Prostaglandin Analogs, Cholinergic Receptors Agonists, Fixed Combination Agents

Prostaglandin analogs – there’s a whole
bunch of them available now. They open the drain but not through the regular
drain. They open up the drain through the uveal scleral
outflow. They work quite well but they do have some
local side effects that can be—depending on the patient—either desirable or bothersome. Conjunctival Hyperemia almost always bothersome,
iris color change almost always thought bothersome and it only happens in the pigmented areas
so if you got somebody that has blue eyes and there’s no pigment they’re going to
stay blue. If you’ve got somebody that’s got blue
with brown spots the spots are going to become more noticeable. Hazel eyes become more brown. If you’ve got somebody with a dark brown
iris it’s not going to matter. Lash growth most people appreciate that although
some of the prostaglandins do tend at least under this Slit lamp to provide more of **** spidery,
unruly lash growth which isn’t always appreciated. And men don’t always appreciate it but the
other thing we’ve been seen recently is prostaglandin associated periorbitopathy (that’s
a mouthful), which is essentially a reduction of the tissue around the eye now early on
again it can be rather desirable right so you’ve got somebody with some excess bags
under the eyes, apply the prostaglandins things seem to tighten up a little bit like they’ve
had a little laser surgery tightening or sometimes it even looks like they’ve had a lower lid
Bleph. That’s great early on but if it progresses
too far it can actually tighten the lid so much that it’s difficult to obtain a pressure
measurement using Goldman applanation tonometry so this can actually get in the way of your
ability to monitor glaucoma. Now there’s some other things you can get
intraocular inflammation. This is controversial but the prostaglandins
are part of the inflammatory cascade. So it makes perfect sense that they are pro-inflammatory
and indeed there’s evidence that they can increase the risk of macular edema at least
in those patients who are already at risk for macular edema, herpes virus reactivation
can be an issue so you should generally not use this particular drop to lower the pressure
in somebody who has a history of herpes virus infection at least of the eye, and then headaches—
there have been reports of pretty severe nocturnal headaches. Speaking of headaches, Cholinergic Receptors. Pilocarpine that’s the one thing we all
think about with pilocarpine is headache. Now these are still around because they can
still be quite useful for those of our patients with narrow angles but there also still worth
being aware of just in terms of general practice. Because they do work pretty well — they
open the drain through a different mechanism than the ones we’ve talked about. Essentially they provide some tension on the
posterior trabecular meshwork and allow increased outflow. But brow ache poor night vision due to the
meiosis induced myopia and then there are these other issues—retinal detachment more
of an issue with high myopias but of course if you’ve got a retinal detachment and somebody
who has a small pupil that you can’t dilate, that’s an issue. And then less likely but something that was
more commonly seen with the older agents in this class and also when we were using this
drop a lot more, cicatricial conjunctival pemphigoid, corneal endothelial toxicity,
so it’s not just the carbonic anhydrase inhibitors that can give you issues with the
corneal endothelium it’s also pilocarpine. And then band keratopathy. Fortunately we now have these Fixed Combination
Agents. We have three of them here in the US Cosopt®
– Timolol + Dorzolamide, Combigan® ® – Timolol + Brimonidine, Simbrinza® which is Brimonidine
+ Brinzolamide. My current favorite is Simbrinza® simply
because it doesn’t have a Timolol component. Now the other thing to keep in mind here is
that these agents, Cosopt® and Combigan® , the two that are Fixed Combination Agents
which do have Timolol in them, you’re using these twice a day. It’s a twice a day agent where you’re
using timolol twice a day which really is best used once a day in the morning because
the night-time dose doesn’t really help you all that much in terms of the aqueous
production which drops at night anyway. But the other thing is we now know that using
Beta-blockers at night can potentially put patients at risk for what’s called dipping,
which is where their blood pressure drops by 10 points patients who dip are at a much,
much higher risk of progression with their glaucoma. So why in the world would you want to use
a drop that places a beta blocker in the eye but then moves systemically in most patients
at night? Now the other issue here is we’re dosing
these twice a day Cosopt® and Combigan® . Well, Dorzolamide and Brimonidine both work
best three times a day. So the Cosopt® and Combigan® — I’ve
almost entirely eliminated from my practice because in my mind these are just bad compromises. You’re not getting the right dosing on the
Brimonidine and the Dorzolamide and you’re getting too much Timolol and potentially actually
putting your patient at risk if they’re a dipper. Now if you’re worried about dipping, you
can get a 24-hour blood pressure monitoring. It’s not that expensive. It’s not that much of a hassle. Generally you work with the internist. Most internists are happy to do it because
it’s information they’d like anyway but for that reason I’ve really moved to Simbrinza®
using— recommending it three times a day. The patients don’t get that middle of the
day dose so I tell them don’t feel guilty about it just try to do it. We’ve all got more guilt than we need. So those are the drops.

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