(5) HIPERTENSI

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HIPERTENSI

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Angiotensin II (Ang II) generated in the afferent arteriole interacts with AT1 receptors on cellular components of the nephron

Angiotensinogen Ang I

Renin

ACEAng II

AT1R

= AT1 Receptor

Slide SourceHypertension Online

www.hypertensiononline.org4

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Discussion Classification

Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on Algorhythm

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≥100or> 160 Stage 2

90-99or140-159 Stage 1

Hypertension

80-89or120-139Prehypertension

<80and< 120Normal

Diastolic(mm Hg)

Systolic(mm Hg)Category

Classification of Hypertension (JNC VII)

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Category Systolic Diastolic

< 120 and < 80

120-129 and/or 80-84

High Normal 130-139 and/or 85-89

Grade 1 Hypertension 140-159 and/or 90-99

Grade 2 Hypertension 160-179 and/or 100-109

Grade 3 Hypertension ≥ 180 and/or ≥110

Isolated Systolic Hypertension

≥ 140 and < 90

ESH/ESC Classification of BP

Mancia G, et al. J Hypertens 2007;25:1105-1187

OptimalNormal

Slide Source Hypertension Online www.hypertensiononline.org

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Category Systolic Diastolic

< 120 and < 80

Pre Hipertensi 120-139 and/or 80-89

Grade 1 Hypertension 140-159 and/or 90-99

Grade 2 Hypertension ≥ 160-179 and/or ≥ 100

Isolated Systolic Hypertension

≥ 140 and < 90

Indonesian Classification of BP

Sumber, Sani,2008

Normal

Slide Source Hypertension Online www.hypertensiononline.org

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Discussion Classification

Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on Algorhythm

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Complications of Hypertension:End-Organ Damage

Chobanian AV, et al. JAMA. 2003;289:2560-2572.

Peripheral Vascular Disease Renal

Failure,Proteinuria

LVH, CHD, CHFHemorrhage,Stroke

Retinopathy

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

Hypertension

Slide SourceHypertension Online

www.hypertensiononline.org 11

Discussion Classification

Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on Algorhythm

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Assessment of Hypertensive Patients

Contributing factors

Complications of hypertension

Causes of secondary hypertension

Target of blood pressure

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2009 Canadian Hypertension Education Program Recommendations

Assess and manage contributive factor in hypertensive patients i.e.

• Dislipidemia

• Disglycemia (e.g. impaired fasting glucose, diabetes)

• Obesity

• Unhealthy eating

• Physical inactivity

Assessment of Hypertension

Slide SourceHypertension Online

www.hypertensiononline.org

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2009 Canadian Hypertension Education Program Recommendations

Search for exogenous potentially modifiable factors that can induce/aggravate hypertension

Prescription Drugs:• NSAIDs, including COXIBS (e.g. celecoxib)

• Corticosteroids and anabolic steroids

• Oral contraceptive and sex hormones

• Vasoconstricting/sympathomimetic decongestants

• Calcineurin inhibitors (cyclosporin, tacrolimus)

• Erythropoietin and analogues

• Monoamine oxidase inhibitors (MAOIs)

• Other sympathomemetics e.g. Midodrine

Other:• Licorice root

• Stimulants including cocaine

• Salt

• Excessive alcohol use

• Sleep apnea

Assessment of Hypertension

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Discussion Classification

Background: Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on Algorhythm 16

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Discussion Classification

Background: Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on Algorhythm 18

Lifestyle Modification

Modification RecommendationDecrease of

Sistolic Blood Pressure

Body weight Maintain normal body weight (BMI 18.5-24.9)

5-20 mm Hg every decrease of 10 kg BW

DASH dietConsumption of fruits, vegetables, low fat milk and low fat cheese

8-14 mm Hg

Reducing salt/sodium intake

Reducing sodium to not more than 2.4 g/ day or NaCl 6 g/day

2-8 mm Hg

Increasing physical activity

Aerobic exercise ie. Walking (30 min/day 4-5 days in a week)

4-9 mm Hg

Reducing alcohol consumption

Limiting alcohol consumption to not more than 2 oz/day for man and 1 oz / day for women.

2-4 mm Hg

Source: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JNCVII. JAMA. 2003;289:2560-2572.

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Food Group Daily Serving Examples and Notes

Grains 7 – 8 Whole wheat bread, oatmeal, popcorn

Vegetables 4 – 5 Tomatoes, potatoes, carrots, beans, peas, squash, spinach

Fruits 4 – 5 Apricots, bananas, grapes, oranges, grapefruit, melons

Low-fat or fat-free dairy foods 2 – 3

Fat-free (skim)/low-fat (1%)milk, fat-free,/low fat yogurt, fat free/low fat cheese

Meats, poultry, fish ≤ 2Select only lean meats, trim away fats; broil, roast, or boil, no frying and remove skin from poultry

Nuts, seeds, dry beans 4 – 5 / week Almonds, peanuts, walnuts, sunflower seeds, soybeans, lentils

Fats and oils 2 – 3Soft margarines, low fat mayonaise, vegetables oil (oil, corn, canola, or safflower)

Sweets 5 / weeks Maple syrup, sugar, jelly, jam, hard candy, sorbet

DASH DIET

DASH eating plan available at: http://www.nhibi.nih.gov/health/public/heart/hpb/dash/new_dash.pdf20

Discussion Classification

Background: Why BP should be controlled?

Hypertension Assessment

Target Blood Pressure

Non-pharmacologic Treatment

Pharmacologic Treatment based on Algorhythm 21

History of antihypertensive drugs

Directvasodilators

Alpha-blockers

Peripheralsympatholytics

Ganglion blockers

Veratrumalkaloids

Central α2 agonists

Calciumantagonists-non-DHPs

Beta-blockers

Thiazidediuretics

Calciumantagonists-

DHPs

ARBs

1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2000 2007

ACEinhibitors

DHP, dihydropyridine; ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker

Effectiveness and general tolerability

DRI

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First line classes of antihypertensive drugs

Diuretics− Inhibit the reabsorption of salts and water from kidney tubules

into the bloodstream Calcium-channel antagonists

− Inhibit influx of calcium into cardiac and smooth muscle Beta-blockers

− Inhibit stimulation of beta-adrenergic receptors Angiotensin-converting enzyme (ACE) inhibitors

− Inhibit formation of angiotensin II Angiotensin II receptor blockers (ARBs)

− Inhibit binding of angiotensin II to type 1 angiotensin II − Receptors

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Thiazide Diuretics

Thiazides

Veins • Mechanism: inhibit Na/K pumps in the distal tubule

• Examples:

•Hydrocholorthiazide 12.5-25 mg daily

•Chlorthalidone 12.5-50 mg daily

• Effective first line agent

• As single agent more effective if CrCl >30 ml/min

• Compelling indications: HF, High CAD risk, DM, Stroke, ISH

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Loop Diuretics

ThiazidesLoops

Veins• Mechanism: Inhibit Na/K/Cl ATPase in ascending loop of henle

• Examples:

•Furosemide 20 mg BID

• Typically only beneficial in patients with resistant HTN and evidence of fluid overload;

effective if CrCl <30 ml/min

• MUST be dosed at least twice daily (Lasix = Lasts six hours)

• Administer morning and lunch time to avoid nocturia

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Aldosterone Receptor Antagonists

ThiazidesLoopsAldosterone Ant.

Veins • Mechanism: inhibit receptor aldosterone reducing Na & water retention

• Examples:

•Spironolactone 25 mg daily

• Can provide as much as 25 mmHg BP reduction on top of 4 drug regimen in resistant hypertension

• Monitor SCr and K

• Compelling indications: HF

Am J Hypertension. 2003; 16:925-930.26

Beta Blockers

Beta Blockers

Heart• Mechanism: Competitively inhibit the binding of catecholamines to beta-adrenergic receptors

• Examples:

•Atenolol 25-100 mg QD, Metoprolol 25 -100 mg BID, Bisoprolol 2.5 – 10 mg QD

•Carvedilol 6.25-50 mg (alfa+Beta) BID

• Monitor: HR, Blood Glucose in DM

• Not contraindicated in asthma or COPD but use caution

• Compelling indications: HF, post-MI, High CAD risk, DM

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CCB Non-Dihydropyridine: Diltiazem and Verapamil

DiltiazemVerapamil

Heart• Mechanism: Decrease calcium influx into cells of vascular smooth muscle and myocardium

• Examples:

•Diltiazem Long acting; CD 100 -400 mg

•Verapamil 60-480 mg, long acting SR

• Monitor: HR

• Verapamil causes constipation

• Relatively contraindicated in HF

• Compelling indications: DM, High CAD risk

Arteries

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CCB: Dihydropyridine

Dihydropyridine CCBs

Arteries• Mechanism: Decrease calcium influx into cells of vascular smooth muscle

• Examples:

•Amlodipine 2.5-10 mg PO daily

•Felodipine 2.5-10 mg PO daily

• OROS/GITS. Do not use immediate release nifedipine

• Monitor: Peripheral edema, HR (can cause tachycardia)

• Good add on agent if cost is not an issue

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ACE Inhibitors

ACEI

• Mechanism: inhibiting synthesis of angiotensin II inhibit vasoconstriction

• Examples:

•ACEI: Captopril 12.5 -50 BID, Enalapril 2.5-40 mg daily –BID, Lisinopril 5 – 40 mg daily, Imidapril 5-10 QD, Perindopril 4-8 mg QD, Ramipril 2.5-20 mg

• Monitor: S Cr, K

• Compelling indications: HF, post-MI, High CAD risk, DM, CKD, Stroke

Arteries

Veins

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ARB’s

ARB

• Mechanism: blocking action of angiotensin II inhibit vasoconstriction

• Examples:

•ARB: Irbesartan 150-300 mg QD, Losartan 25-100 mg BID, Olmesartan 20-40 mg, Telmisartan 20-80 mg, Valsartan 90-160 mgQD

• Monitor: S Cr, K

• Compelling indications: HF, post-MI, High CAD risk, DM, CKD, Stroke

Arteries

Veins

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Alpha1 Blockers

Alpha1 Blockers

Arteries• Mechanism: Inhibit peripheral post-synaptic alpha1 receptors vasodilation

• Examples:

•Terazosin 1 – 20 mg daily

•Doxazosin 1 – 16 mg daily

• Cause marked orthostatic hypotension, give dose at bedtime

• Consider only as add on therapy

• Can be beneficial in patients with BPH

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Central Acting Agents

Central Acting Mechanism:Clonidine

Heart • Mechanism: false neurotransmitters reduce sympathetic outflow reducing sympathetic tone

• Examples:

•Clonidine 0.75-0.6 mg bid, Methyldopa 250 mg-1000 mg BID (Pregnancy), Reserpin 0,1 -0,25 mg QD

• Monitor: HR (bradycardia)

• Side effects often limiting: Dry mouth, orthostatic, sedation

• Withdrawal/Rebound effect

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Vasodilators

Dihydropyridine CCBsHydralazineMinoxidil

Arteries• Mechanism: Direct vasodilation of arterioles via increased intracellular cAMP

• Examples:

•Hydralazine 20-400 mg BID-QID

•Minoxidil 2.5-40 mg PO daily-BID

• Monitor: HR (can cause reflex tachycardia), Na/Water retention

• Hydralazine is an alternative in HF if ACEI contraindicated

• Consider minoxidil in refractory patients on multi-drug regimens

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Direct Renin Inhibitor; ALISKIREN• Monotherapy effective in lowering SBP and DBP in hypertensive patients

• Effective also in combination with a thiazide diuretic, a CCB and an ACE inhibitor or an ARB

• Protect against subclinical organ damage when combined with an ARB=➔ the available evidence justifies its use in hypertension, in combination with other agents. Mancia et al.Reappraisal of ESC Hypertension Guidelines 2007

NEWER ANTIHYPERTENSIVE AGENTS

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Hypertension treatment strategy: JNC VIILifestyle modifications

Not at goal blood pressure (<140/90 mmHg)(<130/80 mmHg for patients with diabetes or chronic kidney disease)

Initial drug choices

Without compelling indications

With compelling indications

Stage 1 hypertension(SBP 140-159 or DBP90-99 mmHg)Thiazide-type diuretics for most. May consider ACE-I, ARB, BB, CCBor combination

Stage 2 hypertension(SBP ≥160 or DBP ≥100 mmHg)Two-drug combination formost (usually thiazide-typediuretic and ACE-I or ARB, or BB, or CCB)

Drug(s) for the compelling indications

Other antihypertensiveDrugs (diuretics, ACE-I, ARB, BB, CCB) as needed

Not at blood pressure goal

Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist.

JNC VII. JAMA 2003;289:2560-2572

SBP, systolic blood pressure; DBP, diastolic blood pressure; ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker

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Treatment initiation: JNC VII

Normal Pre-hypertensionStage 1 hypertensionStage 2 hypertension

Lifestyle modificationEncourage Yes Yes Yes

Initial drug therapy

Without compelling indicationNo antihypertensive drug indicatedThiazide-type diuretics for most; may consider ACE-I, ARB, BB, CCB, or combinationTwo-drug combination for most (usually thiazide-type diuretic and ACE-I or ARB or BB or CCB)

With compelling indicationsDrug(s) for compelling indicationsDrug(s) for compelling indications; other antihypertensive drugs (diuretics, ACE-I, ARB, BB, CCB) as needed

ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker

JNC VII. JAMA 2003;289:2560-257237

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Follow-up

Hypertensive patients are recommended to be followed at least every month

Follow-up visits are used to:− Increase the intensity of lifestyle and drug

therapy,

− Monitor the response to therapy

− Assess adherence

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Summary Hypertension is becoming a burden to the

community due to impact on target organs & premature death.

Treatment has proven to reduce morbidity & mortality, but majority of patients were not treated adequately.

Aggressive treatment shown benefit in achieving target blood pressure.

More frequent follow up will be necessary for patients with stage 2 hypertension or patients with comorbid conditions.

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Thank you