Ocular Pharmacology Flashcards
Prolonging time in the _____ facilitates drug absorption into the eye
cul-de-sac
What drug structures are best suited for transcorneal absorption?
-drugs with hydrophilic and lipophilic properties because cornea is “fat-water-fat” (epithelial-fat-endothelium)
How does systemic absorption of topical ophthalic meds occur?
primarily: nasolacrimal drainage. (systemic SE possible from topical meds because they avoid first pass metabolism)
Also: transcorneal absorp into aq humor via trabecular network pathway
Corneal route–>aquous humor–>iris–> systemic
conjunctiva–>sclera–>ciliary body
nasolacrimal route
Elimination
-localized biotransformations due to presence of enzyme systems including esterases.
(esters can penetrate cornea and get turned to active drug by esterases)
Primary open angle glaucoma
- leading cause of blindness in Af Am
- RFs: increased IOP, FH, myopia, HTN
- Prophylactic reduction of IOP reduces progression to glaucoma
- reduction of IOP is helpful treatment
- Ciliary body secretes aqueous humor–> drains into angle of Schlemm
- runs around eye close to outer margin of iris
- Glaucoma assoc w/ increased IOP (>22, normal is 10-15), nerve damage can occur–>blindness
treatment:
-surgery (may not be poss)
-topical drugs that LOWER IOP
Initial: prostaglandin analog (PA)
-Good response to PA, but short of target–>add Beta blocker OR carbonic anhydrase inhibitor OR alpha 2 agonist
-d/c PA if poor response
Drugs to treat open angle glaucoma that increase outflow of aqueous humor
Drugs that INCREASE OUTFLOW of aq humor:
-PA analogs like Latanoprost (SE: brown iris, eyelash lengthening and darkening, ocular irritation, few systemic SE)
-Alpha adrenergic agonists (Brimonidine):
selective topical alpha2 agonists (can be used as add on therapy); MOA: increase outflow of aq hum AND inhibits formation of aq humor. (SE: red eye, ocular irritation; CNS depression (hypotension, somnolence); apnea in kids under 2)
Cholinergic agonists (miotics): less commonly used today
- lower IOP by causing muscarinic induced contraction of ciliary muscle–>outflow
- Pilocarpine
- Echothiophate (ACE-I)–>less frequent admin bc organophosphate, but assoc with cataract development (SE: Ciliary spasm leading to headaches, myopia, dim vision (small pupil).)
Drugs used to treat open angle glaucoma that reduce PRODUCTION of aqueous humor
-Beta adrenergic antagonists: Timolol
Next most common after PA analogs
-Beta 2 receptors found preferentially in eye–>want selective
-Reduces aq humor produc via block of Beta receptor pathway; SE: Relative contraindication in patients with bradycardia, heart block, heart failure, asthma or obstructive airway disease.
Carbonic anhydrase inhibitors: Dorzolamide. Can be used as add-on second or third line therapy.
-inhib of CA in ciliary body epithelium reduces bicarb ion formation which reduces fluid transport and IOP
SE: bitter taste
Muscarinic antagonists
- dilate pupil
- occlude canal of Schlemm
- raise IOP (precipitate (closed angle) glaucoma)
Closed angle glaucoma
miosis (cholinergic agonist, used to produce rapid fall in IOP, by lowering resistance to outflow of aq hum–>induce miosis and contraction of ciliary muscle (free entrance of canal of Schlemm) along w/ apraclonidine and timolol (synergistic IOP lowering)
Acetazolamide: CA inhibitor, blocks aq humor formation
Mannitol or glycerol: osmotic diuretics that produce intraocular dehydration
Absorption of ocular drugs
rate and extent determined by:
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
Following instillation, appearance of drug in aqueous humor is dependent on passive diffusion through the cornea
Drug concentration gradient between tear film and cornea and conjunctival epithelium provides driving force for diffusion
Bacterial conjunctivitis
-red eye, discharge, minimal loss of vision, pain.
-S. aureus, s. pneumo, h. influenzae, m catarrhalis (kids)
-ointment preferred if poorly compliant
Treatment shortens course and reduces spread
-erythromycin or polymixin-trimethoprim
-Alternates: azithromycin, fluoroquinolones
Avoid aminoglycocides (contact dermatitis, resistance)
Bacterial keratitis (aka corneal ulcers)
-often follows injury/abrasion
-CONTACT lens associated
-pain, white spot on cornea, decreased vision
-Mild: treat empirically (see bacterial conjunc)
More severe: should be referred; fluoroquinolones for pseudomonas, cipro or tobramycin, or vancomycin for MRSA
HSV Keratitis
- most common cause of ulceration in developed countries
- acute onset, pain, blurred vision, watery discharge
- Antivirals hasten resolution
- Oral acyclovir
- Topical trifluridine
- avoid topical steroids for active epithelial disease
Viral conjunctivitis
-Adenovirus most common cause
Self-limiting infection with NO specific antiviral treatment available
• Symptomatic relief can be obtained with OTC antihistamine or decongestant drops
• Some relief can also be provided by lubricant ointments, cold compress
Mydriatics (antichol or alpha1 adrenergic agonists) are contraindicated in:
angle-closure glaucoma
