Term
Acetozolamide:
SOA, MOA, Effects on Urinary Electrolytes, Effects on Plasma Electrolytes: |
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Definition
Site of action: Proximal convoluted tubule
MOA: Carbonic anhydrase inhibitor
Effect on urinary electolytes:
Sodium - slightly increase
Potassium - increase
[H+] - decrease (urinary pH is increased)
Effect on plasma electrolytes:
Potassium - decrease
[H+] - increase (pH decreases)
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Term
Loop Diuretics:
Prototypical drug, SOA, MOA, Effect on urinary electolytes,Effect on plasma electrolytes:
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Definition
Prototypical drug = furosemide
Site of action: Ascending loop of Henle
MOA: Inhibits Na/K/Cl transport
Comments: Inhibits TGF, decreases this autoregulatory function and increases renal blood flow, "High ceiling" diuretic, loop diuretics most effective at removing water/Na/Cl, indicated for hypercalcemia and hyperkalemia.
Effect on urinary electolytes:
Sodium - increase
Potassium - increase
Calcium - increase
Magnessium - increase
Effect on plasma electrolytes:
Potassium - decrease
Calcium - decrease
Magnessium - decrease
Uric acid - increase
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Term
Thiazides:
SOA, MOA, Effects on Urinary Electrolytes, Effects on Plasma Electrolytes: |
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Definition
Site of action: Distal convoluted tubule
MOA: Inhibits reabsorption of Na/Cl (high urinary sodium secondarily inhibits potassium exchange)
Comment: Ceiling diuretic, unusual in that may produce hyperosmolar urine, non-diuretic effect = lowers systemic vascular resistance (useful in managing hypertension), and may increase serum cholesterol and LDL.
Effect on urinary electolytes:
Sodium - increase
Potassium - increase
Calcium - decrease
Magnessium - increase
Effect on plasma electrolytes:
Potassium - decrease
Calcium - increase
Uric acid - increase
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Term
Mannitol
SOA, Effect on Urinary Electrolytes: |
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Definition
Site of action: Loop of Henle
Effect on urinary electolytes:
Sodium - increase
Potassium - increase
Calcium - increase
Magnessium - increase
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Term
Spironolactone:
SOA, MOA, Effevt on Urinary Electrolytes: |
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Definition
Site of action: Distal tubule and collecting duct
MOA: Aldosterone antagonist (note aldosterone increases potassium and H+ excretion)
Comment: Potassium sparing, only active if aldosterone is active
Effect on urinary electolytes:
Sodium - increased
Potassium - decreased
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Term
Triamterene:
SOA, MOA Effect on Urinary Electrolytes:
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Definition
Site of action: Distal tubule and collecting duct
MOA: Block Na-channels
Comment: Potassium sparing (potassium effects usually more clinically important than effects on sodium), often used in combination with thiazide
Effect on urinary electolytes:
Sodium - mild increase
Potassium - decrease
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Term
Be prepared to discuss all figures in Chapter 22
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Definition
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Term
| Compare the actions and indications of thiazide diuretics and furosemide. |
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Definition
Thiazides: They all affect the distal tubule, and all have equal maximum diuretic effects. Increasing the dose above normal does not promote further diuretic response – ceiling diuretics.
MOA: Decrease reabsorption of Na by inhibition of Na/Cl channel cotransporter on the luminal membrane of the distal convoluted tubule. As a result they increase concentration of Na and Cl in the tubular fluid. Because of site of action on the luminal membrane, these drugs must be excreted into the tubular lumen to be effective, therefore they lose efficacy in decreased renal function. Used in treatment of hypertension because they are inexpensive, and well tolerated. They cause a lower peripheral resistance without having a major diuretic effect.These actions indirectly lead to less potassium being reabsorbed in the DCT and collecting ducts.
Furosemide: MOA: Furosemide is a loop diuretic: Inhibit the cotransport Na/K/Cl in the luminal membrane of ascending limb of the loop of Henle, decreasing reabsorption of these ions. Loop diuretics (e.g Furosemide) are the drugs of choice for reducing the acute pulmonary edema of heart failure d/t their diuretic effect. Useful in emergency situations (such as pulmonary edema) especially when given IV d/t their rapid onset of action. Also useful in treating hypercalcemia, because they stimulate tubular Ca excretion. Also useful in treatment of hyperkalemia. Furosemide (or loop diuretics in general) will work promptly even in patients with poor renal function as opposed to thiazides.
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Term
| Discuss the differences in MOA and indications between spironolactone and triamterene. |
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Definition
Spironolactone is used to treat certain patients with hyperaldosteronism, low potassium levels; and in patients with edema caused by various conditions, including heart, liver, or kidney disease. Spironolactone is also used alone or with other medications to treat high blood pressure. Spironolactone is an aldosterone receptor antagonists. It causes the kidneys to eliminate unneeded water and sodium from the body into the urine, but reduces the loss of potassium from the body.
Triamterene is a potassium sparing diuretic used in combination with thiazide diuretics for the treatment of hypertension and edema. Triamterene directly blocks the epithelial sodium channel (ENaC) on the lumen side of the kidney collecting tubule.
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Term
What is the diuretic of choice for diabetes insipidus? For the acute treatment of pulmonary edema/heart failure?
For hyperkalemia? For cirrhotic patient who is retaining water due to secondary hyperaldosteronism? |
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Definition
Diabetes insipidus: thiazide diuretics
Thiazides have the ability to produce a hyperosmolar urine. Can substitute for antidiuretic hormone in the treatment of DI.
Pulmonary edema / heart failure: Loop diuretics
During heart failure the kidneys, as a compensatory mechanism, retain more salt and water as a means of raising blood volume and increase venous return, the diseased heart cannot keep up with the increased vascular volume so pulmonary edema ensues. Loop diuretics are commonly used for their rapid onset (especially IV).
Hyperkalemia: Loop diuretics
The large amount of Na presented to the collecting tubule results in increased exchange of tubular Na for potassium, decreasing potassium.
Secondary hyperaldosteronism: potassium-sparing diuretic
Secondary hyperaldosternoism results from the decreased ability of the liver to inactivate the steroid hormone and leads to increased Na and water reabsorbtion, increased vascular volume, and exacerbation of fluid accumulation benefit from K sparing diuretics. Aldosterone acts on the distal tubules and collecting ducts of the nephron, causing the conservation of sodium, secretion of potassium, increased water retention, and increased blood pressure. The amount of aldosterone secreted is a direct function of the serum potassium, since the liver is not inactivating aldosterone this mechanism is faulted. A K+ sparing diuretic would work by acting as an aldosterone antagonist, since the increased aldosterone is causing potassium excretion. More specifically, the drug of choice = spironolactone (not triamterene).
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Term
A 75yo woman with hypertension is being treated with thiazide. Her blood pressure responds and reads at 120/76mmHg. After several months on the medication, she complains of being tired and weak. An analysis of the blood indicates low values for which of the following?
A. Calcium
B. Uric Acid
C. Potassium
D. Sodium
E. Glucose |
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Definition
C. Hypokalemia is a common adverse effect of the thiazides and causes fatigue and lethargy in the patients. Supplementation with potassium chloride or with foods high in K+ correct the problem. Alternatively, one may add a potassium-sparing diuretic like spironolactone. Calcium, uric acid, and glucose, are usually elevated by thiazide diuretics. The sodium loss does not weaken the patient. |
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Term
Which of the following drugs is contraindicated in a patient with hyperkalemia?
A. Acetazolamide
B. Chlorothizide
C. Ethacrynic Acid
D. Chlorthalidone
E. Spironolactone |
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Definition
E. Spironolactone acts in the collecting tubules to inhibit Na+ reabsorption and K+ excretion. It is extremely important that patients who are treated with any potassium-sparing diuretic be closely monitored for potassium levels. Exogenous potassium supplementation is usually discontinued when potassium-sparing diuretic therapy is instituted and the spironlactone is contraindicated in patients whith hyperkalemia. The other drugs promote the excretion of potassium |
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Term
Which would be the initial treatment choice to manage the hypertension in an African-American woman with a past medical history of gout and severe hypokalemia?
A. Hydrochlorothiazide
B. Spironolactone
C. Alsartan
D. Atenolol
E. Enalapril |
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Definition
B. Aftican American patients wit hypertension respond poorly to valsartan, atenolol, and enalapril. Hydrochlorothizide is generally considered the first-line drug. However, and because of the patient's medical history of hypokalemia and gout, spironolactone is the drug of choice. Additionally, the feminizing hormonal effects of spironolactone may be bothersome in men, but not in women. |
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