Pharmacology- Diuretic Drugs

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Diseases causing high levels of kidney reabsorption of NaCl lead to...

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water retention
Inc blood volume
edema in tissues

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Body response to heart failure causes...

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Kidney responds as if there were a decrease in blood volume
Kidney retains more salt and water to raise blood volume
Diseased heart cannot increase output which results in edema

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Body response to hepatic ascites...

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Complication of cirrhosis
Caused by obstruction of blood flow in the portal system-->inc portal BP
Colloidal osmotic pressure of blood decreased due to impaired synthesis of plasma protins by diseased liver
Fluid escapes and collects in abdomen

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Body response to nephrotic system..

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Loss of protein from plasma reduces colloidal osmotic pressure--> edema
Low plasma volume stimulates aldosterone secretion
Leads to retention of Na and fluid--> more edema

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Body response to premenstural edema...

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excess of estrogen facilitates loss of fluid into extracellular space

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Nonedematous states that you would use diuretics for..

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HTN--> reduce Blood volume and dilate arteroiles
Hypercalcemia--> loop diuretics promot calcium excretion
Diabetes insipidus--> polyuria/polydypsia--> reduces plasma volume, causing drop in glomerular filtration and reabsorption of Na and water

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Increasing the dose above normal does not promot further diuretic response

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Celing diuretics

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First modern diuretic that was active orally

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Chlorothiazide

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Newer deriviatives of thiazide diuretics

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hydrochlorothiazide
chlorthalidone

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Thiazide like diuretics--> not true thiazides

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chlorthalidone, indapamide, metolazone

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Thiazide Mechanism of Action

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Act in distal tubules to decrease reabsportion of Na by inhibition of Na/Cl cotransporter in the distal tubule
Must have good renal function

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Therapeutic uses for thiazides

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HTN- mainstay of antihypertensive meds
(inexpensive and well tolerated)
Heart failure- reducing extracellular volume in mild-moderate heart failure
(if thiazides fail use loop diuretic)
Hypercalciuria- calcium oxalate stones in urinary tract
DI- produce hyperosmolar urine--> sub for anti-diuretic hormone in tx of nephrotic DI

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most frequent adverse effect of thiazide diuretics

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K+ depletion
Suppliment with diet (citrus fruits, bananas, prunes)
Overcome by Spironolactone- interferes with aldosterone action
or Triameterene- retains K+

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Adverse events of thiazise diuretics

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Hyperuricemia- inc serum uric acid
Volume depletion- orthostatic HTN
Hypercalcemia- inhibit Ca secretion
Hyperglycemia- impaired release of insulin
Hyperlipidemia- inc in serum cholesterol and serum LDL
Hypersensitivity- dermatits, interstitial nephritis

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Thiazide like analog with a very long duration of action

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Chlorthalidone

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Thiazide like analog that causes Na excretion in advnaced renal failure

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Metolazone

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Thiazide like analog that has significant anti-HTN action with minimal diuretic effects

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Indapamide

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What part of the kidney do loop/high celing diuretics work on?

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The ascending limb of the loop of Henle

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Most commonly used loop diuretics

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furosemide

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Much more potent loop diuretics

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bumetanide

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Loop Diuretics

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Highest efficacy in mobilizing Na and Cl
Produces copious amounts of urine

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Mechanism of action for Loop Diuretics

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Inhibit cotransport of Na/K/2Cl- in ascending limb of loop of Henle

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Loop diuretic action on the body

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Acts promptly among pts with poor renal function
Increases Ca content of urine
Hypomagnesia
Decreased renal vascular resistance
Increased renal blood flow

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Therapeutic uses of Loop diuretics

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Hypercalcemia
Hyperkalemia
Reduces pulmonary edema of heart failure

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Adverse effects of Loop diuretics

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Ototoxicity- ethacrynic acid
Hyperuricemia- blocks secretion--> gouty attacks
Hypovolemia
K+ depletion--> hypokalemic alkalosis

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Major use of K+ Sparing Diuretics

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HTN tx in conjunction with thiazide

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Where in the kidneys do K+ sparing durietics act?

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collectinv tubules to inhibit Na reabsorption and k+ excretion

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K+ Sparing diuretics

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Triamterene
Amiloride
Spironolactone

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Mechanism of action for Spironolactone

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antagonism of aldosterone

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Action of spironolactone on the body

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High levels of aldosterone in edematous states
Antagonism of aldosterone results in retention of K and excretion of Na

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Therapeutic uses of Spironolactone

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Diuretic--> low effacy in mobilizing Na
Useful in K+ retention
Given with thiazide of loop to prevent K+ excretion

Heart failure--> prevents remodeling for progressive heart failure

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Diuretic that inhibits enzyme carbonic anhydrase in proximal tubular epitheilal cells

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Carbonic anhydrase inhibitor
Acetazolamide

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Mechanism of action for Acetazolamide

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mild diuresis

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Treatment uses of Acetazolamide

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Treatment of glaucoma
-should not be used in acute attacks (pilocarpine)
Mountain sickness (prophylaxis)

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Osmotic diuretics

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used to maintain urine flow following acute toxic ingestion of substance capable of producing acute renal failure

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Osmotic diuretic mainstay of treatment for...

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increased intracranial pressure, acute renal failure due to shock, or drug toxicities

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Osmotic diuretic

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mannitol- IV