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Flashcards in Ph- Eye Deck (30):

What challenges the delivery of drugs to the eye from systemic absorption?

How should drugs to the eye be delivered?

The eye is separated from systemic circulation by:
1. blood-retinal barrier
2. blood-aqueous barrier
3. blood-vitreous barrier

For this reason, most therapeutic strategies involve:
1. topical delivery with eye drops
2. placement in the inf. fornix [cul-de-sac]
3. retrobulbar, intraocular, intravitreal injection


_____________ is considered a clear risk factor for development of glaucoma and _________________ will cause irreversible damage via induced ischemia in the optic nerve and retina.

Optical hypertension is a risk for glaucoma.

High intraocular pressure will cause irreversible damage via induced ischemia in the optic nerve and retina


Describe the flow of aqueous humor.

1. Ciliary bodies produce and secrete aqueous humor into the posterior chamber
2. flow between the lens and iris into anterior chamber
3. drained through trabecular meshwork into Schlemm's canal and venous return
4. uveosclerol return contributes a SMALL portion of drainage


What is acute congestive glaucoma?
What is the typical cause of blockage?

Narrow angle/closed angle glaucoma

- the angle btw the iris and corneal endothelium is shallow but allows normal flow of aqueous humor

If the iris dilates [mydriasis] it will close the narrow angle causing blockage of aqueous humor and acute rise in intraocular pressure.


What is the treatment for acute closed angle glaucoma?

Miotic drugs because they will constrict the pupil, pulling the iris away from the corneal endothelium opening the passage of aqueous humor.

1. Pilocarpine - musc. agonist
2. Physostigmine- AchEI indirectly stimulating musc.
3. osmotic agents to remove fluid from the eye
4. surgery w/ peripheral iridotomy


What causes chronic simple- open angle glaucoma?

There is NO physical obstruction, but flow through the trabecular network is reduced for unknown reasons


Describe the presentation of open angle/chronic simple glaucoma.
What are the 2 goals of treatment?

It has gradual onset and usually doesn't cause symptoms until partial vision loss.

1. lower intraocular pressure [even if it is in the normal range] by decreasing production of aqueous humor or increasing outflow

2. increase perfusion of the retina and optic nerve


What 3 surgical procedures can be done for open angle glaucoma to help drain aqueous humor?

1. laser trabeculoplasty - open clogged drainage channel

2. trabeculectomy - opening in the sclera that can drain fluid into a bleb on the outer layer of the eyeball

3. drainage implants


What is the mechanism of pilocarpine?
What type of glaucoma does it treat?
What are potential side effects?

It is a muscarinic agonist that increases aqueous outflow by contracting ciliary muscles.
It treats acute glaucoma.

Side effects:
1. accomodative spasm
2. reduced vision in patients with cataracts


What is the mechanism of physostigmine?
What type of glaucoma does it treat?
What is a side effect?

It is an AchE inhibitor that indirectly increases aqueous outflow in the same way as pilocarpine
It treats acute glaucoma.

Side effect:
1. AchE poisoning if systemically absorbed


What are the 2 drugs of choice for monotherapy of chronic open angle glaucoma?
What is the mechanism of action of each?
What are potential side effects?

Timolol is a B-adrenergic antagonist that:
1. inhibits aqueous humor production
2. helps perfuse/prevent ischemia in optic nerves

Side effects:
May exacerbate asthma or COPD if there is systemic absorption

Latanoprost is a prostaglandin F2a analog that increases outflow of aqueous humor via uveoscleral pathway [like epi]. The only side effect is increased iris pigmentation


How is epinephrine used to treat glaucoma?

It is an alpha agonist that:
1. reduces aqueous production
2. improves aqueous humor outflow via uveoscleral pathway


What is the mechanism of action of dorzolamide?
What type of glaucoma is it used to treat?
What are side effects?

Dorzolamide is a carbonic anhydrase inhibitor that reduces production of aqueous humor.

It treats open angle glaucoma.

Side effects: bitter taste, headache, nausea, fatigue


What are mannitol and glycerin used for in the treatment of glaucoma?

They are osmotic agents that reduce aqueous humor volume.


Why does compliance tend to be an issue with using glaucoma meds?

1. irritating side effects [including burning from eye drops]
2. frequent dosing regimens
3. lack of experience benefit


What is macular degeneration?
What part of vision is disrupted?
What age patient does this effect?
What are the 2 types?

It is loss of function of the macular zone [central area of retina]
-this area provides highest detail and color discrimination of vision
-occurs in elderly patients [usually over 75]
1. dry or non-neovascular
2. wet or neovascular


How does the speed of vision loss differ for dry and wet macular degeneration?
What % of macular degeneration is each type?

90% dry, 10% wet

Dry = slow loss of central vision
Wet = rapid decline in central vision --> severe vision loss


What is the characteristic appearance of dry macular degeneration?

Drusens- yellow/white deposits of metabolic products in the retinal pigmented epithelium or optic nerve head

-Large drusen = more severe
More drusens = more severe


What is the characteristic appearance of wet macular degeneration?

Leaky blood vessels in the subretinal space


What are the 3 main strategies for sequestering VEGF to prevent neovascularization in wet macular degeneration?

1. Aptamers [pegatanib]
2. Antibodies [bevacizumab, ranibizumab]
3. Receptor chimeras [aflibercept]


What is the mechanism of action of pegaptanib?

It is a VEGF aptamer that has high affinity binding to VEGF


What is the mechanism of action of ranibizumab?

It is a recombinant human antigen binding fragment derived from bevacizumab [monoclonal Ab to VEGF] that binds VEGF and prevents binding to endogenous receptors


What is the mechanism of action of bevacizumab?

IT is a monoclonal Ab to VEGF and is used for:
1. macular degeneration
2. metastatic colorectal and non-small cell lung cancer

*** much cheaper than ranibizumab


What is the mechanism of action of aflibercept?
What is the benefit of this drug?
What is the major drawback?

chimeric protein with soluble VEGF binding domains.

Injection every 2 months [rather than once a month with the aptamer and antibodies]
Drawback = intravitreal injection with undesired effects


What are acute symptoms of uveitis?
What are chronic symptoms?

1. pain
2. redness
3. photophobia

1. blurred vision
2. dull aches


What is treatment for uveitis?

1. if bc of an infection--> treat the cause
2. if inflammation--> topical corticosteroids [systemic for posterior uveitis]
3. muscarinic antagonists


What are the 2 reasons to use muscarinic antagonists in uveitis?

1. prevent posterior synechia formation between the lens and iris margin
2. relieve ciliary muscle spasm


What topical agents are used to treat allergic conjunctivitis?

1. sympathomimetic agents --> vasoconstriction
2. H1 antagonist --> relieve itching/tearing


In severe cases of strabismus, what drug can be used?

Atropine to produce cycloplegia and blurred vision in the good eye to force the kid to use the shitty eye so it gets better


What drug can be used for closed angle glaucoma AND xerophthalmia?

Pilocarpine is also used at low dose to form tears esp in Sjogren's