Therapeutic 3\5\2011 Diuretics
Diuretics are Drugs that accelerate the rate of urine formation.Result:in removal of sodium and water.
Sodium :
• Where sodium goes, water follows.
• 20 to 25% of all sodium is reabsorbed
into the bloodstream in the loop of Henle,
5 to 10% in the distal tubules, and 3%
in collecting ducts.
• If it is not absorbed, it is excreted with
the urine.
Diuretic Agents include :
Carbonic anhydrase inhibitors(CAIs),Loop diuretics,Osmotic diuretics Potassium-sparing diuretics ,Thiazide and thiazide-like diuretics
(CAIs):
acetazolamide (Diamox) ,methazolamide & dichlorphenamide
Carbonic Anhydrase Inhibitors: Mechanism of Action :
• The enzyme carbonic anhydrase helps to make H+ ions available for exchange with sodium and water in the proximal tubules.
• CAIs block the action of carbonic anhydrase, thus preventing the exchange of H+ ions with sodium and water.
• Inhibition of carbonic anhydrase reduces H+ ion concentration in renal tubules.
• As a result, there is increased excretion of bicarbonate, sodium, water, and potassium.
• Resorption of water is decreased and urine volume is increased.
Carbonic Anhydrase Inhibitors: Therapeutic Uses :
• Adjunct agents in the long-term management of open-angle glaucoma
• Used with miotics to lower intraocular pressure before ocular surgery in certain cases
• Also useful in the treatment of: Glaucoma ,Edema ,Epilepsy &High-altitude sickness
• Acetazolamide is used in the management of edema secondary to CHF when other diuretics are not effective.
• CAIs are less potent diuretics than loop diuretics or thiazides—the metabolic acidosis they induce reduces their diuretic effect in 2 to 4 days.
What are the side effect of CAIs ?:Metabolic acidosis. Drowsiness.Anorexia Paresthesias .Hematuria.Urticaria .Photosensitivity&Melena .
Loop Diuretics :
• bumetanide (Bumex)
• ethacrynic acid (Edecrin)
• furosemide (Lasix)
Loop Diuretics: Mechanism of Action include :Act directly on the ascending limb of the loop of Henle to inhibit sodium and chloride resorption.Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance.
Loop Diuretics: Drug Effects
• Potent diuresis and subsequent loss of fluid
• Decreased fluid volume causes:Reduced BP ,Reduced pulmonary vascular resistance ,Reduced systemic vascular resistance ,Reduced central venous pressure &Reduced left ventricular EDP
• Potassium depletion
Loop Diuretics:Therapeutic Uses For control of Edema associated with CHF or hepatic or renal disease&Control of hypertension.
Loop Diuretics: Side Effects
Body Effects
CNS : Dizziness, headache, tinnitus, blurred vision
GIT: Nausea , Vomiting , Diarrhea
Hematologic: Agranulocytosis, neutropenia, thrombocytopenia
Metabolic: Hypokalemia, hyperglycemia, hyperuricemia
Osmotic Diuretics e.g. Mannitol, Mechanism of Action :
Work in the proximal tubule. Nonabsorbable, producing an osmotic effect
Pull water into the blood vessels and nephrons from the surrounding tissues
Osmotic Diuretics: Drug Effects Reduced cellular edema,Increased urine production, causing diuresis Rapid excretion of water, sodium, and other electrolytes, as well as excretion of toxic substances from the kidney & Reduces excessive intraocular pressure
Osmotic Diuretics: Therapeutic Uses
• Used in the treatment of patients in the early, oliguric phase of ARF
• To promote the excretion of toxic substances
• Reduction of intracranial pressure
• Treatment of cerebral edema
Osmotic Diuretics: Side Effects include Convulsions,Thrombophlebitis ,Pulmonary congestion. Also headaches, chest pains, tachycardia,
blurred vision, chills, and fever.
Potassium-Sparing Diuretics : Amiloride , Spironolactone & triamterene
Potassium-Sparing Diuretics: Mechanism of Action
• Work in collecting ducts and distal convoluted tubules
• Interfere with sodium-potassium exchange
• Competitively bind to aldosterone receptors
• Block the resorption of sodium and water usually induced by aldosterone
Potassium-Sparing Diuretics: Drug Effects
• Prevent potassium from being pumped into the tubule, thus preventing its secretion
• Competitively block the aldosterone receptors and inhibit its action
• The excretion of sodium and water is promoted
Potassium-Sparing Diuretics: Therapeutic Uses
Spironolactone and triamterene :
• Hyperaldosteronism
• Hypertension
• Reversing the potassium loss caused by potassium-losing drugs
Amiloride used in the Treatment of CHF.
Potassium-Sparing Diuretics: Side Effects
Body System Effects
CNS Dizziness, headache
GIT Cramps, nausea, vomiting, diarrhea
Others Urinary frequency,weakness &hyperkalemia
spironolactone Causes gynecomastia, amenorrhea, irregular menses
Thiazide and Thiazide-Like Diuretics :
• hydrochlorothiazide ,chlorothiazide , trichlormethiazide
• Thiazide-like chlorthalidone (Hygroton) &metolazone
Thiazide and Thiazide-Like Diuretics: Mechanism of Action
• Inhibit tubular resorption of sodium and chloride ions
• Action primarily in the ascending loop of Henle and early distal tubule
• Result: water, sodium, and chloride are excreted
• Potassium is also excreted to a lesser extent
• Dilate the arterioles by direct relaxation
Thiazide and Thiazide-Like Diuretics: Drug Effects include Lowered peripheral vascular resistance &Depletion of sodium and water.
Thiazide and Thiazide-Like Diuretics: Therapeutic Uses
• Hypertension
(one of the most prescribed group of agents for this)
• Edematous states
• Idiopathic hypercalciuria
• Diabetes insipidus
• Adjunct agents in treatment of CHF, hepatic cirrhosis
Thiazide and Thiazide-Like Diuretics: Side Effects
Body Systems Effects
CNS Dizziness, headache, blurred vision, paresthesias, Libido?
GIT Anorexia, nausea, vomiting,diarrhea
GU Impotence
Integumentary Urticaria, photosensitivity
Metabolic Hypokalemia, glycosuria,hyperglycemia