Ocular Pharmacology Flashcards
lots of challenges to treat the eye
Lack of penetration
Topical drugs require frequent admin
Long duration of therapy
Drug absorption
Major barriers that change w topical or systemic administration
drug absorption - topical
No problem for superficial infection - deeper is concerning physiological barriers
- tear turn over
- drainage out nasolacrimal ducts
- blinking
All decrease contact time of drug and eye
Anatomic barriers for deeper eye absorption
Multiple layers - lipophilic layers for epithelium and endothelium but hydrophilic in stroma
Topical drug absorption
Lipophilic, unionized, low MW administered frequently @ high doses will reach greater ocular concentrations
Systemic absorption
Blood-aqueous and retinal barriers
- non fenestrated capillaries
- tight junctions
- p-glycoprotein efflux pumps
Systemic drug absorption
Lipophilic, unionized, low MW drugs w minimal protein binding that reach high systemic concentrations will reach greater ocular concentrations
Inflammation and absorption
Inflammation increases drug absorption due to broken down blood ocular barrier
Ideally choose a drug that will have good penetration without factoring in inflammation
Ocular PK
Drug distribution through vitreous humor takes a long time
Drug probably wont be metabolized in the eye
Drainage /elimination through the chamber angle and is often slow. High /frequent dosage+ slow drainage = better chances at reaching high concentrations
Routes of admin
Depends on location of disease
Systemic administration
Appropriate for posterior segment, endophthalmitis, orbital tissues
Also for anterior segment, corneal stroma - depends on degree of inflammation
Systemic is not ideal for corneal surface/conjunctiva
Antibacterial systemic admin
Lipophilic - minocycline, enrofloxaxin, chloramphenicol, macrolides, trimethoprima-sulfa combo
Hydrophilic - B lactams, aminoglycosides
Systemic admin for antifungals
Fluconazole, voriconazole
Itraconazole XX - too lipophilic and will get stuck in stroma
Antivirals - all hydrophilic should be treated topically
topical admin
Corneal surface/conjunctiva disease
Lipophilic drugs are better for penetrating intact cornea
Not preferred for posterior segment disease
Methods to increase topical drugs absorption/efficacy
Increased drug concentration in formula
Increase volume admin
Increase dose frequency***
Decrease corneal thickness
Use specialized formulations
Increase contact time
Stick needle into eye - XX
Increasing concentration of drug in formulation
Will increase absorption across the cornea up to a certain dose - also limited by surface area
Increase drug absorption of topical admin across cornea
Decrease corneal thickness
Higher penetration w corneal ulceration
Alter drug formations
Increase drug contact time
Solutions vs ointments
Subconjunctival infections - steroids, amp b
By pass barriers ^^
Topical antibiotics
Polymyxin B
Bacitracin
Gramicidin
Antifungal formulations
Natamycin
Voriconazole
Amp B
Trifluridine & idozuridine - herpes keratitis
Polymyxin B
Disrupt bacterial cell membrane by interacting w phospholipids - cell wall inhibitor, exclusively Gram Neg
Includes cloistin - Polymyxin E - topical or Endotoxemia but can cause dose dependent nephrotoxic
Polymyxin prevention /mechanism
Binds to lipid end of chain and prevents endotoxic activities
Bacitracin
Topical - not absorbed orally
Disrupts cell wall and peptidoglycan synthesis
Gram positives and negs
Gramicidin
So similar to bacitracin
Combo products for topicals
Polymyxin B, neomycin
Bacitracin, Gramicidin
All considered “triple antibiotic ointment”
Check for steroids**
Do not use steroids for
Corneal ulcerations **
Antifungal formations for eyes
Miconazole- azole antifungal, compounded
Nystatin - not used
Itraconazole - compounded in 30% DMSO
Natamycin - only FDA approved
Voriconazole - injectable formulation given topically
Natamycin
Polyene antifungal similar to amp B
Best spectrum against filamentous fungi - aspergillus, fusarium* common causes of fungal keratitis
Does not penetrate intact cornea
- Natamycin for corneal fungal infection
- voriconazole for stromal or deeper
Fungal keratitis
Voriconazole - good spectrum for aspergillus, fusarium
Formulation stable for 30d after reconstitution
*sterile technique
Amp B
Subconjunctivally infected for refractory infections
- fusarium
Can be irritating and cause conjunctiva tissues to slough off
Viral keratitis
Herpes* cats & horses
Trifluridine & idozuridine
Virostatic = no effect of latent viral particles
Helpful in clearing episodes not infection
