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DIURETIK
VOLUME URINE
ANTI DIURETIK
Classes of Diuretics:
Definitions
Diuretic: substance that promotes the excretion of urine Natriuretic: substance that promotes the renal excretion of sodium
DIURETIK OSMOTIK
TIAZID
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Mechanism:
Drastic reductions in GFR cause dramatically increased proximal tubular water reabsorption and a large drop in urinary excretion Osmotic diuretics are still filtered under these conditions and retain an equivalent amount of water, maintaining urine flow
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Prototype: Acetazolamide
Penghambat karbonik anhidrase CA Inhibitor
Developed from sulfanilamide, after it was noticed that sulfanilamide caused metabolic acidosis and alkaline urine.
Therapeutic Uses
Urinary alkalinization Metabolic alkalosis Glaucoma:
acetazolamide, dorzalamide
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CA Inhibitor Toxicity
Hyperchloremic metabolic acidosis Nephrolithiasis: renal stones Potassium wasting
Sleepy Parastesia Hypersensitivity Contraindicated : hepatic cirrhosis
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Pharmacokinetics
Rapid oral absorption, bioavailability ranges from 65-100% Rapid onset of action extensively bound to plasma proteins secreted by proximal tubule organic acid transporters Blah Blah Blah
Loss of TAL electrostatic driving force: increased excretion of Ca2+, Mg2+ and NH4+ Increased electrostatic driving force in CCD: increased K+ and H+ excretion
Therapeutic Uses
Edema of cardiac, hepatic or renal origin Acute pulmonary edema (parenteral route) Chronic renal failure or nephrosis Hypertension Symptomatic hypercalcemia
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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
Thiazides freely filtered and secreted in proximal tubule Bind to the electroneutral NaCl cotransporter Thiazides impair Na+ and Cl- reabsorption in the early distal tubule: low ceiling
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Pharmacokinetics
Oral administration - absorption poor
Exception Chlorothiazide, Chlorthalidone
Reduced ECF volume (contraction) Reduce blood pressure (lower CO) Reduced GFR
Therapeutic Uses
Edema due to CHF (mild to moderate) Essential hypertension Diabetes insipidus (nephrogenic) Hypercalciuria
Diabetes Insipidus
Thiazides: paradoxical reduction in urine volume Mechanism: volume depletion causes decreased GFR Treatment of Li+ toxicity:
Thiazides useful Li+ reabsorption increased by thiazides. Reduce Li dosage by 50%
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Thiazide Toxicity
Hypokalemia due to:
Increased availability of Na+ for exchange at collecting duct Volume contraction induced aldosterone release
Hyperuricemia
Direct competition of thiazides for urate transport Enhanced proximal tubular reabsorption efficiency
Hyperglycemia
Diminished insulin secretion Related to the fall in serum K+
Diuretik Hemat Kalium potassium-sparing diuretics Diuretik Hemat Kalium potassium-sparing diuretics
Absorpsi melalui oral Metabolisme melalui hati ( triamteren) Mekanisme kerja: - me absorpsi Na+ di tubulus & duktus kolektifus. - melalui reseptor spironolakton - tanpa melalui reseptor triamteren & amiloride
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Spironolactone
Mechanism of action: aldosterone antagonist Aldosterone receptor function Spironolactone prevents conversion of the receptor to active form, thereby preventing the action of aldosterone
Pharmacokinetics
70% absorption in GI tract Extensive first pass effect in liver and enterohepatic circulation Extensively bound to plasma proteins 100% metabolites in urine Active metabolite: canrenone (active) Canrenoate (converted to canrenone)
Therapeutic Uses
Prevent K loss caused by other diuretics in:
Hypertension Refractory edema Heart failure
Administration
Dose orally administered (100 mg/day) Spironolactone/thiazide prep (aldactazide, 25 or 50 mg of each drug in equal ratio)
Primary aldosteronism
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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
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
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
Toksisitas
Hiperkalemia Asidosis metabolik hiperkloremia Ginekomastia Gagal ginjal akut Batu ginjal
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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) Mekanisme kerja Natriuretik Na deplesi reabsorbsi Na >> di tubulus proksimal.
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Function of ADH
ADH increases the permeability of the renal distal tubule and collecting ducts to water. Less free water is excreted in urine Urine volume is decreased Concentration of urine is increased
Diabetes Insipidus
DI is a clinical condition due to a deficit of ADH or due to the kidneys resistance to the effects of ADH. DI may be central (neurogenic) or nephrogenic. DI may be a transient or a permanent condition.
Clinical Management of DI
Goal is to prevent circulatory failure and hyperosmolar encephalopathy. Replace volume deficit and ongoing losses Replace ADH Close monitoring of serum and urine lytes/osmolality
Vasopressin
Available IV, subcutaneous, and intranasal forms DDAVP given intranasally Pitressin IV Therapeutic effect: increase in specific gravity and decrease in urine output within 1 hour of dose.
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