Acetozolamide side effects

[Premedico]

Hi,

Can someone please explain to me how acetozolamide causes 1) ammonia toxicity and 2)neuropathy.

Also, why does hyperosmolality cause hyperkalemia?

Thank you

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[mrmandrake]

Off the top of my head I only know why hyperosmolarity causes hyperkalemia. It is because K+ ions follow water. In a hyperosmotic state, water will leave the ICF and go to ECF and since K+ follows, you get hyperkalemia.

 

[RySerr21]

In the proximal tubule, you have a Na/H exchanger on the luminal membrane thats gonna be pumping Na in to the cell and protons out into the lumen. The protons are being made inside the cell from the reaction of carbonic anhydrase, CO2, and water. So that H+ that is being pumped into the lumen reacts with NH3 to make NH4, which is then excretable and not damaging to your body. If you take a carbonic anhydrase inhibitor, you are going to be inhibiting that reaction (CO2 + H2O ---- HCO3 + H), which is providing you the protons that are being secreted into the lumen and combining with NH3. So, with CA inhibitors you get an increase in NH3, which is not excretable, and you get NH3 toxicity, which I think is what causes the neuropathy.

 

[Premedico]

Awesome! Thanks a lot guys.

 

[drwierdo]

Another possible explanation: In the DCT, the carbonic anhydrase splits CO2 into H+ and HCO3-. The H+ is pumped into the lumen by H+ ATPase while de-novo HCO3- is absorbed into the blood. The pumped H+ buffers with non-titrable acid buffers like the HPO4-- and NH3. When acetazolamide inhibits the CA, there won't be any secretion of H+, so, that the NH3 is not excreted as NH4+ and is absorbed. This leads to ammonia toxicity and neuropathy.

 

[aspiringmd1015]

yes, but know the primary site of action is the PCT.