, approximately 20% of the world’s adults are estimated to have hypertension. • Worldwide, approx. 1 billion people have hypertension, contributing to more than 7.1 million deaths per year. • The age-specific prevalence was • 3.3% in group aged 18-29 yr • 13.2% in group aged 30-39 yr • 22% in group aged 40-49 yr • 37.5% in group aged 50-59 yr • 51% in group aged 60-74 yr
  • 31. PATHOGENESIS OF HYPERTENSION • The multiple mechanism of hypertension constitutes aberrations of the normal physiologic regulation of blood pressure. • Regulation of normal blood pressure: The blood pressure level is a complex trait that is determined by the interaction of multiple genetic, environmental, and demographic factors that influence to hemodynamic variables: cardiac output and total peripheral resistance. • Cardiac output affected by the blood volume, itself greatly dependent on body sodium homeostasis. • Total peripheral resistance is predominantly determined at the level of the arterioles and depends on the effect of neutral and hormonal influence.
  • 32. • Normal vascular tone reflects the balance between humoral vasoconstriction influences (including angiotensin II and catecholamine) and vasodilators (including kinins, prostagladins, and nitric oxide). • Resistance vessels also exhibit autoregulation, whereby increased blood flow induced vasoconstriction to protect against tissue hyper perfusion. • Other local factors such as pH and hypoxia, as well as neuronal interactions (α- and β- adrenergic systems), May important
  • 33. • The kidneys play an important role in blood pressure regulation, as follows: • Through the renin-angiotensin system, the kidney influences both peripheral resistance and sodium homeostasis. • Renin elaborated by the juxta glomerular cells of kidney transforms plasma angiotensinogen to angiotensin I, which is then converted to angiotensin II by angiotensin converting enzyme (ACE). • Angiotensin II raises blood pressure by increasing both peripheral resistance (direct action on vascular SMCs) and blood volume (stimulation of aldosterone secretion, increase in distal tubular reabsorption of sodium).
  • 34. • The kidney also produced a variety of vasodepressor or antihypertensive substances (including prostaglandins and nitric oxide) that presumably counterbalance the vasopressor effects of angiotensin. • When blood volume is reduced, the glomerular filtration rate falls, leading to increased reabsorption of sodium and water by proximal tubules and thereby conserving sodium and expanding blood volume. • Glomerular filtration rate- independent natriuretic factors including atrial natriuretic peptide, secreted by heart atria in response to volume expansion, inhibit sodium reabsorption in distal tubules and cause vasodilation • When renal excretory function is impaired, increased atrial pressure is a compensatory mechanism that helps restore fluid and electrolyte balance.
  • 35. CAUSES 1. Essential Hypertension 2. Renal a) Acute nephritis b) Interstitial nephritis and pyelonephritis c) Polycystic kidneys d) Renal artery stenosis 3. Vascular: Arteriosclerosis, coaractation of aorta. 4. Endocrine: Pheochromocytoma, Cushing’s syndrome, thyrotoxicosis, myxedema. 5. Neurological: Raised intracranial tension, lead encephalopathy, etc. 6. Miscellaneous: Polycythemia, aortic incompetence, toxaemia of pregnancy, gout, etc.
  • 36. Measurement of Blood Pressure • Regulation of Normal Blood Pressure is carried out by : • Systemic Vascular Resistance is an index of arteriolar compliance or constriction throughout the body. It is the resistance that left ventricle must overcome to pump blood through the systemic circulation. • Cardiac Output is the amount of blood pumped by the heart per min. The cardiac output is usually expressed in lit/min. A normal adult has a cardiac output of around 5 liters of blood per minute. Blood Pressure = Cardiac Output (CO) × Systemic Vascular Resistance
  • 37. • Cardiac output can be calculated by following : • Heart rate is the speed of the heartbeat measured by the number of contractions of the heart per minute (bpm). A normal resting heart rate for adults ranges from 60 to 90 beats in a minute. But ideally it is 72 beat/ min. • Stroke volume (SV) is the volume of blood pumped from the left ventricle per beat. The stroke volumes for each ventricle are generally being approximately 70 ml/ beat in a healthy man. • Hence, cardiac output = 72 * 70 = 5040 ml/min • A normal adult has a cardiac output of around 5 liters of blood per minute. Cardiac Output (CO) = Heart Rate (HR) × Stroke Volume (SV)
  • 38. Signs & Symptoms • Severe headache • Fatigue /confusion /dizziness • Vision problems • Chestpain • Difficulty breathing • Irregular heartbeat • Blood in the urine • Pounding in neck orears • It is often called Silent Killer • because it is frequently • asymptomatic until it has becomesevere.
  • 39. Diagnosis • Manometer : Mercury, anaeroid or electronic devices is used in measurement of blood pressure. It should be calibrated frequently and routinely against standards (typically every 6 months) to assure accuracy. • Electrocardiogram : A test that measures the electrical activity, rate, and rhythm of your heartbeat via electrodes attached to your arms, legs, and chest. The results are recorded on graph paper. • Echocardiogram : This is a test that uses ultrasound waves to provide pictures of the heart's valves and chambers so the pumping action of the heart can be studied and measurement of the chambers and wall thickness of the heart can be made.
  • 40.
  • 41. Complication • Heart attack or stroke : High blood pressure can cause hardening and thickening of the arteries (atherosclerosis), which can lead to a heart attack, stroke or other complications. • Heart failure : To pump blood against the higher pressure in your vessels, your heart muscle thickens. Eventually, the thickened muscle may have a hard time pumping enough blood to meet your body's needs, which can lead to heart failure. • Aneurysm : Increased blood pressure can cause your blood vessels to weaken and bulge, forming an aneurysm. If an aneurysm ruptures, it can be life-threatening. • Renal Failure : Weakened and narrowed blood vessels in the kidneys can prevent these organs from functioning normally.
  • 42. • Retinopathy : Thickened, narrowed or torn blood vessels in the eyes can result in vision loss. • Metabolic syndrome. This syndrome is a cluster of disorders of the body's metabolism, including increased waist circumference; high triglycerides; low high-density lipoprotein (HDL) cholesterol, the "good" cholesterol; high blood pressure; and high insulin levels. These conditions make the person more likely to develop diabetes, heart disease and stroke. • Trouble with memory or understanding. Uncontrolled high blood pressure may also affect the ability to think, remember and learn. Trouble with memory or understanding concepts is more common in people with high blood pressure.
  • 43. Management Non-Clinical Management Non-pharmacological management plays an important role in improving 1. in the management of hypertension and overall cardiovascular health. Lifestyle Modification • Weight reduction : Weight-reducing diets in overweight hypertensive persons can result in modest weight loss in the range of 3-9% of body weight and are associated with blood pressure reduction of about 3-6 mmHg. It is advisable for overweight hypertensive patients to lose at least 5% of theirweight. • Quit smoking : Tobacco abuse in any form is found to increase blood pressureacutely.
  • 44. • Avoidance of alcohol intake : Moderation of alcohol consumption is advised. Alcohol consumption elevates BP acutely. Meta analyses have shown that, interventions to reduce alcohol consumption caused a small but significant reduction (3.3/2 mmHg) in both systolic and diastolic blood respectively. • Physical exercise : Aerobic physical exercise for 20–30 minutes per day for at least 5 days per week improves blood pressure and reduces cardiovascular morbidity.
  • 45. 2. Dietary Modification • A diet rich in fruits, vegetables and low fat dairy products with reduced saturated and total fat can substantially lower BP due to high potassium content. More recently, diet high in L-Arginine has been shown to be able to reduce BP by 5.4/2.3 mmHg.
  • 46. • Low sodium diet : High salt intake is associated with significantly increased risk of stroke and total cardiovascular disease. • Typical Indian food provides 4–5 gm of sodium per day. Pickles, salted vegetables and canned fish are rich in sodium and should be avoided. • Intake of 2-3 gm of sodium or less is recommended as per dietary approaches to stop hypertension. • Evidence from published systematic review and meta analyses showed that restricting sodium intake in people with elevated blood pressure in the short term leads to reductions in blood pressure of up to 10.5 mmHg systolic and 2 mmHg diastolic.
  • 47. Clinical Treatment • There are following class of drugs useful for the treatment of Hypertension : • Angiotensin Converting Enzyme (ACE) Inhibitors • Angiotensin Receptor Blockers • Diuretics • Calcium Channel Blockers • β blockers • α blockers • Centrally acting agents • Direct Vasodilators
  • 49. Angiotensin Converting Enzyme (ACE) Inhibitors • These agents reduce blood pressure by blocking the renin-angiotensin system. • They do this by preventing conversion of angiotensin I to the blood pressure raising hormone angiotensin II. • They also increase availability of the vasodilator bradykinin by blocking its breakdown
  • 50. • Use : These drugs have established clinical outcome benefits in patients with heart failure, post–myocardial infarction, left ventricular systolic dysfunction, and diabetic and non- diabetic chronic kidney disease. • Side Effects : They are well tolerated. Their main side effect is cough. Angioedema is an uncommon but potentially serious complication that can threaten airway function. • These drugs can increase serum creatinine by 30% due to reduce pressure within the renal glomerulus which is not harmful. • These drugs must not be used in pregnancy. • Egs., Ramipril • Captopril • Enalapril • Perindopril
  • 51. Angiotensin Receptor Blockers • Angiotensin receptor blockers antagonize the renin angiotensin system. They reduce blood pressure by blocking the action of angiotensin II on its AT1 receptor and thus prevent the vasoconstrictor effects of this receptor. • Egs., Losartan • Valsartan • Telmisartan • Candesartan
  • 52. • Use : These drugs have the same benefits on cardiovascular and renal outcomes as angiotensin-converting enzyme inhibitors like heart failure, post–myocardial infarction, left ventricular systolic dysfunction, and diabetic and non- diabetic chronic kidney disease. • Side Effect : They are well tolerated because they do not cause cough and only rarely cause angioedema and have effects similar to ACE inhibitors, they are generally preferred over ACE inhibitors if they are available and affordable. They also can increase serum creatinine which is not harmful. • These drugs must not be used in pregnancy.
  • 53. Diuretics • These agents work by increasing excretion of sodium by the kidneys and additionally may have some vasodilator effects. • 2 types of diuretics are used in the treatment of Hypertension : • Thiazide diuretic • Loop diuretic
  • 54. • Clinical outcome benefits have been best established with chlorthalidone, indapamide, and hydrochlorothiazide. • Chlorthalidone has more powerful effects on blood pressure than hydrochlorothiazide and has a longer duration of action. • Side Effect : The main side effects of these drugs are metabolic (hypokalemia, hyperglycemia, hyperuricemia). The likelihood of these problems can be reduced by using low doses or by combining with ACE inhibitors or angiotensin receptor blockers, which have been shown to reduce these metabolic changes. Diuretics are most effective with these two combinations. Combining diuretics with potassium-sparing agents also helps to prevent hypokalemia and with calcium channel blockers are also effective.
  • 55. Calcium Channel Blockers These agents reduce blood pressure by blocking the inward flow of calcium ions through the L channels of arterial smooth musclecells. • Ex. Non dihydropyridines : Diltiazem Verapamil Dihydropyridines : Nifedipine Amlodipine
  • 56. • There are 2 main types of calcium channel blockers: dihydropyridines, such as amlodipine and nifedipine, which work by dilating arteries; and nondihydropyridines, such as diltiazem and verapamil, which dilate arteries somewhat less but also reduce heart rate and contractility. Hence Nondihydropyridine are not recommended in patients with heart failure. • Side Effect : The main side effect of calcium channel blockers is peripheral edema, which is most prominent at high doses. • They have powerful blood pressure reducing effects, when combined with ACE inhibitors or angiotensin receptor blockers.
  • 57. βAdrenoreceptor Blockers β blockers reduce Cardiac output and decrease the also release of renin from the kidney. Egs., Propranolol Atenolol Metoprolol Carvediol Acebtalol
  • 58. • Use : They have strong clinical outcome benefits in patients with histories of myocardial infarction and heart failure and are effective in the management of angina pectoris. • Side Effect : The main side effects associated with b-blockers are reduced sexual function, fatigue, and reduced exercise tolerance. • Many of these agents have adverse effects on glucose metabolism and therefore are not recommended in patients at risk of diabetes, especially in combination with diuretics. They may sometimes also be associated with heart block. • The combined α and β blocker, LABETALOL, is widely used intravenously for hypertensive emergencies and is also used orally for treating hypertension in pregnant and breastfeeding women.
  • 59. αAdrenergic Blockers α Blockers reduce blood pressure by blocking arterial α Receptors adrenergic and thus preventing the vasoconstrictor actions of these receptors. Ex., Prazosin Terazosin Doxazosin
  • 60. • Use : These drugs are less widely used as first-step agents than other classes because clinical outcome benefits have not been well established. However, they can be useful in treating resistant hypertension when used in combination with agents diuretics, β blockers, and ACE inhibitors. • To be maximally effective, they should usually be combined with a diuretic. Since α blockers can have somewhat beneficial effects on blood glucose and lipid levels, they can potentially neutralize some of the adverse metabolic effects of diuretics. • The α blockers are effective in treating benign prostatic hypertrophy and so can be a valuable part of hypertension treatment regimens in older men who have this condition.
  • 61. Centrally Acting Agents • These drugs, the most well- known of which are clonidine and methyldopa work primarily by reducing sympathetic outflow from the central nervous system. • Egs., Methyldopa • Clonidine • Clonidine patch
  • 62. • Side Effect : such as drowsiness and dry mouth have reduced their popularity. • Treatment with a clonidine skin patch causes fewer side effects than the oral agent, but the patch is not always available and can be more costly than the tablets. • In certain countries, including the United States, α methyldopa is widely employed for treating hypertension in pregnancy.
  • 63. Direct Vasodilators • Because these agents often cause fluid retention and tachycardia, they are most effective in reducing blood pressure when combined with diuretics and β blockers or sympatholytic agents. For this reason, they are now usually used only as fourth-line or later additions to treatment regimens. • Egs., Hydralazine • Minoxidil
  • 64. • Hydralazine is the more widely used of these agents. The powerful drug minoxidil is sometimes used by specialists in patients whose blood pressures are difficult to control. Fluid retention and tachycardia are frequent problems with minoxidil, as well as unwanted hair growth (particularly in women). Furosemide is often required to cope with the fluid retention.