hypertension and anti hypertensives

8/6/2019 Hypertension and Anti Hypertensives

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HYPERTENSION AND

ANTIHYPERETENSIVES

(COMPLETE)

BYKAMAL SIKANDAR


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HYPERTENSION

AMERICAN SOCIETY OF HYPERTENSION*

They define and classify HTN as aprogressive cardiovascular syndromewith 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 ofHypertension


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65

32%

3%

Undiagnosed Diagnosed Controlled

Hypertension prevalenceand control in Pakistan

In Pakistan

12 Million hypertensive patients


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

Hypertension prevalenceand control worldwide

Controlled

Uncontrolled

Hypertensive

Normotensive

15-20% 3-29%

6 billion

people


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Systolic BP begins to rise significantly

in middle age

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.

60

80

100

120

140

160

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

DBP

Systolic BP

Bloodpressure(mmH

g)

Age (years)

Argentine Blood Pressure study


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WHY TO WORRY IF SOME ONE HAS HIGH BP?

Hypertension

Peripheralvasculardisease Renal failure

LVH, CHD, CHF

Hemorrhage

stroke

CHD = coronary heart diseaseCHF = congestive heart failureLVH = left ventricular hypertrophy

JNC V. Arch Intern Med 1993;153:154183


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Hypertension

Coronory artery Disease Stroke

Congestive Heart Failur

End Stage Renal Disease

Peripheral Vascular Disease

Hypertension

Most important factor for...

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


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

THE LANCET, SEP 2002 EDITION

*Individuals aged 4069 years

Lewington et al. Lancet 2002;360:190313


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TARGET ORGAN DISEASE

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

Cerebrovascular TIA or stroke

Peripheral vascular

Absence of 1 or more major pulses in extremities (except dorsalis pedis) with or without intermittentclaudication; aneurysm

Renal

Serum creatinine 1.5 mg/dl

Proteinuria (1+ or >)

Microalbuminuria

EYE

Retinopathy

Papilledema


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CLASSIFICATION

TWO MAIN TYPES. . .

ESSENTIAL HYPERTENSION. Essential hypertension is the most prevalent hypertension type, affecting 9095% 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)

TheAmerican Journal of Clinical Nutrition reported in 2005 that waist size was a better predictor ofa person's blood pressure than body mass index (BMI). Men should strive for a waist size of 35inches or under and women 33 inches or under

Salt (sodium) sensitivity,

Alcohol intake


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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 essential hypertension.


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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 ofthe cause, arterial pressure becomes elevatedeither due to an increase in cardiac output, anincrease in systemic vascular resistance, orboth. When cardiac output is elevated, it is

generally due to either increasedneurohumoral activation of the heart orincreased blood volume.


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OTHER TYPES

MALIGNANT HYPERTENSI0N.

Malignant hypertension is a complication ofhypertension characterized by very elevatedblood pressure, and organ damage in the eyes,brain, heart and/or kidneys. It is considered ahypertensive emergency. Systolic and diastolicblood pressures are usually greater than200mmHg and 140mmHg, respectively. A

diagnosis of malignant hypertension must showpapilledema. The disorder affects about 1% ofpeople with high blood pressure


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It mostly occurs in people with:

Collagen vascular disorders

Kidney problems Toxemia of pregnancy

Kidney failure

Renal hypertension caused by renal arterystenosis

RESISTANT HYPERTENSION.

Resistant hypertension is defined as blood

pressure that remains elevated above treatmentgoals despite administration of an optimal threedrug regimen that includes a diuretic.


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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 onlyat the doctor's office is called whitecoat hypertension.

Whitecoat hypertension is a result of stress, and willgenerally fade over time as patients become more adjustedto having their blood pressure checked in the doctor'soffice.

Ambulatory blood pressure monitoring and patient self-

measurement using a home blood pressure monitoringdevice is being increasingly used to differentiate it.


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PULMONARY HYPERTENSION.. Pulmonary hypertension is abnormally high blood pressure in the

arteries of the lungs. It makes the right side of the heart need towork harder than normal.

CAUSES

Any condition that causes chronic low oxygen levels in the blood

Autoimmune diseases that damage the lungs, such as sclerodermaand 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)


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The most recent World Health Organisation (WHO)classification of pulmonary hypertension has it in five typesnamely pulmonary arterial hypertension, pulmonaryvenous hypertension, thromboembolic pulmonary

hypertension and miscellaneous pulmonary hypertension ISOLATED SYSTOLIC HYPERTENSION.

If systolic blood pressure is elevated (>140) with a normaldiastolic blood pressure (


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Results of a survey by the Third

National Health and Nutrition

Examination Survey (NHANES)

showed that hypertension treatment

normalized diastolic blood pressureto


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HYPERTENSION AND PREGNANCY

There exist several hypertensive states ofpregnancy:

Gestational hypertension = usually defined as aBP over 140/90 without the presence of proteinin the urine.

Preeclampsia = gestational hypertension (BP >140/90), and proteinuria (>300 mg of protein in a24-hour urine sample). Severe preeclampsiainvolves a BP over 160/110 (with additional signs)

Eclampsia = seizures in a preeclamptic patient

HELLP syndrome = Hemolytic anemia, elevatedliver enzymes and low platelet count


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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, life-

threatening arterial bleeding, or aortic dissection) requirehospitalization 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.


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CLASSIFICATION OF BLOOD

PRESSURE(SEVENTH REPORT OF JOINT

NATIONAL COMMITTEE ON

HYPERTENSION,2004

AND

EUORPEAN SOCIETY OFHYPERTENSION TASK FORCE,2007)


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EUROPEAN

GUIDELINES

AMERICAN

GUIDELINES


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GUIDELINES RECOMMENDATION FOR INDIVIDUALS WITH HYPERTENSION AND DIABETES

BP = blood pressure ESC = European Society of Cardiology

JNC = Joint National Committee WHO = World Health Organization

ESH = European Society of Hypertension ISH = International Society of Hypertension

FOR INDIVIDUALS WITH HYPERTENSION & DIABETES: BP goal

JNC 7 without diabetes or renal disease


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BP Measurement Techniques

Method Brief Description

In-office Two readings, 5 minutes apart, sitting in

chair. Confirm elevated reading in contra

lateral arm.Ambulatory BP monitoring Indicated for evaluation of white-coat HTN.

Absence of 1020% BP decrease during

sleep may indicate increased CVD risk.

Self-measurement Provides information on response to therapy.May help improve adherence to therapy and

evaluate white-coat HTN.


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CVD Risk Factors

Hypertension

Cigarette smoking

Obesity* (BMI >30 kg/m2)

Physical inactivity

Dyslipidemia

Diabetes mellitus

Microalbuminuria or estimated GFR


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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


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HOW WILL YOU MANAGE HYPERTENSIVE PATIENT?

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 end-

organ damage

Diet modification (DASH, sodium restriction)

ModificationApproximate SBP reduction

(range)

Weight reduction 520 mmHg/10 kg weight loss

Adopt DASH eating plan 8

14 mmHg

Dietary sodium reduction 28 mmHg

Physical activity 49 mmHg

Moderation of alcohol consumption 24 mmHg


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Benefits of Lowering BP

Average Percent Reduction

Stroke incidence 3540%

Myocardial infarction 2025%

Heart failure 50%


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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


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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


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ADRENERGIC RECEPTOR ANTAGONISTS

(ALPHA AND BETA BLOCKERS) ALPHA BLOCKERS

doxazosin

phentolamine

indoramin

phenoxybenzamine

prazosin

terazosin

Tolazoline

Despite lowering blood pressure, alpha blockers have significantlypoorer endpoint outcomes than other antihypertensives, and areno longer recommended as a first-line choice in the treatment ofhypertension. However, they may be useful for some men withsymptoms of prostate disease.


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BETA ADRENOCEPTOR BLOCKERS

NON-SELECTIVES--- Alprenolol

Bucindolol

Carteolol

Carvedilol

Labetalol

Nadolol

Penbutolol

Pindolol

Propranolol

Sotalol

Timolol

CARDIO-SELECTIVES---

Acebutolol

Atenolol

Betaxolol

Bisoprolol

Celiprolol

Esmolol

Metoprolol

Nebivolol


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Agents with intrinsicsympathomimeticactivity(ISA)---

Acebutolol

Carteolol

Celiprolol

Mepindolol

Oxprenolol

Pindolol

abetalol

Agents with antioxidanteffect---

Carvedilol

nebivolol


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Agents with greater

aqueous solubility ---

Atenolol

Celiprolol

Nadolol

sotalol

Agents with greater

lipophilicity---

Metoprolol

Propranolol

Timolol

Carvedilol

Bisoprolol


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ADRENERGIC RECEPTOR AGONIST

Alpha-2 agonists(centrally acting antihypertensives): clonidine

methyldopa

Guanfacine

(Methyldopa is one of the most commonly usedantihypertensives in pregnancy alongwithlabetalol,nifedipine and hydralazine)*

*Update on the Use of Antihypertensive Drugs inPregnancy

Tiina Podymow; Phyllis August (Hypertension. 2008;51:960.)

2008 American Heart Association, Inc.


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CALCIUM CHANNEL BLOCKERS

Dihydropyridinesamlodipine

felodipine

isradipine lercanidipine

nicardipine

nifedipine

nimodipine

nitrendipine

Non-Dihydropyridines

diltiazem

verapamil


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DIRECT RENIN INHIBITORS

Renin comes one level higher than

Angiotensin Converting Enzyme (ACE) in the

Renin-Angiotensin System. Inhibitors of renin

can therefore effectively reducehyptertension. Aliskiren (developed bya )a renin inhibitor which has been

approved by the US-FDA for treatment ofhypertension.


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ANGIOTENSIN-CONVERTING ENZYME

INHIBITORS captopril enalapril

fosinopril

lisinopril

perindopril

quinapril

ramipril

trandolapril

Benazepril

Moexipril


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ANGIOTENSIN II RECEPTOR

ANTAGONIST

candesartan

eprosartan

irbesartan

losartan

olmesartan

telmisartan

valsartan


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VASODILATORS

Arterial dilators--- Hydralazine

Minoxidil

Venous dilators--- Organic nitrates

Molsidomine

Mixed dilators---

Potassium channel activators Sodium nitroprusside


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ADRENERGIC NEURON BLOCKERS

Guenethidine-interfere with release of NA

Bretylium-interfere with release of NA

Reserpine-interfere with storage of NA


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Blood Pressure Changes: ARBs

-35

-30

-25

-20

-15

-10

-5

0

BPReduction(mmHg)

SBP DBP

-32 mm Hg

-18mm Hg

BP Reduction With ARBs (W 12)

Losartan

96%

Valsartan

4%

Patients taking ARBs

N = 57

NATIVE data on file


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Blood Pressure Changes: Ca-Antagonists

-35

-30

-25

-20

-15

-10

-5

0

BPReduction(mmH

g)

SBP DBP

-34 mm Hg

-18mm Hg

BP Reduction With Ca-blockers (W 12)

Amlodipine

70%

Verapamil20%

Nefedipine

4%

Diltiazem

5%

Felodipine

1%

Leracanidpine

0%

Patients taking Ca-blockers

N = 391

NATIVE data on file


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Blood Pressure Changes: b-blockers

-35

-30

-25

-20

-15

-10

-5

0

BPReduction(mmH

g)

SBP DBP

-34 mm Hg

-19mm Hg

BP Reduction With b-blockers (W 12)

Atenolol

86%

Metoprolol

7%

Carvedalol

0%

Bisoprolol5%

Nodalol

0%

Propranolol

2%

Patients taking b-blockers

N = 640

NATIVE data on file


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Blood Pressure Changes:Overall

70

85

100

115130

145

160

0 2 4 6 8 10 12

Weeks

BP(mmHg)

SBP DBP

Baseline 166/102Treated 132/84

34 mm Hg

18 mm Hg

NATIVE data on file


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Multiple agents usually required to

achieve BP goals.IDNT*

UKPDS 38

ABCD

MDRD

HOT||

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.

3.6

3.3

2.8

2.7

3

2ALLHAT

(135/85 mm Hg)

(


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Drug class Compellingindications

Compellingcontraindications

Diuretics HF

Elderlypatients

Systolichypertension

Gout

Betablockers

Angina

After MI

Tachyarrhythmias

Heart block*

Angiotensin-

convertingenzyme(ACE)inhibitors

HF

Leftventriculardysfunction

After MI

Diabeticnephropathy

Pregnancy

Hyperkalemia

Bilateral renalarterystenosis

Drug class Compellingindications

Compellingcontraindications

Calciumantagonists

Angina

Elderlypatients

Systolic

hypertension

Heart block

Alphablockers

Prostatichypertrophy

AngiostensinII receptorblockers(ARB)

ACE-

inhibitorcough

Pregnancy

Hyperkalemia

Bilateral renalartery stenosis

WHO-ISH : appropriate drug therapy

for hypertension

*Grade 2 or 3 atrioventricular block.Grade 2 or 3 atrioventricular block with verapamil or diltiazem.

World Health OrganizationInternational Society of Hypertension,J Hypertens, 1999.

Compelling Indications for


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Diabetes

Chronic kidney disease

Recurrent stroke

prevention


Individual Drug Classes

Compelling Indication Initial Therapy Options Clinical Trial Basis

NKF-ADA Guideline,

UKPDS, ALLHAT

NKF Guideline,

Captopril Trial,

RENAAL, IDNT, REIN,

AASK

PROGRESS

Initial Therapy options

THIAZ, BB, ACE, ARB,

CCB

ACEI, ARB

THIAZ, ACEI



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Individual Drug Classes

Compelling Indication Initial Therapy Options Clinical Trial Basis

ACC/AHA Heart Failure

Guideline, MERIT-HF,

COPERNICUS, CIBIS,

SOLVD, AIRE, TRACE,

ValHEFT, RALES

ACC/AHA Post-MI

Guideline, BHAT,

SAVE, Capricorn,EPHESUS

ALLHAT, HOPE,

ANBP2, LIFE,

CONVINCE

THIAZ, BB, ACEI, ARB,

ALDO ANT

BB, ACEI, ALDO ANT

THIAZ, BB, ACE, CCB

Heart failure

Post myocardial

infarction

High CAD risk

Additi l C id ti i


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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, reactiveairways 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.

Additi l C id ti i


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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.


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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 INSTITUTERECOMMENDATIONS) www.nhlbi.nih.gov


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REFRENCES

ARTICLES ISSUED IN CIRCULATION (JOURNAL OFAMERICAN 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/guidelines/hypertension/en)

www.circ.ahajournals.org

www.ash-us.org

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