DIURETICS 2

¢Thiazide diuretics

—Hydrochlorothiazide

—Chlorothiazide

—Trichlormethiazide

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¢Thiazide-like diuretics

—Chlorthalidone

—Metolazone

¢Acts in the distal convoluted tubule.

—Inhibit tubular resorption of sodium, chloride, and potassium ions

—Result: water, sodium, and chloride are excreted

¢Potassium is also excreted to a lesser extent

¢Dilate the arterioles by direct relaxation

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¢Results:

—Lowered peripheral vascular resistance

—Sodium, water, chloride and potassium are excreted

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¢Thiazides should not be used if creatinine clearance is less than 30 to 50 mL/min (normal is 125 mL/min)

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¢Metolazone remains effective to a creatinine clearance of 10 mL/min

¢Hypertension.

¢Adjunct drugs in treatment of edema related to HF, hepatic cirrhosis, corticosteroid therapy.

¢Idiopathic hypercalciuria, Patients with calcium oxalate stones.

¢Diabetes insipidus(Act As ADH, causes concentrated urine)

¢Metabolic: Hypokalemia, glycosuria, hyperglycemia, Decrease insulin release from pancreas), hyperuricemia (Contra indicated in gout)

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¢CNS: Dizziness, headache, blurred vision, paresthesias, decreased libido.

¢GI: Anorexia, nausea,vomiting, diarrhea

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¢GU: Impotence (Structural resemblance with dihydrotestosterone so inhibits binding to receptors)

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¢Integumentary: Urticaria, photosensitivity

¢Amiloride

¢Spironolactone

¢Triamterene

Also known as aldosterone-inhibiting diuretics

¢Interfere with sodium-potassium exchange in collecting ducts and convoluted tubules

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¢Competitively bind to aldosterone receptors

—Block the resorption of sodium and water

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¢Prevent potassium from being pumped into the tubule, thus preventing its secretion

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¢Competitively block the aldosterone receptors and inhibit its action

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¢Sodium and water are excreted

¢spironolactone and triamterene

—Hyperaldosteronism

—Hypertension

—Reversing the potassium loss caused by potassium-losing drugs

—Certain cases of heart failure

—Liver failure

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¢Amiloride

—Treatment of HF

Hyperkalemia

GI: Cramps, nausea,vomiting, diarrhea

CNS: Dizziness, headache

Other: Urinary frequency,  weakness, loss of libido.

Spironolactone

¢Gynecomastia

¢Amenorrhea

¢Irregular menses

¢Postmenopausal bleeding

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¢Osmotic agents (proximal tubule, descending loop of Henle, collecting duct)

—Reduce pre-surgical or post-trauma intracranial pressure

—Prompt removal of renal toxins

—One of the few diuretics that do not remove large amounts of Na+

—Can cause hypernatremia

¢No interaction with transport systems

¢All activity depends on osmotic pressure exerted in lumen

¢Blocks water reabsorption in proximal tubule, descending loop, collecting duct

¢Results in large water loss, smaller electrolyte loss à can result in hypernatremia

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¢Used in the treatment of patients in the early, oliguric phase of ARF

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¢To promote the excretion of toxic substances

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¢Reduction of intracranial pressure

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¢Treatment of cerebral edema

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¢NOT indicated for peripheral edema

¢Convulsions

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¢Thrombophlebitis

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¢Pulmonary congestion

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¢Also headaches, chest pains, tachycardia, blurred vision, chills, and fever

¢Mannitol

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¢Intravenous infusion only

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¢May crystallize when exposed to low temperatures—use of a filter is required

Diuretic	Example	Site of action
Carbonic anhydrase inhibitors	Acetazolamide	PCT
Loop diuretics	Furosimide	Thick ascending loop
Thiazide diuretics	Hydrochlorothiazide	DCT
Potassium sparing diuretics	Spironolactone	DCT and collecting tubules
Osmotic Diuretics	Manitol	PCT, Descending loop of henle and collecting tubules

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¢They all block Na reabsorption along the tubule

¢They all cause hypokalemia EXCEPT K sparing diuretics

¢K sparing diuretics are antiandrogenic EXCEPT Eplerenone

¢Loop diuretics cause sulfa allergy EXCEPT Ethacrynic acid

¢Hyperglycemia mostly caused by Thiazides

¢Only Thiazides cause hypercalcemia, all others cause hypocalcemia

¢Acidosis is seen with carbonic anhydrase inhibitors and K sparing diuretics

¢Alkalosis is seen in loop and Thiazides diuretics

¢Hyperchloremia is seen only in carbonic anhydrase inhibitors

¢Caffeine works on vasodilating the glomerular vessels unlike all other diuretics which work on blocking Na reabsorption

Carbonic anhydrase inhibitors paradoxically cause renal stones because they result in basic urine (bicarbonateuria

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