Ocular Pharmacology

Question 1

Describe the special aspects of ocular pharmacokinetics that influence the effectiveness of the topical route of administration.

Answer 1

The amount of time the drug stays on the eye can be extended with gel, ointment or solid insert formulations.

Extent of absorption depends on:

• Time drugs remains in cul-de-sac of eye
• Degree of elimination by naso-lacrimal drainage
• Drug binding to proteins in tears
• Drug metabolism by enzymes in tears and ocular tissues
• Rate of diffusion across cornea and conjunctiva
• Degree of passive diffusion through cornea into aqueous humor (greatest with drugs that have both lipophilic and hydrophilic properties)

Question 2

What is the normal pathway of aqueous humor in the eye?

Answer 2

aqueous humor is produced by the ciliary processes in the posterior eye→flow through pupil into anterior eye→trabecular meshwork drains the fluid via Schlemm’s canal into the bloodstream

Question 3

What is Glaucoma and what are the goals of treatment of glaucoma?

Answer 3

Glaucoma refers to disorders of the eye that result in damage to the optic nerve. This damage is often due to increased intraocular pressure (IOP) due to defects in the pathway for drainage of aqueous humor. Lowering IOP has been shown to significantly reduce progression in glaucoma.

In open-angle glaucoma, we want to reduce the aqueous humor production or enhance aqueous humor outflow

In closed-angle glaucoma are to reduce pressure rapidly at the time of an attack until surgery can be performed

Question 4

Treatment of Open-angle glaucoma

Answer 4

The goals of treatment for the most common form of glaucoma, open-angle glaucoma, are to reduce aqueous humor production or enhance aqueous humor outflow.

•Drugs that increase flow of aqueous humor: 
         Prostaglandin analogs
	Alpha-adrenergic agonists
	Cholinergic agonists
	Echothiophate

•Drugs that reduce aqueous humor production:
Beta-adrenergic agonists
Carbonic anhydrase inhibitors

Question 5

Treatment of Closed-angle glaucoma

Answer 5

Closed-angle glaucoma results in intermittent rapid fluctuations in IOP due to mechanical blockage of the trabecular system. The goals of treatment for closed-angle glaucoma are to reduce pressure rapidly at the time of an attack until surgery can be performed.

• Drugs that increase flow of aqueous humor rapidly: pilocarpine
• Drugs that reduce aqueous humor production rapidly: acetazolamide
• Drugs that dehydrate the eye to rapidly reduce IOP: mannitol or glycerol

Question 6

Latanoprost

Answer 6

• Prostaglandin analog
• Lower IOP by facilitating aqueous humor outflow through accessory uveosclero pathway
• First-line therapy in open-angle glaucoma as part of stepped approach
• Side effects include brown discoloration of iris, eyelash lengthening, and ocular irritation

Question 7

Brimonidine

Answer 7

• Alpha 2 adrenergic agonsit
• Increases uveoscleral outflow pathway and inhibits aqueous humor production
• Add-on 2nd or 3rd line therapy in open-angle glaucoma
• Side effects include red eye, ocular irritation, CNS depression and apnea in neonates

Question 8

Timolol

Answer 8

• Beta-adrenergic antagonist
• Reduces aqueous humor production
• Next most common drug used for open-angle glaucoma after prostaglandin analog
• Side effects include systemic absorption leads to decreased HR, bronchoconstriction, etc
• CONTRAINDICATED in Pts with bradycardia, heart block, CHF, asthma and COPD

Question 9

Dorzolamide

Answer 9

• Carbonic anhydrase initation
• Inhibiting CA in ciliary body epithelium reduces bicarb ion formation, leading to reduced fluid transport and IOP
• Add-on 2nd or 3rd line in open-angle glaucoma
• Side effects are few if applied topically

Question 10

Pilocarpine

Answer 10

• Muscarinic receptor agonsist
• Lowers IOP through contraction of ciliary muscle (increases aqueous outflow)
• Used in treatment of closed-angle glaucoma
• Not commonly used today for open-angle glaucoma
• Side effects include Ciliary spasm leading to HA, myopia, dim vision