| Transcript |
So, someone asked us to talk about acetazolamide, also known as Diamox. So, acetazolamide, we use in neuro-ophthalmology for Idiopathic Intracranial Hypertension. And Idiopathic Intracranial Hypertension is idiopathic, and it causes intracranial hypertension which means increased intracranial pressure. And so, this order IIH can be treated medically with both acetazolamide and weight loss, and if necessary, surgery. Either a shunting procedure, stenting, or sheath fenestration. We're only going to talk about acetazolamide medical therapy. What you need to know is the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) showed that acetazolamide is effective medical therapy, both for lowering intracranial pressure and for treating the visual field defect of moderate idiopathic intracranial hypertension related vision loss and papilledema. So, there's no question based on the randomized control clinical trial that acetazolamide works for IIH, and that it is our first line medical therapy, in addition to weight loss, for IIH. As you know, most of these patients who have IIH are young, overweight females and so weight loss is our preferred treatment, but Diamox (acetazolamide) is our medical therapy. And so, I normally start at a dosage of 500 milligrams twice a day. But in the IIHTT, we know that we can go to as high as 2 grams, all the way up to 4 grams of Diamox. And normally the rate limiting step is the side effects. The side effects that were seen in the trial but also in my patients are the usual side effects of acetazolamide, which include paresthesias and tingling in the hands and the feet, a metallic taste in the mouth especially for carbonated beverages. Some patients feel fatigue afterwards. It's not a very strong diuretic, so they don't usually complain about going to the bathroom all the time, however it is one of the known side effects. Now you need to know that the major thing that we're worried about with acetazolamide is the metabolic acidosis that follows. The reason is acetazolamide is a carbonic anhydrase inhibitor. What that means is it is an inhibitor of removal of the water (anhydrase) from carbonic acid. And so normally when you have carbonic acid, we can break this carbonic acid down using the carbonic anhydrase to remove the water and generate CO2. So, water and CO2 are easy for our bodies to get rid of. We can breathe off CO2, and we can dump out the water in our urine. And so, these two products are a good thing to have as byproducts when we are breaking down H2CO3. However, if you block the carbonic anhydrase because you are giving a carbonic anhydrase inhibitor, this thing will dissociate into its ionic components, which are H+ and HCO3-. And so, when we have H+ and HCO3-, this will cause problems in the kidney. So, when you're dumping this out into your urine, it will cause the urine to be alkalotic. Alkylurea will result from the dumping of the sodium bicarb into your urine, and that will lead to a metabolic acidosis. So, if we are dumping the bicarb, we're going to be increasing the acid base balance and metabolic acidosis will result. In addition, in your kidney we have very few ways of exchanging these ions, and a plus has to change with a plus. And so, in the kidney, the exchange pump is with sodium. But this sodium also exchanges with potassium. And so, when we are trying to keep the sodium, we are exchanging with the hydrogen, we might be driving potassium out into our urine, and that's why when you're dealing with acetazolamide and its metabolic acidosis, we might end up with a hypokalemia. And that is a potentially life-threatening electrolyte imbalance. In addition, if we're dumping the sodium bicarb, the chloride has to exchange. And so, we might be having a hyperchloremic, hypokalemic metabolic acidosis. And that can make patients feel bad, but it can also cause potentially life-threatening problems. And so, we want to be afraid about acetazolamide in certain conditions. But especially if they are symptomatic from the metabolic acidosis, or if don't actually have Idiopathic Intracranial Hypertension. And the scenario we are most worried about is patients who have cryptococcal meningitis. So, in cryptococcal meningitis, they have intracranial hypertension, but it is not idiopathic. And if you give acetazolamide to that person, it was shown in a randomized control clinical trial that acetazolamide not only didn't help the cryptococcal meningitis people, it was more likely to produce an adverse outcome, and that adverse outcome was death. So, we give acetazolamide to Idiopathic Intracranial Hypertension, but you should use it with caution in other causes of intracranial hypertension, especially if they have metabolic acidosis and probably you shouldn't give it for cryptococcal meningitis even if their intracranial pressure is quite high, because the patients die. And in those cases, we use serial lumbar punctures or even a lumbar drain, rather than the traditional medical therapy of acetazolamide. So, in summary, you should use acetazolamide for IIH. It's our first line. I started 500 milligrams twice a day. We can go up to 2-4 grams. And beware the metabolic acidosis, because it is a carbonic anhydrase inhibitor. |
