Diuretics: 2 Lectures (Handout pgs: 18 - 41) Flashcards Preview

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What is an aquaretic?

A drug which decreases the ability of ADH to increase water permeability of the late distal tubule and collecting duct


What are saluretics? What are the 4 classes?

Drugs which decrease reabsorption of solutes in 1 or more segments of the nephron; Carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics, K-sparing diuretics


What is an osmotic diuretic?

Drug which enters the tubular fluid by glomerular filtration and is neither reabsorbed nor secreted along the nephron. The increased osmotic pressure within the tubule inhibits water reabsorption resulting in a more voluminous diuresis.


What is the main indication for diuretic use?

To maintain normal blood pressure


What are some of the many secondary indications for diuretic use?

Edema, hypo/hyperkalemia, hypo/hypercalcemia, Increased CSF, Increased introcular pressure


1. What class of drug are aminophylline and theophylline? 2. Mechanism of action? 3. Why are these diuretics relatively ineffective?

1. Phosphodiesterase inhibitors 2. Phosphodiesterase inhibitor -> increases cAMP in prox. Tubule cells -> phosphorylation of apical membrane Na/H exchanger causing inhibition of bicarbonate and Na+ absorption 3. Compensation by downstream mechanisms


1. What is the mechanism of loop diuretics? 2. Why are they considered most efficacious? 3. Why does loop diuretic use result in excessive K secretion in the urine?

1. Decrease reabsorption of Na, K, and Cl in thick ascending limb of Henle 2. Theey induce the largest diuresis 3. Compensatory mechanisms downstream in the late distal tubule/collecting duct couples the reabsorption of Na with the secretion of K


1. Where do thiazide diuretics act? 2. Mechanism of action? 3. How are they similar to loop diuretics?

1. Cortical talH/Early distal tubule 2. Decrease Na and Cl reabsorption/Inhibit proximal tubule carbonic anhydrase 3. Increased excretion of K due to compensatory Na reabsorption (they are obligately coupled)


1. Where do potassium sparing diuretics work? 2. Mechanism of action? 3. What other diuretics would you combine with them? Why?

1. Late distal tubule/collecting duct 2. Block the obligate functional coupling of Na reabsorption and K secretion 3.Either a loop diuretic or thiazide diuretic. K sparing diuretics will decrease the amount of Na reabsorbed in the late distal tubule/collecting duct and therefore increase the volume of diureis while maintaining blood K concentration


Describe the mechanism by which loop diuretics increase the time necessary to rid the body of excess fluid intake.

The loop diuretics increase osmolar clearance (Cosm). Therefore, less free water is excreted based on the following equation CH20 = V - Cosm and it takes more time to excrete fluid in excess of solute


What is the countercurrent multiplication ion concentration dependent on?

The magnitude of transcellular solute reabsorption in the medullary thick ascending limb of Henle


In a volume contracted patient, why do loop diuretics increase free water clearance?

A healthy kidney would attempt to concentrate the urine. In a patient on diuretics, there is a lesser countercurrent gradient, and therefore an inability to concentrate urine. This results in less negative free water clearance


What solutes absorbed in the cortical early distal tubule participate in the counter current concentration gradient?

Solutes that are reabsorbed into the cortex do not contribute to the ion concentration gradient.


Describe the process by which thiazide diuretics decrease free water clearance ability

They block solute reabsorption in the distal tubule and therefore decrease the ability to dilute the urine. Osmolar clearance increases therefore decreasing free water clearance


What is a risk of thiazide diuretic use in volume expanded patients?

Because the ability to excrete free water is decreased, it will take a longer time to decrease the excess volume. Therefore, major risk: hyponatremia


Describe the mechanism of the carbonic anhydrase inhibitors

Inhibition of luminal CA leads to the decrease of intracellular H+. Therefore, the Na/H exchanger function decreases limiting the reabsorption of Na and promoting diuresis


What effect do CA inhibitors have on urine pH?

Increased pH


Describe the contents of the diuresis induced by CA inhibitors

Increased excretion of Na, K, and HCO3- in an alkaline urine


What are the major complications of CA inhibitor use?

Hypokalemia (K loss in urine) and metabolic acidosis (bicarb loss in urine)


What are the current uses of CA inhibitors now that they are obsolete as diuretics?

Used to decrease intraocular volume and pressure


What can CA inhibitor-induced metabolic acidosis lead to?

Ammonia generated from renal metabolism is diverted from the urine to accumulation in the ECF creating the risk of hepatic encephalopathy


What two drugs make up aminophylline?

Methylxanthine theophylline and ethylene diamine


Describe the 3 mechanisms of osmotic diuretics

(1) Non reabsorbable solutes increase the osmotic pressure which opposes the isotonic reabsorption of sodium and water. (2) Increased flow of isotonic tubular fluid decreases sodium and chloride reabsorption in the LOH and distal tubule. (3) There is increased blood flow to the renal medulla which decreases the osmotic gradient decreasing urine concentrating ability.


What is the most widely administered osmotic diuretic?



What is the FE of Na for CAI?

< 5%


What are four loop diuretics and what do they act upon?

Furosemide, bumetanide, torsemide, ethacrynic acid; inhibit the Na-K-Cl cotransporter in the talH


How is mannitol administered?



What changes in ECF solute concentration can result from loop diuretic induced ECF volume contraction?

Hyperbicarbonatemia-alkalosis, Hyperuricemia, Increased BUN, Increased serum creatinine


What are the therapeutic indications of mannitol?

Drug OD (drugs eliminated via urine), shock (treat acute renal failure), Increased intraocular/intracranial pressure


What is the mechanism causing hypokalemia in a patient on loop diuretics and thiazide diuretics?

Excess sodium is delivered to the distal tubule which induces potassium secretion and elimination