HIPERTENSIDr, Suhaemi, SpPD,Finasim DEFINISI Tekanan Darah (TD): refleksi kardiovaskular TD sistolik : dipengaruhi oleh curah jantung (CO), dapat berubah dalam waktu singkat (aktifitas fisik ringan, emosi) TD diastolik : refleksi dari resistensi perifer, bila vasokonstriksi arteriol → TD diastolik ↑ sukar dipengaruhi faktor emosi dan aktifitas fisik ringan HIPERTENSI : kondisi abnormal hemodinamik pengaturan/kontrol) → batasan hipertensi dipakai kriteria TD sistolik dan/atau TD diastolik (fungsi If we do not treat the hypertension http://www.lifespan.org/adam/graphics/images/en/18166.jpg Consequences of Hypertension Consequences of Hypertension http://www.jpg .org/vascularcenter/body/stroke.massgeneral. jpg .ndt-educational.Hypertensive nephropathy http://www.org/images/Marcantonifig1. Fundoscopy/ Vascular . DEFINISI • Tekanan nadi (pulse pressure) = TD sistolik – TD diastolik • Tekanan arteri rata-rata (mean arterial pressure/MAP) = (TD sistolik + 2xTD diastolik) 3 . BP = CO x SVR SV x HR BP : blood pressure SVR: systemic vascular-resistance SV : stroke volume HR : heart rate . Blood Pressure Determining Factors Cardiac Output: Stroke Volume Heart Rate Force of Contraction Beta Blockers Calcium Channel Blockers Vasodilators Peripheral Resistance ** BP ACE Inhibitors Blood Volume ** Diuretics ACE Inhibitors . DEFINISI • HIPERTENSI PRIMER (90 – 95%) hipertensi yang tidak diketahui penyebabnya • HIPERTENSI SEKUNDER (5 – 10%) hipertensi yang diketahui penyebabnya . Patogenesis Hipertensi MULTIFAKTORIAL . . merokok. obesitas. genetis • Sistim saraf simpatis : tonus simpatis dan variasi diurnal • Keseimbangan antara modulator vasodilatasi dan vasokonstriksi pembuluh darah : endotel.PATOGENESIS Hipertensi primer : Penyakit multifaktorial • Interaksi faktor-faktor risiko seperti : diet / asupan garam. remodeling endotel. stres. ras. otot polos dan interstitium • Pengaruh sistim otokrin setempat sistem RAA . Angiotensin Glomerulus and Bowman’s Capsule Juxtaglomerular Cells Decreased BP Renin Release Formation of Angiotensin Increased Vasoconstriction Increased Aldosterone with Increased Na++ and Fluid Retention .Renin . FAKTOR2 YANG BERPENGARUH PADA PENGENDALIAN TD asupan Na berlebih jumlah nefron stress perubahan genetis obesitas faktor2 yg berasal dari Endotel retensi Na ginjal permukaan filtrasi Aktifitas Berlebih Saraf simpatiis Renin perubahan Angiotensin membran sel release hiperinsulinemia volume cairan konstriksi vena Preload TEKANAN DARAH Hipertensi kontraktilitas = = CURAH JANTUNG Peningkatan CJ konstriksi fungsional X dan/atau hipertrofi struktural TAHANAN PERIFER Peningkatan TP Kaplan autoregulation . . . 2003 Sep 10. 290(10):1314 .Hipertensi Sekunder Sleep apnea Drug-induced or related causes Chronic kidney disease Primary aldosteronism Renovascular disease Chronic steroid therapy and Cushing’s syndrome Pheochromocytoma Coarctation of the aorta Thyroid or parathyroid disease JNC 7 Express. JAMA. • According to the National Institutes of Health (NIH). if hypertension (HTN) is left untreated – 1/2 of hypertensive clients will die of heart disease – 1/3 of hypertensive clients will die of a stroke – Rest of clients will die of renal failure . Blood Pressure Classification JNC VII BP Classification Normal Prehypertension Stage 1 Hypertension Stage 2 Hypertension SBP mmHg <120 120–139 140–159 DBP mmHg and <80 or or 80–89 90–99 >160 or >100 . Mengapa Tekanan Darah Harus Diturunkan ? . FRAMINGHAM STUDY . HIPERTENSI : The Disease Continuum Early Paradigm Natural History of CVD Progression Elevated BP More Recent Paradigm Target Organ Damage Vascular Dysfunction A Proposed Future Paradigm Elevated BP Target Organ Damage Endothelial Dysfunction Vascular ? Dysfunction Elevated BP LVH Target Organ Damage Renal Damage MI Angina Pectoris Stroke . Hypertension Syndrome It’s More Than Just Blood Pressure Decreased Arterial Compliance Obesity Endothelial Dysfunction Abnormal Glucose Metabolism Abnormal Lipid Metabolism Accelerated Atherogenesis LV Hypertrophy and Dysfunction Abnormal Insulin Metabolism Blood-Clotting Mechanism Changes HYPERTENSION Neurohormonal Dysfunction Renal-Function Changes Kannel WB. JAMA. J Cardiovasc Pharmacol.21(suppl 1):S1-S5. Weber MA et al. J Hum Hypertens.5:417-423.275:1571-1576. Dzau VJ et al. 1993. 1991. . 1996. Deflate cuff at 2 mmHg/sec . Record with cuff at heart level . patient position ( seated. Take BP in both arms at least once. . Repeat measurement at least x2 (first visit: x3) & take average value . standing) & pulse rate. record which arm is used.Routine steps for accurate measurement of blood pressure • Rest the patient (seated) for at least 5 mins in a quiet confortable room . Choose cuff with appropriate width of bladder . disappearance = diastolic reading . Use a calibrated sphygmomanometer (a validated and recently calibrated electronic device may may also be used) . . supine. Measure BP at + 1 & 5 mins after standing ( especially in older patients and those with diabetes). First sound = systolic reading. JNC 7 2003 Ambulatory BP monitoring Self-measurement . May help improve adherence to therapy and evaluate “white-coat” HTN. sitting in chair. Confirm elevated reading in contralateral arm. 5 minutes apart. Provides information on response to therapy. Indicated for evaluation of “white-coat” HTN.BP Measurement Techniques Method In-office Brief Description Two readings. Absence of 10–20% BP decrease during sleep may indicate increased CVD risk. Appropriate cuff size. patients should not take caffeine-containing beverages or smoke for at least two hours before blood pressure is measured.How to measure blood pressure accurately ……… sphygmomanometer Patient should be seated and relaxed. Average the readings. If the first two readings differ by more than 10 mmHg systolic or 6 mmHg diastolic or if the initial readings are high. …………………. preferably for several minutes prior to to the measurement and in a quiet room. take several readings after five minutes of quiet rest. 2004 . Ideally. until consecutive readings do not vary by greater than these amounts.. Australia. cardiovascular. diastolic blood pressure Lewington S. JNC 7. 2002. 2003. systolic blood pressure. et al. DBP.289:2560-2572. JAMA. . CV. SBP. starting at BP 115/75 mm Hg.CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment* 8 7 6 CV mortality risk 5 4 3 2 1 0 115/75 135/85 155/95 175/105 SBP/DBP (mm Hg) *Individuals aged 40-70 years. 60:1903-1913. Lancet. drinking. smoking and taking drugs that affect the blood pressure one hour before measurement. .Preparation for measurement • Patient should abstain from eating. Preparation for measurement • Because a full bladder affects the blood pressure it should have been emptied. . .Preparation for measurement • BP take in quiet room and comfortable temperature. must record room temperature and time of day. BLOOD PRESSURE: MEASUREMENT . Ascultatory method of blood pressure measurement Nokolai Korotkoff. 1905 . 5. 2. No use of substances containing adrenergic stimulants such as phenylephrine or pseudoephedrine (may be present in nasal decongestants or ophthalmic drops). Bladder and bowel comfortable. No tight clothing on arm or forearm. No caffeine. √ 4. .Blood Pressure Assessment: Patient preparation and posture Standardized Preparation: Patient √ 1. stress or pain. Patient should stay silent prior and during the procedure. No acute anxiety. 6. 3. Quiet room with comfortable temperature 7. smoking or nicotine in the preceding 30 minutes. Rest for at least 5 minutes before measurement √ 8. Measuring Blood Pressure Slide 9-36 . . . Cushman WC. . stroke LVH. CHD. CHD = coronary heart disease HF = heart failure. HF Peripheral vascular disease Renal failure TIA = transient ischemic attack. J Clin Hypertens. 2003.Complications of Hypertension: Hypertension is a risk factor TIA. LVH = left ventricular hypertrophy.5(Suppl):14-22. Benefits of Lowering BP Average Percent Reduction Stroke incidence Myocardial infarction Heart failure 35–40% 20–25% 50% . 000 700 600 500 400 326 459 703 300 200 100 46 210 Systolic BP: 105 >>> 185 Cholesterol: 185 Glucose Intol. 1983 105 >>> 185 335 0 0 0 105 >>> 185 335 + 0 0 105 >>> 185 335 + + 0 105 >>> 185 335 + + + .:0 Cigaretes: 0 ECG-LVH: 0 Kannel.Framingham Heart Study (1983) CV Risk Profile 8 Year Probability Per 1. CXR: Cardiomegaly pleural effusions interstitial edema Pulmonary venous redistribution . Echocardiography “Confirm” diagnosis with transthoracic echocardiography – LV dimensions and ejection fraction – Systolic versus diastolic function – Valvular disease – Pulmonary hypertension All patients. Class 1C . Sisi kerja obat anti HT .Bagan 3. Bagan 4. Sistem RAA . and Blood Institute National High Blood Pressure Education Program National Institutes of Health National Heart.S. and Blood Institute The Seventh Report of the Joint National Committee on Prevention. Lung. Department of Health and Human Services National Heart. and Treatment of High Blood Pressure (JNC 7) . Evaluation. Lung. Detection.U. Endocrine Practice 1997.Lifestyle Interventions for Prevention or Treatment of Hypertension Intervention Exercise Weight reduction Alcohol intake reduction Sodium intake reduction Blood Pressure Effect 5-10 mm Hg (>30 min >3x/wk) 1-2 mm Hg/Kg 1 mm Hg/drink/d 1-3 mm Hg/40 mmol/d 3-10 mm Hg DASH diet Adapted from Cushman et al. NEJM 2001.3:106 & Sacks.334:3 . et al. JNC 7 Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mm Hg) (<130/80 mm Hg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling Indications With Compelling Indications Stage 1 Hypertension (SBP 140-159 or DBP 90-99 mm Hg) Thiazide-type diuretics for most May consider ACEI. BB. CCB) as needed Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved Consider consultation with hypertension specialist Chobanian et al. or CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics. BB. JAMA. or ARB. CCB. . 2003. or BB. ACEI. ARB.289:2560-2572. or combination Stage 2 Hypertension (SBP >160 or DBP >100 mm Hg) 2-drug combination for most (usually thiazide-type diuretic and ACEI. ARB. Target Organ Damage Heart • Left ventricular hypertrophy • Angina or prior myocardial infarction • Prior coronary revascularization • Heart failure Brain • Stroke or transient ischemic attack Chronic kidney disease Peripheral arterial disease Retinopathy . or the corresponding estimated GFR.Laboratory Tests Routine Tests • Electrocardiogram • Urinalysis • Blood glucose. creatinine. and hematocrit • Serum potassium. after 9. that includes high-density and 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 and calcium low-density . • Lipid profile.to 12-hour fast. Lifestyle Modification Modification Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Approximate SBP reduction (range) 5–20 mmHg/10 kg weight loss 8–14 mmHg 2–8 mmHg 4–9 mmHg Moderation of alcohol consumption 2–4 mmHg . Classes of Antihypertensive Drugs • • • • • • ACE inhibitors Adrenergic inhibitors Angiotensin II receptor blockers Calcium antagonists Direct vasodilators Diuretics Combination Therapies • -adrenergic blockers and diuretics • ACE inhibitors and diuretics • Angiotensin II receptor antagonists and diuretics • Calcium antagonists and ACE inhibitors • Other combinations Followup • Followup within 1 to 2 months after initiating therapy. • Recognize that high-risk patients often require high dose or combination therapies and shorter intervals between changes in medications. • Consider reasons for lack of responsiveness if blood pressure is uncontrolled after reaching full dose. • Consider reducing dose and number of agents after 1 year at or below goal. Pregnant Women • Chronic hypertension is high blood pressure present before pregnancy or diagnosed before the 20th week of gestation. • Preeclampsia is increased blood pressure that occurs in pregnancy (generally after the 20th week) and is accompanied by edema, proteinuria, or both. • ACE inhibitors and angiotensin II receptor blockers are contraindicated for pregnant women. • Methyldopa is recommended for women diagnosed during pregnancy. Potential synergism with magnesium sulfate may lead to precipitous hypotension.Antihypertensive Drugs Used in Pregnancy These agents* may be used with chronic hypertension (DBP > 100 mm Hg) or acute hypertension (DBP > 105 mm Hg). . and labetalol appear safe and effective in late pregnancy. metoprolol. Atenolol. Central -agonists -blockers and --blockers Calcium antagonists Methyldopa is the drug of choice. *Limited or no controlled trials in pregnant women. *Limited or no controlled trials in pregnant women. ACE inhibitors and angiotensin II receptor blockers are contraindicated. Hydralazine is the parenteral drug of choice based on its long history of safety and efficacy. Diuretics Direct vasodilators Diuretics are recommended for chronic hypertension if prescribed before gestation. . but they are not recommended for preeclampsia.Antihypertensive Drugs Used in Pregnancy (continued) These agents* may be used with chronic hypertension (DBP > 100 mm Hg) or acute hypertension (DBP > 105). Mechanism of Action of Angiotensin II Receptor Antagonists Angiotensinogen Bradykinin ACE inhibitors Angiotensin I Angiotensin II Alternate pathways Inactive peptides AIIRAs ? AT1 receptor ? Vasodilation Attenuate growth and disease progression . 4 g/hari atau NaCl 6 g/hari Berolah raga erobik teratur seperti berjalan kaki (30 men/hari.5-24. and Treatment of High Blood Pressure JNCVII. 4-5 hari seminggu) 8-14 mm Hg Mengurangi asupan garam/sodium Meningkatkan aktifitas fisik 2-8 mm Hg 4-9 mm Hg Source: The Seventh Report of the Joint National Committee on Prevention. Detection. 2003. JAMA.Modifikasi Gaya Hidup untuk Pengendalian Hipertensi Modifikasi Menurunkan berat badan Rekomendasi Pelihara berat badan normal (BMI 18. susu rendah lemak dan rendah lemak jenuh Kurangi natrium sampai tidak lebih dari 2. Evaluation. sayur.289:2560-2572.9) Penurunan Tekanan Darah Sistolik kurang lebih 5-20 mm Hg utk setiap penurunan 10 kg BB Menjalankan menu DASH Konsumsi makanan kaya buah. . ESH-ESC 2007 . Antihypertensive drugs • Alpha blockers • Vasodilators • Calcium Channel Blockers •Angiotensin Receptor Blockers Centrally acting agents Angiotensin Converting Enzyme Inhibitors Beta Blockers Diuretics . Sympatholytics Centrally acting sympatholytics Clonidine α-methyldopa Guanfacine Guanabenz Peripherally acting sympatholytics Metyrosine Guanethidine. Bretylium Reserpine . Guanethidine uptaken into NE vesicle prevent NE release from vesicle Reserpine inhibits accumulation of NE into vesicle .Peripheral Sympatholytics rarely used Metyrosine (or α-methyl-tyrosine): inhibits tyrosine hydroxylase rate-limiting enzyme for NE synthesis Bretylium. fluid retention. lupus-like syndrome only used in severe or refractory hypertension .Direct acting vasodilators Hydralazine liberates NO from vascular endothelium decreases TPR not used as monotherapy bioavailability dependent on genetic factors adverse effects: tachycardia. hypotension. hypertrichosis Minoxidil only used in severe or refractory hypertension . reduces smooth muscle contractility not used as monotherapy long duration of action (~24 hours) adverse effects: tachycardia.Direct acting vasodilators Minoxidil prodrug of N-O sulfate K+ channel opener. fluid retention. Thiazide Diuretics mechanism of action lower plasma volume monotherapy for mild to moderate hypertension ALLHAT: reduction of CVD superior to other agents adjunct agent most effective in patients with normal kidney function Hydrochlorothiazide . Drugs interacting with Renin-Angiotensin system ACE inhibitors: inhibit Angiotensin II formation Angiotension receptor antagonists: block Angiotensin receptor activation . Systemic Effects of ACE inhibitors Reduction in total peripheral resistance systolic and diastolic pressure mean arterial pressure aldosterone secretion cardiac remodeling Increase in regional blood flow in vascular beds large artery compliance . Types of ACE inhibitors Active Molecules Captopril (Capoten) Lisinopril (Prinivil) Enalaprilat Prodrugs: must be biotransformed for activity by esterases •Enalapril Enalaprilat (Vasotec) (Monopril) Enalapril •Fosinopril •Quinapril (Accupril) •Ramipril (Altace) . Side Effects hypotension cough hyperkalemia angioedema renal insufficiency teratogenic skin rash neutropenia proteinuria (protein in urine) ageusia (loss of taste) . Types of AT1 receptor antagonists Losartan (Cozaar) competitive antagonist Valsartan (Diovan) non-competitive Candesartan (Atacand) non-competitive Irbesartan (Aprovel) non-competitive Losartan . Therapeutic Uses same uses as ACE inhibitors excellent for inhibiting cell growth no bradykinin effects no cough useful for hypertension secondary to CHF used for prevention of re-stenosis after angioplasty . Phenoxybenzamine. Dibenamine Selective: Prazosin. Timolol. Pindolol. Esmolol. Terazosin . Betaxolol α1-adrenergic receptor antagonists “α-blockers” Non-selective: Phentolamine. Nadolol. Labetolol Cardioselective: Metoprolol. Atenolol. Doxazosin.Adrenergic receptor antagonists β-adrenergic receptor antagonists “β-blockers” Non-selective: Propranolol. conduction effects in heart NSAID’s blunt β-blocker effects .blockers: Side Effects Bradycardia Bronchospasm Coldness of extremities Heart failure Contraindicated in insulin-dependent diabetes CNS effects Increased plasma triglyceride concentration Decreased plasma HDL concentration Do not use in conjunction with Ca2+ channel lockers. Ca2+ channel antagonists an initial choice for monotherapy of mild to moderate hypertension all antagonists are equally effective for Stage 1 hypertension Verapamil and Diltiazem do not cause reflex tachycardia directly inhibit cardiac chronotropy Effective in low-renin hypertension African-americans Elderly Do not cause fluid retention . . Pregnant women with HTN should be followed carefully. ACEI and ARBs contraindicated in pregnancy. and BP should be checked regularly. In contrast. Development of HTN—consider other forms of contraception.Hypertension in Women Oral contraceptives may increase BP. BBs. preferred for the safety of the fetus. and vasodilators. Methyldopa. HRT does not raise BP. . • High blood pressure is not a contraindication to hormone replacement therapy.Women • Clinical trials have not demonstrated significant differences between men and women in treatment response and outcomes. • Some women using oral contraceptives may have significant increases in blood pressure. or both. • ACE inhibitors and angiotensin II receptor blockers are contraindicated for pregnant women.Pregnant Women • Chronic hypertension is high blood pressure present before pregnancy or diagnosed before the 20th week of gestation. . • Methyldopa is recommended for women diagnosed during pregnancy. proteinuria. • Preeclampsia is increased blood pressure that occurs in pregnancy (generally after the 20th week) and is accompanied by edema. Central -agonists -blockers and --blockers Calcium antagonists Methyldopa is the drug of choice. and labetalol appear safe and effective in late pregnancy. metoprolol. *Limited or no controlled trials in pregnant women. Potential synergism with magnesium sulfate may lead to precipitous hypotension.Antihypertensive Drugs Used in Pregnancy These agents* may be used with chronic hypertension (DBP > 100 mm Hg) or acute hypertension (DBP > 105 mm Hg). . Atenolol. Diuretics Direct vasodilators Diuretics are recommended for chronic hypertension if prescribed before gestation. *Limited or no controlled trials in pregnant women. but they are not recommended for preeclampsia. . ACE inhibitors and angiotensin II receptor blockers are contraindicated.Antihypertensive Drugs Used in Pregnancy (continued) These agents* may be used with chronic hypertension (DBP > 100 mm Hg) or acute hypertension (DBP > 105). Hydralazine is the parenteral drug of choice based on its long history of safety and efficacy.