lec 8: steroids part 2

what do mineralcorticoids do to our system

increase sodium retention and increase BP

(a side effect that we dont want)

what do we want to control our inflammatory/immune system

glucocorticoids

what two corticosteroids have the same MC potency and GC potency

hydrocortisone and cortisone

do prednisone and prednisolone have more GC potency or MC potency

more GC potency

does the half life of the corticosteroids correlate with their GC potency or how are they related?

yes, as you increase in GC potency, you increase in half life 

which is better at controlling inflammation, prednisone or dexamethasone?

dexamethasone is greater

which is the most common prescribed oral steroid

prednisone

as the half life increases, what do you get more of besides GC potency?

HPA suppression

what is HPA

hypothalamus pituitary adrenal gland axis

what is a purely mineralcorticoid itself

fludrocortisone (has so much more mineralcorticoid potency than gluco)

what type of pop. would you give fludrocortisone to?

pts with addison’s disease in which they dont produce enough cortisol to begin with

their BP is really low

suffering from hypotension what corticosteroid would be fantastic?

Fludrocortisone would be beneficial.

is cortisone the active form of the medication that binds to the glucocorticoid receptor internally

no

what binds to the glucocorticoid receptor, is it cortisone or cortisol?

cortisol

when we rx eyedrops, do we care about first pass metabolism?

no it doesnt go to the liver if it’s a solution 

what does the corticosteroid have to pass through in order to get activated?

the liver

cortisone is …

inactive

cortisol is…

active

too much cortisol =

high BP

how does negative feedback play a role in conversion from active back to inactive?

if you have too much active form (ex: cortisol) - that’s not very good so an enzyme found in the kidneys converts it back into the inactive form so that BP doesnt go up too much

what organ plays a HUGE role in regulating our BP 

kidneys 

what does prednisone get converted to and what does it bind to after

gets converted to prednisolone and that binds to the glucocorticoid receptor

are prednisone eyedrops real

no bc we dont have enzymes in our eyes to convert it into the active form

youd rx prednisolone

what does the methyl group added to prednisolone aka methylprednisolone do

gives it extra glucocorticoid activity

what do glucocorticoids do to our body regarding the allergic response?

modulate inflammatory cascade response

what do glucocorticoids do to our body regarding being anti-inflammatory?

less immune cells, less MMP9s, less fibroblasts 

less PLA2 preventing the arachidinic acid pathway 

less edema, decrease capillary mobility 

decrease VEGF 

what do glucocorticoids do to our body regarding the CNS?

mood changes via limbic system

causes people to b more aggressive 

what do glucocorticoids do to our body regarding their energy metabolism?

increase blood glucose

what do glucocorticoids do to our body regarding lipid redistribution?

fat gets shifted more to face and neck region

what do glucocorticoids do to our body regarding the hemo regulation?

increase in RBC & PMN

decrease in eosinophils, basophils, and monocytes 

what do glucocorticoids do to our body regarding the CV regulation?

increase in HR and BP 

what is the most common eyecare steroid administration

topical ocular drops

what is a worry of rx’ing an oral steroid

renal function

it is cleared through the kidneys: but those who have chronic kidney disease be careful (ex: diabetic pts)

what type of administration is triamcinolone (kenalog) for and what is it used for

local injection

used for chalazions

what do inhaled steroids do to our eyes

they’re very potent

can cause an increase in IOP

can cause CSR (central serous retinopathy)

what is central serous retinopathy

fluid accumulates in the retina

what are the inhaled steroid examples

fluticasone (advair, flovent, flonase)

beclomethasone (QVAR)

budesonide (pulmicort, symbicort)

are there IV steroids

yes

what are indications of using oral steroids

temporal arthertitis (cant chew, jaw claudication, HA)

grave’s opthalmopathy

ocular myasthenia gravis

stevens-johnson syndrome

scleritis

what type of hypersensitivity rxn is temporal arthertis?

type IV

what type of hypersensitivity rxn is grave’s ophthalmopathy?

type 2

what type of hypersensitivity rxn is ocular myasthenia gravis

type 2

what type of hypersensitivity rxn is stevens-johnson syndrome

type 4

what type of hypersensitivity rxn is scleritis

begins as type 3 and if untreated becomes type 4

will antihistamines work on type 4

no 

what hypersensitivities are good to use with steroids

type 2-4 is perfect for steroids

type 1 primarily anti-histamines but ur allowed to use steroids as well

how do you know if ur dealing with scleritis and not episcleritiis

drop the pt with phenylephrine

if it’s white - episcleritis

still red - scleritis

scleritis will also be PAINFUL

if you have episcleritis, topical or oral steroids

topical works fine

no need for oral

if you have a scleritis what is tx?

start with oral NSAID

if that doesnt work do an oral steroid

when do you use an oral steroid for endophthalmitis

once you figure out that it is actually a true inflammation and not infectious

should you use a steroid when there is an active infection

NO

get rid of infectious component first and then consider steroid use.

you have a bacterial endophthalmitis what do you do

start with antibiotic treatment

(IV antibiotic tx) then you could rx the oral steroids

you have a funagl endophthalmitis what do you do

start with an antifungal tx first

then rx oral steroids ONCE the infection IS GONE

are oral steroids used for IIH 

yes and they cause it too

what are a few intraocular indications of oral steroids

endophthalmitis

posterior seg:

• vitritis, retinitis, choroiditis

what two meds cause IIH

tetracyclines and oral steroids

& they’re also a tx for IIH

if you have an optic neuritis, can you tx oral steroids initially

NO according to the optic neuritis treatment trial: YOU NEED TO USE IV STEROIDS FIRST THEN ORAL STEROIDS TO SPEED THE RECOVERY

is the outcome the same whether you use the IV steroid first or oral first when tx’ing an optic neuritis ?

yes but it speeds recovery 

using oral steroid by itself is ineffective and it INCREASES the risk of recurrence 

does the diurnal cortisol levels make a difference if it is topically or orally?

topically no

orally yes

what time is ideal to take oral steroids

in the morning after waking up

NOT RIGHT BEFORE BED

(should mimic cortisol levels that occur in the body)

too much cortisol release stimulates what

negative feedback cycle

why is tapering so important with steroids

Tapering is crucial to allow the body to gradually adjust its cortisol production, preventing withdrawal symptoms and adrenal insufficiency.

what are the withdrawal symptoms

HA

lethargy

fainting

weight loss

hypoglycemia

nausea & vomitting

what is great about methylprednisolone pack

easy to follow the taper schedule

decrease dosage of cortisol gradually so that HPA axis knows that it needs to start making it’s own cortisol again

a higher dosage taken for a serious condition calls for a ?

long taper 

what is the rebound inflammation that occurs

after discontinuing corticosteroids, leading to increased symptoms of the underlying condition

“need to trick ur body into believing everything is good”

do you also taper ophthalmic steroids

yes

how do you avoid relapse of the condition

make sure the pt follows the taper schedule even beyond resolution of inflammation to make sure that they have eradicated everything 

topical steroids are most effective in acute or chronic

acute

which is more responsive to topical steroids, anterior or posterior seg of the eye

anterior 

as you get further in the back of the eye, what type of steroid do you use

IV

what is durezol (difluprednate)

most POTENT topical steroid

doesnt have BAK (has sorbic acid instead)

the fluorinated molecules gives it incredible corneal penetration = increase anti-inflammatory activity = increase side effects

INCREASE IN IOP (>30mmHg)

an emulsion - doesnt need to be shaken

what is pred forte (prednisolone acetate)

1% suspension (NEED TO SHAKE)

the most used

inexpensive

available everywhere

what is lotemax (loteprednol etabonate)

only ester based steroid 

the ointment form is the ONLY PRESERVATIVE FREE TOPICAL OINTMENT

need to be shaken (suspension)

used to tx some uveitis’ and post-op cataract surgeries

are steroids hydrophobic or hydrophilic in nature

hydrophobic

if someone doesnt shake their suspension, what happens

prob gonna get rebound inflammation bc med isnt even going in their eye

how does lotemax get deactivated in the eye

since this is the ONLY ESTER TOPICAL STEROID

the esterases in the eye deactivate it = less side effects = less inflammation

less IOP issues, less cataract issues

does difluoprednate have any MC potency and how is it’s GC potency

NO MC potency

HAS A LOT (224) GC POTENCY

is it harder to deactive durezol and pred forte

yes, bc they are ketone molecules

esp the durezol bc it has the fluoride molecules which allow it to be there longer 

is there oral difluprednate

no just topical form

what are the mild strength topical steroids

they’re basically the same as the strong molecules just a lower concentration

what is pred mild

it’s prednisolone acetate but at 0.12% concentration instead of 1%

does flurometholone penetrate the anterior chamber well

no not as good as the others

used for filamentary keratitis, episcleritis, some allergic conjunctivitis’

treating ocular surface disease so we dont care that it gets into the AC

less increase in IOP

can mild strength topical steroids cause an increase in IOP

yes it is possible

name a few mild strength topical steroids

alrex

flarex

FML

FML S.O.P

Pred Mild

what is lotemax SM gel 0.38%

has a polycarbophyll which is a viscosity agent that makes it a gel formulation

instead of 0.5%, it’s 0.38% bc the gel keeps it there much longer

SM - submicron

^ particle size is smaller so it can pass through the tears more easily

has 2x the penetration as compared to lotemax gel

has lower BAK than the others

what is so good about amplify nanoparticles than regular suspension eye drops

nanoparticles are so tiny that they can pass through the mucus layer of the tear film

the suspensions are larger so they get stuck at the mucin layer level and sometimes dont even get to the cornea or even AC 

you get more drug delivered to the cornea 

what are the two new loteprednol formulations

eysuvis 0.25% and inveltys 1%

eysuvis 0.25%

tx for dry eye flares (not controlled by current therapy)

80% of pts with dry eye suffer from flares

triggers cytokine storm

inveltys 1%

post operative inflammation pain following ocular surgery

only BID dosing bc of the amplified molecule

what is typical dosing after cataract surgery with a steroid

4x a day 

what is lotemax also good for

safe for long term SAC & VAK

what are steroid implants

dextenza - put in the nasolacrimal duct (good for pts that you dont wanna give an eyedrop or cant put in an eyedrop)

gradually releases dexamethasone

does the amount of glucocorticoid activity correlate to the amount of dosing

yes, the more you dose = the more glucocorticoid activity you get (suppression of corneal inflammation) 

what can you use topical steroid for?

blepharitis, contact dermatitis, and chalazion

should you use an antibiotic for contact dermatitis

no just a topical steroid

what do you use on severe bleph

antibiotic + steroid

what can you use on chalazions

IV injection steroid (kenalog)

for surgeries, do you want a topical steroid

yes bc surgery is a controlled trauma to the eye so yes use a steroid bc of inflammation

cells an flare come from what

blood aqueous barrier being compromised

steroids responsible for getting rid of that