Kuliah Diuretik UWK

7/27/2019 Kuliah Diuretik UWK

1/23

Budhi Setiawan

Pharmacology

Wijaya Kusuma University


2/23


3/23

Overview Caution:

Hyponatremia and pulmonary congestion ECF volume -> PULMONARY EDEMA

Contraindicated: ANURIAdue to renal disease They can complicateCongestive Heart Failure!

Mannitol (IV) Clinical Use:

Prevent or tx Oliguric phase ofAcute Renal Failure Prevent anuria from Hemolysis, Rhabdomiolysis Intracranial pressure inCerebral Edema IOP Promote urinary excretion oftoxic substances


4/23

Urea (IV) Clinical Use:

Intracranial pressure inCerebral Edema IOP

Glycerin (Oral) Clinical Use: Glaucoma

Metabolized to glucose => HYPERglycemia Isosorbide (Oral)

Clinical Use: IOP and acute glaucoma attack after intraocular surgery


5/23

Overview MOA (PCT)

Inhibits reabsorption of:

Na+, bicarb, water, and indirectly K+. Refer to notes for exact mechanism

Clinical Uses:

1. Glaucoma

2. Urinary Alkalinization

3. Tx for MetabolicAlkalosis4. High altitude sickness


6/23

Acetazolamide Methazolamide Dorzolamide (only used for Glaucoma)

Brinzolamide (only used for Glaucoma)

Toxicity

1. Metabolic Acidosis

2.

Renal Stones Ca Salt3. Renal Potassium Wasting

4. Drowsiness and Paresthesia


7/23

Overview MOA (ALH)

Inhibit the Na/K/Cl cotransport of the luminalmembrane

Ascending limb of the LOOP of Henle. Clinical Use:

1. Pulmonary edema2. EdemaCirrhosis3. Nephrotic Syndrome4. CHF5. Hypertension6. Hypercalcemia induced by Malignancy


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SE: RISK of ARRHYTHMIAS

[electrolyte] : Na, K, Cl, Ca, and Mg Ototoxicity

Inhibition of electrolyte transport in ENDOLYMPH Hypokalemic Metabolic Alkalosis Allergic Reaction


9/23

Rx Interactions Aminoglycosides Digoxin - risk ofarrhythmias NSAIDS

InhibitsPG-mediated in RBF=> diuretic effects Quinidine Potentially fatal Torsades de pointes

Hypokalemia => risk of arrhythmias


10/23

Furosemide (Lasix) MOA:

Dilate Veins => Venous Capacitance Clinical Use:PULMONARY EDEMA

Torsemide Bumetanide (diuretic action 4-6 hrs) Ethacrynic Acid

MOST Ototoxic!But NOT aSulfa


11/23

Overview MOA(DCT)

Blocks Cl site of the Na/Clcotransporter (LM) The kidneys ability to [urine] during hydropenia isNOT altered.

Clinical Use1. Hypertension2. CHF3. Hepatic cirrhosis4. Nephrotic Syndrome assoc. edema


12/23

Chlorothiazide Hydrochlorothiazide Bendroflumethiazide Indapamide

Longest t1/2 = last up to 72 hours

Hydroflumethiazide Trichlormethiazide Methyclothiazide


13/23

Overview SE: Like effects on electrolytes as loop diuretics

NotOtotoxic Caution:

Quinidine Potentially fatal Torsades de pointes Gout= plasma [uric acid]

Metolazone Chlorthalidone

Long t1/2 = 24-72 hrs


14/23

Na+ Channel Blockers (DCT & CD) Triamterene Amiloride

Aldosterone Receptor Agonist Spironolactone

SE:

Hyperkalemia(ACEI & ARB side effect) Gynecomastia, impotence, hirsutism, menstrual,

irregularities, libido


15/23

Agonist : ADH & Desmopressin Antagonist : Demeclocycline & Lithium

cAMP causes the insertion of additional waterchannel into the luminal membrane

Antagonists inhibit the action of ADH

Agonist for diabetes insipidus tx

Antagonists for SIADH tx


16/23

Agonist : Hyponatremia & Hypertension Demeclocycline : Bone & Teeth Abnormality

Lithium : Nephrogenic Diabetes Insipidus


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19/23

Drugs Used in Congestive Heart Failure

Positive Inotropic Vasodilators Miscellaneous

Drugs Drugs

Cardiac

Glycosides

PDE

Inhibitors

Beta

Agonists

Nitroprusside

NitratesHydralazine

Loop Diuretics

ACE Inhibitors

Beta Blockers

SpironolactoneThiazide


20/23

Digoxin, Digitoxin, Ouabain Inhibition Na+/K+ ATPase

Alters Na+/Ca2+ exchanger

Increase intracellular Ca2+

is stored SR Increase contractile force

Clinical use Congestive Heart Failure

It doesnt prolong life

Dosing regiment must be careful and monitored

Atrial fibrillation


21/23

Reduction in digoxin clearance : Quinidine,Amiodarone, Verapamil, etc

Reduce Potassium Serum : Loop diuretics,Thiazides Induce toxicity

Digitalis induced vomiting may depletemagnesium serum facilitate toxicity

Digitalis Toxicity are arrhythmias, nausea,

vomiting and diarrhea Toxicity TX Correction K+/Mg+ serum,

Antiarrhythmia drugs, Digoxin Antibodies


22/23

DIURETICS Furosemide Pulmonary Congestion & Edema

Thiazides Mild Chronic Failure

Spironolactone Long Term Benefit in Chronic CHF

ACE INHIBITORS Reduce Mortality & Morbidity in CHF

First Line Drugs in CHF

ARBs probably have similar effect

BETA 1 SELECTIVE ADRENOCEPTOR AGONIST Dobutamine & Dopamine are useful for acute CHF

They are not appropriate for chronic failure


23/23

Beta Adrenoceptor Antagonists They have been shown in long term studies to reduce

progression chronic CHF

They are not value in acute CHF

Phosphodiesterase Inhibitors Amrinone & Milrinone increase cAMP by inhibiting its

breakdown Ca2+ intracellular increase

They also cause vasodilatation

They should not be used in chronic CHF

Vasodilators Nitroprusside & Nitroglycerin is often used for acute CHF

Hydralazine & Isosorbide dinitrate for chronic CHF

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Kuliah Diuretik UWK