11/16/2010 1 Diuretik & Anti-Diuretik Dept. Farmakologi dan Terapeutik, Fakultas Kedokteran Universitas Sumatera Utara VOLUME URINE DIURETIK ANTI DIURETIK Classes of Diuretics: Definitions Diuretic: • substance that promotes the excretion of urine Natriuretic: • substance that promotes the renal excretion of sodium DIURETIK DIURETIK DIURETIK OSMOTIK PENGHAMBAT KARBONIK ANHIDRASE DIURETIK KUAT TIAZID DIURETIK HEMAT KALIUM
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Drug Interactions• Displacement of plasma protein binding of
clofibrate and warfarin
• Li+ clearance is decreased
• Loop diuretics increase renal toxicity of cephalosporin antibiotics
• Additive toxicity w/ other ototoxic drugs
• Inhibitors of organic acid transport (probenecid, NSAID's) shift the dose-response curve of loop diuretics to the right
thiazide and thiazide-like diuretics
Mechanism of Action
• Thiazides freely filtered and secreted in proximal tubule• Bind to the electroneutral NaCl cotransporter• Thiazides impair Na+ and Cl- reabsorption in the early
(aldactazide, 25 or 50 mg of each drug in equal ratio)
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Toxicity• Hyperkalemia - avoid excessive K
supplementation when patient is on spironolactone
• Androgen like effects due to it steroid structure
• Gynecomastia• GI disturbances
Triamterene and Amiloride
• Non-steroid in structure, not aldosterone antagonists
Mechanism of Action• Blockade of apical Na+
channel in the principal cells of the CCD
• Amiloride: blocks the Na/H exchanger (higher concentrations)
• Blockade of the electrogenic entry of sodium causes a drop in apical membrane potential (less negative), which is the driving force for K+ secretion
Pharmacokinetics• Triamterine
– 50% absorption of oral dose– 60% bound to plasma proteins– Extensive hepatic metabolism with active
metabolites– Secreted by proximal tubule via organic cation
transporters
• Amiloride– 50% absorption of oral dose– not bound to plasma proteins– not metabolized, excreted in urine unchanged– Secreted by proximal tubular cation transporters
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Therapeutic uses
• Eliminate K wasting effects of other diuretics in:– Edema
– Hypertension
Toxicity
• Hyperkalemia. Avoid K+ supplementation
• Drug interaction - do not use in combination with spironolactone since the potassium sparing effect is greater than additive
• Caution with ACE inhibitors
• Reversible azotemia (triamterine)
• Triamterene nephrolithiasis. 1 in 1500 patients
summary
• Indikasi• Keadaan mineralo kortikoid >> akibat
– hipersekresi primer : sindrom Cohn, produk ACTH ektopik
– aldosteronisme sekunder , misalnya:• gagal jantung kongestif
• sirosis hepatis
• sindroma nefrotik
• Toksisitas– Hiperkalemia
– Asidosis metabolik hiperkloremia
– Ginekomastia
– Gagal ginjal akut
– Batu ginjal
Antagonis ADH
� Absorpsi melalui oral
� Metabolisme: hati
� Eliminasi: melalui sekresi tubulus ginjal
� Mekanisme kerja :
menghambat efek ADH pd tub.kolektivus
Indikasi
* SIADH (sindrome of Inappropriate ADH secretion)
* Penyebab lain yang menyebabkan pe↑ ADH
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Toksisitas
* Diabetes insipidus nefrogenik
* Gagal ginjal :
- gagal ginjal akut
- nepritis intertitial kronis
* Lain :- gemetar
- penurunan mental
- kardiotoksik
- ggn.fungsi tiroid
- leukositosis
Anti diuretik
1. ADH
- vasopresin (alamiah)
- desmopresin (sintesis)
* Absorpsi peroral : tidak efektif karena segera mengalami
inaktifasi oleh tripsin.
* Mekanisme kerja pengaturan sekresi ADH diatur oleh
konsep :
1. Osmoreseptor
dehidrasi � osmolalitas plasma >> �
sekresi ADH >>
2. Reseptor volume
volume darah yang beredar ↓� perangsangan sekresi ADH ↑ .
3. Stres emosional atau fisik
4. Obat : - nikotin
- klofibrat
- siklofodfamid
- antidepresan trisiklik
- karbamezepin
- diuretik
2.Benzotiadiazid
� untuk yang resisten terhadap ADH (diabetes insipidus nefrogen)