HYPERTENSION AND ANTIHYPERETENSI VES (COMPLETE) BY KAMAL

HYPERTENSION

AMERICAN SOCIETY OF HYPERTENSION

They define and classify HTN as a progressive cardiovascular syndrome with many causes that result in both functional and structural changes to the heart and vascular system .

The new definition incorporates : The presence or absence of risk factors, Early disease markers, Target-organ damage

Abstracts of the 20th Annual Scientific Meeting of the American Society of Hypertension

Hypertension prevalence and control in Pakistan

In Pakistan 12 Million hypertensive patients 3 %

3% 2

6% 5
Undia gnose d Dia gnose d Controlle d

Hypertension prevalence and control worldwide

6 billion people

15 - 20 %

329 %

Hypertensive Normotensive

Controlled Uncontrolled

Rocella EJ . Paper presented at ASH . New York , May 1999 .

Systolic BP begins to rise significantly in middle age

160

Argentine Blood Pressure study

Systolic BP

Blood pressure ( mm Hg )

140

120

100

80

60

DBP
15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75 - 84 85 - 99

Age ( years )
Epidemiologic data based on the Argentine Blood Pressure study that included a sample of 10,462 noninstitutionalized subjects from 16 Argentine regions. Subjects ranged from 15 to 99 years. BP was measured during a 6-month period by physicians on 2 different days at an interval no greater than 1 week. Galarza et al, Hypertension, 1997.

WHY TO WORRY IF SOME ONE HAS HIGH BP?

Hypertension
Hemorrhage stroke LVH, CHD, CHF

Peripheral vascular disease

CHD = coronary heart disease CHF = congestive heart failure LVH = left ventricular hypertrophy

JNC V . Arch Intern Med 1993 ; 153 : 154 183

Retinopathy

Renal failure

Hypertension Most important factor for...

Hypertension

Coronory artery Disease

Stroke

Peripheral Vascular Disease End Stage Renal Disease

Congestive Heart Failure

Medical clinics of America Vol. 81, Number 5, September 1997

THE LANCET , SEP 2002 EDITION

CARDIO VASCULAR MORTALITY RISK DOUBLES WITH EACH 20 / 10 MMHG INCREMENT IN SYSTOLIC / DIASTOLIC BP *

* Individuals aged 40 69 years Lewington et al . Lancet 2002 ; 360 : 1903 13

TARGET ORGAN DISEASE v Risks of CVD at any level of elevated BP are increased several fold for patients with TOD

Manifestations of TOD Cardiac Clinical, electrocardiograph, or radiologic evidence of CAD LVH or strain by ECG or LVH by echo Left ventricular dysfunction or cardiac failure Cereb rovascular TIA or stroke Perip heral vasc ular Absence of 1 or more major pulses in extremities (except dorsalis pedis) with or without intermittent claudication; aneurysm Renal Serum creatinine 1.5 mg/dl Proteinuria (1+ or >) Microalbuminuria EYE Retinopathy Papilledema

CLASSIFICATION
TWO MAIN TYPES. . . Essential hypertension is the most prevalent hypertension type, affecting 90 95% of hypertensive patients. Although no direct cause has been identified, there are many factors such as sedentary lifestyle smoking Stress visceral obesity potassium deficiency obesity (more than 85% of cases occur in those with a body mass index greater than 25) The American Journal of Clinical Nutrition reported in 2005 that waist size was a better predictor of a person's blood pressure than body mass index (BMI). Men should strive for a waist size of 35 inches or under and women 33 inches or under Salt (sodium) sensitivity, Alcohol intake

ESSENTIAL HYPERTENSION.

vitamin D deficiency Risk also increases with aging, some inherited genetic mutations having a family history of hypertension. An elevated level of renin, sympathetic nervous system overactivity. Insulin resistance, which is a component of syndrome X (or the metabolic syndrome), is also thought to contribute to hypertension. Recent studies have implicated low birth weight as a risk factor for adult

 SECONDRY HYPERTENSION. Secondary hypertension is high blood pressure that's caused by another medical condition. There are many known conditions that can cause secondary hypertension. Regardless of the cause, arterial pressure becomes elevated either due to an increase in cardiac output, an increase in systemic vascular resistance, or both. When cardiac output is elevated, it is generally due to either increased neurohumoral

OTHER TYPES
MALIGNANT HYPERTENSI0N. Malignant hypertension is a complication of hypertension characterized by very elevated blood pressure, and organ damage in the eyes, brain, heart and/or kidneys. It is considered a hypertensive emergency. Systolic and diastolic blood pressures are usually greater than 200mmHg and 140mmHg, respectively. A diagnosis of malignant hypertension must show papilledema. The disorder affects about 1% of people with high blood

It mostly occurs in people with: Collagen vascular disorders Kidney problems Toxemia of pregnancy Kidney failure Renal hypertension caused by renal artery stenosis RESISTANT HYPERTENSION. Resistant hypertension is defined as blood pressure that remains elevated above treatment goals despite administration of an optimal three drug regimen that includes a diuretic.

 CAUSES-- Patient noncompliance with treatment Secondary hypertension (Usually from overactive adrenal glands) Fluid retention (usually expansion from kidney failure). WHITE COAT HYPERTENSI0N.. The phenomenon of high blood pressure which occurs only at the doctor's office is called whitecoat hypertension. Whitecoat hypertension is a result of stress, and will generally fade over time as patients become more adjusted to having their blood pressure checked in the doctor's office. Ambulatory blood pressure monitoring and patient self-measurement using a home blood pressure monitoring device is being increasingly used to differentiate it.

 PULMONARY HYPERTENSION..
Pulmonary hypertension is abnormally high blood pressure in the arteries of the lungs. It makes the right side of the heart need to work harder than normal. CAUSES Any condition that causes chronic low oxygen levels in the blood Autoimmune diseases that damage the lungs, such as scleroderma and rheumatoid arthritis Certain birth defects of the heart Certain diet medications Congestive heart failure History of a blood clot in the lung HIV infection Lung or heart valve disease Obstructive sleep apnea Treatment (epoprostenol and Bosentan)

 The most recent World Health Organisation (WHO) classification of pulmonary hypertension has it in five types namely pulmonary arterial hypertension, pulmonary venous hypertension, thromboembolic pulmonary hypertension and miscellaneous pulmonary hypertension ISOLATED SYSTOLIC HYPERTENSION. If systolic blood pressure is elevated (>140) with a normal diastolic blood pressure (<90), it is called "isolated systolic hypertension. This disorder primarily affects older people(>60 YEARS) and is characterized by an increased (wide) pulse pressure. ISOLATED DIASTOLIC PRESSURE If arterial stiffness is normal or low even when arteriolar resistance increases, this becomes a case of high diastolic blood pressure. For this cause doctors may use isolated diastolic

 Results of a survey by the Third National Health and Nutrition Examination Survey (NHANES) showed that hypertension treatment normalized diastolic blood pressure to <90mm Hg in 89.7% of patients and only to <140mm Hg of systolic pressure in 49.0% of patients.

 HYPERTENSION AND PREGNANCY There exist several hypertensive states of pregnancy: Gestational hypertension = usually defined as a BP over 140/90 without the presence of protein in the urine. Preeclampsia = gestational hypertension (BP > 140/90), and proteinuria (>300mg of protein in a 24-hour urine sample). Severe preeclampsia involves a BP over 160/110 (with additional signs) Eclampsia = seizures in a preeclamptic patient HELLP syndrome = Hemolytic anemia, elevated liver enzymes and

Hypertensive Urgencies and Emergencies

Patients with marked BP elevations and acute TOD (e.g., encephalopathy, myocardial infarction, unstable angina, pulmonary edema, eclampsia, stroke, head trauma, lifethreatening arterial bleeding, or aortic dissection) require hospitalization and parenteral drug therapy. Patients with markedly elevated BP but without acute TOD usually do not require hospitalization, but should receive immediate combination oral antihypertensive therapy.

CLASSIFICATION OF BLOOD PRESSURE

(SEVENTH REPORT OF JOINT NATIONAL COMMITTEE ON HYPERTENSION,2004 AND EUORPEAN SOCIETY OF HYPERTENSION TASK FORCE,2007)

EUROPEAN GUIDELINE S

AMERICAN GUIDELINE S

GUIDELINES RECOMMENDATION FOR INDIVIDUALS WITH HYPERTENSION AND DIABETES

FOR INDIVIDUALS WITH HYPERTENSION & DIABETES :

BP goal
< 140 / 90 mmHg < 130 / 80 mmHg < 140 / 90 mmHg < 130 / 80 mmHg < 140 / 90 mmHg < 130 / 80 mmHg

JNC 7

without diabetes or renal disease with diabetes or renal disease

ESH / ESC

without diabetes with diabetes

WHO / ISH

without diabetes with diabetes

BP = blood pressure Cardiology JNC = Joint National Committee ESH = European Society of Hypertension Hypertension

ESC = European Society of WHO = World Health Organization ISH = International Society of

BP Measurement Techniques
Method In-office Ambulatory BP monitoring Self-measurement Brief Description Two readings, 5 minutes apart, sitting in chair. Confirm elevated reading in contra Indicated for evaluation of lateral arm. white-coat HTN. Absence of 10 20% BP decrease during sleep may Provides information onrisk. indicate increased CVD response to therapy. May help improve adherence to therapy and evaluate white-coat HTN.

CVD Risk Factors

Hypertension

Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia Diabetes mellitus Microalbuminuria or estimated GFR <60 ml/min Age (older than 55 for men, 65 for women) Family history of premature CVD (men under age 55 or women under age 65)

*Components of the metabolic syndrome.

Laboratory Tests
Routine Tests Electrocardiogram Urinalysis Blood glucose, and hematocrit Serum potassium, creatinine, or the corresponding estimated GFR, and calcium Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and triglycerides Optional tests Measurement of urinary albumin excretion or albumin/creatinine ratio More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

HOW WILL YOU MANAGE HYPERTENSIVE PATIENT?

v NON - PHARMACOLOGIC TREATMENT
LIFESTYLE MODIFICATION Used as adjunctive therapy to anti-HTN meds Can lower BP and reduce CVD risk at minimal cost and risk to patient Attempt for 3 to 6 months before initiating drug therapy if patients in early stage of HTN and free of endorgan damage Diet modification (DASH, sodium restriction)

Modification
Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity

Approximate SBP reduction ( range )

5 20mmHg / 10 kg weight loss 8 14 mmHg 2 8 mmHg 4 9 mmHg

Moderation of alcohol consumption 2 4 mmHg

Benefits of Lowering BP

Average Percent Reduction 3540% infarction 50% Stroke incidence Myocardial 2025% Heart failure

ANTIHYPERTENSIVE DRUGS
Diuretics Adrenergic receptor antagonists Adrenergic receptor agonists Calcium channel blockers Renin Inhibitors ACE inhibitors Angiotensin II receptor antagonists Vasodilators Centrally acting adrenergic drugs

DIURETICS
Diuretics help the kidneys eliminate excess salt and water from the body's tissues and blood.

Loop diuretics bumetanide ethacrynic acid furosemide torsemide

Thiazide diuretics: epitizide Hydrochlorothiazide and chlorothiazide bendroflumethiazide

Thiazide-like diuretics: indapamide chlorthalidone metolazone

Potassium-sparing diuretics amiloride triamterene spironolactone

ADRENERGIC RECEPTOR ANTAGONISTS (ALPHA AND BETA BLOCKERS)

ALPHA BLOCKERS doxazosin phentolamine indoramin phenoxybenzamine prazosin terazosin Tolazoline Despite lowering blood pressure, alpha blockers have significantly poorer endpoint outcomes than other antihypertensives, and are no longer recommended as a first-line choice in the treatment of hypertension. However, they may be useful for some men with symptoms of prostate disease.

BETA ADRENOCEPTOR BLOCKERS

NON-SELECTIVES--Alprenolol Bucindolol Carteolol Carvedilol Labetalol Nadolol Penbutolol Pindolol Propranolol Sotalol Timolol CARDIOSELECTIVES---

Acebutolol Atenolol Betaxolol Bisoprolol Celiprolol Esmolol Metoprolol Nebivolol

BETA ADRENOCEPTOR BLOCKERS

Agents with intrinsic sympathomimeti c activity(ISA)-- Acebutolol Carteolol Celiprolol Mepindolol Oxprenolol Pindolol abetalol Agents with antioxidant effect-- Carvedilol nebivolol

BETA ADRENOCEPTOR BLOCKERS

Agents with greater aqueous solubility ---Atenolol Celiprolol Nadolol sotalol Agents with greater lipophilicity-- Metoprolol Propranolol Timolol Carvedilol Bisoprolol

ADRENERGIC RECEPTOR AGONIST

Alpha-2 agonists(centrally acting antihypertensives):
clonidine methyldopa Guanfacine (Methyldopa is one of the most commonly used antihypertensives in pregnancy alongwith labetalol,nifedipine and hydralazine)*

*Update on the Use of Antihypertensive Drugs in Pregnancy Tiina Podymow; Phyllis August (Hypertension. 2008;51:960.) 2008 American Heart Association, Inc.

CALCIUM CHANNEL BLOCKERS

Dihydropyridines amlodipine felodipine isradipine lercanidipine nicardipine nifedipine nimodipine nitrendipine NonDihydropyridin es diltiazem verapamil

DIRECT RENIN INHIBITORS

Renin comes one level higher than Angiotensin Converting Enzyme (ACE) in the Renin-Angiotensin System. Inhibitors of renin can therefore effectively reduce hyptertension. Aliskiren(developed by a )a renin inhibitor which has been approved by the US-FDA for treatment of hypertension.

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

captopril enalapril fosinopril lisinopril perindopril quinapril ramipril trandolapril Benazepril Moexipril

ANGIOTENSIN II RECEPTOR ANTAGONIST

candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan

VASODILATORS

Arterial dilators--Hydralazine Minoxidil Venous dilators--Organic nitrates Molsidomine Mixed dilators--Potassium channel activators Sodium nitroprusside

ADRENERGIC NEURON BLOCKERS

Guenethidine-interfere with release of NA Bretylium-interfere with release of NA Reserpine-interfere with storage of NA

Blood Pressure Changes: ARBs

BP Reduction With ARBs (W 12) Patients taking ARBs
0 -5 -1 0
Valsartan 4%

-18mm Hg

BP Reduction (mm Hg)

-1 5 -2 0 -2 5 -3 0 -3 5

-32 mm Hg
SBP DBP
Losartan 96%

N = 57

NATIVE data on file

Blood Pressure Changes: Ca-Antagonists

BP Reduction With Ca-blockers (W 12) Patients taking Ca-blockers
0 -5

Nefedipine 4%

Leracanidpine 0% Felodipine 1%

-1 0

-18mm Hg

-1 5 BP Reduction (mm Hg)

Verapamil 20%

-2 0

-2 5

-3 0

-34 mm Hg
SBP DBP

Diltiazem 5%

Amlodipine 70%

-3 5

N = 391

NATIVE data on file

Blood Pressure Changes: -blockers

BP Reduction With -blockers (W 12) Patients taking -blockers
0 -5

-1 0

-19mm Hg

-1 5 BP Reduction (mm Hg)

Carvedalol 0% Metoprolol 7% Bisoprolol 5%

Propranolol 2%

Nodalol 0%

-2 0

-2 5

-3 0

-34 mm Hg
Atenolol 86%
SBP DBP

-3 5

N = 640

NATIVE data on file

Blood Pressure Changes: Overall

160
BP (mm Hg)

145 130 115 100 85 70 0 2 4 SBP 6

Weeks

34 mm Hg
Baseline 166/102 Treated 132/84

18 mm Hg
8 DBP 10 12

NATIVE data on file

Multiple agents usually required to achieve BP goals.

IDNT * ( 135 / 85 mm Hg ) 3 UKPDS 38 (< 85 mm Hg diastolic ) ABCD MDRD (< 75 mm Hg diastolic ) (< 92 mm Hg mean arterial pressure ) 3.3 2 2.7 2.8 3.6

HOT || (< 80 mm Hg diastolic ) ALLHAT

(< 140 / 90 mm Hg )

Number of agents needed

*Irebesartan Diabetic Nephropathy Trial. United Kingdom Prospective Diabetes Study. Appropriate Blood Pressure Control in Diabetes. Modification of Diet in Renal Disease. || Hypertension Optimal Treatment. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Adapted from Lewis et al, N Engl J Med, 2001; Bakris et al, Am J Kidney Dis, 2000; Cushman et al, J Clin Hypertens, 2002.

WHO-ISH : appropriate drug therapy for hypertension

Drug class Diuretics Compelling indications

Elderly patients Systolic Heart block* Beta blockers hypertension Angina After MI Tachyarrhythm ias Pregnancy AngiotensinHF converting Left ventricular Hyperkalemia enzyme (ACE) dysfunction Bilateral renal inhibitors After MI artery stenosis Diabetic

HF

Compelling contraindications Gout

Drug class Calcium antagonists Alpha blockers

Compelling Compelling indications contraindications Angina Heart block Elderly patients Systolic Prostatic hypertension hypertrophy
Pregnancy Hyperkalemia Bilateral renal artery stenosis

Angiostensin II ACEreceptor inhibitor blockers (ARB) cough

nephropathy

*Grade 2 or 3 atrioventricular block.

Grade

2 or 3 atrioventricular block with verapamil or diltiazem.

World Health OrganizationInternational Society of Hypertens

Compelling Indications for Individual Drug Classes

Compelling Indication Diabetes Chronic kidney disease Initial Therapy options Options THIAZ, BB, ACE, ARB, CCB ACEI, ARB Clinical Trial Basis NKF-ADA Guideline, UKPDS, ALLHAT NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK PROGRESS

Recurrent stroke prevention

THIAZ, ACEI

Compelling Indications for Individual Drug Classes

Compelling Indication Heart failure Post myocardial infarction High CAD risk Initial Therapy Options THIAZ, BB, ACEI, ARB, ALDO ANT Clinical Trial Basis ACC/AHA Heart Failure Guideline, ACC/AHA Post-MI MERIT-HF, Guideline, ,BHAT, , COPERNICUS CIBIS , ALLHAT, HOPE, ANBP2 SAVE, ,Capricorn, , SOLVD CONVINCE LIFE, AIRE, TRACE EPHESUS, RALES ValHEFT

BB, ACEI, ALDO ANT

THIAZ, BB, ACE, CCB

Additional Considerations in Antihypertensive Drug Choices

Potential unfavorable effects Thiazide diuretics should be used cautiously in gout or a history of significant hyponatremia. BBs should be generally avoided in patients with asthma, reactive airways disease, or second- or third-degree heart block. ACEIs and ARBs are contraindicated in pregnant women or those likely to become pregnant. ACEIs should not be used in individuals with a history of angioedema. Aldosterone antagonists and potassium-sparing diuretics can cause hyperkalemia.

Additional Considerations in Antihypertensive Drug Choices

Potential favorable effects Thiazide-type diuretics useful in slowing demineralization in osteoporosis. BBs useful in the treatment of atrial tachyarrhythmias/fibrillation, migraine, thyrotoxicosis (short-term), essential tremor, or perioperative HTN. CCBs useful in Raynauds syndrome and certain arrhythmias. Alpha-blockers useful in prostatism.

REFRENCES

Goodman and Gillman 11th edition Evidence-Based Management of Hypertension BY Matthew R. Weir The Dash Diet for Hypertension BY Thomas Moore Rang and Dale's pharmacology 4th edition Katzung Basic and Clinical Pharmacology, 10nth Edition JNC VII REPORT ON HYPERTENSION ESH GUIDELINES 2007 AND 2009 U.S DEPARTMENT OF HEALTH AND HUMAN SERVICES (NATIONAL HEART,LUNG AND BLOOD INSTITUTE RECOMMENDATIONS)

REFRENCES
ARTICLES ISSUED IN CIRCULATION (JOURNAL OF AMERICAN HEART ASSOCIATION) THE LANCET(Volume 376, Issue 9739, Page 415) ARTICLES ISSUED IN HYPERTENSION (JOURNAL OF AMERICAN HEART ASSOCIATION) NOVARTIS LIBRARY WHO/ISH GUIDELINES ON HYPERTENSION (www.who.int/cardiovascular_diseases/gui delines/hypertension/en) www.circ.ahajournals.org www.ash-us.org