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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