Diuretics

Question 1

What is the mechanism of action of the carbonic anhydrase inhibitors?

Answer 1

Inhibit luminal carbonic anhydrase at the proximal tubule –causes less activity of Na/H antiporter–decreased HCO3 and Na+ (and water) reabsorption

Question 2

What are the three carbonic anhydrase inhibitors?

Answer 2

Acetazolamide
Methazolamide
Dichlorphenamide

Question 3

What are the uses of carbonic anhydrase inhibitors–acetazolamide, methazolamide, dichlorphenamide?

Answer 3

Decrease intraocular volume/pressure

Prevention and tx of mountain sickness

Question 4

What are the side effects of the carbonic anhydrase inhibitors?

Answer 4

Increased K+ excretion and metabolic acidosis

ONLY diuretic causing hypokalemia and acidosis
Normally hyperkalemia and acidosis

Question 5

Carbonic anhydrase inhibitors are contraindicated in?

Answer 5

Cirrhotic patients

Alkalization of urine– increased serum ammonia–> hepatic encephalopathy

Question 6

What is the mechanism of action of aminophylline, a bronchodilator?

Answer 6

Phosphodiesterase inhibition and enhanced signaling via increased cAMP and cGMP–works at proximal tubule–decreased HCO3 and Na+ (and water) reabsorption

Question 7

What are the uses of aminophylline?

Answer 7

Reduce inflammation and bronchospasm in moderate to severe asthma

NOT used as diuretic

Question 8

What is the mechanism of action of mannitol?

Answer 8

Opposes water and sodium reabsorption at proximal tubule–increased osmolarity of tubular fluid

Question 9

What are the uses of mannitol?

Answer 9

Increased clearance of drugs
Minimize renal faillure–shock or surgery
Decrease intraocular or intracranial pressures
Diagnose oliguria

Question 10

What is the major side effect of mannitol?

Answer 10

Risk of pulmonary edema

Question 11

What is the mechanism of action of the loop diuretics?

Answer 11

Inhibit Cl portion of Na-K-2Cl cotransporter in luminal membrane at medullary and cortical (proximal) talH

Decreased K+, Ca2+, and Na+ reabsorption

Resultant K+ loss

Question 12

What are the uses of the loop diuretics?

Answer 12

Crisis edema–pulmonary, CHF, cirrhosis
Hypercalcemia
Drug toxicity/OD
Severe HTN in setting of CHF or cirrhosis

Question 13

What loop diuretic should be given when pt has sulfa allergy?

Answer 13

Ethacrynic acid

Question 14

What are the 4 main loop diuretics?

Answer 14

Furosemide
Bumetanide
Torsemide
Ethacrynic acid

Question 15

What are the major side effects of loop diuretics?

Answer 15

Hypokalemia/hypocalcemia/hypomagnesemia--arrhythmia 
Contraction alkalosis
Increased BUN and creatinine
Ototoxicity--esp with aminoglycoside 
Hyperglycemia 
Gout

Question 16

What is the mechanism of action the the thiazide and thiazide like diuretics?

Answer 16

Inhibits Cl portion of the Na-Cl cotransporter in the luminal membrane at the early distal tubule

Decreased Na+ (and water) reabsorption
Increased Ca++ reabsorption
Resultant K+ loss

Question 17

What are the uses the the thiazide diuretics?

Answer 17

HTN–intravascular contraction
Chronic edema–cardiac insufficiency
Idiopathic hypercalciuria (stones)
Nephrogenic diabetes insipidus

Question 18

What are the 2 main thiazide diuretics?

Answer 18

Chlorothiazide

Hydrocholorothiazide

Question 19

What are the 4 major thiazide-like diuretics?

Answer 19

Chlorthalidone
Quinethazone
Metolazone
Indapamide

Question 20

Which thiazide-like diuretic has additional uses and what are they?

Answer 20

Chlorthalidone

Besides
HTN--intravascular contraction
Chronic edema--cardiac insufficiency
Idiopathic hypercalciuria (stones)
Nephrogenic diabetes insipidus 

It also reduces stroke risk and CHF events

Question 21

What are the side effects of the thiazide and thiazide like diuretics?

Answer 21

Hypokalemia/hypercalcemia
Contraction alkalosis
Increased BUN and creatinine 
Hyperglycemia 
Gout

Question 22

What drug has a lethal interaction with the thiazide diuretics?

Answer 22

Quinidine–v. tach–fib–> due to hyperkalemia

Question 23

What do the thiazide diuretics do to free water clearance

Answer 23

decreases positive free water clearance

Question 24

What do the loops do to free water clearance?

Answer 24

Decrease positive and negative free water clearance

Question 25

What is the mechanism of action of amiloride and triamterene?

Answer 25

K+ sparing diuretics--renal ENaC inhbiitor Blocks Na channel and Na/H antiproton in lumenal membrane at the late distal tubule and collecting duct Decreased K+ secretion and distal tubule acid secretion Increased Ca++ absorption

Question 26

What are the uses of amiloride?

Answer 26

Combination with other diuretics to prevent hypokalemia Edema Idiopathic hypercalciuria (stones) Lithium-induced polyuria and toxicity Liddle syndrome-- high blood pressure associated with low plasma renin activity, metabolic alkalosis, low blood potassium, and normal to low levels of aldosterone Mucociliary clearance

Question 27

What are the side effects of amiloride and triamterene?

Answer 27

Hyperkalemia in pts with renal failure or on ACE inhibitors

Question 28

The use of amiloride and triamterene are contraindicated in pts with?

Answer 28

renal failure and ACEi/ARB use

Question 29

What are the uses of triamterene?

Answer 29

Combination with other diuretics to prevent hypokalemia | Edema

Question 30

What is the K+ sparring diuretic that is an aldosterone receptor antagonist?

Answer 30

Spironolactone

Question 31

What is the mechanism of action of spironolactone?

Answer 31

Competes for aldosterone receptor--inhibiting mRNA transcription and translation Decreased Na and K channels Decreased number and activity of Na-K-ATPase pumps in the late distal tubule and collecting duct--> decreased K+ secretion and distal tubule acid secretion

Question 32

What are the uses of spironolactone?

Answer 32

``` Reduction in CHF mortality Combination with other diuretics to prevent hypokalemia Edema Primary and secondary aldosteronism HTN Anti-testosterone agent ```

Question 33

What are the side effects of spironolactone?

Answer 33

Hyperkalemia in pts with renal failure or on ACE inhibitors Male pts--may have gynecomastia, ED, and loss of libido Female pts--may have amenorrhea, breast soreness, and oligomenorrhea

Question 34

The use of spironolactone is contraindicated in pts with?

Answer 34

Renal failure-- can cause hyperkalemia Requires a salt-restricted diet--so aldosterone is present to compete with

Question 35

What are the 2 vasopressin (ADH) receptor antagonist and where is there site of action?

Answer 35

Conivaptan Tolvaptan Works at collecting duct--increased free water excretion

Question 36

What are conivaptan and tolvaptan used for?

Answer 36

hyponatremia--SIADH and CHF