Beta blockers, Selective Alpha Adrenergic Agonist, CAIs for Glaucoma
So in terms of the Beta-blockers—Timoptic, Betaxolol (and others) pretty much, all we use is Timoptic for most of our patients unless they’ve got some cardiovascular issues. These have been around for a very, very long time, we know they work well, and they work by turning down the faucet. So the Beta-blockers supress aqueous production and they do that do that by inhibiting c-AMP (cyclic mp). Now— again we’re not going to go into all of the scientific, and laboratory bench work on all of this because it’s a lot to take in. And if you want that the papers are available you can break out or dust off your old textbooks but I just want to make sure we get through everything today, which is quite a bit. One other thing is although you’ve got some paper there and some pens to take notes for pearls and what not, don’t worry about getting all of these. My plan is at some point to make these slides available online and when I do so (I will) we’ll send out a notice to everyone.
So in terms of the Beta-blockers – although they’re cheap, widely available, and tolerated by most people there are some issues with them. They can cause ocular irritation (topically) but more concerning is Bradycardia (so low heart rate), arrhythmia (irregular heart rate), heart block (systemic just stop the heart), systemic hypotension (so low blood pressure) and even heart failure. And traditionally we’ve been told well you know be careful about using these in your elderly patients because they might be more sensitive to the Beta-blockers. So you know think you’ve got somebody who’s young and healthy shouldn’t be a problem. Be careful though. I once had a patient who is in his 40s—an athlete, stocky guy— gave him a timolol, told him beforehand (thankfully) that these were issues, he ended up in the emergency room the first night that he took a Beta-blockers because he was—although his heart rate was reasonable for an athlete in the 50s and 60s, when he took the Beta-blockers – because he started off so low, he dropped down below 40. So you do need to be careful about that.
Basically anyone who’s not really healthy or really unhealthy should be okay. But if you’ve got an athlete or somebody who’s elderly and in terms of their cardiovascular status not so strong, you should be worried. Now they’re also non-cardiac issues: Central nervous system depression, impotence – if you’ve got somebody who’s taking the blue pill probably not a great candidate for Beta-blockers (by blue pill you all understand Viagra or its fellow agents). More importantly than that, it may mask signs of hypoglycemia.
So if you’ve got diabetic patients who fluctuate a lot and occasionally have hypoglycemic episodes, you do not want to use Beta-blockers. It can also exacerbate asthma and you know from the things that I just mentioned, I think it’s pretty clear to see it can also result in death. We don’t see it very often but it does happen. “Selective” Alpha Adrenergic Agonists Selective Alpha Adrenergic Agonist is the next class I’m going to look at and that’s basically Brimonidine works by turning down the faucet and the selective one such as Brimonidine also opened the drain.
So it’s nice this particular agent actually does both. But as we’re aware it causes ocular irritation and more worrisome than ocular irritation is the Follicular Conjunctivitis – this can happen up to 15% of the time and when it happens it could be whopping and you have no choice but to discontinue. Of interest is you can also see eyelid retraction, contact dermatitis and occasionally, although, we don’t think of it that often a headache. Other things: dry mouth, systemic hypotension, so it’s not just the Beta-blockers. Bradycardia, Arrhythmia, Death – it’s unlikely but we can see it. But with regard to these last three here it’s most worrisome in infants and small children. The adrenergic agonist should not be used in infants and small children because of the risk of central nervous system depression and death. Now interestingly there are a couple of potential benefits of the selective alpha adrenergic agonist such as Brimonidine.
One is if you’ve got somebody with a small ptosis of approximately one millimeter, Brimonidine is a great medical way to treat a small ptosis. It’ll lift the eyelid by about a millimeter. Also in terms of normal tension glaucoma there is evidence that between a Beta-blockers and an alpha adrenergic agonist (Brimonidine), that even with the same amount of intraocular pressure lowering, patients do better with Brimonidine. So in other words their visual fields are more stable – less likely to get worse over time.
Carbonic Anhydrase Inhibitors (CAIs) The Carbonic Anhydrase Inhibitors (the next class that we’ll talk about) so basically the Azopt® Brinzolamide and & Trusopt Dorzolamide. These work by turning down the faucet – decreasing aqueous production. Carbonic anhydrase is present in the ciliary epithelium. Now, the problem is that you have to actually block about 90% of the enzyme in order to get the effect that you want.
So the problem with these is that they don’t actually work all that well. Of the drops we’ve talked about so far, they’re the least likely to work. Fortunately they don’t have too many side effects – irritation (that seems to be pretty common with anything that you’re going to use), punctate keratopathy, some blurred vision and some bitter taste. As I was saying 90% blocking has to occur to get an effect 15% reduction pressure – not that impressive. Now importantly, carbonic anhydrase is also used by the corneal endothelium in order to pump fluid out of the cornea. So if you’ve got somebody with a corneal endothelial dysfunction this may not be the best choice. Lower pressure but might swell the cornea up a bit.
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