1. FARMAKOTERAPI HIPERTENSI

2. Adalah kenaikan TD arteri yg tetap (JNC-7 = Joint National Committee)
HIPERTENSI :
Adalah kenaikan TD arteri yg tetap
(JNC-7 = Joint National Committee)

3. KLASIFIKASI TEK DARAH JNC-7
KLASIFIKASI SISTOL(mmHg) DIASTOL (mmHg)
Normal
<120
and
<80
Prehypertension
120–139 or
80–89
Stage 1 Hypertension
140–159 or
90–99
Stage 2 Hypertension
>160 or
>100

4. Bila TDD < 90 mmHg & TDS ≥ 140 mmHg = isolated systole HT
Bila TDD/TDS >
180/120 mmHg
Crisis Hypertenson

5. Definitions
HPT emergency(crisis): Is characterized by a severe elevation in BP, complicated by evidence of impending or progressive target/end organ dysfunction VS
HPT urgency: is a severe elevation in BP without progressive target organ dysfunction
NB – these definitions do not specify absolute BP levels

6. Goal BP The Truth is Treatment Goal
Keep B.P. < 140/90 mm Hg in each patient
This may be revised to 120/80 may be ? 110/70
MRFIT’s cut off values are 115/75 mm Hg
The Truth is
It is essential to keep the B.P at or below the goal
But, It also matters how the goal B.P. is achieved !

7. PATOFISIOLOGI HT A.Hipertensi esensial (HT primer)= HT
Idiopatik, yg blm jelas penyebabnya.Dipenga-
ruhi usia, kelamin, merokok, kholesterol, BB
B.Hipertensi sekunder. Dipengaruhi oleh obat,
penyakit ginjal, penyakit endokrin (DM, tiroid
, Cushing)

8. Hypertension
Hypertension means high blood pressure. High blood pressure is an increased pressure in your blood vessels, and therefore there is less space for your blood to travel through
It can be caused by many factors such as stress, high cholesterol, and inactivity. It is classified into mild, moderate, and severe hypertension. If you have mild, moderate, or severe hypertension, you have an increased risk of having a heart attack or a stroke.

9. Atherosclerosis – Time line
Content Points:
The pathological effects of atherosclerosis occur over decades. A subtle injury to the endothelium initiates the atherosclerotic process.3 Endothelial dysfunction underlies many stages in the progression of atherosclerosis from earliest onset to the lesions that result in coronary heart disease (CHD).4
Foam cells may infiltrate the vessel, progressing to a fatty streak. As the lesion progresses, small pools of extracellular lipid form within the smooth muscle layers, disrupting the intimal lining of the vessel. Progression to an advanced lesion, or atheroma, occurs when accumulated lipid, cells, and other plaque components disrupt the arterial wall.
Progression of atheroma involves accumulation of smooth muscle cells that elaborate extracellular matrix macromolecules. Once the plaque becomes fibrous, the danger of rupture increases. This type of advanced lesion can be found beginning in the fourth decade of life.
The clinically important complication of atheroma usually involve thrombosis. Arterial stenoses by themselves seldom cause acute unstable angina or acute myocardial infarction. Indeed, sizable atheroma may remain silent for decades or produce only stable symptoms, such as angina, precipitated by increased demand.
Thrombus formation usually occurs because of physical disruption of atherosclerotic plaque. The majority of coronary thromboses result from a rupture of the plaque’s protective fibrous cap, which permits contact between blood and the highly thrombogenic material located in the lesion’s lipid core.
The endothelium participates in the atherosclerotic process and remodeling through secretion of specific compounds.1 These will be discussed in later slides.

10. Endothelial NO Balance

11. Hypertension
Tingkat tekanan darah adalah fungsi dari cardiac output dikalikan dengan resistensi perifer (perlawanan dalam pembuluh darah ke aliran darah)
Dasar hemodinamik hipertensi
MAP = CO x TPR
MAP=mean arteria pressure; CO=cardiac output; TPR=total resistence perifer
The diameter of the blood vessel affects blood flow.
When the diameter is decreased, as in CHD, resistance and blood pressure increases.
Two classes of of hypertension.  In 90-95% of patients presenting with hypertension, the cause is unknown.  This condition is called primary (or essential) hypertension.  The remaining 5-10% of hypertensive patients have hypertension that results secondarily from renal disease, endocrine disorders, or other identifiable causes. This form of hypertension is called secondary hypertension.
Hemodynamic basis of hypertension.  Regardless of the origin of hypertension, the actual increase in arterial blood pressure is caused by either an increase in systemic vascular resistance (SVR) or an increase in cardiac output (CO). The former is determined by the vascular tone (i.e., state of constriction) of systemic resistance vessels, whereas the latter is determined by heart rate and stroke volume.  Therefore, in order to understand how arterial blood pressure can become elevated, it is necessary to understand the mechanisms that regulate both SVR and CO. 

13. Determinants of arterial pressure
Cardiac output
Stroke volume
Heart rate
Peripheral resistance
Vascular structure
Vascular function
1:22 PM

14. Regulation of arterial pressure (АP) by hemodynamic system
Formula: АP = CO · PR
CO – cardiac output
PR – peripheral vascular resistance (depended to arterioles tone)
CO leads to PR and АP normalizes finally
PR leads to CO and АP normalizes finally
AP normal range:
Systolic – (equilibration ) mm Hg
Diastolic – (equilibration ) mm Hg

16. FAKTOR RESIKO HT Faktor resiko mayor Hipertensi Merokok
Obesitas (BMI ≥30)
Immobilitas
Dislipidemia
Diabetes mellitus
Mikroalbuminuria atau perkiraan GFR<60 ml/min
Umur (>55 tahun untuk laki-laki, >65 tahun untuk perempuan)
Riwayat keluarga untuk penyakit kardiovaskular prematur (laki-laki < 55
tahun atau perempuan < 65 tahun)

17. Diseases Attributable to Hypertension
Stroke
Coronary heart disease
Heart failure
Cerebral hemorrhage
Myocardial infarction
Slide 5
Studies show that a multitude of diseases are attributable to hypertension.
They include:
• Heart failure
• Coronary heart disease
• Myocardial infarction
• Left ventricular hypertrophy and failure
• Aortic aneurysm
• Peripheral vascular disease
• Retinopathy
• Hypertensive encephalopathy
• Chronic kidney failure
• Cerebral hemorrhage
• Stroke
With so many diseases linked to hypertension, prompt and effective treatments have the potential to reduce many complications.
Dustan HP, et al. Arch Intern Med 1996; 156:
Left ventricular hypertrophy
Hypertension
Chronic kidney failure
Aortic aneurysm
Hypertensive encephalopathy
Retinopathy
All
Vascular
Peripheral vascular disease
Adapted from: Arch Intern Med 1996; 156:

18. Target Organ Damage (TOD)
Heart
Left ventricular hypertrophy (LVH)
Angina or prior myocardial infarction (CHD)
Prior Coronary revascularization PTCA or CABG
Heart failure (Systolic / Diastolic dysfunction)
Brain
CVA Stroke or Transient Ischemic Attack (TIA)
Kidney : Chronic kidney disease and CRF
Vessels : Peripheral arterial disease PVD
Eyes : Hypertensive Retinopathy

20. Role of the vasopressin in arterial hypertension pathogenesis

22. Prevalence of Hypertension by Age
18-29
30-39
40-49
50-59
60-69
70-79
80+
% Hypertensive 4 11 21 44 54 64 65
Can you see that age is a risk factor?

23. Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure 50%
MANFAAT MENURUNKAN TD
Stroke incidence 35–40%
Myocardial infarction 20–25%
Heart failure 50%

24. Tanda-Tanda Klinik HT 1. Pusing paroksismal 2. Berkeringat 3
Tanda-Tanda Klinik HT 1.Pusing paroksismal 2.Berkeringat 3.Takikardia 4.Palpitasi

25. Organ yg terkena HT : Heart Brain Stroke or transient ischemic attack
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

26. Untreated hypertension can result in:
Arteriosclerosis --Kidney damage
Heart Attack --Stroke
Enlarged heart --Blindness

27. Normal weight 350 to 450 g

28. Transverse Section of HEART - LVH
10 mm
25 mm
In cross section,  this view of the heart shows the left ventricle in the center left of the picture. The heart is from a severe hypertensive.  The left ventricle is grossly thickened.  The myocardial fibers have undergone hypertrophy

29. Target Organ Damage
What is single most imp. predictor of CHD, HF, Death ? What time course of HT to LVH to LVF to death ? Can LVH be regressed at all ? Will drugs help to regress LVH and ↓TOD ? How important is Micro-albuminuria ?

30. Progression of HT to LVH to HF
Progression of hypertension to LVH and heart failure
Content Points:
The two principal factors contributing to heart failure are hypertension and coronary artery disease, but hypertension is the more common. Hypertension is very frequently the initial step in pathophysiologic progression to heart failure, which is a complex syndrome that involves a variety of linked hemodynamic and metabolic changes.65
LVH and associated left ventricular dysfunction are among the most common cardiac sequelae of hypertension.
LVH leads to heart failure through various mechanisms. Initially, mild LVH allows the heart to compensate for increases in vascular resistance. Ultimately, the increase in left ventricular wall thickness and left ventricular remodeling lead to diastolic dysfunction and subsequently to systolic dysfunction.
In addition to pressure-related mechanical strain, pathologic changes that are a direct result of stimulation of the renin-angiotensin system also contribute to LVH.
Clinically overt heart failure develops when the hypertrophied left ventricle can no longer maintain its output and begins the downward spiral of ventricular dilatation and symptomatic disease.
The structural and functional changes associated with hypertension and the development of LVH and heart failure occur over decades and are preventable with effective antihypertensive treatment.

31. NON – FARMAKOLOGI FARMAKOLOGI
TERAPI :
NON – FARMAKOLOGI
FARMAKOLOGI

32. 3.Achieve SBP goal especially in persons >50 years of age.
TUJUAN TERAPI HT :
1.Reduce CVD and renal morbidity and mortality.
2.Treat to BP <140/90 mmHg (Umum) or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.
3.Achieve SBP goal especially in persons >50 years of age.

33. Tx NON-FARMAKOLOGI PENCEGAHAN & TERAPI 1.Bagi yg obese, turunkan BB
2.Diet garam (≤ 2.4g/hr)
3.Kurangi konsumsi lemak
4.Tidak merokok, kurangi kopi & alkohol
5.Istirahat cukup
6.Olahraga teratur.

35. A.ACE-1 / ACE-2 (ARB) / ALFA1-BLOCKER
Tx FARMAKOLOGI
A B C D
A.ACE-1 / ACE-2 (ARB) / ALFA1-BLOCKER
B.BETA-BLOCKERS
C.CA-ANTAGONISTS
D.DIURETICS

36. Anti Hypertensive drug classes
ACEi – Angiotensin converting enzyme
inhibitors – Enalapril- let us call them ‘A’
ARB – Angiotensin Receptor Blockers –
Losartan - Let us call them also as ‘A’
BB – Beta Receptor Blockers – Metoprolol,
Carveidilol, Atenelol - let us call them ‘B’
CCB – Calcium channel blockers – Amlodepine
Verapamil, Diltiazem - let us call them ‘C’
Diuretics – Hydrochlor Thiaz.- Furosemide,
Spiranolactone - let us call them ‘ D ’

40. Target Organ Damage - Assessment
Routine Tests
Electrocardiogram, Echocardiography (desirable)
Urinalysis for proteinuria, Microalbuminuria
Blood glucose (F and PP), and Hematocrit
Serum Na and K, Creatinine or GFR, Calcium
Lipid Profile complete, Eye examination, ABI
Optional tests
X-Ray Chest PA
24 hr. urine albumin excretion or ACR
More extensive testing is not generally indicated

41. Terapi Kombinasi Rasional kombinasi obat antihipertensi:
Ada 6 alasan mengapa pengobatan kombinasi pada hipertensi dianjurkan:
1. Mempunyai efek aditif
2. Mempunyai efek sinergisme
3. Mempunyai sifat saling mengisi
4. Penurunan efek samping masing-masing obat
5. Mempunyai cara kerja yang saling mengisi
pada organ target tertentu
6. Adanya “fixed dose combination” akan
meningkatkan kepatuhan pasien (adherence)

42. Hypertension – Why Combinations ?
If goal BP is not achieved by a single drug in full dose
Then adding another agent will help achieve the goal BP
Two agents sometimes nullify each others side effects
Fixed dose combinations will reduce the no. of tablets
Once daily formulations are good for compliance
Sustained release or LA formulations for 24 h BP control
If three drugs can’t achieve goal BP – Resistant HT

43. ANTIHIPERTENSI DI PUSKESMAS
1.Propanolol / Bisoprolol
2.Nifedipin / Adalat OROS /
Amlodipin
3.Captopril / Lisinopril
4.HCT / Spironolakton
5.Reserpin

44. Fixed-dose combination yang paling efektif adalah sebagai berikut:
1. Penghambat enzim konversi angiotensin (ACEI)
dengan diuretik
2. Penyekat reseptor angiotensin II (ARB) dengan
diuretik
3. Penyekat beta dengan diuretik
4. Diuretik dengan agen penahan kalium
5. Penghambat enzim konversi angiotensin (ACEI)
dengan antagonis kalsium
6. Agonis α-2 dengan diuretik
7. Penyekat α-1 dengan diuretic

46. Lifestyle Modifications
ALGORITMA Tx HT
Lifestyle Modifications
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension (SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.
Without Compelling Indications
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.
With Compelling Indications
Not at Goal Blood Pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

48. 2000’s (cont) JNC 7 (cont) Diuretics first
Addition of a second drug from a different class
> 2 drugs (combo good)
>160/100-start with 2 drugs (diuretic/BB, diuretic/ACEI, diuretic/ARB, diuretic/CCB)
Multiple drugs if CAD, DM, Renal disease
Monotherapy response rate 40-50%
Multiple meds response rate 75-80%
Racial differences in response disappear with multiple drugs

49. Logical Combinations Diuretic b-blocker CCB ACE inhibitor a-blocker -
         -
  ü
  ü*
* Verapamil + beta-blocker = absolute contra-indication    
Kieran McGlade Nov 2001
Department of General Practice QUB

50. INDICATIONS CONTRAINDICATIONS
Compelling and possible indications and contrindications for the major classes of antihypertensive drugs
                               
INDICATIONS               CONTRAINDICATIONS
CLASSS OF DRUG
COMPELLING
POSSIBLE
a-blockers
Prostatism
Dyslipidaemia
Postural Hypotension
Unrinary incontinence
Angiotensin converting enzyme (ACE) inhibitors
Heart failure Left ventricular dysfunction
Chronic renal disease * Type II diabetic nephropathy
Renal impairment * Peripheral vascular disease †
Pregnancy Renovascular disease
Angiotensin II receptor antagonists
Cough induced by ACE inhibitor ‡ 
Heart failure Intolerance of other antihypertensive drugs
Peripheral vascular disease
b-blockers
Myocardial infarction Angina
Heart failure  
Heart failure Dyslipidaemia Peripheral vascular disease
Asthma or COPD Heart block
Calcium antagonists (dihydropyridine)
Isolated systolic hypertension (ISH) in elderly patients
Angina Elderly patients
  _
   _
Calcium antagonists (rate limiting)
Angina
Myocardial infarction
Combination with b-blockade
Heart block Heart failure
Thiazides
Elderly patients including ISH
Gout
*  ACE inhibitors may be beneficial in chronic renal failure but should be used with caution. Close supervision and specialist  advice are needed when there is established and significant renal impairment †   Caution with ACE inhibitors and angiotensin II receptor antagonists in peripheral vascular disease because of association with renovascular disease.
‡   If ACE inhibitor indicated f  b-blockers may worsen heart failure, but in specialist hands may be used to treat heart failure  British Hypertension Society Guidelines 2000
Kieran McGlade Nov 2001
Department of General Practice QUB

51. KLASIFIKASI & MANAGEMEN HT PADA DEWASA
BP classification
SBP* mmHg
DBP* mmHg
Lifestyle modification
Initial drug therapy
Without compelling indication
With compelling indications
Normal
<120
and <80
Encourage
Prehypertension
120–139
or 80–89
Yes
No antihypertensive drug indicated.
Drug(s) for compelling indications. ‡
Stage 1 Hypertension
140–159
or 90–99
Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.
Drug(s) for the compelling indications.‡
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.
Stage 2 Hypertension
>160
or >100
Two-drug combination for most† (usually thiazide-type diuretic and ACEI or ARB or BB or CCB).

53. OBAT-OBAT LAIN YG SERING DIGUNAKAN
UTK Px HT ANTIPLATELET LIPID LOWERING OBAT DIABETES NEUROPROTEKTAN ANTIARITMIA DLL-NYA

54. HATI-HATI MENGGUNAKAN :
Presription Drugs:
NSAIDs, including Coxibs
Corticosteroids and anabolic steroids
Oral contraceptive and sex hormones
Vasoconstricting/sympathomimetic decongestants
(ephedrin, PPA, Pseudoefedrin)
Calcineurin inhibitors (cyclosporin, tacrolimus)
Erythropoietin and analogues
Monoamine oxidase inhibitors (MAOIs)
Other:
Licorice root
Stimulants including cocaine, amfetamin (Ecstasy, Sabu2)
Garam
Excessive alcohol use

55. CONTOH KASUS RESEP Dr.Jantung Dr.Jantung R/.Tanapres 10 mg XXX
R/.Bisoprolol 5 mg XXX
S.0-0-1
R/.Letonal 25 mg XXX
R/.Analsik XV
S.3dd 1
Pro : Tn. LK
Dr.Jantung
R/.Cedocard 5 mg 90
S. 3 dd 1
R/.Concor 2.5 mg 30 S
R/.Rhinofed XV S
R/.OBH Combi 1 fl
S. 3 dd C
R/.Xanax 0.5 mg 30
S.0-0-1
Pro : Ny.Zakky

56. TERIMA KASIH