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66 Cards in this Set
- Front
- Back
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What are the loop diuretics to know?
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Expensive fur boots
-Ethacrynic acid -Furosemide -Bumetanide |
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What is another name for loop diuretics?
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High ceiling diuretics
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What is the target site of action of the loop diuretics?
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Cortical and Medullary segments of the ascending LOH
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What is the mechanism of the loop diuretics?
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Inhibition of active Na/Cl countertransport
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What is the result of inhibition of Cl reabsorption in the thick limb of the asc LOH?
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-Increased Cl excretion
-Increased Na excretion |
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What additional effect do Furosemide and Bumetanide have at high doses?
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Inhibition of carbonic anhydrase in the prox tubule.
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Remember, what is the function of the cortical/medullary ascending limb of the LOH?
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Medullary - concentration of urine
Cortical - dilution of urine So loop diuretics prevent BOTH |
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How potent are the loop diuretics?
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Very potent - 20-30% of the filtered load of Na is excreted!
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How do the loop diuretics affect renal hemodynamics?
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-Increase RBF
-Often increase GFR |
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How do the loop diuretics affect Potassium handling?
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-K excretion increases due to more Na available in the distal tubule lumen for Na/K exchange
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What are 2 other solutes for which renal handling is altered by loop diuretics? How?
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-Urate (more reabsorption)
-Calcium (more excretion) |
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So what is the net effect of the loop diuretics on the urine?
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-Urine volume increases
-Increased excretion of Na/Cl/K/Ca |
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What are the loop diuretics used to treat?
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Edema due to cardiac, hepatic, or renal disease.
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What is the onset/duration of the loop diuretics effects?
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-Fast onset of diuresis 15m
-Short duration of effets 2-3 hrs |
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What are the loop diuretics used for treating in addition to edema dt organ disease?
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-Acute pulmonary edema
-Hypertension resistant to other anti-hypertensives |
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Why wouldn't the loop diuretics be favorable over the thiazides for treating hypertension?
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Loop diuretics have more side effects
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So when are the loops used over thiazides for treating hypertension?
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When thiazides just don't work well enough
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How are the loop diuretics administered?
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By oral or IV
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What are 5 side effects of loop diuretics?
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-Hypokalemia
-Hyperuricemia -Hyperglycemia (furosemide) -Ototoxicity -Hypovolemia -Alkalosis |
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In what patients are hyperuricemia and hyperglycemia mostly a problem?
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Gout or diabetics
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How does the increased Cl excretion seen in Loop diuretic treatment affect plasma pH?
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Causes a Hypochloric alkalosis (Bicarb reabsorption increases along with increased Cl excretion to maintain plasma anion balance)
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What loop diuretics are most associated with ototoxicity at high doses?
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-Ethacrynic acid most
-Furosemide next -Bumetanide last |
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Why is hypovolemia associated with loop diuretics bad?
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It can result in CV collapse
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What are the 3 thiazide diuretics?
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-Chlorothiazide
-Hydrochlorothiazide -Metolazone |
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What is the target site of action of the Thiazides?
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Na/Cl symporter in the
-CORTICAL asc limb of LOH -Distal Tubule |
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How do the Thiazides get into the renal tubule?
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By OAT
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What effect do the thiazides have on urine filtrate by inhibiting Na/Cl symport in the cortical ascending limb?
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The urine can't be diluted (but it can still be concentrated in the medullary ascending limb)
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What is the effect of Increased Na/Cl excretion on K handling?
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Increased K excretion (more Na available for exchange in the distal tubule)
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For what 2 other solutes is renal handling affected by the thiazides?
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-Urate (enhanced reabsorption)
-Calcium (reduced excretion) |
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So how is the urine volume and content changed by the thiazides?
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-Increased volume
-Increased Na/Cl/K/HCO3 excretion as a Hypertonic urine |
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How are the thiazides administered?
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Orally
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What is the onset and duration of the thiazides like?
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-Rapid onset - 60 min
-Long duration of action |
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How do the thiazides affect renal hemodynamics?
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They reduce the GFR
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Why is it important to remember that the thiazides reduce the GFR?
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They should NOT be given to patients whose GFR is <25 ml/min
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What are 4 conditions the Thiazides are used for treating?
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-Management of edema in CHF
-Hypertension -Hypercalciuria in patients w/ renal calculi -Diabetes insipidus |
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Why are the thiazides used for treating diabetes insipidus?
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Because these patients have decreased levels of ADH, so are unable to lose enough water; thiazides increase urine flow.
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How do the side effects of the thiazides compare to those of the loop diuretics in general? Why?
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Fewer - because they have a slower onset and activity
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What are 3 side effects of the Thiazide diuretics?
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-Hypokalemia
-Hyperuricemia -Hyperglycemia |
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Why do the thiazides cause hyperuricemia?
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Because the drug competes with urate for OAT secretion
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Why do the thiazides cause hyperglycemia?
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They reduce insulin secretion
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When should the thiazides NOT be given?
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When the GFR is <25 ml/min
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What additional plasma level do the thiazides alter? How?
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pH - cause Hypochloric Alkalosis
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What are the 2 flavors of K sparing diuretics?
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1. Aldosterone antagonists
2. Na channel inhibitors |
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What are the 2 Aldosterone antagonists?
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-Spironolactone
-Eplerenone |
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How do the Aldosterone antagonists work?
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By competing with Aldosterone at the mineralocorticoid receptor on the distal tubule - thus Aldo is required for them to work.
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How do the aldosterone antagonists affect the urine volume and content?
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-Increased urine volume
-Increase Sodium excretion -Decrease Potassium excretion |
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How effective are the Aldo antagonists as diuretics?
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Weak
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What are the 3 therapeutic uses of aldosterone antagonists?
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-Hypertension
-Refractory edema -Primary aldosteronism |
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Why are the Aldosterone antagonists used as diuretics if they are so weak?
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Because they can help the effects of thiazide or loop diuretics, but decrease K loss
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What is the duration of action of the Aldosterone antagonists?
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Long - 24 hrs
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What are 2 toxic side effects of the aldosterone antagonists?
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-Hyperkalemia
-Gynecomastia |
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What do you have to be careful of in giving Aldo antagonists in light of the hyperkalemia they can induce?
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-Don't give K supplements
-Careful if giving to patients with severe renal insufficiency |
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Which aldosterone antagonist is more associated with causing gynecomastia? How does this occur?
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Spironolactone - it is a weak progesterone agonist so gynecomastia develops in longterm use.
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And what are the 2 Na channel inhibitors that are K sparing diuretics?
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-Triamterene
-Amiloride |
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What is the target of action of the Na Channel inhibitors?
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Na/H exchanger in the principle cells of the late distal tubule and early cortical collecting duct
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What effect does inhibition of sodium reabsorption by the principle cells at the apical membrane have?
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Reduced Na/K ATPase exchange at the basal membrane - reduced K excretion
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How do Triamterene and Amiloride affect urine volume and content?
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-Increase urine volume
-Increase Na content -Decrease K content |
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What do you have to be careful of when giving Triamterene?
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Giving too high of concentrations - will reduce the GFR - bad in patients with renal impairment!
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And what are the 2 Na channel inhibitors that are K sparing diuretics?
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-Triamterene
-Amiloride |
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What is the target of action of the Na Channel inhibitors?
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Na/H exchanger in the principle cells of the late distal tubule and early cortical collecting duct
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What effect does inhibition of sodium reabsorption by the principle cells at the apical membrane have?
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Reduced Na/K ATPase exchange at the basal membrane - reduced K excretion
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How do Triamterene and Amiloride affect urine volume and content?
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-Increase urine volume
-Increase Na content -Decrease K content |
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What do you have to be careful of when giving Triamterene?
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Giving too high of concentrations - will reduce the GFR - bad in patients with renal impairment!
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What are 2 side effects of the Na channel inhibitors?
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-Hyperkalemia (don't give with K supplements)
-Azotemia (mild) |
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What are the 2 main therapeutic uses of the thiazide diuretics?
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-Edema/HTN
-In combo with a thiazide or loop diuretic |
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What SHOULDN'T be done with the K sparing diuretics?
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Never give together - their effects are ADDITIVE and will result in severe hyperkalemia!
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