3.4 Diuretics Flashcards
What are the therapeutic indications for diuretics?
What are the five functional zones of the nephrons and what does each do?
- proximal convoluted tubule = reabsorption
- descending loop of Henle = urine being concentrated
- ascending loop of Henle = dilution of the urine
- distal convoluted tubule = finetuning electrolytes Na+, CL-, Ca2++ (mostly reabsorption)
- collecting tubule & duct = fine tuning (salts, volume, acid-base)
In the context of diuresis, define:
secretion
reabsorption
passive reabsorption
active reabsorption
Where is the majority of water reabsorbed from the urine?
Descending loop of henle.
What are the diuretic sites of action for:
What are the two important cell types in the collecting tubule? What do they do?
Which is affected by aldosterone and what does it do?
Aldosterine targets the principal cell and initiates the ATP pump to lead reabsorption of Na+ and secretion of K+.
Intercalated cells manage acid/base balance (H+/HCO3) through active pumping.
What is the effect of ADH on the collecting tubule and water in urine?
ADH makes the collecting tubule permeable to water, which removes it from water and concentrates urine.
What is the action of K sparing diuretics?
Are they strong or weak diuretics? Why?
What does it treat?
What are major concerns?
What are off-label uses of spiranolactone?
- K Sparing DIuretics block Na+ reabsorption and prevent K+ secretion at the collecting duct.
- Weak because at this point in the nephron there is a limited amount of sodium to impact.
- It treats secondary hyperaldosteronism. It treats heart failure by preventing binding of aldosterone, helping to reverse remodeling of the heart. Treats ascites, which is mediated by hyperaldosteronism.
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Off-label uses of spiranolactone:
- __Also blocks androgen receptors; useful for polycystic ovarian syndrome and male-to-female transgender hormonal therapy.
What are adverse effects of the K sparing diuretics:
Spiranolactone?
Triamterene?
What is the purpose of the collecting duct?
What is exchanged?
How can water be reabsorbed here?
How does aldosterone affect the collecting tubule? What is the effect on potassium?
Aldosterone initiates the ATP pump in princpal cells of the collecting tubule wall. This pump takes a K+ from the body and reabsorbs Na+ from urine, bringing with it water. This can result in hypokalemia.
Vasopressin and ADH also work at the collecting tubule. Normall the collecting duct is impermeable to water, but in the presence of ADH water can be reabsorbed.
Where do potassium sparing diuretcs impact the nephron?
What is exchanged at the distal convoluted tubule?
Is the volume of water modified in this section?
Water can not be exchanged in distal convoluted tubule, so volume is not effected. The composition is finetuned.
What section of the nephron do thiazide diuretics affect?
Can you get more effect with higher doses?
What is a drug allergy concern?
How does the body compensate for the thiazide blocking of NaCl reabsorption in the DCT? What is the consequence of this?
Even though NaCl reabsorption is blocked DCT, the collecting tubule cells can work to reabsorb it there. However, this active transport requires K+ to be used and excreted, leading to hypokalemia.
What are purposes and significant adverse effects of thiazide diuretics?
What are the four major loop diuretics?
What is their mechanism and effect?
- Bumetanide
- Furosemide
- Torsemide
- Ethacrynic acid
They have the greatest efficacy for removal of Na and Cl, and release copious amounts of urine. They do this by blocking the Na/K/Cl pump in the ascending loop.
One consequence is that Mg and Ca are not reabsorbed, lleaving the urine more concentrated when it reaches the DCT.
What is the consequence of loop diuretics blocking the Na/Cl/K transporter in the ascending loop of henle?
There will be more Na/Cl/K and more Mg and Ca in the urine (more concentrated) when it reaches the DCT. Sodium and half of the extra cloride can be reabsorbed, as well as calcium. But Mg, K and half of the extra Cl go on to the collecting duct. There is no mechanism for Mg and K reabsorption in the collecting duct. This will be excreted, risking imbalance.
The extra solutes in the urine requrie water, meaning there will be less water reabsorbed.
Summarize the mechanism of loop diurectics.
What happens if Cl is low?
What are therapeutic uses for loop diuretics?
What are adverse effects of loop diurectics?
What is the general purpose of the dscending loop of henle?
Water is reabsorbed and urine/salts concentrate by 3x
What is the purpose of the proximal convoluted tubule?
Generally, its job is to deliver isotonic urine to the loop of henle. It does this by reabsorbing glucose, amino acids, Na+, bicarb
What does acetazolamide (carbonic anhydrase inhibitor) waste?
What is significant about this?
By instagating the wasting of bicarb this alkalizes urine and retains Cl-. This is helpful when you have wasted Cloride with other diureticz, acetazolamide can be used to correct this by retaining Cl-.
What are adverse effects of acetazolamide (carbonic anhydrase inhibitor)?
Review urinary secretion effects of diuretics.
