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Glaucoma drugs Glaucoma is a major cause of blindness and of great pharmacologic interest because the chronic form often responds to drug therapy. The primary manifestation is increased intraocular pressure not initially associated with symptoms. Without treatment, increased intraocular pressure results in damage to the retina and optic nerve, with restriction of visual fields and, eventually, blindness. Intraocular pressure is easily measured as part of the routine ophthalmologic examination. Two major types of glaucoma are recognized: open angle and closed-angle (also called narrow-angle). The closed-angle form is associated with a shallow anterior chamber, in which a dilated iris can occlude the outflow drainage pathway at the angle between the cornea and the ciliary body (see Figure 6–9). This form is associated with acute and painful increases of pressure, which must be controlled on an emergency basis with drugs or prevented by surgical removal of part of the iris (iridectomy). The open-angle form of glaucoma is a chronic condition, and treatment is largely pharmacologic. Because intraocular pressure is a function of the balance between fluid input and drainage out of the globe, the strategies for the treatment of open-angle glaucoma fall into two classes: reduction of aqueous humor secretion and enhancement of aqueous outflow. Five general groups of drugs—cholinomimetics, a agonists, β blockers, prostaglandin F2a analogs, and diuretics—have been found to be useful in reducing intraocular pressure and can be related to these strategies as shown in Table 10–3. Of the five drug groups listed in Table 10–3, the prostaglandin analogs and the β blockers are the most popular. This popularity results from convenience (once- or twice-daily dosing) and relative lack of adverse effects (except, in the case of β blockers, in patients with asthma or cardiac pacemaker or conduction pathway disease). Other drugs that have been reported to reduce intraocular pressure include prostaglandin E2 and marijuana. The use of drugs in acute closed-angle glaucoma is limited to cholinomimetics, acetazolamide, and osmotic agents preceding surgery. The onset of action of the other agents is too slow in this situation. First, you need to know that glaucoma involves (usually) increased intraocular pressure because of the amount or accumulation of aqueous fluid. B2 receptors in the ciliary body produce aqueous when stimulated, aqueous enters the posterior chamber (the area between the lens and iris= "inflow tract"), which then drains through the pupil and into the anterior chamber (the area between the lens and the cornea = "angle"), which then drains through the trabecular meshwork, into the canals of schlemm, to the episcleral vein and then goes back to the general circulation. Ideally, the rate of production should equal the rate of drainage. 2 types of glaucoma: Closed/Narrow Angle Glaucoma (means the ciliary epithelium is causing the lens and iris to stick together) so there is pressure/fluid buildup in the posterior chamber. These patients might not have elevated intraocular pressure b/c that is measuring the pressure of fluid in the anterior chamber, which is not the problem here. -- This type is either chronic, but usually is an acute/emergency attack and is precipitated by pupil dilation; At the ciliary muscle, B2 stimulation overrides the M3 stimulation and causes the muscle to relax and leads to dilation (for distant vision)- this pulls the zonular fibers and flattens the lens and makes the posterior chamber even smaller. Also, when the iris radial muscle (alpha1) is stimulated, the pupil dilates and closes the angle as well (this is why you don't give Epinephrine to someone with closed angle glaucoma). Closed angle glaucoma is treated usually with pilocarpine or carbachol because they stimulate M3 receptors (contraction of the iris circular muscle- this pulls the trabecular meshwork away and increases the amount of aqueous drained, the ciliary muscle also has M3 but these are only for accomodation), First Aid also says you can use physostigmine or echothiophate (these would be longer acting because of the anticholinesterase effect- long duration of M3 stimulation), but in reality - these really aren't used, maybe echothiophate, but rarely and only in serious conditions. The more common type is Open Angle Glaucoma: either the trabecular meshwork (M3) is obstructing the canal of schlemm and causing accumulation of aqueous in the anterior chamber OR the ciliary body is producing (a2) or releasing (B) too much aqueous and it can't be drained quickly enough. You have high intraocular pressure, but usually no eye pain because accomodation is not affected. You can treat this by: -alpha2 agonists to vasoconstrict the ciliary body and prevent excess production of aqueous -beta blockers to stop the ciliary body from releasing too much aqueous -prostaglandins to vasodilate the canals of schlemm and increase outflow -direct/indirect cholinergics to increase outflow (M3) -if the person's intraocular pressure is super high you'll likely also give a carbonic anhydrase inhibitor to decrease synthesis of aqueous in the ciliary body (there are also combined a2 agonists/ b2 blockers and b2 blockers/ CI inhibitors for someone who has a really high IOP) Ultimately selection depends on what type of glaucoma (open or closed), and if it is open, you need to know if it is due to overproduction or undersecretion. I don't think on the USMLE they would expect you to differentiate this, they'd probably just ask drug mechanism or contraindications /side effects (ex, Beta blockers could have systemic effects, prostaglandins cause iris to darken and lashes to lengthen) Also they could ask about opiods which cause miosis because of central parasympathetic stimulation and used to be used in eye surgeries. In closed angle, it depends on the etiology. With age the lens will get larger and push into the ciliary epithelium, then fluid is not getting into the AC (this can be a really big cataract, or just natural rigidity w/ age) and then the angle between the iris and the trabecular meshwork closes; again, little to no flow in or out of the AC. You could have really significant hyperopia (far sighted) which makes your eye longer and narrower, and that makes the angle between the iris and the cornea (where the trabecular meshwork is) smaller naturally. This does't get to be a problem until you're old and the lens is more rigid and pushes up into the iris and sticks to the ciliary epithelium, OR if you take a drug that causes dilation OR if you have trauma or an infection (esp. iritis/uveitis) that causes local inflammation. Then there is little to no flow into or out of the anterior chamber. So for terminology sake, there is "primary narrow angle glaucoma" which is the old person with natural changes. Technically the young hyperopic person is also primary narrow angle, but the closure usually doesn't occur until there is a secondary trigger, or until the person gets old = "angle closure". So the angle actually closing is the final part of the attack, but what causes the angle to close is the enlargement of the lens and adherence to the ciliary epithelium in an already susceptible eye- so now the person is not filling the AC with new aqueous nor are they draining the old aqueous--which is why the person's eye becomes hard, red, and painful. I can't recall ever seeing Epi used to treat glaucoma (too many adverse systemic effects), but since it's an alpha agonist it would decrease aqueous production. Dilation isn't a problem in open angle glaucoma since there is no defect in the drainage angle (just like dilation isn't a problem in a "normal" eye). It's really rare/unusual for someone to have combined open-closed angle glaucoma; you really either have one or the other. ---------------------------------------------------------------------------------------------------------------------- 1. Alpha agonists (i.e. epinephrine) - contraindicated in acute angle closure glaucoma because they cause mydriasis, which puts more pressure on the blockage. Also contraindicated in hypertension for obvious reasons. 2. Beta blockers (i.e. timolol) - contraindicated whenever beta blockers are contraindicated for other reasons. 3. Diuretics (i.e. acetazolamide, mannitol) - DOC in angle closure, but contraindicated wherever acetazolamide/mannitol are contraindicated. 4. Prostaglandin analogs (i.e. latanoprost) - usually the DOC in outpatient management of open-angle glaucoma. 5. Cholinergics (i.e. pilocarpine) - contraindicated wherever cholinergics are contraindicated. Latanoprost, a stable long-acting PGF2derivative, was the first prostanoid used for glaucoma. The success of latanoprost has stimulated development of similar prostanoids with ocular hypotensive effects, and bimatoprost, travoprost, and unoprostone are now available. These drugs act at the FP receptor and are administered as drops into the conjunctival sac once or twice daily. Adverse effects include irreversible brown pigmentation of the iris and eyelashes, drying of the eyes, and conjunctivitis. Alprostadil (PGE1) may be used for its smooth musclerelaxing effects to maintain the ductus arteriosus patent in some neonates awaiting cardiac surgery and in the treatment of impotence. Misoprostol, a PGE1 derivative, is a cytoprotective prostaglandin used in preventing peptic ulcer and in combination with mifepristone (RU-486) for terminating early pregnancies. Dinoprostone (PGE2) and PGF2` are used in obstetrics to induce labor. Latanoprost and several similar compounds are topically active PGF2derivatives used in ophthalmology to reduce intraocular pressure in open-angle glaucoma or ocular hypertension Cholinergics effects; Drugs should avoid them in case of glaucoma: Anticholinergic Actions such as (atropine, scopolamine, H1 blockers, TCA, amantadine) Anticholinergic Actions; confusion, dry mouth, cycloplegia, and urinary retention, constipation, precipitation of glaucoma, blurred vision.