HIPERTENSI

DEFINISI

� Blood pressure:

� is the pressure of the blood against the walls of the arteries.

� results from two forces. � One is created by the heart as it pumps blood into the arteries � One is created by the heart as it pumps blood into the arteries

and through the circulatory system.

� The other is the force of the arteries as they resist the blood flow.

Tekanan darah

� Systolic blood pressure is a measure of blood pressure while the heart is beating

� Diastolic pressure is a measure of blood pressure while the heart is relaxed, between heartbeats. while the heart is relaxed, between heartbeats.

TEKANAN DARAH

CARDIAC OUTPUT RESISTENSI PERIFER

HIPERTENSI

� Hypertension is defined by persistent elevation of arterial blood pressure (BP).

� The Seventh Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) classifies adult BPBlood Pressure (JNC 7) classifies adult BP

� isolated systolic hypertension: Patients with diastolic blood pressure (DBP) values <90 mm Hg and systolic blood pressure (SBP) values ≥140 mm Hg

A hypertensive crisis (BP >180/120 mm Hg) may be categorized as either :

� a hypertensive emergency (extreme BP elevation with acute or progressing target organ damage) or

a hypertensive urgency (severe BP elevation without � a hypertensive urgency (severe BP elevation without acute or progressing target organ injury)

PREVALENSI DAN EPIDEMIOLOGI

� Prevalensi nasional Hipertensi Pada Penduduk Umur > 18 Tahun adalah sebesar 29,8%

� 31% penduduk Amerika mengalami hipertensi ≥ 140/90 mmHg

� Tekanan darah akan meningkat dengan bertambahnya usia (hipertensi banyak terjadi pada lansia)

� menurut WHO prevalensi hipertensi di dunia 33.6% pd thn 2006

ETIOLOGI

� Hipertensi primer (90%): tidak diketahuipenyebabnya, hanya bisa dikontrol (faktor genetik)

� Hipertensi sekunder (10%): � disfungsi ginjal, gagal ginjal kronis, penyakit thyroid, Cushing � disfungsi ginjal, gagal ginjal kronis, penyakit thyroid, Cushing

syndrome

� Obat: dekongestan, steroid, NSAID

� Makanan: Natrium, etanol, tiramin

Multiple factors may contribute to the development of primary hypertension, including:

� Humoral abnormalities involving the renin-angiotensin-aldosterone system, natriuretic Hormone, or hyperinsulinemia;

� A pathologic disturbance in the CNS, autonomic nerve fibers, adrenergic receptors, or baroreceptors;

� Abnormalities in either the renal or tissue autoregulatory� Abnormalities in either the renal or tissue autoregulatoryprocesses for sodium excretion, plasma volume, and arteriolar constriction;

� A deficiency in the local synthesis of vasodilatingsubstances in the vascular endothelium, such as prostacyclin, bradykinin, and nitric oxide, or an increase in production of vasoconstricting substances such as angiotensin II and endothelin I;

� A high sodium intake and increased circulating natriuretic hormone inhibition of intracellular sodium transport, resulting in increased vascular reactivity and a rise in BP; and

� Increased intracellular concentration of calcium, � Increased intracellular concentration of calcium, leading to altered vascular smooth muscle function and increased peripheral vascular resistance.

PATOFISIOLOGI

� Malfungsi sistem renin-angiotensin-aldosteron

PATOPHYSIOLOGY

� Renin is an enzyme secreted into the blood from the kidneys

� sensitive to changes in blood flow and blood pressure

� The primary stimulus for increased renin secretion is decreased blood flow to the kidneys, which may

� The primary stimulus for increased renin secretion is decreased blood flow to the kidneys, which may be caused by loss of sodium and water (as a result of diarrhea, persistent vomiting, or excessive perspiration)

� Renin catalyzes the conversion of angiotensinogen into angiotensin I

PATOPHYSIOLOGY

� An enzyme in the serum called angiotensin-converting enzyme (ACE) then converts angiotensin I into angiotensin II

� Angiotensin II acts via receptors in the adrenal glands to stimulate the secretion of aldosterone:

which stimulates salt and water reabsorption by the � which stimulates salt and water reabsorption by the kidneys,

� and the constriction of small arteries (arterioles), which causes an increase in blood pressure.

� Angiotensin II further constricts blood vesselsthrough its inhibitory actions on the reuptake into nerve terminals of the hormone norepinephrine

80-89120-139Prehypertension

<80<120Normal

Diastolic BP

(mm Hg)

Systolic BP

(mm Hg)

Blood pressure

classification

JNC VII: Classification of blood pressure

or

or

≥≥≥≥100≥≥≥≥160Stage 2

hypertension

90-99140-159Stage 1

hypertension

80-89120-139Prehypertension or

or

or

The JNC VII. JAMA 2003;289:2560-72

JNC VII and ESH−−−−ESC summary: target blood pressure goals

Type of hypertensionType of hypertension BP goal (mmHg)BP goal (mmHg)

Uncomplicated <140/90

ComplicatedComplicated

Diabetes mellitus <130/80

Kidney disease <130/80

Chobanian et al. JAMA 2003;289:2560−72

Guidelines Committee. J Hypertens 2003;21:1011−53

Kaplan (Clinical Hypertension, 9th ed.,2006) Kaplan (Clinical Hypertension, 9th ed.,2006)

“BP target is “ to lower BP below the threshold for “BP target is “ to lower BP below the threshold for

starting therapy”starting therapy”

KOMPLIKASI HIPERTENSI

� Otak: stroke

� Jantung: penyakit jantung koroner, gagal jantung

� Mata: hipertensif retinopati

� Ginjal : gagal ginjal (kreatinin tinggi, proteinuria)� Ginjal : gagal ginjal (kreatinin tinggi, proteinuria)

� Penyakit vaskular perifer: aneurisma

KOMPLIKASI

� Risk of CV disease doubles with every 20/10 mm Hg increase.

� Even patients with prehypertension have an increased risk of CV disease.

DIAGNOSIS

� Silent killer

� Pengukuran tekanan darah (sesuaikan dgn klasifikasi tekanan darah JNC VII)

Evaluasi hipertensi

TERAPI

� Nonfarmakologi

� Farmakologi:

� Tujuan: menurunkan mortalitas dan morbiditas yang berhubungan dengan kerusakan hipertensi

� Mortalitas dan morbiditas berkaitan dgn organ target spt: � Mortalitas dan morbiditas berkaitan dgn organ target spt: kejadian kardiovaskular/serebrovaskular, gagal jantung, penyakit ginjal

Terapi nonfarmakologi

Terapi Farmakologi

� first-line options: Diuretic, ACE inhibitor, ARB, and CCB

� β-Blockers may be used either to treat a specific compelling indication or as combination therapy with a primary antihypertensive agent for therapy with a primary antihypertensive agent for patients without a compelling indication.

� α1-Blockers, direct renin inhibitors, central α2-agonists, peripheral adrenergic antagonists, and direct arterial vasodilators are alternatives that may be used in select patients after primary agents.

Terapi farmakologi

Indikasi khusus

� Gagal jantung: ACEI, diuretik, beta blocker, ARB

� Pasca IM: beta blocker, ACEI

� Penyakit iskemia jantung: beta blocker, CCB

� Penyakit ginjal kronis: ACEI, ARB, diuretik loop

Penyakit serebrovaskular: ACEI dan diuretik tiazid� Penyakit serebrovaskular: ACEI dan diuretik tiazid

� Wanita hamil: metil dopa, beta blocker, vasodilator

� Preeklamsia: hidralazin iv, metil dopa

� Hipertensi urgensi

� Hipertensi emergensi� Hipertensi emergensi

Algoritma terapi hipertensi

Oral antihypertensive drugs*

Class Drug (Trade Name) Usual dose range in mg/day (Daily Frequency)

ACE inhibitors

benazepril (Lotensin†) 10–40 (1–2)

captopril (Capoten†) 25–100 (2)

enalapril (Vasotec†) 2.5–40 (1–2)

fosinopril (Monopril) 10–40 (1)

lisinopril (Prinivil, Zestril†) 10–40 (1)

moexipril (Univasc) 7.5–30 (1)

perindopril (Aceon) 4–8 (1–2)

quinapril (Accupril) 10–40 (1)

ramipril (Altace) 2.5–20 (1)

trandolapril (Mavik) 1–4 (1)

Angiotensin II antagonists

candesartan (Atacand) 8–32 (1)

eprosartan (Tevetan) 400–800 (1–2)

irbesartan (Avapro) 150–300 (1)

losartan (Cozaar) 25–100 (1–2)

olmesartan (Benicar) 20–40 (1)

telmisartan (Micardis) 20–80 (1)

valsartan (Diovan) 80–320 (1)

Classification Classification

Calcium AntagonistsCalcium AntagonistsGeneration:

First Second Third Latest

Verapamil

Nifedipine

Diltiazem

Felodipine RTD

Isradipine CR

Verapamil SR

Amlodipine LercanidipineLercanidipine

(hydrophilic) (lipophilic)(lipophilic)

Diltiazem Verapamil SR

Nifedipine GITS

Diltiazem CD

J Clin Basic Cardiol 1999;2:155

DIURETIK

� Tiazid: HCT

� Loop: furosemid

� Hemat kalium: amilorid, triamteren

� Antagonis aldosteron: spironolakton� Antagonis aldosteron: spironolakton

ES diuretik tiazid, loop:

� hipokalemia, hipomagnesia, hiperkalsemia, hiperuriemia, hiperglikemia, hiperlipidemia, dandisfungsi seksual

ACE Inhibitor

� Menghambat angiotensin I menjadi angiotensin II

� Angiotensin II adalah vasokonstriktor kuat dan jg merangsang sekresi aldosteron

� ACEI memblok degradasi bradikinin--�meningkatkan efek penurunan tekanan darah dan meningkatkan efek penurunan tekanan darah dan ES batuk kering

Penyekat reseptor angiotensin II (ARB)

� Efek angiotensin II: vasokonstriksi, pelepasan aldosteron, aktivasi simpatik, pelepasan hormon antidiuretik

Beta blocker

� Adrenoseptor beta-1 dan beta-2 terdistribusi di seluruh tubuh

� Beta -1:

� terdapat banyak di jantung dan ginjal

� Menaikkan denyut jantung, kotraktilits, pelepasan renin

� Beta-2:

� terdapat di paru-paru, liver, pankreas dan otot halus rteri

� Sekresi insulin dan glikogenolisis

� Bronkodilatasi dan vasodilatasi

� Beta blocker:

� Kardioselektif kecil kemungkinan terjadi spasme bronkus dan

vasokonstriksi (beta-1 blocker)

� Beta-2 blocker: Vasokonstriksi dan spasme bronkus, hiperglikemia

Antihipertensi alternatif

Alfa 1 blocker

� Prazosin, terazosin, doxazosin

� Bekerja pada pembuluh darah perifr, menghambatambilan katekolamin pd sel otot halus menyebabkanvasodilatasi dan menurunkan tekanan darah.

Menguntungkan utk laki-laki dgn BPH (benign � Menguntungkan utk laki-laki dgn BPH (benign prostatic hyperplasia)---� memblok reseptorpostsinaptik alfa-1 adrenergik di tempat kapsulprostat, menyebabkan relaksasi dan berkuranghambatan keluarnya aliran urin.

Agonis alfa 2 central

� Klonidin dan metil dopa

� Menurunkan tekanan darah dengan merangsangreseptor alfa- adrenergik di otak--�menurunkanaliran simpatetik dari pusat vasomotor di otak(meningkatkan akt parasimpatetik) dan(meningkatkan akt parasimpatetik) danmenurunkan tonus vagal---� menurunkan denyutjantung, cardiac output, resistensi perifer total, aktplasma renin, dan reflex baroreseptor.

� Klonidin utk hipertensi yang resisten obat pilihanutama pada kehamilan

Reserpin

Mekanisme kerja:

� Reserpin menurunkan tekanan darah dgnmengosongkan norefinefrin dari ujung sarafsimpatetik dan memblok perjalanan NE ke granulpenyimpanannya.penyimpanannya.

� Mengosongkan katekolamin dari otak danmiokardium: sedasi, depresi dan berkurangnyacurah jantung

Reserpin…

� Mulai kerja dan waktu paruh lambat: dosispemberian 1x/hari.

� Perlu 2-6 minggu efek antihipertensi terlihat

� Dapat menyebabkan retensi natrium dan air perlukombinasi dgn diuretik (tiazid)kombinasi dgn diuretik (tiazid)

� Hambatan akt simpatetik (meningkatkan aktparasimpatetik) terlihat ES: hidung tersumbat, sekresi asam lambung meningkat, diare, bradikardia

Vasodilator arteri langsung

� Hidralazin, minoksidil

Mekanisme kerja:

� relaksasi langsung otot polos arteriolar tetapi tdkmenyebabkan vasodilatasi ke pembuluh darah vena.

� Penurunn tekanan perfusi yg kuat mengaktifkanrefleks baroreseptor menyebabkan aliran simpatetikmeningkat --� meningkatkan denyut jantung, curahjantung dan pelepasan renin ---�takifilaksis, efekhipotensi akan hilang dgn pemakaian seterusnya. Efek ini dpt diatasi dgn penggunaan beta blocker bersamaan.

Interaksi obat

Studi kasus

� L.N. is a 49-year-old white woman with a history of type 2 diabetes, obesity, hypertension, and migraine headaches. The patient was diagnosed with type 2 diabetes 9 years ago when she presented with mild polyuria and polydipsia. L.N. is 5′4″ and has always been on the large side, with her weight fluctuating between 165 and 185 lb.

� Initial treatment for her diabetes consisted of an oral sulfonylurea with the rapid addition of metformin. Her diabetes has been under fair control with a most recent hemoglobin A1c of 7.4%. Hypertension was diagnosed 5 years ago when blood pressure (BP) measured � Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in the office was noted to be consistently elevated in the range of 160/90 mmHg on three occasions. L.N. was initially treated with lisinopril, starting at 10 mg daily and increasing to 20 mg daily, yet her BP control has fluctuated.

� One year ago, microalbuminuria was detected on an annual urine screen, with 1,943 mg/dl of microalbumin identified on a spot urine sample. L.N. comes into the office today for her usual follow-up visit for diabetes. Physical examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78 bpm.

Pertanyaan

� Apa pengaruh mengontrol tekanan darah pada pasien DM

� Berapa target tekanan darah pd pasien DM

� Obat antihipertensi yg mana yg direkomendasikan utk pasien tsbutk pasien tsb

JELASKAN ISTILAH BERIKUT

� Pheochromocytoma

� Ortostatik hipotensi

� Chushing syndrome

� Atherosklerosis� Atherosklerosis

� Hirsutisme

� Morbiditas

� Mortalitas

� Infark miokard

� Stroke iskemia

� Intrinsic sympathomimetic activity