Opthalmology Flashcards
Ocular bioavailability
5-10% due to the protective mechanisms
Anatomy of the eye
Iris - colour of the eye
Sclera - White part of the eye
Lens - Focuses and sharpens image.
Ciliary body - Produces aqueous humour
Pupil - Allows light to hit the retina
Conjuctiva - Lines the eyelids and covers the sclera
Optic nerve - Transmits visual information from retina to the brain.
Cornea - Refracts light
Macular - Central part of retina which is light sensitive.
Tear film layers
- Lipid layer produced by meibomian glands responsible for preventing tear evaporation acting as a barrier to prevent dryness.
- Mucous layer is sticky and allows tears to be held for longer. It also contains immunoglobulins and lysosomes to aid the trapping of bacteria and dirt.
- Aqueous layer secreted by lacrimal glands have nutrients dissolved in the layer.
- Epithelial layer.
Nasolacrimal apparatus
The drainage of eye drops causing its loss and drug not getting enough time to act.
Ocular membranes
Three membranes - conjunctiva, sclera and cornea.
SA of sclera is 5/6 whereas SA of cornea is 1/6
Conjunctiva
- Mucuous membrane that lines ocular surface, excluding cornea and inner eyelid
- Goblet cells secrete mucuous for anchoring the precorneal tear film and fighting infections
Cornea
- Transparent tissue of eye that refracts light.
- Avascular, non pigmented and richly supplied with long ciliary sensory nerves with three layers - epithelium (LIPID), stroma (AQUEOUS) and endothelium (LIPID) creating an impermeable sandwich layer.
- Passing cornea gives direct access to anterior chamber
Sclera
- White part of eye
- Highly vascularised and leaky (not good barrier).
- Can lead to systemic absorption of drug.
- Allows drug to access both anteripr and posterior segments.
- Hydrophilic so hydrophilic drugs get absorbed quickly.
Topical applications
Advantages:
- Less systemic side effects
- Simpler
- Overcomes hepatic first pass metabolism
Disadvantages:
- Extensive and rapid drug drainage.
- High tear fluid turnover
- Less than 5% of drug penetrates cornea due to corneal impermeability.
- Leads to pulse entry
- Non specific absorption
- Ocular metabolism
Factors affecting drug delivery
- Surface tension (too high, won’t spread)
- Acidic, basic, hypo/hyperosmotic causes reflex blinking -> nasolacrimal drainage
- If not clear then affects vision
- Prodrug tends to be more permeable
- Polymers make drug more viscous prolonging retention and contact time - leads to discomfort
- Gels/ointments tend to be sticky.
Preservatives
- Surfactants
- Hydrophobic tail and hydrophilic head
- Perturb bacterial cells.
Ointments
- Non aqueous
- Hydrocarbon base i.e. petroleum
- Avoids nasolacrimal drainage
- Increases eye surface contact time
- Doesn’t get diluted by tear film
- Tends to affects vision - may cause some discomfort or ocular irritation
Gels
- Water soluble
- May cause pulse entry
- Increasing viscosity leads to reflex blinking and rapid elimination of drug
- May cause blurred vision and matted eye lids.
Suspensions
- Need to be shaken adequately before use
- Sterilisation is an important step in production - may lead to physical instability and aggregation
- Particle size needs to be less than 10 microns.
- Costly to make
- Achieve only moderate bioavailibility
Gel forming eye drops
- Has a trigger in the tear i.e. Ca2+. temperature, pH, solvent exchange
- Transforms drop to gel
- Prolongs retention
