Ocular Anti-Inflammatory Agents

Question 1

What are the physiologic actions/roles of glucocorticoids?

Answer 1

Interacts with hormones that affect sympathetic responses (thyroid hormone and epinephrine)

Question 2

At what concentration do you see the physiologic effects of glucocorticoids? What are these effects?

Answer 2

20-25mg
Carbohydrate Metabolism - Increasing glucose synthesis by breaking down glycogen, amino acids and proteins, antagonizing insulin

Question 3

At what concentration do you see the pharmacologic effects of glucocorticoids? What are these effects?

Answer 3

More than 25mg
CNS - Mood changes, euphoria and if higher schizophrenia
Lymphoid tissue decreases in number and see reduced immune responses
Anti-inflammatory effects

Question 4

List the ways cortisol can act as an anti-inflammatory agent

Answer 4

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.

Question 5

Though the exact mehcanism isn’t established, what is the speculated MOA for cortisol?

Answer 5

Binding to genome to modify transcription

Question 6

The use of glucocorticoids in treating inflammation is a cure, true or false?

Answer 6

False, only treats the symptoms

Question 7

GCS inhibition of inflammatory mediators is performed how?

Answer 7

Indirect by affecting transcription of mediators

Cyclooxgenase-2 (though this can be directly inhibited too), Endothelin-1 and PLA2 all affected

Question 8

GCS effects are central or peripheral effects?

Answer 8

Peripheral

Question 9

Describe the local (peripheral) effects of GCS

Answer 9

Effects on fibroblasts - Inhibiting cell activity, less regeneration, less scar formation and WBCs
Affecting permeability
Epithelial regeneration
Lysosome stabilization (less tissue damage)

Question 10

What GCS drugs could be selected to have minimum hypertensive effect (sodium retention)

Answer 10

Triamcinolone
Betamethasone
Dexamethasone

Question 11

What GCS drugs could be selected for alternate day therapy (based on duration of action alone)?

Answer 11

Cortisol
Cortisone
Fludrocortisone

Question 12

What is the difference between prednisolone and prednisone?

Answer 12

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

Question 13

How do the efficacy of prednisone and cortisol compare?

Answer 13

Exactly the same efficacy, however prednisolone is 4 times as potent (binding related)

Question 14

In Addison’s disease what is the main problem and how can it be solved with a GCS?

Answer 14

Adrenal gland is atrophic and cannot produce cortisol and aldosterone.
Fludocortisone has great GCS activity and very potent mineralcorticoid activity and can replace both

Question 15

Unlike systemic GCS drugs, topical GCS drugs are based on what to determine solubility?

Answer 15

Ability to cross the cornea and not the duration of action like systemic GCS drugs

Question 16

Describe the acetate, alcohol and sodium salt preparations for GCS

Answer 16

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’

Question 17

Describe the metabolism of: Cortisol, Prednisolone, Dexamethasone, Flurometholone, Loteprednol and Difluprednate

Answer 17

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

Question 18

Describe the GCS, Flurometholone

Answer 18

Fast intraocular metabolism, doesn’t have big toxicities and NO STEROID Responses

Question 19

What are the advantages for topical administration of a drug?

Answer 19

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

Question 20

What are the disadvantages for topical administration of a drug?

Answer 20

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

Question 21

Why would one use a low concentration GCS over a high concentration GCS?

Answer 21

Extraocular infection where the ocular penetration from a high ocncentration isn’t needed

Question 22

What are the advantages for periocular injection administration of a drug?

Answer 22

Get a very high drug concentration into deep eye (where it needs to go)
Can treat uniocular disease avoiding systemic problems and compliance

Question 23

What are the disadvantages for periocular injection administration of a drug?

Answer 23

Quite uncomfortable
Can develop adrenal suppression
Accidental intraocular not periocular/orbital infections
Allergy to diluent
Ulceration of conjunctiva
Exophthalmos
Papilledema

Question 24

What are the advantages for systemic administration of a drug?

Answer 24

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

Question 25

What are the disadvantages for systemic administration of a drug?

Answer 25

Adrenal suppression and other significant systemic effects

Question 26

Inhalation would be the best route for what kind of condition?

Answer 26

Asthmatic to avoid systemic problems

Question 27

Discuss the indications for GCS therapy in ocular disease

Answer 27

Any active inflammatory process
Injury to the eye
Many conditions like - Allergic conjunctivitis, uveitis and ACIDIC chemical burns

Question 28

What are some general guidelines to treating with GCS?

Answer 28

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

Question 29

If you need to up the treatment, do you increase frequency or concentration?

Answer 29

Frequency