4 - Pharmacology and meds Flashcards
(41 cards)
Challenges of eye’s natural defences on topical drug administration and effectiveness.
Blink out drops applied.
Tear film dilutes medications applied.
Corneal epithelium is biphasic barrier so drugs cannot get through very easily so have to have both hydrophilic and hydrophobic properties.
Normal drainage removes drugs from the eyes quickly.
CALT may mount reaction to some drugs put into the eye
Internal ocular homeostasis.
Blood ocular barrier - second-line physical and chemical barrier – stops infectious organisms and inflammatory debris getting into the eye and disrupting it, so also a barrier to drugs.
- protects vision by maintaining clear ocular media.
Anything that goes into the eye must come out of the eye so drugs must have certain properties as no lymphatic drainage and exit through the BOB.
Production should be equal to drainage.
- Administration and treatment routes as a general rule based on target site.
- Owner (and patient) compliance.
- Surface and anterior segment = topicals.
Posterior segment = systemic. - High frequency regime?
Cost?
Pain/head-shy?
Ideal property of topical eye drug.
Non-irritant - maximises patient acceptance and owner compliance.
- Irritants induce inflammation > increased tear osmolarity > increased drug protein-binding > reduces drug availability for absorption > less efficacy.
- Irritants > epiphora > dilution.
- pH 4.5-9 quoted for comfort.
- Normal tear pH 7.4 is best.
2 main routes of topical medication penetration.
Transcellular = across corneal epithelial cell.
Paracellular = in between individual cells.
Corneal structure and drug passage.
Corneal epithelium is a largely lipophilic barrier so lipid soluble drugs cross this more easily.
Corneal stroma is hydrophilic so polar water soluble drugs cross more easily.
Descemet’s membrane is a supporting membrane.
Endothelium is a lipophilic barrier (although less significant than the epithelium) so lipid soluble drugs cross more easily.
What does the transcellular route rely on the molecule being?
What does the paracellular route rely on the molecule being?
Lipophilic-hydrophilic balanced drug e.g. chloramphenicol.
Small molecular weight to pass between tight junctions (0.6-3nm).
Where would the target site of an aqueous drug tend to be and why?
Ocular surface as unable to achieve intraocular penetration very well as less lipid soluble but generally adequate for surface disease such as allergic conjunctivitis.
In what instances should use of steroids in the eye be avoided? - why?
Corneal ulcers - steroids stop the immune system allowing the healing of the ulcer.
How else can topical drug penetration into the eye be improved?
Combining drugs with organic salts e.g. prednisolone acetate - slightly changes the chemical formula.
Addition of preservatives that disrupt the corneal epithelial barrier to allow further penetration so can delay healing in some situations. - recommend preservative free if >q4hrs (often slightly more expensive).
Some drugs designed to be less irritant by being formulated to a uniform and micronized suspension to improve tear retention.
Relationship between particle size and retention time.
Larger the particles, the longer the retention time and persistence of therapeutic drug concentration.
Properties and advantages of topical eye ointments.
Disadvantages?
Lipophilic character so retained in surface of tear film and retained for extended periods on ocular surface.
As low as 0.5% dose volume clearance per minute so significant amounts retained 4hrs after dosing.
Suitable for BID dosing (e.g. easier for equines).
Can be difficult to get as close to the patient as is needed to apply sufficiently.
Can be difficult to squeeze the tube as thicker substance.
Order of application of eye drops.
Solution > micronised > Gel > Ointment.
Retention in tear of…
1. solution.
2. suspension.
3. gel.
4. ointment.
- 5-10 mins max.
- Up to an hour.
- Few hours.
- Several hours.
Ease of admin of…
1. solution.
2. suspension.
3. gel.
4. ointment.
- easy to drop.
- thicker.
- close to the eye.
- more challenging.
Frequency of application of…
1. Solutions.
2. Suspensions.
3. Gels.
4. Ointments.
- q1-6hrs.
- q2-12hrs.
- q2-6hrs.
- q4-12hrs.
- What is the normal volume of human tear film?
- Normal tear turnover.
- Average volume of 1 eye drop?
- Max volume palpebral fissure can hold?
- 7-10 microlitres.
- ~1 microlitre per min.
- 40 microlitres.
- 25-30 microlitres.
How long should be left between different topical medication application on the eye?
10 mins.
How is the use of subconjunctival injections useful?
Advantage?
Disadvantage?
Where patient compliance is low for drops that need to be given over a couple of days.
Some of the drug is absorbed across the sclera and episclera, some absorbed into anterior chamber via limbal blood vessels.
Leaks slowly onto the conjunctival and corneal surfaces, slow release medication administration via injection site (for a day or 2) – aqueous will last for ~12hrs at most.
– BUT, once drug is in, cannot take it out.
Sustained release implants.
Types of conditions effective for?
Drug within silicone vehicle e.g. cyclosporine.
Implanted subconjunctivally/episcleral.
Equine Recurrent Uveitis, Kaeratoconjunctivitis Sicca (canine).
- What does the penetration of systemic medication for the eye depend on?
- Common choices for systemic tx of the eye.
- Integrity of BAB and BRB, which is reduced in uveitis.
Lipid solubility.
Molecular weight of the drug - low molecular weight molecules cross most easily.
Degree of protein binding. - Chloramphenicol, doxycycline (small), trimethoprim/sulphonamides (lipid), amoxy/clav.
Ocular therapeutic classes.
Antimicrobial.
Anti-inflammatory.
Anti-glaucoma drugs.
Mydriatics.
Local anaesthetics.
Tear replacement and stimulants.
Anti-collagenase.
*many topical drops human meds, few licensed vet products, be aware of cascade, gain informed consent.
Bacteriostatic antimicrobial eye medications.
Chloramphenicol (gram+ and gram-).
Fusidic acid (gram+) – prescription only (Isathal).
Macrolides (toxo).
Trimethoprim/sulphonamide (KCS risk).
Tetracyclines (chlamydia) (q3-4hrs).
Bactericidal antimicrobial eye medications.
Aminoglycosides (gentamicin) (2/3 line).
Bacitracin (gram +).
Cephalosporins.
Fluoroquinolones (NOT 1st line) (Exocin).
Penicillins (NOT 1st line).
Polymixin (gram-).
Vancomycin.
