ocular pharm

Question 1

What are some important features of ocular pharm kinetics to keep in mind?

Answer 1

• Most drugs are available as ophthalmic solutions; agents with limited solubility can be prepared as suspensions.
• The time that a drug remains on the surface of the eye can be prolonged with certain formulations including gels, ointments, and solid inserts. Prolonging the time in the cul-de-sac facilitates drug absorption into the eye.

Question 2

If you want a localized ocular drug effect, what absorption route is targeted?

Answer 2

• Absorption via transcorneal and transconjunctival-scleral routes is desired for localized ocular drug effects. The rate and extent of absorption into ocular structures is determined by: (general, determined by passive diffusion through cornea, driven by concentration gradient)
♣ Time drug remains in cul-de-sac and precorneal tear film
♣ Elimination by nasolacrimal drainage
♣ Drug binding to tear proteins
♣ Drug metabolism by tear and tissue enzymes
♣ Diffusion across cornea and conjunctiva

Question 3

For hydrophilic and hydrophobic properties, how can you consider the architecture of the eye?

Answer 3

♣ In addition, the cornea can be considered as a trilamellar “fat-water-fat” (i.e., epithelial-stromal-endothelial) structure, thus drugs with both hydrophilic and lipophilic properties would be best suited for transcorneal absorption

Question 4

Can a topically administered ocular drug get into systemic circulation?

Answer 4

Yes, through three different paths. Primarily thorugh nasolacrimal drainage
• Systemic absorption-distribution of topically administered ophthalmic medications primarily occurs via nasolacrimal drainage. Since absorption from the nasal mucosa avoids first-pass metabolism, systemic side effects from topical medications are possible (esp. with chronic use).
• Distribution to the systemic circulation is also possible following transcorneal absorption into the aqueous humor via the trabecular network pathway.

Question 5

How are occular drugs eliminated?

Answer 5

• Localized biotransformation of ocular drugs can be significant due to the presence of a variety of enzyme systems (most important being esterases)
• Esterases are of particular importance in the context of prodrug development for enhancement of corneal permeability.
*These drugs are synthesized as esters of the active compound which possess greater lipid solubility and ability to penetrate the cornea where they are subsequently converted to the active drug by the action of tissue esterases (e.g., latanoprost, a prodrug for prostaglandin F2).

Question 6

What are the risk factors for retinal damage due to glaucoma?

Answer 6

• Risk factors associated with glaucomatous nerve damage include: increased intraocular pressure (IOP), positive family history of glaucoma, African-American heritage, and possibly myopia and hypertension.

Question 7

What is the overall goal in glaucoma treatment?

Answer 7

Reduce intraocular pressure. For whatever reason this really diminishes risk of retinal damage

Question 8

What is the normal pathway for secretion of aqueous humor?

Answer 8

• Aqueous humor is secreted slowly and continuously by the cells of the epithelium covering the ciliary body drains into the canal of Schlemm (runs around the eye close to the outer margin of the iris).

Question 9

what is normal IOP and what is glaucoma?

Answer 9

IOP is usually 10-15 mm Hg above atmospheric, which keeps the eye slightly distended
Glaucoma is associated with increased IOP (> 22 mm Hg), which damages the eye and is one of the most common preventable causes of blindness

Question 10

The mainstay of wide-angle (chronic simple) glaucoma treatment is pharm managment. What is used?

Answer 10

o Initial - prostaglandin analog (PA) as monotherapy
o Good response to PA but short of target - add β-blocker OR carbonic anhydrase inhibitor OR α2 agonist
o Poor response to PA - Discontinue PA and substitute other class
*combo is usually better for greater reduction
*toleration of side effects is key for drug choice

Question 11

What drugs increase outflow of aqueous humor?

Answer 11

♣ Prostaglandin analogs: Latanoprost (Xalatan), topical PGF2 prodrug.

• Alpha-adrenergic agonists: Brimonidine
• Cholinergic agonists (pilocarpine, echothiophate)

Question 12

What drugs decrease production of aqueous humor?

Answer 12

• Beta-adrenergic antagonists. Timolol

* Carbonic anhydrase inhibitors. Dorzolamide (these are the ONLY oral formulation occular drugs)

Question 13

What do Beta blockers do in the eye?

Answer 13

decrease production of aqueous humor

*timolol

Question 14

What do muscarinic agonists do in the eye?

Answer 14

• contract circular fibers and pupil
• relax lens for near vision
• these things enhance drainage
• thus, it’s important to remember that a side effect of muscarinic antagonists is an increase in IOP

Question 15

What is going on in closed angle glaucoma?

Answer 15

• Pathophysiology involves mechanical blockage of the trabecular meshwork by the peripheral iris. Blockage occurs intermittently and results in extreme fluctuations in IOP that may need to be treated as an emergency to avoid visual loss.

Question 16

what is the treatment for closed angle glaucoma?

Answer 16

• in general, use pharm to really DECREASE IOP until you can get to surgical correction
• pilocarpine (muscarinic agonist) + apraclonidine (alpha2 agonist)+ timolol (beta-blocker)
• acetazolamide (diuretic, carbonic anhydrase inhibitor) (IV/PO)
• mannitol or glycerol (osmotic diuretic)

Question 17

What are the common pathogens responsible for bacterial conjunctivitis?

Answer 17

Red eye with discharge; minimal loss of vision and pain.
*Most common adult pathogens are S. aureus, S. pneumoniae, and H. influenzae with M. catarrhalis also common in children.

Question 18

What’s the pharm treatment for bacterial conjunctivitis?

Answer 18

• empiric therapy is usually initiated with erythromycin (Ilotycin® ointment) or polymixin-trimethoprim (Polytrim® drops). Ointment is preferred for children or those patients with poor compliance.
• azithromycin drops in children or sulfa allergy patients
• fluoroquinolones (moxifloxacin-gatifloxacin)
• AVOID aminoglycosides because of contact dermatitis and resistance

Question 19

What is the pharm treatment for bacterial keratitis?

Answer 19

Often follows injury or abrasion, or commonly is contact lens wear associated; pain, white spot on cornea, with decrease in vision.
• Mild, small, more peripheral infections are treated empirically with broad spectrum topical antibiotics (as above for conjunctivitis) to prevent superinfection.
• More severe, central, or larger infections, as well as contact lens abrasions should be referred. Topical therapy for Pseudomonas with fluoroquinolones (ofloxacin-Ocuflox®, moxifloxacin-Vigamox®), ciprofloxacin-Ciloxan or tobramycin-Tobrex®, or fortified vancomycin for MRSA.

Question 20

You should do what when you see a severe (central or large) bacterial keratitis case?

Answer 20

REFER
*Topical therapy for Pseudomonas with fluoroquinolones (ofloxacin-Ocuflox®, moxifloxacin-Vigamox®), ciprofloxacin-Ciloxan or tobramycin-Tobrex®, or fortified vancomycin for MRSA.

Question 21

What is the pharm treatment for viral keratitis or conjunctivitis?

Answer 21

*HSV keratitis
*Most common cause of ulceration in developed countries. Acute onset with variable symptoms of pain, visual blurring, and watery discharge. Antiviral medications hasten the resolution of the keratitis.
• Oral (acyclovir) and topical (trifluridine-Viroptic®) agents are equally effective and oral agents are easier to use
Avoid use of topical steroids for active epithelial disease
*viral conjunctivitis - no specific antiviral. use OTC antihistamines, decongestant drops or lubricant ointments for symptomatic releif