Ocular Anti-Inflammatory Agents Flashcards
What are the physiologic actions/roles of glucocorticoids?
Interacts with hormones that affect sympathetic responses (thyroid hormone and epinephrine)
At what concentration do you see the physiologic effects of glucocorticoids? What are these effects?
20-25mg
Carbohydrate Metabolism - Increasing glucose synthesis by breaking down glycogen, amino acids and proteins, antagonizing insulin
At what concentration do you see the pharmacologic effects of glucocorticoids? What are these effects?
More than 25mg
CNS - Mood changes, euphoria and if higher schizophrenia
Lymphoid tissue decreases in number and see reduced immune responses
Anti-inflammatory effects
List the ways cortisol can act as an anti-inflammatory agent
Decreasing inflammation - decreased capillary permeability, edema, protelin leakage, WBC migration, fibroblast/capillary neovascularization, fibrin deposition, collagen deposition, and less scar formation overall. Decreased epithelial regeneration (healing), stabilizing membranes and preventing lysozyme release.
Though the exact mehcanism isn’t established, what is the speculated MOA for cortisol?
Binding to genome to modify transcription
The use of glucocorticoids in treating inflammation is a cure, true or false?
False, only treats the symptoms
GCS inhibition of inflammatory mediators is performed how?
Indirect by affecting transcription of mediators
Cyclooxgenase-2 (though this can be directly inhibited too), Endothelin-1 and PLA2 all affected
GCS effects are central or peripheral effects?
Peripheral
Describe the local (peripheral) effects of GCS
Effects on fibroblasts - Inhibiting cell activity, less regeneration, less scar formation and WBCs
Affecting permeability
Epithelial regeneration
Lysosome stabilization (less tissue damage)
What GCS drugs could be selected to have minimum hypertensive effect (sodium retention)
Triamcinolone
Betamethasone
Dexamethasone
What GCS drugs could be selected for alternate day therapy (based on duration of action alone)?
Cortisol
Cortisone
Fludrocortisone
What is the difference between prednisolone and prednisone?
Prednisone is taken orally and must be activated by enzymes in the liver to become prednisolone
Prednisolone can be used topically in the eye as it is already active, but may not last as long due to not having to be metabolized
How do the efficacy of prednisone and cortisol compare?
Exactly the same efficacy, however prednisolone is 4 times as potent (binding related)
In Addison’s disease what is the main problem and how can it be solved with a GCS?
Adrenal gland is atrophic and cannot produce cortisol and aldosterone.
Fludocortisone has great GCS activity and very potent mineralcorticoid activity and can replace both
Unlike systemic GCS drugs, topical GCS drugs are based on what to determine solubility?
Ability to cross the cornea and not the duration of action like systemic GCS drugs
Describe the acetate, alcohol and sodium salt preparations for GCS
Acetate and Alcohols have much greater ability to cross cornea and much more effective topically than sodium salts.
Acetate/Alcohol
Best penetration/effect topically.
In suspensions (Shake well)
Not very water soluble
Sodium Phosphates
Solution form
Less effective but less irritation and can be used more frequently ‘better compliance’
Describe the metabolism of: Cortisol, Prednisolone, Dexamethasone, Flurometholone, Loteprednol and Difluprednate
Cortisol is ‘short’ (8-12 hours)
Prednisolone is intermediate (12-36 hours)
Dexamethasone is long (36-72 hours)
Flurometholone has a fast intraocular metabolism as the alcohol form is more quickly metabolized than the acetate form.
Loteprednol - Site specific and metabolized in the eye, inactivated if it leaves
Difluprednate - metabolized to active product
Describe the GCS, Flurometholone
Fast intraocular metabolism, doesn’t have big toxicities and NO STEROID Responses
What are the advantages for topical administration of a drug?
Most important for the eye
Safest if done right
Simple to apply, drug placed where it’s needed and kept localized
Good ocular penetration and can reach back to iris/ciliary body
Can also treat uni-ocular disease and avoids most systemic effects
What are the disadvantages for topical administration of a drug?
Can develop the systemic toxicity –> adrenal suppression even with topical use
Aggravating ulcers due to reducing immune system
Occassional conjunctival infection
Epithelial keratopathy which is very rare
Why would one use a low concentration GCS over a high concentration GCS?
Extraocular infection where the ocular penetration from a high ocncentration isn’t needed
What are the advantages for periocular injection administration of a drug?
Get a very high drug concentration into deep eye (where it needs to go)
Can treat uniocular disease avoiding systemic problems and compliance
What are the disadvantages for periocular injection administration of a drug?
Quite uncomfortable Can develop adrenal suppression Accidental intraocular not periocular/orbital infections Allergy to diluent Ulceration of conjunctiva Exophthalmos Papilledema
What are the advantages for systemic administration of a drug?
May be the only mode of treatment for some things like uveitis where topical can't penetrate Good for systemic inflammation Supplemental to topical Easy to take May reach all the eye Can use alternate day therapy
What are the disadvantages for systemic administration of a drug?
Adrenal suppression and other significant systemic effects
Inhalation would be the best route for what kind of condition?
Asthmatic to avoid systemic problems
Discuss the indications for GCS therapy in ocular disease
Any active inflammatory process
Injury to the eye
Many conditions like - Allergic conjunctivitis, uveitis and ACIDIC chemical burns
What are some general guidelines to treating with GCS?
Don’t be conservative, treat hard and immediately
Frequent follow ups
Taper off high dose/long-term therapy
Ideal is a short term with the lowest dose we can get away with
If you need to up the treatment, do you increase frequency or concentration?
Frequency
