Oral Carbonic Anhydrase Inhibitors – Glaucoma Medications | Driving with Dr. David Richardson

Hello, I’m Dr. David Richardson, a cataract and glaucoma surgeon in Southern California. And during my commute, I like to discuss those topics that there’s simply not enough time to discuss in detail during a typical office appointment. So, today, I’d like to discuss a class of glaucoma treatments. This class is the carbonic anhydrase inhibitor class of medications and, in particular, I’m going to focus on the oral medications today, the ones that are taken by mouth. And at a later time, I will discuss the eye drop or the topical treatment. 

Alright, let’s get going. 

So, the carbonic anhydrase inhibitor class has been around for about three quarters of a century as such it is one of the longest available treatments for glaucoma and it’s actually quite an effective glaucoma treatment. It works by reducing the amount of fluid that’s produced in the ciliary body. The ciliary body is tissue behind the iris or the colored part of the eye that produces fluid that then bathes all of the internal surfaces of the eye, takes nutrients, removes waste products and then it drains through the trabecular meshwork into the schlemm’s canal and out the collector channel system. Now open angle glaucoma is thought to be due to a problem of the trabecular meshwork or the drainage grate as it’s commonly called among surgeons. Now, this treatment, the carbonic anhydrase inhibitor class like most of the glaucoma medications, does not work at the trabecular meshwork. It works at the level of the production of fluid. Now acetazolamide is the main generic version of the oral carbonic anhydrase inhibitors. The other one is methazolamide of the two acetazolamida. It is generally the one that’s prescribed the most because it’s more effective. It’s generally taken four times a day in the generic form although there is an extended release form that can be taken twice a day. This is generally preferred among physicians as well as patients. But, unfortunately, even though this cost of medications has been around for over 70 years and you would think that because of that it would be inexpensive, over the last few years, it’s gone from being very affordable to quite unaffordable and especially the extended release versions. So when would this class of oral medications be prescribed? Well, because of some things I’m going to tell you about in a few moments. 

This class is generally reserved for those who have very high intraocular pressures uncontrolled with eye drops, or those who are in what we call the perioperative period so either anticipating surgery and we need to do something to emergently get their pressures down. Or after surgery, if they experience what’s called an intraocular pressure spike which is relatively common after glaucoma surgery, you can have pressures that are too high for a while and too low for a while. And you have to do what you can to get them into the sweet spot. This is a very effective medication for that. But the problem is that it has a number of side effects. Some of these side effects are localized to the eye, so for example, the need to change prescription glasses because of induced myopia which is becoming more nearsighted. Now this is usually transient, so it starts when you take the medication. It tends to get a little better with time and then it should resolve when the medication is discontinued. The other thing oddly enough is that it can actually put someone at risk for developing angle closure, so the angle, where the trabecular meshwork is, closes off. You end up with a very high pressure which could lead to a sudden loss of vision. Now the irony, of course, is that we often use diamox which is the brand name of acetazolamide to treat very high pressures even those from angle closure. So, this is an unlikely risk but it is one that has to be considered. Then, there are a number of systemic issues and side effects with this classic medication when taken orally. Especially, there can be an odd metallic taste that is experienced especially common with carbonated beverages which would be really annoying if you’re a coke fan or pepsi depending on which side you’re on. There can be some tingling of fingers, frequent urination,  acetyl sulfide and methazolamide that do end up acting as diuretics. And all of those things are pretty annoying but not life-threatening. There are other things that are a bit more than just annoying. One is gastrointestinal distress. Now this can range from just upset stomach to cramps nausea vomiting diarrhea which, of course, diarrhea is bad enough that could be significant in terms of one’s health. No fortunately, the issue with diarrhea and the gastrointestinal issues tend to be addressed with just taking the medications with food. And as much as possible, I’ll try to mention what the ways are to reduce the associated risk. 

So I just parked in my office parking lot, so I’ll try to finish this up now. But there are a number of risks of this particular medication we’ve not even gotten to the really important ones. There can be some fatigue, lethargy, depression and even impotence which is a particular syndrome that’s noted with this class of medications, kidney stones as a diuretic. This particular diuretic you’re at increased risk of that. The best way to avoid that or to reduce the risk is actually to keep hydrated and then there are some rare, but life-threatening issues you can have what’s called an acidosis in which case the blood becomes more acidic. If it’s mild, it’s not a big deal but, more severe acidosis could lead to hospitalization. Hypokalemia which is a low potassium that is transient usually just starts with the initiation of the medication and then gets better. For most people, all that needs to be done is improved dietary supplementation, so eating bananas, spinach, broccoli or sometimes a supplement. Then there are some very serious but rare fortunately potential side effects. One is called stevens-johnson syndrome, in which the mucous membranes. It just starts falling apart and this can be life-threatening and often requires hospitalization and intense medical treatment. And then the other one that is fortunately very very rare but definitely life-threatening is what’s called aplastic anemia in which case the body just stops producing blood cells. Now this can’t be detected by laboratory testing. And so, generally, what’s done or what’s recommended is just that people are aware of the issues, symptoms of anemia, so trouble breathing, the loss of energy and fatigue. Of course, we talked about the other side effects which are fatigue and loss of energy. So that makes it a little difficult to detect, and then bleeding issues. So, for all of these reasons as you can imagine, this class of medications is not prescribed very frequently and I’ve not even gotten to the end. Quickly you should avoid these medications when already taking the thiazide class of diuretics. When already taking digitals, there may be some overlap in terms of allergy with those who have an allergy to sulfa medications although that is not agreed upon by everyone. So in summary, as a class the carbonic anhydrase inhibitors work really well to lower pressure but, when taken orally come with a long list of side effects that range from annoying to life-threatening and so for this reason we really don’t prescribe them, except when an individual is at high risk of rapidly losing vision from a very elevated intraocular pressure. There are exceptions to that eye as well as other ophthalmologists have patients who are taking these chronically and doing quite well on them but, in general we do try to avoid them if we can and and so that will then set the stage for my next video which will be discussing the same class as an eye drop and essentially what happens with that risk benefit ratio in the eye drop form. 

Alright, hope you found this informative and I’ll see you again shortly I hope

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