Medications and How They Work
Chat Highlights
August 21, 2002

Norma Devine, Editor

On Wednesday, August 21, 2002, Dr. Rick Wilson, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Medications and How They Work."

Moderator:  Dr. Rick, we know that some glaucoma medications decrease the production of the aqueous humor and some increase its outflow.  Could you start by telling us about those medications and how they work?  

Dr. Rick Wilson:  Trusopt and Azopt, which are carbonic anhydrase inhibitors (CAI's), and Alphagan and Iopidine, which are alpha-adrenergic agonists, work by decreasing the production of aqueous fluid.  Beta blockers work the same way.  They are Timoptic, Betoptic, Betoptic-S, Ocupress, Betimol, and OptiPranolol.  

Moderator:  Aren't there also some oral CAI's that decrease the production of the fluid?

Dr. Rick Wilson:  There's Diamox, and we used to have Neptazane, but I think they recently stopped making it.  

Moderator:  What are some of the side effects of Alphagan and Iopidine?

Dr. Rick Wilson:  The side effects include red eye, dry mouth, fatigue, headache, allergy, and skin reaction.

P:  And what are some of the side effects of the beta blockers you mentioned?

Dr. Rick Wilson:  The side effects include fatigue, shortness of breath, slow heart rate, depression, hair loss, impotence and worsening of asthma. 

P:  How long before you notice hair loss?

Dr. Rick Wilson:  Usually three to six months.  

P:  If you had asthma as a child, should you avoid beta blockers?

Dr. Rick Wilson:  There is the possibility that beta blockers could cause a recurrence.  

Moderator:  Dr. Rick, what are the names and side effects of some of the drugs that increase the outflow of the aqueous humor?

Dr. Rick Wilson:  Pilocarpine, carbachol, and phospholine iodide (miotics) work by increasing fluid outflow.  The side effects include small pupil, headache, blurred vision, change in refraction, decreased visual field, retinal detachment.  The prostaglandins -- Xalatan, Rescula, Travatan, and Lumigan -- work by increasing fluid outflow via an alternative pathway.  The side effects are change of iris color, red eye, eye irritation or inflammation, flu-like syndrome and arthritis.

P:  How do miotics work?

Dr. Rick Wilson:  Miotics pull on the ciliary muscle, which is inserted into the back of the trabecular meshwork. This pulls the spaces between the meshwork open more and increases the flow of fluid out of the eye.

P:  Why do patients using pilocarpine have brow aches and headaches? 

Dr. Rick Wilson:  That is just in the beginning, before the muscles in the iris and ciliary body get used to working all the time. 

Moderator:  What are the pathways for the drainage of the aqueous humor?

Dr. Rick Wilson:  The aqueous humor, as far as we know, exits mostly out the trabecular meshwork to the canal of Schlemm and into the aqueous veins on the surface of the eye.

P:  Is there another pathway for the outflow?  

Dr. Rick Wilson:  The second main pathway is into the spaces between the muscle fibers of the ciliary muscle of the eye and out through the wall of the eye into the aqueous veins.  

Moderator:  Are some of the meds designed to use only one of those two pathways?

Dr. Rick Wilson:  All use mainly one or the other, although some like Lumigan, more than the other prostaglandins, are said by the manufacturer to act on both outflow pathways.

P:  If the venous pressure is up (for example, due to Graves' ophthalmopathy), even the uveoscleral (prostaglandin- mediated) pathway will be compromised, right? 

Dr. Rick Wilson:  The uveoscleral pathway will be compromised much less than the trabecular meshwork, but all may be compromised.

P:  I'm having no side effects from using Lumigan, but I've only been using it for three weeks.  When are the side effects usually noticed?  

Dr. Rick Wilson:  The redness and irritation are usually maximal in the first week, although the surface toxicity can mount up over time.  The changes in iris color and lash growth may take months.

P:  Why do many glaucoma specialists treat their patients with four or more different eyedrops?  I was on five at one time.  Didn't you say in this chat room that more than three are useless?  

Dr. Rick Wilson:  Occasionally, the fourth drop can be successful, but most often not. 

P:  Do a large percentage of patients suffer from side effects?

Dr. Rick Wilson:  Yes, I'm afraid they do.  Most of the side effects are more a nuisance, like dry mouth or stinging, but some compromise the quality of life.

P:  How do medications work when the angle is closed?

Dr. Rick Wilson:  The aqueous suppressors work fine, because they work back on the ciliary body, where the fluid is made. That is behind the iris. The outflow enhancers are usually ineffective if the angle is closed.

P:  Which is more toxic, Xalatan or Lumigan?

Dr. Rick Wilson:  Lumigan, hands down.

Moderator:  Since there are only two mechanisms of action (increasing outflow and decreasing production), how effective is it to add drugs of the same type? 

Dr. Rick Wilson:  It is increasingly less effective the more you add, sort of like beating a dead horse.  One can only beat down the ciliary body so much.

Moderator:  How long should a glaucoma patient remain on three or more kinds of drops that have different mechanisms of action before stopping one to find out what the effect is?  

Dr. Rick Wilson:  In patients who have been on medications for a long time, we do not do a good job of checking whether the meds are still working.  The extra visits are an expense to the patient and take a lot of the doctor's time.

P:  How do you tell if a newly added medication is working?

Dr. Rick Wilson:  Medications should always be added as a one-eyed trial to see whether the intraocular pressure in that eye drops relative to the intraocular pressure in the other eye. If it does, then we think the medication is working.  

P:  I have been on five kinds of drops for a long time.  A new glaucoma specialist has now reduced that number to three, but since Cosopt is a combination of two meds, that's really four.  What do you think?

Dr. Rick Wilson:  I have no one on five medicines, as almost certainly not all five are effective.

P:  If Cosopt does not work as a therapy of second choice, what would you suggest as a third choice?

Dr. Rick Wilson:  Have you tried a prostaglandin?  According to one paper at the American Glaucoma Society meeting, a good combination was Trusopt plus a prostaglandin analog.  Alphagan would also be a good combination, if you haven't used it before.

P:  Are there any corneal problems associated specifically with carbachol?

Dr. Rick Wilson:  There are with Pilogel, but not with carbachol, to my knowledge. 

P:  Can anything be done to offset the flu-like side effects of Lumigan?

Dr. Rick Wilson:  Aspirin can be taken, but the side effects can be chronic and often require discontinuation.  

P:  What can be done about fatigue and is that a side effect of Lumigan? 

Dr. Rick Wilson:  Lumigan causes a tired feeling in the eye, but I don't hear about it causing fatigue.  

Moderator:  What can patients do to minimize side effects?

Dr. Rick Wilson:  That depends upon the side effect. Any specific thoughts?

Moderator:  How about occluding the puncta?

Dr. Rick Wilson:  Patients can use punctal occlusion and passive lid closure after instilling the drop to cut down on the absorption of the drop into the body.  That cuts down systemic absorption greatly.  

P:  What is "passive lid closure?"

Dr. Rick Wilson:  Passive lid closure is just closing the eye gently for three minutes after putting in the drop.

P:  I have exfoliative glaucoma and my intraocular pressures go up when my pupils are dilated.  I may have to have surgery on my spine and I'm concerned about the anesthetic dilating my pupils, as well as being in a face-down position during surgery.  Are there any compounds that especially ought to be avoided for someone whose IOPs (intraocular pressure) increase with dilation of the pupils?   

Dr. Rick Wilson:  The biggest risk for general anesthesia, if your angles are sufficiently deep, is if your systemic blood pressure drops too low for the blood flow to your eye.

P:  Dr. Wilson, for two years my IOPs have been 24 to 26 mm Hg.  I have no loss of optic nerve tissue, my visual field tests and two HRTs (Heidelberg Retinal Tomograph) show no changes and no damage.  The cupping on both eyes is less than 0.1.  I am 38 years old, male, Caucasian, with no history whatsoever of glaucoma in my family.   Yesterday, my ophthalmologist said I need to start taking drops (Travatan).  He recently read the results of the Ocular Hypertension Treatment Study that indicates the sooner you start taking medication, the better.  He said that I am a borderline case, and that he does not know what to do, but it would be best to start using the drops.  I feel very insecure and troubled.  I know if I start using the drops, that will continue for the rest of my life.  I would greatly appreciate your suggestions.  

Dr. Rick Wilson:  The first thing you need is to have your central corneal thickness measured.  If your cornea is thick, your real pressures may be absolutely normal, but give a high reading with applanation tonometry.  You need photographs of the optic nerve, and a short wave-length, automated perimetry evaluation for a baseline.  According to what you have said, most glaucoma specialists would probably not treat you.  

Moderator:  Thank you very much for all your help tonight, Dr. Rick.   

Dr. Rick Wilson:  Next Wednesday night, Elliot Werner will be here to discuss the results of the Ocular Hypertension Treatment Study.  I hope you will have lots of good questions ready to ask him. 

End of highlights for August 21, 2002.

On August 28, Dr. Werner discussed "Ocular Hypertension Treatment Study (OHTS)" in the Chat room. Click here for highlights of that meeting.

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