HYPERTENSIONNavdeep Singh

Marivic Zerrudo

INTRODUCTIONThe heart is a hollow muscular

organ that is somewhat pyramid and lies within the pericardium in the mediastinum.

Reference: Snell

SURFACES OF THE HEART

•Sternocostal surface•Diaphragmatic surface•Base of the heart•Apex of the heart

BORDERS•Apex – left ventricle, 5th left intercostal space 3.5 in from the midline

•Superior – formed by the roots of the great blood vessels, extends from a point on the 2nd left costal cartilage 0.5 in from the edge of the sternum to a point on the 3rd right costal cartilage from the edge of the sternum

•Right border – right atrium, extends from a point on the 3rd right costal cartilage 0.5 in from the edge of the sternum downward to a point on the 6th right costal cartilage 0.5 in from the edge of the sternum

BORDERS

•Left border – left ventricle, extends from a point on the 2nd left costal cartilage 0.5 in from the edge of the sternum to the apex beat of the heart

•Inferior border – right ventricle and the apical part of the left ventricle, extends from a point on the 6th right costal cartilage 0.5 in from the edge of the sternum to the apex beat

ANATOMY OF THE HEART

ChambersRight atriumRight ventricleLeft atriumLeft ventricle

HEART ANATOMY

VALVES Semilunar valves

Aortic valve Pulmonary valve Atrioventricular

valves Mitral valve Tricuspid valve

o Sinoatrial (SA) node pacemaker of the heart o Atrioventricular (AV) node o Bundle of His o Right and left bundle branches

SPECIALIZED EXCITATORY AND CONDUCTING MYOCYTES

BLOOD SUPPLY:

(3) Major Epicardial Coronary arteries: a. Left Anterior Descending Artery

- Anterior wall- Anterior two thirds of septum- Entire apex of heart, circumferentially

b. Left Circumflex Coronary Artery- Posterior, lateral left aspect of heart.

c. Right Coronary Artery- Posterior one third of septum, inferior

aspect, and posterior wall of heart

BLOOD VESSELS: TYPES

Arteries and arterioles – carry blood away from the heartArterioles – control conduits- Has a strong muscular wall that can close the arteriole completely or can, by relaxing, dilate it several fold, thus, can regulate blood flow and pressure

Capillaries – where nutrient and gas exchange occur

Veins and venules – carry blood toward the heart.

- much less smooth muscle

HYPERTENSIONDefinitions: A progressive cardiovascular syndrome arising

from complex and interrelated etiologies Early markers of the syndrome often are

present before elevated blood pressure is observed. Therefore, hypertension cannot be classified solely by discrete blood pressure thresholds.

Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidney, brain vasculature, and other organs and lead to premature morbidity and death.

Pharmacy Times (Hypertension: Beyond JNC 7) page 32, March 2006

EPIDEMIOLOGY

prevalence of hypertension blood pressure levels rate of age-related

blood pressure increase

Hypertension is present in all populations

It accounts for 6 % of deaths worldwide.

Reference: Harrison

vary among countries and among subpopulations within a country.

EPIDEMIOLOGYTop ten provinces with the highest

hypertension prevalence 1. Guimaras (80.1%)2. Camiguin (60.4%)3. Quirino (54.1%)4. Sultan Kudarat (51.4%)5. Pasay City (50.7%)6. Muntinlupa City (50.6%)7. Las Pinas (49.1%)8. Davao Oriental (44.8%)9. Catanduanes (40.9%) 10.Kalinga (39.3%).Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf

EPIDEMIOLOGYBottom ten province/area with the lowest

hypertension prevalence1. San Juan (0%)2. Marinduque (2.6%)3. Tawi Tawi (3.0%)4. Navotas (4.6%)5. Northern Samar (5.2%)6. Misamis Occidental (8.3%)7. Masbate (8.5%)8. Bataan (10.4%)9. Siquijor (10.43%)10. Sorsogon(11.4%)

Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf

MORTALITY STATISTICS > HYPERTENSIVE HEART DISEASE (2004) BY COUNTRY

RANK COUNTRIES DEATHS

# 1   United States: 23,761 deaths 

# 2   Germany: 13,253 deaths 

# 3   Brazil: 11,561 deaths 

# 4   Romania: 9,347 deaths 

# 5   Mexico: 3,795 deaths 

# 6   Colombia: 3,672 deaths 

# 7   Japan: 3,375 deaths 

# 8   South Africa: 3,216 deaths 

# 9   Poland: 2,741 deaths 

# 10   Hungary: 2,713 deaths 

Reference: http://www.nationmaster.com/graph/mor_hyp_hea_dis-mortality-hypertensive-heart-desease

Prevalence of Hypertension in the U.S. (HARRISON’S INTERNAL MEDICINE)

33.5 % among Hispanic Blacks 28.9 % among Hispanic Whites 20.7 % among Mexican Americans

Out of the world, incidence of high blood pressure is highest in African Americans

36.7% of African American men have high blood pressure

One in three blacks have hypertension 30% of African American male deaths are connected to

hypertension/high blood pressure 27.9% of Latin American male deaths are connected to

hypertension/high blood pressure Reference: http://library.thinkquest.org/trio/TTQ03033/hypertension_statistics.htm

EPIDEMIOLOGY

In the United States, average systolic blood pressure is higher for men than for women during early adulthood.

At age 60 and older, systolic blood pressures of women are higher than men.

Diastolic blood pressure increases progressively with age until about 55 years old, after which, it tends to decrease.

EPIDEMIOLOGY

EPIDEMIOLOGY

Philippines9.6M are hypertensive 15.4M are predisposed to be hypertensive

among adults, 20 years and overfor over 5 years, hypertension ranks as the

fifth leading cause of morbidity

Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf 2005

EPIDEMIOLOGY

Hypertension increases with age. Among aged ≥ 60, prevalence is 65.4 %. In African Americans, it appears earlier.

Obesity and weight gain are strong and independent risk factors.

Sixty percent of hypertensive patients are > 20 % overweight.

TYPES OF HYPERTENSION

PRIMARY HYPERTENSION90 % of all cases, high BP with na

apparent causeFactors – genetics, race, gender, age, diet,

weight, lifestyle SECONDARY HYPERTENSION

10 % of all cases, high BP by pre-existing physical condition such as kidney or thyroid condition

MECHANISMS OF HYPERTENSION

intravascular volumeautonomic nervous systemrenin-angiotensin-aldosterone

systemvascular mechanisms.

INTRAVASCULAR VOLUME

Primary determinant of arterial pressure over the long term

Cardiac output • Directly related to stroke volume and heart rate• Directly related to arterial pressure• There is an increase with arterial pressure with

increased cardiac output. This occurs with increased blood volume.

CO = SV x HRArterial pressure = CO x TPR

AUTONOMIC NERVOUS SYSTEM

Maintains cardiovascular homeostasis via pressure, volume, and chemoreceptor signals.

Adrenergic reflexes modulate blood pressure over the short term.

Adrenergic function with hormonal and volume related factors contributes to the long term regulation of blood pressure.

RENIN- ANGIOTENSIN-ALDOSTERONE SYSTEM

It contributes to blood pressure regulation via the vasoconstrictor properties of angiotensin IIthe sodium retaining properties of aldosterone.

Renin is an aspartyl protease found in the kidney. Active renin once relased into the circulation

cleaves angiotensinogen to form an inactive decopeptide, angiotensin I.

A converting enzyme, located primarily but not exclusively in the pulmonary circulation, converts angiotensin I to the active octapeptide, angiotensin II.

Angiotensin II further stimulates release of aldosterone.

RENIN- ANGIOTENSIN-ALDOSTERONE SYSTEM

Primary Stimuli for Renin SecretionDecreased NaCl transport in the thick ascending loop of Henle

Decreased pressure or stretch within the renal afferent arteriole

Sympathetic nervous system stimulation of renin-secreting cells via ß1

adrenoreceptors

RENIN- ANGIOTENSIN-ALDOSTERONE SYSTEM

VASCULAR MECHANISMS

The decrease in lumen size of blood vessels significantly increases resistance. This contributes to increased peripheral

resistance. This may occur in cases of arteriosclerosis

where there is plaque formation in the vessel wall reducing the diameter of a lumen.

The stiffness of a blood vessel also contributes to resistance. It is found in most hypertensive patients and in

the elderly.

IDENTIFIABLE CAUSES OF HYPERTENSION

Chronic kidney diseaseRenal parenchymal disease

Altered excretory function – defects in renal excretion of salt and water

Altered RAAS – ischemic changes resulting from intrarenal scarring may activate the RAAS abd contribute to hypertension in patient with early or advanced renal failure

Coarctation of the aorta

IDENTIFIABLE CAUSES OF HYPERTENSION

Cushing’s syndrome glucocorticoid excess resulting from exogenous

glucocorticoid therapy Hypertension may occur because cortisol has

mineralocorticoid-like effects and therefore leads to the retention of sodium and water

Other glucocorticoid excess states – remediable hyperaldosteronism

Chronic steroid therapy

IDENTIFIABLE CAUSES OF HYPERTENSION

Drug induced or drug related Oral contraceptives – hypertension occurs as a result of estrogen-

induced increases in angiotensin synthesis in the liver

Obstructive uropathy Primary aldosteronism and other mineralocorticoid

excess states By inducing sodium and water retention leading to

expansion of the ECF volume Often accompanied by hypokalemia because

mineralocorticoids promote renal potassium excretion in the collecting duct of the nephron

Pheochromocytoma Tumors of the adrenal medulla increases the secretion of

the catecholamines leading to hypertension

IDENTIFIABLE CAUSES OF HYPERTENSION

Renovascular hypertension Result from complex interplay between activation of

the renin-angiotensin-angiotensin-aldosterone system and the sympathetic nervous sytem

Sleep apnea

Thyroid or parathyroid disease

GENETICS OF HYPERTENSION Genetic abnormalities associated with several rare

forms of hypertension, includes the following: mineralocorticoid-remediable aldosteronism 11beta-hydroxylase and 17alpha-hydroxylase

deficiencies Liddle’s syndrome, the syndrome of apparent

mineralocorticoid excess pseudohypoaldosteronism type

Candidate genes angiotensinogen alpha-adducin, beta- and DA-adrenergic receptors beta-3 subunit of G proteins

RISK FACTORS:

Modifiable Unhealthy lifestyle

which include Cigarette smoking unmanaged stress salty food

consumptionphysical inactivitybeing overweight

Reference: http://www.nscb.gov.ph/ncs/10thNCS/papers/contributed%20papers/cps-10/cps10-02.pdf

Non modifiable factors genetic

predisposition to hypertension

disease condition like diabetes heart disease kidney disease high cholesterol

level stroke increasing age

PATIENT EVALUATION:

Objectives: to assess lifestyle and identify other

cardiovascular risk factors or concomitant disorders that may affect prognosis and guide treatment

to reveal identifiable causes of high BP to assess the presence or absence of target

organ damage and CVD

Patient evaluation methodsmedical historyphysical examinationroutine laboratory tests

Urinalysis, CBC, electrolytes, renal function test, FBS, total cholesterol, HDL, 12-L ECG

Optional laboratory testsCreatinine clearance, microalbuminuria, 24-hr urinary protein, blood calcium, uric acid, fasting triglycerides/LDL, HgbA1C, TSH, Echocardiography

PATIENT EVALUATION:

The physical examination includes the following: an appropriate measurement of BPwith verification in the contralateral arm; an

examination of the optic fundia calculation of body mass index (BMI) (measurement

of waist circumference is also very useful)an auscultation for carotid, abdominal, and femoral

bruits; a palpation of the thyroid glanda thorough examination of the heart and lungsan examination of the abdomen for enlarged kidneys,

masses, distended urinary bladder, and abnormal aortic pulsation

a palpation of the lower extremities for edema and pulses

Neurological assessment.

PATIENT EVALUATION:

DIAGNOSIS: Because most individuals with hypertension do not

exhibit any symptoms or feelings of malaise, they may assume that their blood pressure is normal.

Occasionally, if blood pressure reaches extreme levels, individuals may experience some symptoms, such as the following:DizzinessDiplopiaHeadacheShortness of breathChest painAbdominal pain

 JNC-7 BLOOD PRESSURE CLASSIFICATION

Classification Systolic Pressure Diastolic Pressure

< 120 < 80

Pre-hypertension 120-139 80-89

Hypertension

Stage 1 140-159 90-99

Stage 2 >159 >100

ACCURATE BLOOD PRESSURE MEASUREMENT IN THE OFFICE Persons should be seated quietly for atleast 5

minutes in a chair, with feet on the floor, and arm supported at heart level.

Caffeine, exercise, and smoking should be avoided for at least 30 minutes prior to measurement.

Measurement of BP in the standing position is indicated periodically, especially in those at risk for postural hypotension, prior to necessary drug dose or adding a drug, and in those who report symptoms consistent with reduced BP upon standing.

An appropriately sized cuff (cuff bladder encircling at least 80 percent of the arm) should be used to ensure accuracy.

ACCURATE BLOOD PRESSURE MEASUREMENT IN THE OFFICE At least two measurements should be made and the

average recorded. For manual determinations, palpated radial pulse

obliteration pressure should be used to estimate SBP—the cuff should then be inflated 20–30 mmHg above this level for the auscultatory determinations; the cuff deflation rate for auscultatory readings should be 2 mmHg per second.

SBP is the point at which the first of two or more Korotkoff sounds is heard (onset of phase 1), and the disappearance of Korotkoff sound (onset of phase 5) is used to define DBP.

Clinicians should provide to patients, verbally and in writing, their specific BP numbers and the BP goal of their treatment.

TREATMENT

Although there is no known cure to hypertension, it is

treatable using various pharmacologic and

nonpharmacologic measures.

GOALS OF THERAPY

The ultimate public health goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality.

Since most persons with hypertension, especially those >50 years of age, will reach the DBP goal once the SBP goal is achieved, the primary focus should be on attaining the SBP goal.

Treating SBP and DBP to targets that are <140/90 mmHg is associated with a decrease in CVD complications.

In patients with hypertension and diabetes or renal disease, the BP goal is <130/80 mmHg.

TREATMENT

Non-pharmacologic Lifestyle modification

Pharmacologic Thiaz BB ACEI ARB ALDO ANT CCB

ACHIEVING BLOOD PRESSURE CONTROL IN INDIVIDUAL PATIENTS: Therapy begins with lifestyle modification The maximum protection against combined

cardiovascular endpoints is achieved with pressures <135–140 mmHg for systolic blood pressure and <80–85 mmHg for diastolic blood pressure

More aggressive blood pressure targets for blood pressure control (e.g., blood pressure < 130/80 mmHg) may be appropriate for patients with diabetes, CHD, chronic kidney disease, or with additional cardiovascular disease risk factors.

In diabetic patients, effective blood pressure control reduces the risk of cardiovascular events and death as well as the risk for microvascular disease (nephropathy, retinopathy).

ACHIEVING BLOOD PRESSURE CONTROL IN INDIVIDUAL PATIENTS: Risk reduction is greater in diabetic than in nondiabetic

individuals. If BP goal is not achieved via lifestyle modification, thiazide-

type diuretics should be used as initial therapy for most patients, either alone or in combination with one of the other classes (ACEIs, ARBs, BBs, CCBs) that have also been shown to reduce one or more hypertensive complications in randomized controlled outcome trials.

If the initial drug selected is not tolerated or is contraindicated, then a drug from one of the other classes proven to reduce cardiovascular events should be substituted.

Since most hypertensive patients will require two or more antihypertensive medications to achieve their BP goals, addition of a second drug from a different class should be initiated when use of a single agent in adequate doses fails to achieve the goal.

ACHIEVING BLOOD PRESSURE CONTROL IN INDIVIDUAL PATIENTS: When BP is >20 mmHg above systolic goal or 10

mmHg above diastolic goal, consideration should be given to initiate therapy with two drugs, either as separate prescriptions or in fixed-dose combinations.

The initiation of therapy with more than one drug increases the likelihood of achieving BP goal in a more timely fashion.

The use of multidrug combinations often produce greater BP reduction at lower doses of the component agents, resulting in fewer side effects.

The use of fixed-dose combinations may be more convenient and simplify the treatment regimen, and may cost less than the individual components prescribed separately.

ACHIEVING BLOOD PRESSURE CONTROL IN INDIVIDUAL PATIENTS: Use of generic drugs should be considered to

reduce prescription costs, and the cost of separate prescription of multiple drugs available generically may be less than nongeneric, fixed-dose combinations.

The starting dose of most fixed-dose combinations is usually below the doses used in clinical outcome trials, and the doses of these agents should be titrated upward to achieve the BP goal before adding other drugs.

Caution is advised in initiating therapy with multiple agents, particularly in some older persons and in those at risk for orthostatic hypotension, such as diabetics with autonomic dysfunction.

LIFESTYLE MODIFICATIONS

Adoption of healthy lifestyles by all persons is critical for the prevention of high BP and is an indispensable part of the management of those with hypertension.

Weight loss of as little as 10 lbs (4.5 kg) reduces BP and/or prevents hypertension in a large proportion of overweight persons, although the ideal is to maintain normal body weight.

BP is also benefited by adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan which is a diet rich in fruits, vegetables, and lowfat dairy products with a reduced content of dietary cholesterol as well as saturated and total fat (modification of whole diet).

LIFESTYLE MODIFICATIONS

Reduce dietary sodium intake to no 2–8 mmHg94-96 more than 100 mmol per day (2.4 g sodium or 6 g sodium chloride).

Engage in regular aerobic physical 4–9 mmHg activity such as brisk walking (at least 30 min per day, most days of the week).

Moderation of alcohol - limit consumption to no more than 2–4 mmHg consumption

PHARMACOLOGIC TREATMENT

A large number of drugs are currently available for reducing BP.

More than two-thirds of hypertensive individuals cannot be controlled on one drug and will require two or more antihypertensive agents selected from different drug classes.

In hypertensive patients with lower BP goals or with substantially elevated BP, three or more antihypertensive drugs may be required.

DIURETICS

Low-dose thiazide diuretics are often used as first-line agents, alone or in combination with other antihypertensive drugs.

Thiazides inhibit the Na+/Cl– pump in the distal convoluted tubule and, hence, increase sodium excretion. Long term, they may also act as vasodilators.

Thiazides are safe, efficacious, and inexpensive and reduce clinical events.

They provide additive blood pressure–lowering effects when combined with beta blockers, ACE inhibitors, or angiotensin receptor blockers.

DIURETICS

In contrast, addition of a diuretic to a calcium channel blocker is less effective.

Usual doses of hydrochlorothiazide range from 6.25–50 mg/d. Owing to an increased incidence of metabolic side effects (hypokalemia, insulin resistance, increased cholesterol), higher doses are generally not recommended.

The main pharmacologic target for loop diuretics is the Na+-K+-2Cl– cotransporter in the thick ascending limb of the loop of Henle.

Loop diuretics are generally reserved for hypertensive patients with reduced glomerular filtration rates [reflected in serum creatinine > 220 mol/L (>2.5 mg/dL)], CHF, or sodium retention and edema for some other reason such as treatment with a potent vasodilator, e.g., minoxidil.

DIURETICS Indapamide – non-thiazide sulfonamide diuretic

with both diuretic and vasodilator activity Amiloride – inhibits smooth muscle responses to

contractile stimuli, probably through effects on transmembrane and intracellular calcium movement that are independent of its action on sodium excretion

Thiazide diuretics – appropriate for most patients with mild to moderate HTN and normal renal and cardiac fxn

Loop diuretics – powerful for severe HTN Potassium-sparing diuretics – Useful both to

avoid excessive potassium depletion, particularly in patients taking digitalis and to enhance the natriuretic effects of other diuretics

DIURETICS Loop diuretics

1As single dose or in two divided doses

Drug Total daily oral dose

Bumetanide 0.5 – 2 mg

Ethacrynic acid

50 – 200 mg

Furosemide 20 – 80 mg

Torsemide 5 – 20 mg

POTASSIUM-SPARING DIURETICS & COMBINATION PREPARATIONS

1Eplerenone is currently approved for use only in HTN

TRADE NAME AGENT HYDROCHLOROTHIAZIDE

Adactazide Spironolactone 25 mg 50 mg

Aldactone Spironolactone 25, 50, 100 mg

Dyazide Triamterene 37.5 mg 25 mg

Dyrenium Triamterene 50 or 100 mg

Inspra 1 Eplerenone 25, 50 or 100 mg

Maxzide Triamterene 75 mg 50 mg

Maxzide-25 mg Triamterene 37.5 mg 25 mg

Midamor Amiloride 5 mg

Moduretic Amiloride 5 mg 50 mg

THIAZIDES AND RELATED DIURETICS

DRUG TOTAL DAILY ORAL DOSE

FREQUENCY OF ADMINISTRATION

Bendroflumethiazide

2.5-10 mg Single dose

Chlorothiazide 0.5-2 g Two divided doses

Chlorthalidone1 25-50 mg Single dose

Hydrochlorothiazide

25-100 mg Single dose

Hydroflumethiazide

12.5-50 mg Two divided doses

Indapamide1 2.5-10 mg Single dose

Methyclothiazide 2.5-10 mg Single dose

Metolazone1 2.5-10 mg Single dose

Polythiazide 1-4 mg Single dose

Quinethazone1 25-100 mg Single dose

Trichlormethiazide 1-4 mg Single dose

1Not a thiazide but a sulfonamide qualitatively similar to the thiazides

BLOCKERS OF THE RENIN-ANGIOTENSIN SYSTEM ACE inhibitors decrease the production of

angiotensin II, increase bradykinin levels, and reduce sympathetic nervous system activity. Angiotensin II receptor blockers provide selective blockade of AT1 receptors, and the effect of angiotensin II on unblocked AT2 receptors may augment the hypotensive effect.

Both classes of agents are effective antihypertensive agents that may be used as monotherapy or in combination with diuretics, calcium antagonists, and alpha-blocking agents.

Side effects of ACE inhibitors and angiotensin receptor blockers include functional renal insufficiency due to efferent renal arteriolar dilatation in a kidney with a stenotic lesion of the renal artery.

BLOCKERS OF THE RENIN-ANGIOTENSIN SYSTEM Additional predisposing conditions to renal

insufficiency induced by these agents include dehydration, CHF, and use of nonsteroidal anti-inflammatory drugs.

Dry cough occurs in 15% of patients, and angioedema occurs in <1% of patients taking ACE inhibitors.

Angioedema occurs most commonly in individuals of Asian origin and more commonly in African Americans than in Caucasians.

Hyperkalemia due to hypoaldosteronism is an occasional side effect of both ACE inhibitors and angiotensin receptor blockers.

ACE INHIBITORS

Captopril – oral: 25 mg, 50 mg tablets Enalapril – oral: 5, 10, 20 mg tablets

• Parenteral: 1.25 mg enalaprilat/ml Benazepril Fosinopril Lisinopril Moexipril Perindopril Quinapril Ramipril Trandolapril

ALDOSTERONE ANTAGONISTS

Spironolactone is a nonselective aldosterone antagonist that may be used alone or in combination with a thiazide diuretic.

It may be a particularly effective agent in patients with low-renin essential hypertension, resistant hypertension, and primary aldosteronism.

In patients with CHF, low-dose spironolactone reduces mortality and hospitalizations for heart failure when given in addition to conventional therapy with ACE inhibitors, digoxin, and loop diuretics.

ALDOSTERONE ANTAGONISTS

Because spironolactone binds to progesterone and androgen receptors, side effects may include gynecomastia, impotence, and menstrual abnormalities.

These side effects are circumvented by a newer agent, eplerenone, which is a selective aldosterone antagonist.

BETA BLOCKERS

Adrenergic receptor blockers lower blood pressure by decreasing cardiac output, due to a reduction of heart rate and contractility.

Other proposed mechanisms by which beta blockers lower blood pressure include a central nervous system effect, and inhibition of renin release.

Beta blockers are particularly effective in hypertensive patients with tachycardia, and their hypotensive potency is enhanced by coadministration with a diuretic.

In lower doses, some beta blockers selectively inhibit cardiac receptors and have less influence on receptors on bronchial and vascular smooth muscle cells; however, there seems to be no difference in the antihypertensive potencies of cardio-selective and non-selective beta blockers.

BETA BLOCKERS

Certain beta blockers have intrinsic sympathomimetic activity, and it is uncertain whether this constitutes an overall advantage or disadvantage in cardiac therapy.

Beta blockers without intrinsic sympathomimetic activity decrease the rate of sudden death, overall mortality, and recurrent myocardial infarction.

In patients with CHF, beta blockers have been shown to reduce the risks of hospitalization and mortality. Carvedilol and labetalol block both receptors and peripheral -adrenergic receptors.

The potential advantages of combined adrenergic blockade in treating hypertension remain to be determined.

BETA BLOCKERS Propanolol – oral: 10, 20, 40, 60, 80 90 mg tab

4-8 mg/mL oral solution; Intensol 80 mg/mL sol

Oral sustained-release: 60, 80, 120, 160 mg cap

Parenteral: 1mg/mL for injection Metoprolol – oral: 50, 100 mg tab

Oral sustained-release: 25, 50, 100, 200 mg tab Parenteral: 1mg/mL for injection

Nadolol, Carteolol, Atenolol, Betalol, Bioprolol Pindolol, Acebutolol, Penbutolol Labetalol, Carvedilol

ADRENERGIC BLOCKERS Postsynaptic, selective adrenoreceptor antagonists

lower blood pressure by decreasing peripheral vascular resistance.

They are effective antihypertensive agents, used either as monotherapy or in combination with other agents.

However, in clinical trials of hypertensive patients, alpha blockade has not been shown to reduce cardiovascular morbidity and mortality or to provide as much protection against CHF as other classes of antihypertensive agents.

ADRENERGIC BLOCKERS These agents are also effective in treating

lower urinary tract symptoms in men with prostatic hypertrophy.

Nonselective -adrenoreceptor antagonists bind to postsynaptic and presynaptic receptors and are primarily used for the management of patients with pheochromocytoma.

SYMPATHOLYTIC AGENTS

Centrally acting sympathetic agonists decrease peripheral resistance by inhibiting sympathetic outflow.

They may be particularly useful in patients with autonomic neuropathy who have wide variations in blood pressure due to baroreceptor denervation.

Drawbacks include somnolence, dry mouth, and rebound hypertension on withdrawal.

SYMPATHOLYTIC AGENTS

Peripheral sympatholytics decrease peripheral resistance and venous constriction by depleting nerve terminal norepinephrine.

Although potentially effective antihypertensive agents, their usefulness is limited by orthostatic hypotension, sexual dysfunction, and numerous drug-drug interactions.

CALCIUM CHANNEL BLOCKERS Calcium antagonists reduce vascular

resistance through L-channel blockade, which reduces intracellular calcium and blunts vasoconstriction.

This is a heterogeneous group of agents that

includes drugs in the following three classes: phenylalkylamines (verapamil), benzothiazepines (diltiazem), and 1,4-dihydropyridines (nifedipine-like).

CALCIUM CHANNEL BLOCKERS Used alone and in combination with other

agents (ACE inhibitors, beta blockers, adrenergic blockers), calcium antagonists effectively lower blood pressure; however, it is unclear if adding a diuretic to a calcium blocker results in a further lowering of blood pressure.

Side effects of flushing, headache, and edema with dihydropyridine use are related to their potencies as arteriolar dilators; edema is due to an increase in transcapillary pressure gradients, not to net salt and water retention.

DIRECT VASODILATORS

These agents decrease peripheral resistance and concomitantly activate mechanisms that defend arterial pressure, notably the sympathetic nervous system, the renin-angiotensin-aldosterone system, and sodium retention.

Usually, they are not considered first-line agents but are most effective when added to a combination that includes a diuretic and a beta blocker.

DIRECT VASODILATORS Hydralazine is a potent direct vasodilator

that has antioxidant and nitric-oxide enhancing actions, and minoxidil is a particularly potent agent and is most frequently used in patients with renal insufficiency who are refractory to all other drugs.

Hydralazine may induce a lupus-like syndrome, and side effects of minoxidil include hypertrichosis and pericardial effusion

CHOICE OF ANTIHYPERTENSIVE DRUG BASED ON PATIENT CHARACTERISTICS Diabetic patients and those with chronic

kidney disease: use ace inhibitors or angiotensin II to delay nephropathy.

Young patients : use beta blockers

Coronary artey disease patients : use beta blockers, Ca- antagonists. Avoid hydralazine.

Heart failure patients : use ACE-inhibitors and/or diuretics. Generally avoid beta blockers and Ca-antagonists.

CHOICE OF ANTIHYPERTENSIVE DRUG BASED ON PATIENT CHARACTERISTICS Athletes : Avoid beta blockers and diuretics.

Broncho-pulmonary disease patients : Use verapamil and other Ca-antagonists. Avoid beta blockers.

Peripheral Vascular disease patients : Use calcium-antagonists, vasodilators, or ACE- inhibitors. Avoid beta blockers.

Dyslipidemic patient : Avoid beta blockers and diuretics.

CHOICE OF ANTIHYPERTENSIVE DRUG BASED ON PATIENT CHARACTERISTICS End stage renal disease patients : use Ca-

antagonist, diuretics and centrally acting agents. Caution on ACE- inhibitors.

For stroke patient : Use ACE-inhibitors and/or diuretics.

Elderly patients : Use diuretics. Generally use lower dosages.

FOLLOWUP AND MONITORING:

Once antihypertensive drug therapy is initiated, most patients should return for followup and adjustment of medications at monthly intervals or until the BP goal is reached.

More frequent visits will be necessary for patients with stage 2 hypertension or with complicating comorbid conditions.

Serum potassium and creatinine should be monitored at least one to two times per year.

After BP is at goal and stable, followup visits can usually be at 3- to 6-month intervals.

FOLLOWUP AND MONITORING:

Comorbidities such as HF, associated diseases such as diabetes, and the need for laboratory tests influence the frequency of visits.

Other cardiovascular risk factors should be monitored and treated to their respective goals, and tobacco avoidance must be promoted vigorously.

Low dose aspirin therapy should be considered only when BP is controlled because of the increased risk of hemorrhagic stroke when the hypertension is not controlled.

BENEFITS OF LOWERING BLOOD PRESSURE

In clinical trials, antihypertensive therapy has been associated with reductions in (1) stroke incidence averaging 35–40 percent(2) myocardial infarction (MI), averaging 20–

25 percent(3) HF, averaging >50 percent

BENEFITS OF LOWERING BLOOD PRESSURE

It is estimated that in patients with stage 1 hypertension (SBP 140–159 mmHg and/or DBP 90–99 mmHg) and additional cardiovascular risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

In the added presence of CVD or target organ damage, only nine patients would require such BP reduction to prevent one death.

RESISTANT HYPERTENSION

Refers to patients with blood pressures persistently >140/90 mmHg despite taking three or more antihypertensive agents, including a diuretic, in reasonable combination and at full doses.

Resistant or difficult-to-control hypertension is more common in patients >60 years than in younger patients.

CAUSES OF RESISTANT HYPERTENSION Improper Blood Pressure Measurement

Volume overloadExcess sodium intakeVolume retention from kidney disease Inadequate diuretic therapy

CAUSES OF RESISTANT HYPERTENSION Drug-induced or other causes

Nonadherence Inadequate doses Inappropriate combinations Nonsteroidal anti-inflammatory drugs; cyclooxygenase 2

inhibitors Cocaine, amphetamines, other illicit drugs Sympathomimetics (decongestants, anorectics) Oral contraceptive hormones Adrenal steroid hormones Cyclosporine and tacrolimus Erythropoietin Licorice (including some chewing tobacco) Selected over-the-counter dietary supplements and medicines

(e.g., ephedra, ma huang, bitter orange) Associated conditions

Obesity Excess alcohol intake

ORTHOSTATIC HYPOTENSION BP measurements are typically recorded in the

sitting position. This practice, while convenient for the practitioner,

limits the ability to diagnose OH. Normally, standing is accompanied by a small

increase in DBP and a small decrease in SBP when compared to supine values.

OH is present when there is a supine-to-standing BP decrease >20 mmHg systolic or >10 mmHg diastolic.

ORTHOSTATIC HYPOTENSION There is more OH in diabetic individuals. There is a strong correlation between the severity

of OH and premature death as well as increased incidents of falls and fractures.

The causes of OH include severe volume depletion, baroreflex dysfunction, autonomicinsufficiency, and certain venodilator antihypertensive drugs, especially alpha blockers and alpha-beta blockers.

Diuretics and nitrates may further aggravate OH.

ORTHOSTATIC HYPOTENSION In treating older hypertensive patients, clinicians

should be alert to potential OH symptoms such as postural unsteadiness, dizziness, or even fainting.

Lying and standing BPs should be obtained periodically in all hypertensive individuals over age 50.

OH is a common barrier to intensive BP control that should be clearly documented; if present, drug therapy should be adjusted accordingly and appropriate warnings given to patients.

HYPERTENSIVE CRISES: EMERGENCIES AND URGENCIES

Hypertensive emergencies are characterized by severe elevations in BP (>180/120 mmHg) complicated by evidence of impending or progressive target organ dysfunction.

They require immediate BP reduction (not necessarily to normal) to prevent or limit target organ damage.

Examples include hypertensive encephalopathy, intracerebral hemorrhage, acute MI, acute left ventricular failure with pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm, or eclampsia.

HYPERTENSIVE CRISES: EMERGENCIES AND URGENCIES

Hypertensive urgencies are those situations associated with severe elevations in BP without progressive target organ dysfunction.

Examples include upper levels of stage II hypertension associated with severe headache, shortness of breath, epistaxis, or severe anxiety.

Majority of these patients present as noncompliant or inadequately treated hypertensive individuals, often with little or no evidence of target organ damage.

Early triage to establish the appropriate therapeutic strategies for these patients is critical to limiting morbidity and mortality.

HYPERTENSIVE CRISES: EMERGENCIES AND URGENCIES

Patients with hypertensive emergencies should be admitted to an intensive care unit for continuous monitoring of BP and parenteral administration of an appropriate agent.

The initial goal of therapy in hypertensive emergencies is to reduce mean arterial BP by no more than 25 percent (within minutes to 1 hour), then if stable, to 160/100–110 mmHg within the next 2–6 hours.

Excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia should be avoided.

For this reason, short-acting nifedipine is no longer considered acceptable in the initial treatment of hypertensive emergencies or urgencies.

HYPERTENSIVE CRISES: EMERGENCIES AND URGENCIES

If this level of BP is well tolerated and the patient is clinically stable, further gradual reductions toward a normal BP can be implemented in the next 24–48 hours.

Exceptions to the above recommendationPatients with an ischemic stroke in which there is

no clear evidence from clinical trials to support the use of immediate antihypertensive treatment

patients with aortic dissection who should have their SBP lowered to <100 mmHg if tolerated

patients in whom BP is lowered to enable the use of thrombolytic agents.

HYPERTENSIVE CRISES: EMERGENCIES AND URGENCIES

Some patients with hypertensive urgencies may benefit from treatment with an oral, short-acting agent such as captopril, labetalol, or clonidine followed by several hours of observation.

However, there is no evidence to suggest that failure to aggressively lower BP in the ER is associated with any increased short-term risk to the patient who presents with severe hypertension.

Such a patient may also benefit from adjustment in their antihypertensive therapy, particularly the use of combination drugs, or reinstitution of medications if noncompliance is a problem.

HYPERTENSIVE CRISES: EMERGENCIES AND URGENCIES

Most importantly, patients should not leave the ER without a confirmed follow up visit within several days.

Unfortunately, the term “urgency” has led to overly aggressive management of many patients with severe, uncomplicated hypertension.

Oral loading doses of antihypertensive agents can lead to cumulative effects causing hypotension.

PREVENTION Primary - measures include activities that help avoid

hypertensionExample : avoid fatty foods or exercise daily like

atleast 30 minutes walking

Secondary - identify and treat asymptomatic persons who have already developed risk factors or preclinical disease but in whom the condition is not clinically apparentExample : early case finding and screening tests

Tertiary - activities involve the care of established disease, with attempts made to restore to highest function, minimize the negative effects of disease, and prevent disease-related complications