Eye pharmacology Flashcards
Ocular pharmacology
Routes of administration
2 routes, depends on site of disease and pharmacokinetic properties of the agent
- Topical
- Systemic
Topical admin facts
• Most effective for issues with anterior segment: surface structures and AS
• Convenient, specific, minimal systemic effect
• Drug admin directly into eye, penetrates into eye via cornea/ sclera drained by lacrimal system, entering systemic through conjunctival and nasal mucosal vessels
• Dropper bottle delivers almost 3X palpebral fissure holding capacity
• Intraocular bioavailability is relatively poor
o 1-10% drug reaches anterior chamber
o Can be improved by inc retention time on ocular surface AND optimising ability of drug to penetrate cornea
Systemic admin facts
• Most effective for issues with Posterior Segment
To improve the intraocular bioavailability…
Normally only 1-10% topically applied drugs will reach Anterior chamber = bioavailability
- increase retention time on ocular surface
- Optimise the ability of the drug to penetrate the cornea
What does persistence of a drug depend on?
How is this useful
- Its formulation
- useful to change corneal retention
• Solution
• Suspension - too big, inc irritance, inc blinking and tear, smaller = shorter persistence
• Ointment - oily base = much reduced freq of application vs solution
• Viscous fluids/gels - too V = irritant. But inc V inc retention
• Colloidal systems consisting of liposomes or nanoparticles - limited drug loading ability so improved bioavailability. Although v expensive to manufacture
• Solid delivery - impregnated contact lenses
• Sub-conjunctival injection - good for farmers alhtough risk to damage eye
How is a drug administered topically distributed?
- Drained by lacrimal drainage system
- Penetrates into the eye via cornea/sclera
- Enters systemic circulation through conjunctival and nasal mucosal vessels
- falls off eye
Corneal penetration- what are they layers?
- anterior epithelium -
- stroma - v watery part of eye
- endothelium - really thin and leaky
For drug to pass each layer of the Cornea what does it need to be?
- anterior epithelium - drug lipid soluble or paracellular (between cells) or transcellular, through cells (paracellular is limited, only v small molecules can use this route)
- stroma - drug water soluble
- endothelium - thin and leaky so doesn’t matter tooooo much
What route do drugs that are
a) lipid soluble
B) water soluble
use to pass through corneal epithelium
- Lipid-soluble drugs follow the transcellular route
- Water-soluble drugs follow the paracellular route but as The superficial layers of corneal epithelium possess tight junctions which limit the paracellular movement of drugs – only very small molecules can use this route.
Factors affecting corneal penetration
- a lot of diseases of the eye are inflammatory or infectious = lot of protein adn puss = issue for drugs to get to cornea!
- inc freq admin
- clear gunk and pus
- damaging anterior epithelium of cornea, create an ulcer to inc corneal penetration of water soluble drugs! (v rare
Is non corneal penetration possible?
Large, hydrophilic molecules can still enter the eyeball, by absorbing across the conjunctiva and sclera
- conjunctival epithelium permits much more movement of molecules between cells than the corneal epithelium
- From the conjunctiva, the drug can penetrate the eye via the sclera (the sclera is up to 10 times as permeable as the cornea!) and enter the posterior segment or enter the scleral vessels and end up in the ciliary body.
Sytemic absorption of topical agents
How can this happen?
- Highly vascular tissues such as the conjunctiva and the mucosa of the nasolacrimal duct and nasopharynx of enable absorption of topical agents into the bloodstream, and hence these agents can have systemic effects
- Drug is drained away (exposure to vascular tissue)
A lot of drugs what in the eyeball
are metabolised
enter the eyeball as a pre drug and metabolised to active ingredient within
Topical drug distribution: Corneal Absorption
- high and approx equal levels in aq humour and anterior uvea
poor distribution to posterior segment
Topical drug distribution: Non corneal route
Why
- levels higher in anterior uvea than aq humour
As they get to the iris/ ciliary body through blood supply rather than aq humour
