||Summary: Idiopathic Intracranial Hypertension (IIH) • Increased intracranial pressure of an idiopathic nature • Treated with acetazolamide/weight loss + surgery as deemed necessary o Acetazolamide (Diamox) is an effective first-line therapy according to IIH Treatment Trial (IIHTT) -Lowers intracranial pressure -Treats vision loss and papilledema stemming from IIH IIH Patients and Treatment • Tend to be young, overweight females o Weight loss is preferred treatment • Acetazolamide is effective medical therapy o Normal dosage is 500 mg a day -IIHTT allows for dosage of up to 2-4 grams/day o Dosage limited by side effects -Paresthesias -Tingling in hands/feet -Metallic taste in mouth following consumption of carbonated beverages -Fatigue -Frequent urination is a known side effect, but a rare complaint from IIH patients treated with acetazolamide Metabolic Acidosis due to Acetazolamide Treatment • Acetazolamide is a carbonic anhydrase inhibitor o Removes water from carbonic acid o Generates water and carbon dioxide -Water and carbon dioxide are easily removed from body -good byproducts • Carbonic anhydrase inhibition prevents build of these good byproducts o Carbonic acid will subsequently dissociate into hydrogen and bicarbonate ions -Kidney pushes bicarb into urine -alkylurea + metabolic acidosis • Na+/H+ exchangers and Na+/K+ pumps result in potassium being pushed into urine HYPOkalemia (life threatening) • Chloride/bicarbonate exchanger impacted due to dumping of bicarbonate into urine HYPERchloremia (life threatening and causes patient discomfort) •Hypokalemic hyperchloremic metabolic acidosis o Acetazolamide contraindicated for patients without IIH or with metabolic acidosis due to potentially life-threatening electrolyte imbalances Cryptococcal Meningitis • Cryptococcal meningitis results in non-idiopathic intracranial hypertension o Acetazolamide administration during clinical trials for cryptococcal meningitis patients resulted in adverse outcomes (death) • Serial lumbar puncture or lumbar drain used to relieve intracranial pressure instead of acetazolamide for cryptococcal meningitis patients [Transcription of video] "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." Questions Any thoughts on other medications to treat Diamox, such as methazolamide, and their effectiveness? • Methazolamide can effectively substitute for Diamox when the side-effects of Diamox are intolerable. Other suggested medications for effective treatment of IIH include Topiramate and Furosemide. I have just been diagnosed with IIH and have been taking Diamox - does it cause severe stomach pain? • Stomach pain is a potential side effect of Diamox treatment. It is recommended to take Diamox with a meal in order to prevent stomach discomfort. Can you develop the kidney problems if the dose is too high? I take 1000 mg at night and have for 5 years. I have lost weight and dose has not been adjusted since. I am having a lot of kidney issues, even stones. • High dosages of Diamox can lead to problems with the kidney. It is important to talk with your provider about severe side effects in order to evaluate the benefits of treatment. Would it be beneficial to take a potassium vitamin along with acetazolamide to prevent any issues? • Potassium supplements are often used to treat low potassium levels caused by acetazolamide. Talk with your doctor to determine if a potassium supplement is recommended in your treatment plan.