Budhi Setiawan Pharmacology Wijaya Kusuma University

Overview
Caution:
Hyponatremia and pulmonary congestion
ECF volume -> PULMONARY EDEMA

Contraindicated: ANURIA due to renal disease

Mannitol (IV)
Clinical Use:

They can complicate Congestive Heart Failure!

Prevent or tx Oliguric phase of Acute Renal Failure Prevent anuria from Hemolysis, Rhabdomiolysis Intracranial pressure in Cerebral Edema IOP Promote urinary excretion of toxic substances

Urea (IV)

Clinical Use:

Glycerin (Oral)

Intracranial pressure in Cerebral Edema IOP

Clinical Use: Glaucoma

Isosorbide (Oral)
Clinical Use:

Metabolized to glucose => HYPERglycemia

IOP and acute glaucoma attack after intraocular surgery

Overview
MOA (PCT)
Inhibits reabsorption of:
Na+, bicarb, water, and indirectly K+. Refer to notes for exact mechanism

Clinical Uses:
1. 2. 3. 4.

Glaucoma Urinary Alkalinization Tx for Metabolic Alkalosis High altitude sickness

Acetazolamide Methazolamide Dorzolamide (only used for Glaucoma) Brinzolamide (only used for Glaucoma)

Toxicity 1. Metabolic Acidosis 2. Renal Stones Ca Salt 3. Renal Potassium Wasting 4. Drowsiness and Paresthesia

Overview

MOA (ALH)

Inhibit the Na/K/Cl cotransport of the luminal membrane

Ascending limb of the LOOP of Henle.

Clinical Use:
1. 2. 3. 4. 5. 6.

Pulmonary edema Edema Cirrhosis Nephrotic Syndrome CHF Hypertension Hypercalcemia induced by Malignancy

 SE:
RISK of ARRHYTHMIAS
[electrolyte] : Na, K, Cl, Ca, and Mg

Ototoxicity
Inhibition of electrolyte transport in ENDOLYMPH

Hypokalemic Metabolic Alkalosis Allergic Reaction

 Rx Interactions
Aminoglycosides Digoxin - risk of arrhythmias NSAIDS
Inhibits PG-mediated in RBF => diuretic effects

Quinidine Potentially fatal Torsades de pointes

Hypokalemia => risk of arrhythmias

Furosemide (Lasix)
MOA:
Dilate Veins => Venous Capacitance

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

MOST Ototoxic!
But NOT a Sulfa

Clinical Use: PULMONARY EDEMA

Overview

MOA (DCT)

1. 2. 3. 4.

Clinical Use

Blocks Cl site of the Na/Cl cotransporter (LM) The kidneys ability to [urine] during hydropenia is NOT altered. Hypertension CHF Hepatic cirrhosis Nephrotic Syndrome assoc. edema

Chlorothiazide Hydrochlorothiazide Bendroflumethiazide Indapamide

Hydroflumethiazide Trichlormethiazide Methyclothiazide

Longest t1/2 = last up to 72 hours

Overview
SE: Like effects on electrolytes as loop diuretics
Not Ototoxic

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

Metolazone Chlorthalidone
Long t1/2 = 24-72 hrs

Na+ Channel Blockers (DCT & CD)

Aldosterone Receptor Agonist

Spironolactone
SE:

Triamterene Amiloride

Hyperkalemia (ACEI & ARB side effect)

Gynecomastia, impotence, hirsutism, menstrual, irregularities, libido

Agonist : ADH & Desmopressin Antagonist : Demeclocycline & Lithium cAMP causes the insertion of additional water channel into the luminal membrane Antagonists inhibit the action of ADH Agonist for diabetes insipidus tx Antagonists for SIADH tx

Agonist : Hyponatremia & Hypertension Demeclocycline : Bone & Teeth Abnormality Lithium : Nephrogenic Diabetes Insipidus

Drugs Used in Congestive Heart Failure Positive Inotropic Drugs Vasodilators Miscellaneous Drugs
Loop Diuretics ACE Inhibitors Beta Blockers Spironolactone Thiazide

Cardiac Glycosides

Beta Agonists

PDE Inhibitors

Nitroprusside Nitrates Hydralazine

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

Reduction in digoxin clearance : Quinidine, Amiodarone, Verapamil, etc Reduce Potassium Serum : Loop diuretics, Thiazides Induce toxicity Digitalis induced vomiting may deplete magnesium serum facilitate toxicity Digitalis Toxicity are arrhythmias, nausea, vomiting and diarrhea Toxicity TX Correction K+/Mg+ serum, Antiarrhythmia drugs, Digoxin Antibodies

DIURETICS
Furosemide Pulmonary Congestion & Edema Thiazides Mild Chronic Failure Spironolactone Long Term Benefit in Chronic CHF Reduce Mortality & Morbidity in CHF First Line Drugs in CHF ARBs probably have similar effect

ACE INHIBITORS

BETA 1 SELECTIVE ADRENOCEPTOR AGONIST

Dobutamine & Dopamine are useful for acute CHF They are not appropriate for chronic failure

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