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Hydrochlorothiazide for Diabetes Insipidus?

Discussion in 'Step I' started by medstu2006, Jun 4, 2008.

  1. medstu2006

    medstu2006 Senior Member
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    I don't undersand the mechanism of how Hydrochlorothiazide is used to treat nephrogenic diabetes insipidus. I understand that it works at the early distal convoluted tubule and inhibits the NaCl absorption thereby inc the osmolarity of the urine. But so what? The distal tubule is impermeable to water and so is the collecting tubule in the absence of ADH.
    Now, since this is nephrogenic DI, there is ADH present but the collecting tubule does not have the receptors for it. So you are still losing water like you used to, it's just a little more concentrated.
    So it is that some tubules do have receptors and it is those tubules that inc water absorption when a thiazide is used?
     
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  3. Rogue Synapse

    Rogue Synapse The Dude Has Got No Mercy
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    Yeah I didn't understand this either. I think UW even said it was a poorly understood mechanism. Or maybe it's just that I poorly understand it. Because it's so much easier to know something when you understand it, there are only a limited number of things I can just blindly commit to memory without a good explanation, and I've decided that this might have to be one of them.
     
  4. obiwan

    obiwan Junior Member
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    goljan says that by worsening the volume depletion, your kidneys will increase salt/water reabsorption at the proximal tubule.
     
  5. alpha06

    alpha06 Senior Member
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    Thiazides---->inhibit NaCl in DCT------>increased Na excretion------>ECF contraction---->decrease GFR------------>ultimately increase in Na and water resorption in PCT---->decrease urine output.

    I hope I did that right.:rolleyes:

    Don't know if this answers your Q tho.



    Dang-it obiwan, you beat me to the punch...
     
  6. medstu2006

    medstu2006 Senior Member
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    That makes sense.
    There were 2 renal drugs that I thought were used for treatments that didn't make sense. One was thiazides for nephrogenic DA and the other was ACE inhibitors for diabetic nephropathy. Goljan explained the latter in his audio and you guys helped with the former. Thanks guys.
     
  7. It'sElectric

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    So would thiazides work on central DI as well? I can't imagine why not, but I wanted to make sure.
     
  8. alpha06

    alpha06 Senior Member
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    No. For CDI, there is little to no ADH so we give desmopressin to correct it.
     
  9. It'sElectric

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    Yes, yes, I understand that. I was just curious as to whether they would still work (albeit, not as well), since the mechanism seems to work out.
     
  10. alpha06

    alpha06 Senior Member
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    Well....i guess technically you could use thiazides, but it just wouldn't be the DOC for CDI on boards. It would be like going in circles, when you can just solve the problem head-on.
     
  11. Waqar Kabir

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    Well this mechanism seems plausible but I am still confused. I mean how does Thiazide cause diuresis in a normal person i.e a person not having nephrogenic diabetes insipidus??
    According to this mechanism if we only use thiazide therapy that would decrease urine output:
    "Thiazides---->inhibit NaCl in DCT------>increased Na excretion------>ECF contraction---->decrease GFR------------>ultimately increase in Na and water resorption in PCT---->decrease urine output"
    BUT Thiazide is a diuretic. It should not decrease urine output. Instead it should increase output. So what I am asking is what happens differently in a normal patient (not suffering from nephrogenic diabetes insipidus) which causes diuresis and not antidiuresis when we use thiazide??
     
  12. Transposony

    Transposony Do or do not, There is no try
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    Thiazide is a weak diuretic. So, it doesn't cause much diuresis. The reason it is effective in hypertension is because it causes vasodilation by opening K channels in vessels. The same reason it causes hyperglycemia (i.e. by opening K channels in beta cells of pancreas --> decreases Insulin release)

    Thiazides---->Inhibit Na/Cl cotransporter in DCT------>increased Na delivery to collecting duct ------> increased Aldosterone secretion from Principal cells ------> increased Na resorption and water follows.
    So, basically you are making Aldosterone do the work as ADH isn't working.
     
  13. ray656712

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    Increased urine output isn't the therapeutic effect in HTN, but it IS the therapeutic effect in CHF, and other causes of edema. So the question still remains....why do we see this paradoxical effect in patients with nephrogenic DI?
     
  14. zhopv10

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    It's an indirect effect. I believe the mechanism is that the increase sodium excretion leads to volume contraction and decreased GFR this in turn leads to increased sodium and water reabsorption in the PCT thus leading to less water and solute to be lost lost in the collecting duct. Here is a link to an older albeit decent seeming article about it. http://m.jasn.asnjournals.org/content/15/11/2948.full
     
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  15. dfib slim

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    This is pretty much the explanation in UWorld for step 2.
     
  16. Transposony

    Transposony Do or do not, There is no try
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    It appears that both mechanisms are involved.

    From Goodman & Gilman's The Pharmacological Basis of Therapeutics:

     

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