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PENDAHULUAN
KLASIFIKASI
JNC 7 Report 2003
ETIOLOGI
Primer:
Belum diketahui
(mis:genetik)
Sekunder :
Renal
Adrenal
Faktor Biologi lain
Eksogen
Mean BP = Output
Total Systemic
Vascular Resistance
Increased
Vasoconstriction
Adrenergic Stimuli
Angiotensin II
Endothelin
Endothelium-derived
Contracting Factors
Thromboxane
*Endothelium-derived
Hyperpolarizing Factors
Textor SC. Atlas of Diseases of the Kidney, 2001.
Decreased
Vasodilation
Prostacyclin
Nitric oxide
EDHF*
Penyakit Arteri
Patogenesis
Patogenesis Komplikasi
Komplikasi Hipertensi
Hipertensi pada
pada Ginjal
Ginjal
Hipertensi kronis
Merusak autoregulasi ginjal
Permeabilitas kapiler
Proteinuri (mikroalbuminuri)
Hukum Homeostasis
Reabsorbsi protein
oleh sel tubulus berlebihan
(stressor)
Ekspresi sitokin :
Robbin, 2005
Hypertension
Hypertension Complication
Complication Pathogenesis
Pathogenesis
Chronic hypertension
Endothelial Stressor
Expression
TNF
Apoptosis
Necrosis
IL1
IL6
TGF1
Plaque
HCRP
Fibrosis
Atherosclerosis
Robbin, 2008
Renal
Failure
Coronary
Heart Disease
Cerebral
- Stroke
- Dementia
- Parkinson
Appetite
KAKHEKTIN
Hypotalamus
CHACECTIC (THIN)
PG2
FEVER
+ ILI
Aspirin
(Endogenic Pyrogen)
Serum Amyloid
Hepatosit
Fibrinogen
Syntase
ILI
IL6
CRP
Vasopressor receptors
Proteolitic
TNF
Chachexia
Fat Cells
Endhotel
Tissue Factor
Contraction
Vascular smooth muscle cells
Heart
Vasodilatation
Shock
Strong Activation
Trombo Modulin
Shringking
Permeability
Coagulation
Exudation
Inflammation cells
Congestion
Protealitic
Membrane Receptor Disruption
(Brata Widjaya, 2009; Bambang P, 2010)
Anemia
Homosistein
PDGF
Diabetes
Natrium
oxLDL
ENZIM NADPH OKSIDASE
Stres Oksidatif
Anti Oksidan
Bradikinin
Disfungsi Endothel
Aterosklerosis
(Bambang P; Prevent Vascular Damage 2013)
10 20 x Morbiditas / Mortalitas
Age
Family History
Gender Diabetes
Hypertensio
Dyslipidemia
Anemia
PTH
PO4
GFR
ADMA
LVH
CHF
Smoking
Inflamation
Non-modifiable
ET
CRP
ROS
Uremia-related
- AGEP
- AOPP
- Homosistein
PVD
CAD
MI
(Bambang P; Prevent Vascular Damage 2013)
NO Synthase
NO + Citrulline
L-Arginine
Oxidative
stress
ADMA
Asymetric Dimethyl
Arginine
Citrulline
DDAH
Dimethylamino
hydrolase
Renal excretion
JASN 15:S77, 2007
PGK
ROS
Agep
AOPP
Homosistein
Makrofag
Merusak
Gliko Protein & Nephrin
APOPTOSIS
ENDOTEL
Merusak IKB
NFKB
Albuminuri
ATEROSKLEROSIS
STROKE
KORONER
PGK
(Bambang P, 2012)
Angiotensin II
Endotelin
Vasokonstriksi
Iskemi
Defisiensi Aerob Metabolik
Gangguan pompa Na
Retensi Na
Retensi Air Intra Sel
Udem Intra Sel
Sel pecah / Onkosis
Robbin, 2007
Glomerulus
1
Pressure in the
afferent arteriole
Distal tubule
Na+ at the macula densa
Distal tubule
Renin Angiotensin
System (1)
Classical "circulating" system (RAS):
Angiotensin II
Aldosterone
ACE
Angiotensin I
Na+-retention
K+-loss
Renin
Angiotensinogen
Adapt. from Dominiak & Unger (eds.) in Ang IIAT1-Receptor Antagonists, Steinkopff (1997)
Renin
macula
densa
Blood
pressure
Na+
Sympathetic
system
Renin Angiotensin
System (2)
Local "tissue-bound" system (RAS):
Angiotensinogen
Renin
inactive fragments
Angiotensin I
ACE
Bradykinin
B1
B2
t-PA
Cathepsin G
Tonin
Chymases
Cathepsin G
CAGE
Angiotensin II
AT1
AT2
Renin Angiotensin
System (3)
Distribution of ACE:
10%
RAS
90%
Circulating (Plasma)
Local (Tissue)
PROTECTION
Long-term effects
cardiovascular/
renal homeostasis
Mod. from Dzau V, Arch Intern Med 153 (1993)
Pengelolaan Hipertensi
1.
2.
3.
Farmakologi
Target Terapi
KONDISI
TEKANAN
DARAH
Hipertensi Sistolik/Diastolik
140/90
Diabetes
130/90
CKD
130/90
125/75
Diuretik
Short acting
Furosemid (lasix)2
chlorothiazide(Diuril)3
Intermediate
Hidroclrotiazide(Apo-Hydro, AquazideH,Dichlotride, Hydrodiuril, HydroSaluric, Hydrochlorot, Microzide,
Esidrex, and Oretic)4
Long Acting
Chlorthalidone(Hygroton, Tenoretic)3
Hidroflumetazid (Saluron)4
Bendrofluazide(aprinox)4
Clopamide (aquex)4
Polythiazide(Renese)4
Spironolacton (Aldactone, Novo-Spiroton, Aldactazide, Spiractin, Spirotone, Verospiron or Berlactone) 5
Acetazolamide (Diamox)6
b. Non Selektif
- Asebutolol
- Propanolol
- ISA:
- Metoprolol
- Timolol
- Pindolol
- Atenolol
- Nadolol
- Oksprenolol
- Bisoprolol
- Sotalol
- Alprenolol
- Pindolol
- Oksprenolol
- Alprenolol
- Labetalol*
- Sotalol
- Oksprenolol
- Nadolol
- Labetalol*
- Atenolol
- Metoprolol
b. Lipofilik
- Labetalol**
- Non ISA:
- Metoprolol
- Asebutolol
- Timolol
- Propanolol
- Bisoprolol
- Alprenolol
- Asebutolol
- Pindolol
- Atenolol
- Bisoprolol
- Propanolol
- Timolol
- Nadolol
- Sotalol
Caantagonis1
1. Long Acting:
Amlodipin(Norvasc)
Felodipin(Plendil)
Short Acting:
Dehidropiridin:
Nifedipin (Adalat)
Non Dehidroperidin
Diltiazem(Cardizem)
Verapamil(Calan, Isoptin)
KESIMPULAN
1. Pencegahan hipertensi harus sedini mungkin (pre-hipertensi)
2. Pengelolaan hipertensi harus diwaspadai faktor resiko yg lain
3.
4.
a.
b.
c.
5.
6.
(sindrom metabolik)
Program non-drug treatment wajib dijalankan penderita
Patogenesis hipertensi harus dipelajari dengan baik dalam rangka :
Memilih obat yang tepat
Memilih kombinasi obat
Meminimalkan efek samping
Target penurunan tensi sedapat mungkin mendekati ideal (harus
bertahap)
Pengelolaan krisis hipertensi harus memilih obat yg tepat, target
penurunan tensi sesuai protokol (supaya reversibel)
Terima kasih