Drugs and the eye Flashcards
list the 3 routes of administration of drugs
- topical
- intra-ocular
- systemic
list the 3 forms of topical routes of drug administration and describe each form
- solutions: for drugs which are soluble
- suspensions: for drugs which are not soluble e.g. steroid eye drops, which is a hydrophobic molecule, the suspension is an emulsion i.e. yo shake the bottle and this puts the molecule back into the solution
- ointments: used to increase the duration/content on the ocular surface, but can make vision smeary
list the 2 forms of intra-ocular routes of drug administration and describe each form
- injection: e.g. lucentis which treats AMD
- insert: drug is impregnated into insert and then into the vitreous where it is released over time e.g. steroids or antibiotics
list the 2 forms of systemic routes for drug administration
- oral
- injection
list the 7 pharmacological/therapeutic classes of drug and what the use/formulation of the drug depends on
- anti-invectives
- corticosteroids/anti-inflammatory
- anti-glaucoma
- dry eye
- mydriatics/cycloplegics
- local anaesthetics
- peri-operative
depending on the site of action will determine how to formulate the drug
what is drug bioavailability determined by
the unique pharmacokinetic properties of the eye
name 3 factors that influence the delivery of topical drugs to the eye
- pre-corneal factors e.g. tear film
- corneal penetration e.g. via cornea
- inside the eye
what does a single drop from a conventional dropper bottle exceed
the capacity of the conjunctival sac
what has a major influence of the drug on pre-corneal retention time
the tear turn over rate
what pre corneal component exceeds corneal penetration, what implication does this have and how can it be reduced
- nasolacrimal drainage
- higher rates of drainage occur with larger drop sizes and this is vulnerable to being systemically absorbed across the nasal mucosa causing systemic toxicity
- putting pressure on puncta after instillation can avoid/reduce systemic absorption
what part of the eye is the main route of entry for topical medication
the cornea
which form of drugs penetrate the corneal epithelium and endothelium rapidly
lipid soluble drugs
what part of the cornea limits the passage of lipophilic formulations of drugs
the hydrophilic stroma
what type of drugs contributes to optimal corneal penetration
drugs which possess a combination of hydrophilic and hydrophobic properties
e.g. a weak acid depending on the pH it is in
what can influence the rate of drug penetration
ocular morbidity
where are the drugs distributed, following corneal penetration/inside the eye
into the aqueous humour
what occurs with the drug in the aqueous humour (inside the eye)
drug-target interaction
how are drugs eliminated from the anterior chamber (inside the eye)
by a combination of aqueous turnover and absorption across the tissues of the anterior uvea
_______ binding can also influence bioavailability inside the eye
melanin binding can also influence bioavailability inside the eye
what 2 things are involved in drug-target interaction
- enzymes
- receptors
which enzymes are involved with drug-target interaction
carbonic anhydrase inhibitors e.g dorzolomide
give 2 example of drugs which bind to receptors during drug-target interaction
- beta blockers e.g. timolol
- muscarinic e.g. cyclopentolate
give 5 examples of enzymes that are involved in ocular drug metabolism
- esterases
- monoamine oxidase
- N-acetyltransferase
- oxidoreductase
- catechol-O-methyltransferase
where in the eye are drug metabolising enzymes usually found and what happens to the drug as it passes through this structure
in the cornea
as the drug passes through the cornea it is acted upon by these enzymes and transformed chemically through its transit
during drug metabolism, some drugs are broken down by ocular tissues during penetration ________________________
limiting their effectiveness
what are some pathways during drug metabolism exploited by
exploited by pro-drugs
how do pro-drugs exploit some pathways during drug metabolism
where the breakdown product is more efficacious than the parent compound e.g. the anti-glaucoma drug latanoprost is metabolised by esterases on the transit through the cornea
how are drugs excreted following corneal penetration and distribution
drugs are eliminated from the aqueous humour, by a combination of aqueous turnover and absorption across the tissues of the anterior uvea
what is an additional factor to drug excretion which can influence bioavailability and may predispose to toxicity
drug binding to the pigmented tissues of the iris and ciliary body
list 3 factors influencing systemic drug delivery to the eye
- blood-ocular barriers
- plasma protein binding
- active transport
how does plasma protein binding influence systemic drug delivery to the eye
as most drugs bind to plasma proteins which are big molecules that can’t pass the barriers such as tight junctions at the blood/aqueous barrier or the iris blood vessels which are very tight
what does the blood aqueous barrier limit
the free access of systemic drugs to the anterior chamber
what are the main components of the blood aqueous barrier
the “tight” ciliary epithelium and low permeability of the iris blood vessels
what happens to the blood aqueous barrier when the eye is inflamed
the blood aqueous barrier can break down and increase drug bioavailability
what is the blood retinal barrier formed by
tight junctions between capillary endothelial cells and retinal pigment epithelial cells
what does the blood retinal barrier limit the passage of and name an exception
all the but the smallest lipid-soluble molecules
thats why lucentis is injected into the eye
what has been identified at the blood retinal barrier
several drug transporters
no drug is __________________
indefinitely stable
what should a drug ideally have
a long shelf life
what do some certain formulations of drugs require
specific storage conditions e.g. low temperature or absence of light
what may a soluble form of drug need and why
a specific pH to retain solubility
what can insoluble drugs be prepared as
suspensions
what is a drug subject to once opened if packaged as a multi dose bottle
oxidative damage and bacterial contamination
name some sterilisation method used on ophthalmic preparations
- heat
- sterile filtration (filters the bacteria out)
what are added to multi dose formulations of ophthalmic drugs in order to keep them sterile
preservatives
what type of ophthalmic drug is preservative free
intra-ocular products
what are excipients
inactive ingredients
name 6 excipients (inactive ingredients) used in ophthalmic formulations
- preservatives
- buffers
- antioxidants
- vicious agents
- tonicity-adjusting agents
- pH adjusting agents
what is the use for antioxidants in ophthalmic drugs
prevent or delay deterioration/breakdown of the drug by oxygen in the air
list 3 examples of antioxidants in ophthalmic drugs
- EDTA
- sodium bisulphite
- sodium metabisulphite
what is the use for preservatives in ophthalmic drugs
destroys or inhibits the growth of micro-organisms
list 4 examples of preservatives in ophthalmic drugs
- benzalkonium chloride (BAK)
- phenyl mercuric nitrate
- polyquad
- newer less toxic preservatives
which preservative is toxic to the ocular surface
benzalkonium chloride (BAK)
list 5 examples of the newer less toxic preservatives now available
- purite (stabilised oxychloro complex)
- sofzia (composed of boric acid)
- propylene glycol
- sorbitol chloride
- zinc chloride
what type of compound is benzalkonium chloride (BAK)
quaternary ammonium compound
benzalkonium chloride (BAK) is the most _________________
widely used preservative
which micro organisms is benzalkonium chloride (BAK) effective against
a wide range of GM +ve and GM -ve organisms
what concentration is benzalkonium chloride (BAK) available in
0.004 - 0.02%
benzalkonium chloride (BAK) has excellent ________ _______
chemical stability
benzalkonium chloride (BAK) can affect _____________ _____________
corneal penetration
what can benzalkonium chloride (BAK) not be used with and why
contact lenses as it binds to hydrogel lenses
list all the 6 things that the increased effect of preservatives has on the eye of people who use eyedrops for life/long term
- stinging or burning
- dry eye sensation
- tearing
- anterior blepharitis
- conjunctival follicles
- superficial punctate keratitis
what type of newer ophthalmic preservative is polyquarternium (polyquad)
a polymeric quaternary ammonium antimicrobial preservative
where is polyquarternium (polyquad) found
contact lens solutions and several artificial tear formulations
what has polyquarternium (polyquad) proven to have
less toxicity on corneal epithelial cells than BAK
what type of newer ophthalmic preservative is purite
a microbicide with a broad spectrum of antimicrobial activity
what does purite have very low toxicity to
mammalian cells
where does the preservative purite preserve the solution in and what happens to it following exposure to light
it preserves the solution in the bottle
but following exposure to light, is dissociates into water, sodium and chloride ions and oxygen
what is the use for buffers in ophthalmic drugs
it maintains the ophthalmic products in the pH range 6-8 which is the most comfortable for ophthalmic instillation
name two examples of buffers
- boric acid
- potassium bicarbonate
what is the use for viscous agents in ophthalmic drugs
increases contact time of the drug with the ocular surface by increasing viscosity of the preparation
name 3 examples of vicious agents
- methyl cellulose
- poly vinyl alcohol
- carbomers
what is the use for osmolarity adjusting agents
it creates an isotonic solution to improve comfort
what is the usual concentration of osmolarity adjusting agents
0.6 - 1.8%
name 2 examples of osmolarity adjusting agents
- mannitol
- NaCl
what is the use for pH adjusting agents
to create a pH that ensures optimal stability and tolerability
name 2 examples of pH adjusting agents
- hydrochloric acid
- sodium hydroxide
