Alpha Agonists – Glaucoma Medications | Driving with Dr. David Richardson
Hello, my name is Dr. David Richardson. I’m a cataract and glaucoma surgeon in Southern California. Today I’d like to talk about a class of glaucoma medications, called the alpha agonist class.
So let’s get going!
Now the alpha agonist class has been around for many decades and it works primarily at the ciliary body which is where fluid in the eye is produced. So what the alpha agonist class does, like most of the topical or eye drop glaucoma medications, is to actually reduce the amount of fluid that’s produced by this tissue, called the ciliary body. Now the interesting thing about the alpha agonist class however is that that’s not the only mechanism that it uses like the prostaglandin analog class, it also allows fluid to leave the eye through what’s called the uveoscleral pathway which is what we’d consider to be an accessory pathway. It’s not the main pathway. The main pathway is through the traumatic meshwork and that’s actually where the problem with most open angle glaucoma tends to be. It’s at the trabecular meshwork so this eye drop not only reduces the amount of fluid that’s produced, but it also allows fluid to escape the eye around the primary problem, the trabecular meshwork. Now the other interesting thing about this class of medications the alpha agonist is that there’s some evidence that it may actually provide what’s called a neuroprotective effect, so an intraocular pressure or iop independent separate benefit to the optic nerve which is a central nerve. The evidence for this is based on a mouse laboratory mouse model in which mice had their optic nerves crushed. So pretty awful those mice who were treated with an alpha agonist had less damage to their optic nerves than those mice that were not treated with the alpha agonist. Now crushing an optic nerve is pretty different from what happens with glaucoma which tends to be kind of a slow progressive damage to the optic nerve over many years but, nonetheless, one might posit that if this class of medications can help the optic nerve survive a traumatic damage, then perhaps the class of medications can also help with longer term damage. We don’t know for sure but there is some other evidence that suggests this may be the case and I’ll talk about that in a bit.
Now then the question arises. Okay well, it’s got all these mechanisms. That’s nice but, how does it really work? So in humans who use this drop, does it work well?, and indeed it does. The brimonidine which is the primary alpha agonist drug available in the United States actually works about as well as timolol but, without many of the systemic side effects of timolol, but not quite as well as the prostaglandin analog class which is the most effective topical medication class for treatment of glaucoma. So that’s actually very effective which makes it a very commonly prescribed eye drop. Now how is this prescribed? In terms of what’s the opportunity where a physician might say let’s prescribe this class of medications. But although it works quite well, it tends not to be what you would call a first line therapy. Most of the time brimonidine is prescribed as a second line. So after someone has been started on, saying a prostaglandin analog or perhaps timolol and the primary reason for that is the dosing that we’ll get to in a little bit.
Now as far as how it’s supplied, brimonidine in the United States is available in the branded name alphagan P which is a 0.1 percent concentration and also available generically as 0.15 and 0.2 percent. Now the brand is preferred because the lower the concentration, the lower the risk of side effects. And we’ll talk about those in more detail later. But also the elf alphagan P uses a special preservative, called pyrite which essentially keeps bacteria from growing in the bottle once the eye drop hits the tear film. The preservative is inactivated, so that decreases the amount of potential damage to the corneal surface which is possible over time with the most commonly used preservative benzyl comanium chloride. Or back the other thing with bak is that it can potentially cause damage to the trabecular meshwork which is the part of the drainage system. That’s already damaged in open amino glaucoma so you certainly want to avoid damaging it further with a drop that’s meant to actually prevent damage. So most of the available alphagan or brimonidine rather comes in multi-use bottles and is just brimonity. But you can also get brimonidine in what’s called a fixed combination. A fixed combination is essentially two or more individual medications in one bottle, so you can get brimonidine combined with timolol and the brand name for that is combigan. You can get brimonidine combined with brinzolamide which is a carbonic anhydrase inhibitor that goes by the brand name simbrinza and that’s a nice combination because there’s no real systemic issue since there’s no timolol or beta blocker in it. And then there’s brimonidine, plus dorzolamide which is available through a compounding pharmacy in New Jersey called impromise. The nice thing about this particular formulation is that it’s preservative free, so no preservative, no damage to the surface of the eye or the trabecular meshwork.
So I’ve already arrived at the office. It seems that I am always talking too long here but there’s still a fair amount to go over in this class. So let me go through that and then sum it up so we’ve gone over the issues of preservative, how this class of medication is supplied. Now, of course, one of the other issues that comes up within a prescription is cost. Now cost is very much dependent on one’s insurance. If the brand is covered by insurance, then that’s really what I recommend because of the advantages that we’ve already talked about. If the brand is not covered, then the two generics that are available the 0.15 percent and the 0.2 have very different coverage among insurance companies. Most insurance companies will not cover the 0.15 which makes it almost as expensive as the brand. And between the two, I would definitely choose the brand over the generic 0.15. The 0.2 percent is almost universally covered but, it does have a higher rate of the side effects that we’ll discuss in a moment.
If your insurance does not cover even the 0.2, then I recommend that you search for a good price through one of the online sites that can help guide you with cash prices. I recommend goodrx.com to my patients as well as to you know anyone on these videos. I have no financial relationship with goodrx. It just seems to work to save my patients a lot of money so highly recommend that if you’re going to pay cash prices and if you have a high co-pay, it’s worth checking just because your cash price could potentially be less than your co-pay. Now how is the brimonidine class or the alpha agonist class? Primarily brimonidine in the US is used well generally. It’s prescribed twice a day and that’s true whether it’s in the brimonidine only or the fixed combination. There is some evidence that it works better three times a day but that third-time-of-the-day dose which is generally the middle of the day is really hard to get in and during our busy lives. So I generally recommend that my patients take it twice a day if you remember a middle-of-the-day dose, then bonus. But don’t feel guilty about it if you don’t get it in because it will still work twice a day. Now I’ve talked about or alluded to side effects. It’s important to know about side effects with every medication. Of course most side effects don’t occur or are quite mild and you know we’re always looking at the risk benefit trade-off the risk of permanent loss of vision with glaucoma versus the side effects. So let’s go over the side effects.
Some of which are pretty mild and some which could be potentially quite bothersome or even serious depending on the individual. So local side effects include irritation or a sense of dryness. That’s true with almost all of the preserved glaucoma medications hybrimia which just means that the white part of the eye gets red or congested and that is more common with the higher concentrations. The 0.2 percent generic has a higher likelihood of resulting in a red eye than the purity preserved 0.1 percent branded alpha again P. I’m an allergic reaction. There’s about a 10 to 15 percent chance of developing an allergy to this class of medications, at some point, over the course of the therapy. And this risk is higher with the higher concentrations. Another reason why preserve, I prefer the pure right preserved alpha again P 0.1. Alright dry mouth can be an issue and then a mild pupil dilation. It’s not usually notable in those with dark irises but in those who have light irises, mild asymmetry can be noted if brimonidine is taken just in one eye. If it’s taken in both eyes most people don’t notice it at all and then the other interesting thing is it can actually lift the eyelid just a bitu, usually by only a half a millimeter to a millimeter which can actually be advantageous. So for many older adults who have a bit of a ptosis which means a drooped lid by often a millimeter or two, this can actually help the cosmetic appearance of course if it’s not desirable. Then if it’s used again in just one eye, that can be an issue and then there are the issues of systemic side effects. Now, fortunately, for the bra monitoring class, unlike the beta blocker class, systemic side effects are quite rare in healthy adults but they can be a bit more common in the elderly and glaucoma being more common as we get older. That’s important to be aware of but they’re especially worrisome among children. So these side effects include a headache, again quite rare but occasionally seen low blood pressure. So just like the beta blocker class, the alpha agonist class can lower blood pressure but the really worrisome things are lethargy. And apnea apnea means discontinuation of breathing. So breathing just stops and those two things are actually a pretty high risk among infants and young children. So brimonidine is generally what we call contraindicated in children under five years old.
Now how can you minimize the side effects? Well, of course, try as much as possible to prescribe just to healthy adults. It’s not always possible. So be aware of the side effects. Avoid it in young children. But then there’s also the issue that we’ve already talked about and that using the lower concentration forms of brimonidine will reduce the likelihood of all of the side effects, unfortunately the side effects of red eye. And an allergy are not going to respond to the same kind of treatment, the either punctal occlusion or the balled up tissue that would benefit those systemic side effects. Now one other thing that’s worth discussing is interaction with other medications. Fortunately with brimonidine, there aren’t a lot of interactions with other classes of medications and the one class that it is known to interact with which is the monoamine oxidase or mao inhibitors are hardly prescribed anymore. Those are actually the first class of antidepressants, approved by the FDA in the US but we’ve pretty much moved away from the maois with the SSRIS and tricyclics and things like that. So, it’s unlikely that interaction would occur now. But it’s worth stating that the brimonidine or alpha agonist class should not be prescribed with mao inhibitors.
So in summary, the alpha agonist class is an effective class that works through multiple mechanisms. May have a neuroprotective benefit which is generally prescribed as a second line treatment although there is an exception to that that I neglected to mention and that is that those who have what’s called normal tension or low tension glaucoma may actually enjoy an added benefit in terms of protecting them from progressive loss of of their visual fields over time compared to say timol. So both timolol and brimonidine were studied and even though they both lowered the intraocular pressure about the same amount, those with normal tension glaucoma who were given brimonidine actually did better over time and so that is one case where brimonidine may be a good first line agent that is for someone with normal tension glaucoma.
So to continue the summary, back to that, the side effect profile is usually mild and well tolerated with the exception in children and it can be quite affordable depending on the insurance coverage as there are generics available although the brand is definitely preferable in this class of medications. So anyway I know this has been a very long video but again I feel that the topics of intraocular pressure lowering classes of medications is so important because almost everybody who has glaucoma is taking one or more of these medications. And it’s important to be aware of the pluses and minuses of each class, the nuances, the costs, all of these things. So I think that it’s probably worthwhile spending 15 plus minutes together on this topic anyway. I hope you agree and if so, I’ll keep making these videos and hopefully providing some useful information that clearly there’s no time in a typical office visit with an ophthalmologist to have a 15 plus minute conversation on one class of glaucoma medications.
So this is my commuting opportunity and parking lot opportunity to share this with you all right have a good day!
David Richardson, MD
Medical Director, San Marino Eye
David Richardson, M.D. is recognized as one of the top cataract and glaucoma surgeons in the US and is among an elite group of glaucoma surgeons in the country performing the highly specialized canaloplasty procedure. Morever, Dr. Richardson is one of only a few surgeons in the greater Los Angeles area that performs MicroPulse P3™ “Cyclophotocoagulation” (MP3) glaucoma laser surgery. Dr. Richardson graduated Magna Cum Laude from the University of Southern California and earned his Medical Degree from Harvard Medical School. He completed his ophthalmology residency at the LAC+USC Medical Center/ Doheny Eye Institute. Dr. Richardson is also an Ambassador of Glaucoma Research Foundation.