Steroids

corticosteroids

steroid hormones synthesized by the adrenal cortex that play diverse physiologic roles in the body

mineralocorticoids

• produced in outer layer of adrenal cortex (zona glomerulosa)

• aldosterone

• secretion is primarily controlled by RAAS

• regulate mineral/electrolyte balance

glucocorticoids

• produced in middle layer of adrenal cortex (zona fasciculata)

• cortisol

• secretion is primarily controlled by ACTH

• stress hormones

androgens

• produced in middle layer of adrenal cortex (zona fasciculata)

• DHEA

• secretion is primarily controlled by ACTH

• sex hormones

HPA axis

what regulates the glucocorticoid levels in the body?

8am

cortisol levels follow the circadian rhythm & peak around ______

negative

________ feedback maintains cortisol levels in an appropriate range

1. metabolism of carbs/protein/fat

2. maintenance of electrolytes & fluids

3. preserve normal CV, immune, renal, skeletal, endocrine, & nervous system functioning

4. increase cortisol levels in response to stress (trauma, hemorrhage, infections, surgery, hypoglycemia, cold, pain)

list some normal physiologic functions of glucocorticoids

cortisol, aldosterone

glucocorticoid receptors have a high affinity for ______ but a lower affinity for _______

aldosterone & cortisol

glucocorticoid receptors have a high affinity for ____________

cytoplasm

where are steroid receptors located?

inhibition of phospholipase A2 → inhibition of prostaglandins, thromboxanes, & leukotrienes

inhibition of lymphocytes, cytokines, fibroblasts, mast cells, neutrophils, basophils, monocytes, macrophages

MoA of glucocorticoids

decrease

glucocorticoids _________ (increase/decrease) inflammatory responses

decrease

glucocorticoids _________ (increase/decrease) immunologic responses

increase

glucocorticoids _________ (increase/decrease) liver glycogen deposition

increase

glucocorticoids _________ (increase/decrease) gluconeogenesis

increase

glucocorticoids _________ (increase/decrease) glucose output from liver

decrease

glucocorticoids _________ (increase/decrease) glucose utilization

increase

glucocorticoids _________ (increase/decrease) protein catabolism

increase

glucocorticoids _________ (increase/decrease) bone catabolism

decrease

glucocorticoids _________ (increase/decrease) ACTH

fluctuate

glucocorticoids _________ mood

increase

glucocorticoids _________ (increase/decrease) gastric acid & pepsin

increase

glucocorticoids _________ (increase/decrease) mineralocorticoid effects - Na+ reabsorption & K+/H+ excretion

hyper

glucocorticoids result in _______glycemia (hyper/hypo)

muscle wasting

how do high levels of glucocorticoids affect muscle in the body?

buffalo hump, moon facies, increased supraclavicular area, fat loss in extremities

how do high levels of glucocorticoids affect body fat distribution?

increase

all glucocorticoids __________ IOP

steroid induced ocular hypertension

IOP increase of more than 10mmHg from baseline for a patient taking steroids

all

steroid induced ocular hypertension can occur with what types of steroid administration?

intravitreal > periocular injections > topical = oral

rank these routes of drug administration by their risk of steroid induced ocular hypertension: (most to least)

topical, periocular injections, intravitreal injection, oral

1. physical & mechanical changes in TM

2. inhibition of proteases & TM endothelial phagocytosis

3. deposition of substance in TM

what are the TM outflow resistance mechanisms?

1. primary open angle glaucoma/glaucoma suspect

2. first degree relative w/ POAG

3. history of previous steroid-induced IOP elevation

4. very young age or elderly

5. high myopia

6. type 1 DM

7. connective tissue disease

8. penetrating keratoplasty

what things increase the risk of steroid induced ocular hypertension?

2-6wks (but can be sooner or later)

on average, IOP increase from steroids takes _____ from initial use

1-4wks

typically IOP normalizes w/in ______ of stopping topical, oral, IV, inhaled, or intranasal steroids

longer

the longer the duration of steroid treatment, the ________ it can take to normalize after stopping therapy

posterior subcapsular

all glucocorticoids can cause _____________ cataracts

contraindicated

steroids are _______ (cautioned/contraindicated) in herpes simplex epithelial keratitis

delayed wound healing, increased risk of infection, worsened infection

all glucocorticoids decrease the body’s immune response which results in…

adrenal cortical atrophy (adrenal crisis)

• can start within weeks of starting steroid therapy

• due to HPA axis suppression

• body does not have enough cortisol to function

• steroids must be TAPERED to prevent this

PO

what is the dosage form of prednisone?

PO, IV

what is the dosage form of methylprednisolone?

prednisone

• dosing:

  • PO

  • 1x/day in morning

  • take w/ food or milk, PPI

  • can split higher doses to 2-4 smaller ones throughout day

  • higher doses taken for >1wk require tapering

• advantages:

  • flexible dosing options

• uses:

  • mild to moderate ocular inflammatory disorders

  • severe inflammation

ischemic bone necrosis

doses of >60mg/day of oral prednisone can increase the risk for __________

methylprednisolone (Medrol Dose-Pak)

• dosing:

  • PO

  • 1x/day in morning

  • take w/ food or milk, PPI

• advantages:

  • easy to administer

  • easy to taper

• disadvantages:

  • less effective than prednisone therapy

• uses:

  • good for less severe inflammation

methylprednisolone

• dosing:

  • IV

  • given w/ PPI

• uses:

  • optic neuritis

  • giant cell arteritis/arteritic ischemic optic neuropathy

cortisol like effects (altered fat distribution, increased infections, poor wound healing, osteoporosis, myopathy, purpura, HTN, acne, hyperglycemia)

systemic SE of oral steroids

1. increased IOP

2. PSC

3. increased risk of bleeding/bruising (subconj heme)

4. increased risk of infections

5. myopic RE shift

6. delayed wound healing

7. papilledema

ocular SE of oral steroids

1. DM

2. infectious disease

3. chronic renal failure

4. congestive heart failure

5. systemic HTN

what are the cautions for oral steroids?

1. peptic ulcers

2. osteoporosis

3. psychoses

4. TBI

what are the contraindications for oral steroids?

difluprednate, prednisolone acetate, prednisolone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, fluoromethalone alcohol, fluoromethalone acetate

list the ketone based topical steroids

loteprednol etabonate

list the ester based topical steroids

emulsion

dosage form of difluprednate

suspension

dosage form of prednisolone acetate

solution

dosage form of prednisolone sodium phosphate

suspension

dosage form of dexamethasone

solution

dosage form of dexamethasone sodium phosphate

suspension, ung

dosage form of fluoromethalone alcohol

suspension

dosage form of fluoromethalone acetate

ung, gel, suspension

dosage form of loteprednol etabonate

pink or white

cap color of topical steroids

liver

ketone steroids depend on _______ metabolism to become inactive

ocular esterases

ester steroids are rapidly inactivated by _________

lower incidence of PSC & IOP elevation

why are “soft” steroids (loteprednol) a better option steroid in some cases?

lipophilic

are acetate/alcohol derivative steroids lipophilic or hydrophilic?

suspensions/ung

acetate & alcohol derivative steroids are available as _________ (dosage form)

better

acetate & alcohol derivative steroids should be able to penetrate the intact cornea _______ (better/worse) than water-soluble phosphates

hydrophilic

are salt derivative steroids (sodium phosphate/hydrochlorides) lipophilic or hydrophilic?

solutions

salt derivative steroids are generally formulated as _________ (dosage form?)

less

salt derivative steroids are ______ effective in suppressing inflammation

topical acetate or alcohol

what type of steroid is best for uninflamed eyes with intact epithelium?

topical phosphates

what type of steroid is best for uninflamed eyes w/o intact epithelium?

topical acetates

what type of steroid is best for inflamed eyes w/ intact epithelium?

difluprednate, prednisolone, dexamethasone, loteprednol

what topical steroids have high potency?

fluoromethalone alcohol, fluoromethalone acetate

what topical steroids have moderate potency?

lower concentration prednisolone, lower concentration loteprednol

what topical steroids have weak potency?

1. difluprednate

2. prednisolone acetate

3. loteprednol

4. dexamethasone

5. fluorometholone acetate

6. fluorometholone alcohol

7. loteprednol

8. prednisolone

9. hydrocortisone to eyelids

list the topical steroids by relative clinical anti-inflammatory efficacy (most to least)

1. difluprednate

2. dexamethasone

3. prednisolone acetate

4. loteprednol

5. fluorometholone acetate

6. fluorometholone alcohol

7. loteprednol

8. prednisolone

9. hydrocortisone to lids

list the topical steroids by relative propensity to cause IOP increase & PSC (most to least)

difluprednate

• newest topical steroid

• dosage form: emulsion

• FDA approval:

  • management of inflammation & pain after intraocular surgery

• indications:

  • more severe anterior inflammatory conditions (uveitis, scleritis, stubborn ME)

• advantages

  • 56x greater receptor binding affinity than prednisolone acetate

  • superior IOL penetration than prednisolone acetate → higher therapeutic concentrations in posterior segment

  • requires ½ the dosing frequency of Pred Forte

• disadvantages:

  • very high propensity to raise IOP to very high levels

  • more prone to cause SPK

• pregnancy: C

prednisolone

• dosage form:

  • acetate suspension

  • phosphate solution

• indications:

  • acetate form has enhanced anti-inflammatory effects

• advantages:

  • potent

  • very effective

• pregnancy: C

loteprednol etabonate

• “soft” steroid

• ester based

• indications:

  • ideal for conditions requiring long-term tx

• advantages:

  • less likely to increase IOP or cause PSC

• disadvantages:

  • less effective than difluprednate/prednisolone

Lotemax (0.5% gel-drops, ung, suspension)

• topical loteprednol etabonate form

• indication:

  • steroid responsive inflammatory conditions of palpebral/bulbar conj, cornea, & ant seg

• preservative:

  • BAK

  • ung is PF

• pregnancy: C

Alrex (0.2% suspension)

• topical loteprednol etabonate form

• indication:

  • seasonal allergic conjunctivitis

• preservative: BAK

• pregnancy: C

Lotemax SM (0.38% gel)

• topical loteprednol etabonate form

• sub-micron technology

• indication:

  • tx of post-op inflammation & pain following ocular surgery

• advantages:

  • improved contact time

  • improved AC penetration

• preservative: BAK

• pregnancy: C

Inveltys (1.0% suspension)

• topical loteprednol etabonate form

• indication:

  • tx of post-op inflammation & pain following ocular surgery

• mucus penetrating nanoparticles

• preservative: BAK

• pregnancy: C

Eysuvis (0.25% suspension)

• topical loteprednol etabonate form

• indications:

  • short term tx for DED

• preservative:

  • BAK

• pregnancy/lactation: no sufficient studies

dexamethasone

• close analog of cortisol

• dosage form:

  • available as alcohol (susp) or phosphate (sol) derivative

• advantages:

  • very potent

• disadvantages:

  • greater propensity to increase IOP

• preservative: BAK

• pregnancy: C

tobramycin antibiotic

the phosphate form of dexamethasone is more commonly given in combination with ______________-

fluorometholone

• fluorinated analog of progesterone

• dosage forms:

  • formulated as alcohol & acetate derivatives

• advantages:

  • relatively low potential for increased IOP

• disadvantages:

  • relatively weak compared to difluprednate, prednisolone, dexamethasone, & loteprednol

• preservative: BAK

• pregnancy: C

1. ocular HTN

2. PSC

3. secondary infection

4. delayed corneal epithelial healing

5. SPK

6. increased risk of bleeding (subconj heme)

7. corneal melt

8. mydriasis

9. ptosis

list the ocular effects of topical steroid therapy

1. active viral diseases of cornea & conjunctiva (HSK, vaccinia, varicella)

2. mycobacterial infections of eye

3. fungal diseases of eye

what are the contraindications of topical steroids?

hydrocortisone

• OTC

• dosage forms:

  • 0.5-1% cream or ung

• indications:

  • dermatological conditions

• SE:

  • increased IOP

  • PSC cataracts

  • skin thinning

  • permanent skin pigmentation changes

triamcinolone acetonide (Kenalog, Triesence), dexamethasone (Dexycu)

what steroids are given via periocular injections? (sub-tenon’s, subconjunctival, retrobulbar)

dexamethasone (Dexycu)

what steroids are given intracameral/peri-ocular?

fluocinolone acetonide (Retisert, Iluvien, Yutiq), dexamethasone (Ozurdex)

what steroids are given via intravitreal implants?

triamcinolone acetonide (Kenalog, Triesence)

what steroids are given via intravitreal injection?

triamcinolone acetonide (Xipere)

what steroids are given via suprachoroidal injection

peri-ocular local injection

• administered by subconj, sub-Tenon’s capsule, or retrobulbar injection

• effective during surgical procedures, supplemental to topical or systemic admin in severe inflammation, & in non-compliant pts

• used in chronic conditions (anterior uveitis)

• used in intralesional injection (chalazia)

• SE:

  • skin depigmentation

  • scleral thinning/melt

  • globe perforation

  • optic nerve atrophy

  • increased IOP

  • PSC

darker pigmented skin

what patients are intralesional injections of chalazion contraindicated for?

dexamethasone intracameral injection (Dexycu)

• dosage form:

  • 9% intraocular suspension

  • single-dose, sustained release

  • delivered via cannula & placed in posterior chamber

• indication:

  • post-op cataract inflammation

• effects can last up to 30days