Few questions about CHF, aldosterone, and furosemide

[docjohn101]

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I understand that the beta-blockers are given to CHF, as are diuretics, but which are prefered, thiazides or furosemides. Also, spironolactone is also given to help with remodeling, Basically, what is the preference of drugs for CHF and their function?

Also, does vasopressin works on the medullary collecting duct and aldosterone works on the cortical collecting duct is that correct?

One more question: If a furosemide is given, does that mean less water will be absorbed from the descending loop of henle to prevent over-tonicity?

Thanks!

 

[Phloston]

I understand that the beta-blockers are given to CHF, as are diuretics, but which are prefered, thiazides or furosemides. Also, spironolactone is also given to help with remodeling, Basically, what is the preference of drugs for CHF and their function?

It depends on the patient, but in terms of the CHF specifically, if the prognosis looks poor, I would use a loop over a thiazide to drop the volume status more greatly. If the prognosis looks really really poor (and the oedema were very severe), I would actually give bumetanide over furosemide. If the patient had a Hx of sensorineural hearing loss, I would give torsemide if I insisted on giving the loop. You're also probably aware that you'd give ethacrynic acid if the patient has a sulfa allergy and would never give a loop if the patient has recent use of aminoglycosides.

If the CHF were minor to moderate, a thiazide is less overkill (like using NaBH4 on acetone instead of LAH). This would also be a winner if the patient's had a Hx of nephrolithiasis (thiazides induce hypocalciuria). I wouldn't give a thiazide if the patient has Sjogren's (progression of parenchymal stones). If the patient has increased creatinine but non-severe CHF, I would give metolazone, since it's better at lower GFRs.

Also, does vasopressin works on the medullary collecting duct and aldosterone works on the cortical collecting duct is that correct?

It's to my understanding that both the medullary and cortical collecting ducts contain principal and intercalated cells.

ADH binds to the V2 receptor (G-alpha-s [carries a seven-transmembrane domain structure]) on the basolateral membrane of the principal cells, with subsequent insertion of aquaporins on the apical membrane.

Aldosterone binds an intracytoplasmic receptor in both principal and intercalated cells. The former activates the basolateral Na+/K+-antiporter on principal cells and the latter the apical K+/H+-antiporter on intercalated cells.

One more question: If a furosemide is given, does that mean less water will be absorbed from the descending loop of henle to prevent over-tonicity?

Thanks!

I would think that a loop diuretic would not change descending loop reabsorption of water in any way that is quantitatively significant, particularly since the major osmolarity checkpoints, via ADH and aldosterone, are distal.

 

[lemonade90]

First aid 12 says that ACE inhibitors, B blockers, ARB and spironolactone reduce mortality. The thiazide, loop diuretics, and nitrates are key for symptomatic relief.

As I understand heart failure, you need to increase the effectiveness of the work done by the heart to prevent total body ischemia-aka cardiogenic shock (vs. angina in which you need to decrease the work done by the heart to decrease cardiac ischemia). You would like to inc preload, dec afterload, inc contractility/HR. Since you cannot use Starling's curve to increase preload and output (i.e. the cardiac fx curve is maxed out with sarcomeres beyond their optimal point of cross bridging) and sustained HR over a long time period in a CHF is probably not a good idea, you must rely on changes contractility and afterload.

ACE, ARB, sprinolactone and all the diuretics cut afterload and the work the heart must do, so it can eject more blood. Digoxin is good because it increases contractility and output (although I vaguely remember somewhere that this drug is bad for some reason). B blockers seem like a bad idea because they would slow the heart and decreased output but are good for remodeling somehow. I suppose spirinolactone is needed because if you just use thiazide and furosemide, you have a risk of becoming hypokalemic and trigger arrhythmias. You also want to eliminate the body's compensatory mechanisms to retain fluid despite diuretics (i.e. RAS and increased reabsorption at the proximal tubule) which would kick in if you used diuretics alone.

From what I remember, using furosemide would abolish the medullary interstitial concentration gradient because the ions that the thick ascending loop transports are used to create the gradient for the collecting duct and descending loop of henle to use. So yes, less water should be reabsorbed.

 

[Phloston]

From what I remember, using furosemide would abolish the medullary interstitial concentration gradient because the ions that the thick ascending loop transports are used to create the gradient for the collecting duct and descending loop of henle to use. So yes, less water should be reabsorbed.

HY Kidney says that H2O movement in the descending loop occurs both paracellularly and via aquaporin insertion. I could imagine that the loop-induced decreased osmolarity of the interstitium might ebb the paracellular absorption, but I had still been thinking that the difference wouldn't be significant until aquaporin regulation has time to change, which probably wouldn't occur in the time frame immediately following drug administration.

 

[Phloston]

ACE, ARB, sprinolactone and all the diuretics cut afterload and the work the heart must do, so it can eject more blood.

The former two should reduce afterload based on net decreased ATII effects on ATI receptors, but I would think that spironolactone (and eplerenone), as well as the loops and thiazides, would predominantly function via reducing preload.

 

[lemonade90]

The former two should reduce afterload based on net decreased ATII effects on ATI receptors, but I would think that spironolactone (and eplerenone), as well as the loops and thiazides, would predominantly function via reducing preload.

Yes you are right, sorry about the confusion...spirinolactone is key for preload not afterload. ARBs and ACEs are also useful for preload. You can also improve CHF by reducing preload as the myofibers and actin reach a more optimal cross linking arrangement.

With regards to the AQ2 issue, why would you get water going into the interstitum? It was my undrestanding that AQ2 is not dependent on primary or secondary active transport. If there is no gradient/osmosis...why would water go into the luminal cell and then go into the interstitum?