Steroids: Adverse Reactions PDF

Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Diane T. Adamczyk, OD Copyright © 2024 37 37 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions OVERVIEW PSC ^IOP Secondary ocular infection Retardation of corneal epithelial healing Uveitis Mydriasis Ptosis T...

Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Diane T. Adamczyk, OD Copyright © 2024 37 37 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions OVERVIEW PSC ^IOP Secondary ocular infection Retardation of corneal epithelial healing Uveitis Mydriasis Ptosis Transient ocular discomfort Diane T. Adamczyk, OD Copyright © 2024 38 38 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Cataracts ◦ Result from systemic, topical, cutaneous, nasal aerosols, inhalation ◦ PSC ◦ Dosage and duration ◦ Prednisone x 1-4 years ◦ 11% if 15mg Diane T. Adamczyk, OD Copyright © 2024 39 -any variety way of administering steroids can cause cataracts however certain way are going be more likely to cause cataracts over others -ex. If a pt is using a topical steroid for a prolonged period of time that’s going be more likely to cause a cataract than someone taking nasal aerosol -this pt who has a cataract is young and we can tell bc there is not a lot of cortex which develops as you get older and the pt also has a yellowish tinge at the back where the PSC is located -highlighted puts you at higher risk for cataracts -once you develop of PSC it’s not irreversible even if you stop taking the steroid and the only way to remove it is by taking the lens out 39 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Cataracts ◦ Systemic steroids: ◦ Adults: usually not < 1yr tx, regardless dose ◦ Children: lower doses, shorter period ◦ Topical steroids à from prolonged use ◦ Permanent, D/C = stable Diane T. Adamczyk, OD Copyright © 2024 40 40 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Cataract pathogenesis: ◦ Multifactorial: aka lots of reasons ◦ Includes individual susceptibility ◦ Steroid interaction with lens particles ◦ Steroid enters lens fiber cells Ø React with specific amino groups of lens crystallins Ø Conformational change in cells Ø Protein aggregation ◦ Inhibit sodium-potassium pump in lens epithelium ◦ > lead accumulation water in lens fibers and agglutination of lens proteins Diane T. Adamczyk, OD Copyright © 2024 41 41 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Associated with ocular hypertension and OAG: Steroid responder ◦ Oral ◦ Intravitreal ◦ Periocular injection ◦ Creams, lotions, ointments on lids, face Diane T. Adamczyk, OD Copyright © 2024 42 -steroid responder can happen from any form of administration of the steroid but it is seen more with topical bc it’s right there 42 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Steroid responders (topical): ◦ 33% steroid responders ◦ 18-36% general population: ◦ Moderate increase of 5mmHg or > ◦ 46-92% in patient with POAG Diane T. Adamczyk, OD Copyright © 2024 43 -if the pt has a history of POAG you’re more likely to have a propensity to have a rise in IOP with a concurrent use of steroid 43 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions ^IOP (Topical Steroid) ◦ Can affect normal and glaucoma patients ◦ > elevation “GL” patients ◦ Genetic tendency ◦ 70% of 1st degree offspring of Gl patient have ^IOP of 5MM ◦ FH important ◦ Other factors: Increase the risk of a pt being a steroid responder ◦ Age ◦ Myope >-5 ◦ Kruckenberg spindles Diane T. Adamczyk, OD Copyright © 2024 44 44 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions High responders (4-6%) ◦ IOP ^ >15mmHg AND ◦ >31mmHg ◦ After daily steroid use for 4-6 weeks Moderate responders (1/3) ◦ 6-15 mmHg ◦ IOP 20-31mmHg Nonresponder (2/3) ◦ leading to accumulation of polymerized glycosaminoglycans in TM ◦ Presence glycosaminoglycans ◦ Obstruct meshwork and outflow Diane T. Adamczyk, OD Copyright © 2024 49 -steroids affect GAGs by preventing them breaking down into smaller components so obstructing the TM and less outflow increasing the IOP à another theory 49 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reaction Increase IOP Mechanism: ◦ Increase in expression of collagen, elastin, or fibronectin in extracellular matrix ◦ Accumulation of abnormal extracellular material in Schlemm canal > increase outflow resistance Diane T. Adamczyk, OD Copyright © 2024 50 -by increasing expression of collagen elastin fibronectin in the extracellular matrix its clogging up drainage mechanism 50 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions ^IOP (Topical) ◦ 2-8 weeks treatment ◦ Dexamethasone, prednisolone, hydrocortisone, FML ◦ 3 weeks - prednisolone, dexamethasone ◦ 5 weeks - rimexolone, fluorometholone ◦ Reversible ◦ 1-3 weeks Diane T. Adamczyk, OD Copyright © 2024 51 -when do we see a pt become a steroid responder once put on steroids? à it can vary but in timeframe but is usually seen 2-8 weeks into treatment but it’s a wide range and depends on type of steroid pt is on -dexamethasone is known to rise IOP and can be seen sooner than the other drugs listed -glaucoma pts can rise IOP much sooner than 2-8 weeks esp depending on how long they’re on the steroid -before putting the pt on a steroid you want to check their pressure as a baseline to monitor overtime bc the longer the pt is on a steroid, the more possibility of them having a response increases 51 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions ^IOP ◦ Management ◦ Taper steroid ◦ Switch eg. loteprednol 0.5% ◦ Add glaucoma med Diane T. Adamczyk, OD Copyright © 2024 52 -ex. Pt has an iritis and needs to be on steroid to get it under control and pt has rise in IOP you have to see your options and should manage the steroid -if the pt is on the steroid for a long time and the IOP is increasing and their inflammation is getting better consider tapering the pt to help with the rise in IOP -can also switch to another drug that won’t cause a huge rise in IOP such as loteprednol which is a site-specific drug but can still cause a rise in IOP just less than other steroids such as dexamethasone -if pt has chronic iritis you don’t have too many options of switching or tapering so instead you might want to consider adding a glaucoma med to help with the IOP 52 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Infection ◦ Steroids decrease immune defense mechanisms, therefore lower resistance to infection ◦ Steroids mask disease symptoms ◦ Increased susceptibility to viral, fungal, bacterial infection Diane T. Adamczyk, OD Copyright © 2024 53 -steroids cause a decrease in immune system leads to getting an infection -steroids make everything feel better but it may mask the symptoms and underlying disease bc remember steroids go after the inflammation not the actual disease (goes after the effects of the disease that lead to the inflammatory process) and may increase the susceptibility to viruses, fungi, bacteria etc. 53 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Corneal epithelial healing ◦ Retard ◦ Systemic and topical Uveitis ◦ Paradoxical ◦ Greater in blacks vs whites ◦ Pain, photophobia, blurred vision, ciliary flush, C&F Diane T. Adamczyk, OD Copyright © 2024 54 -corneal healing is retarded by oral and topical steroids -steroids are also being used to treat uveitis but sometimes exacerbates and not really sure why it causes a paradoxical 54 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Mydriasis and Ptosis à might be related to the vehicle used in the topical steroid ◦ Topical ◦ Temporary mydriasis ◦ Vehicle Ocular discomfort Steroid induced calcium deposits Diane T. Adamczyk, OD Copyright © 2024 55 55 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Adverse Reactions Topical or periocular: few systemic effects Intralesion injection: adrenal suppression ◦ Children Diane T. Adamczyk, OD Copyright © 2024 56 -with topical administration, we don’t see adrenal suppression but it is seen in children 56 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Caution and Contraindication Diane T. Adamczyk, OD Copyright © 2024 57 57 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Caution Topical and Systemic: ◦ Glaucoma ◦ Infection Systemic ◦ Diabetes mellitus ◦ Chronic renal failure ◦ Congestive heart failure ◦ Hypertension Diane T. Adamczyk, OD Copyright © 2024 58 -monitor glaucoma pt carefully that are taking either topical or systemic steroids esp if the IOP goes from 15-40 mmHg -check for any infections bc of suppression of immune system 58 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Contraindications Topical and Systemic: ◦ Epithelial herpes simplex Systemic: ◦ Peptic ulcer ◦ Osteoporosis ◦ Psychosis Diane T. Adamczyk, OD Copyright © 2024 59 59 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Patient Follow Up Topical: ◦ Evaluate: ◦ cornea (SPK, herpetic, fungal keratitis), ◦ lens, à can develop posterior sub cataracts (PSC) ◦ IOP Systemic: ◦ Monitor: ◦ ◦ ◦ ◦ Diane T. Adamczyk, OD Copyright © 2024 hypertension, GL, cataract, blood glucose 60 60 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Bioavailability Diane T. Adamczyk, OD Copyright © 2024 61 61 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Bioavailability Water soluble salts à don’t have to shake ◦ Solutions Lipid soluble derivatives ◦ Suspensions (have to shake), ointments Diane T. Adamczyk, OD Copyright © 2024 62 62 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Bioavailability Variable penetrance into cornea ◦ Cornea properties ◦ Hydrophobic (epithelium and endothelium lipid layer) ◦ Hydrophilic layers (aqueous media of stroma) ◦ Deepithelization (removal, inflammation) alters hydrophobic corneal surface, water soluble preparations penetrate better Diane T. Adamczyk, OD Copyright © 2024 63 -depending on the type of steroid we’re going to see how well its going to get across the cornea if lipid soluble or water soluble -if we remove the epithelium (barrier), this effects how the steroid gets through the cornea as well as inflammation has an effect as it alters the hydrophobic corneal surface so water soluble steroids penetrate better bc lipo soluble steroid will get thru the epithelium easily 63 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Anti-Inflammatory Efficacy Anti-InflamEfficacy (%) Steroid Epithelium: Intact Absent Pred acetate 1% 51 53 Pred phosphate 1% 28 47 Fluorometholone acetate 0.1% 48 Fluorometholone alcohol 0.25% 35 Fluorometholone alcohol 0.1% 31 37 Dexamethasone acetate 0.1% 55 60 Dexamethasone alcohol 0.1% 40 42 Dexamethasone phosphate 0.1% 19 22 COP/B&J, p266 Diane T. Adamczyk, OD Copyright © 2024 64 -table shows that when the epithelium is absent, steroids such as pred phosphate the efficacy increases bc they’re water soluble -understand that the acetate in pred and dexamethasone has a greater anti-inflammatory effect compared to the alcohol or phosphate 64 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Bioavailability Variable penetrance into cornea ◦ Steroid formulation properties ◦ Acetate derivatives ◦ More lipophilic/fat soluble ◦ Alcohol derivatives ◦ Intermediate lipophilicity (between acetate and salt) ◦ Salts (sodium phosphate, hydrochloride) ◦ More hydrophilic/water soluble Diane T. Adamczyk, OD Copyright © 2024 65 -understand this concept and its effect on the ocular surface 65 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Bioavailability Corneal penetration ◦ Acetate > alcohol > phosphate à all you really need to remember/understand! ◦ Intact epithelium + inflammation: ◦ >phosphate levels in anterior chamber of inflamed vs uninflamed eye ◦ Intact epithelium + inflammation : ◦ acetate > phosphate ◦ Intact/nonintact epithelium + inflammation ◦ Acetate/alcohol > phosphate Diane T. Adamczyk, OD Copyright © 2024 66 66 Anti-Inflammatory Drugs: Steroids Pharm II Suspensions Diane T. Adamczyk, OD Copyright © 2024 67 -suspensions are particularly seen in steroids bc most steroids are delivered as suspensions 67 Anti-Inflammatory Drugs: Steroids Pharm II The Drugs Diane T. Adamczyk, OD Copyright © 2024 68 68 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Prednisolone Synthetic analog of hydrocortisone (cortisol) Ketone based Usage: external, intraocular inflammations Most effective steroid for anterior segment inflammation (with challengers for the “most”) Diane T. Adamczyk, OD Copyright © 2024 69 -prednisone is the systemic steroid and prednisolone is the topical -most steroids are ketone based and the exception is loteprednol 69 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Prednisolone Acetate, phosphate derivatives Anti-inflammation: ◦ Acetate > phosphate (cornea intact/non) ◦ Increased affinity for receptor Diane T. Adamczyk, OD Copyright © 2024 70 -acetate has greater corneal penetration than phosphate and this is impt if you’re dealing with an anterior chamber inflammation you may not want it to get into the eye so well bc if it gets into the eye, it will go in go into the steroid receptors in the TM and increase the IOP so you want to use a steroid that doesn’t penetrate too well 70 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Anti-Inflammatory Efficacy Anti-InflamEfficacy (%) Steroid Epithelium: Intact Absent Pred acetate 1% 51 53 Pred phosphate 1% 28 47 Fluorometholone acetate 0.1% Fluorometholone alcohol 0.25% Fluorometholone alcohol 0.1% 48 35 31 37 Dexamethasone alcohol 0.1% 55 60 Dexamethasone phosphate 0.1% 40 42 19 22 Dexamethasone acetate 0.1% COP/B&J, p266 Diane T. Adamczyk, OD Copyright © 2024 71 71 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Prednisolone Prednisolone acetate 0.125%, 1% (suspension) ◦ 0.125%: Pred Mild ◦ 1%: Pred Forte SHAKE BEFORE USE!!! Diane T. Adamczyk, OD Copyright © 2024 72 72 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Prednisolone Prednisolone sodium phosphate 1% (solution) ◦ Generic Diane T. Adamczyk, OD Copyright © 2024 73 73 Anti-Inflammatory Drugs: Steroids Diane T. Adamczyk, OD Copyright © 2024 Pharm II 74 -study looked at the varieties of prednisolone and compared the generic version of the acetate with the predforte brand name and found that the prednisolone particles in predforte were smaller and more uniform allowing them to stay in suspension much longer 74 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Dexamethasone Structurally related to cortisol Ketone based Alcohol, phosphate derivative Alcohol > anti-inflam phosphate (intact/non epithelium) ◦ Phosphate less binding to receptor Diane T. Adamczyk, OD Copyright © 2024 75 -dexamethasone is a strong anti-inflammatory -not the go to drug bc it has an greater effect of increasing IOP so that’s why clinicians shy away from it -the alcohol has a higher anti-inflammatory effect than the phosphate 75 Anti-Inflammatory Drugs: Steroids Pharm II Steroids: Anti-Inflammatory Efficacy Anti-InflamEfficacy (%) Steroid Epithelium: Intact Absent Pred acetate 1% 51 53 Pred phosphate 1% 28 47 Fluorometholone acetate 0.1% 48 Fluorometholone alcohol 0.25% 35 Fluorometholone alcohol 0.1% 31 37 Dexamethasone acetate 0.1% 55 60 Dexamethasone alcohol 0.1% 40 42 Dexamethasone phosphate 0.1% 19 22 COP/B&J, p266 Diane T. Adamczyk, OD Copyright © 2024 76 76 Anti-Inflammatory Drugs: Steroids Pharm II Steroid: Dexamethasone Dexamethasone alcohol 0.1% (suspension) ◦ Maxidex Dexamethasone sodium phosphate ◦ Solution 0.1% Diane T. Adamczyk, OD Copyright © 2024 77 -alcohol is the suspension and phosphate is the solution 77 Anti-Inflammatory Drugs: Steroids Pharm II Dextenza (dexamethasone ophthalmic insert) 0.4mg Intracanalicular use Indications: Ocular inflammation and pain after ophthalmic surgery (Nov 2018) Ocular itch associated with allergic conjunctivitis (Oct 2021) Single insert: 0.4mg dexamethasone for up to 30 days Diane T. Adamczyk, OD Copyright © 2024 78 -intracanalicular dexamethasone à drug is put in the canula and continuously releases the drug and lasts about 30 days -originally approve for after ophthalmic surgery such as cataract but now approved by FDA for allergic conjunctivitis -continuous release so pt doesn’t have to constantly put drops in 78 Anti-Inflammatory Drugs: Steroids Pharm II Dextenza (dexamethasone ophthalmic insert) 0.4 mg DEXTENZA (dexamethasone ophthalmic insert): ◦ 30 day insert (resorbs) ◦ No preservative ◦ Contraindication: infection, dacryocystitis ◦ Caution/Warning: infection, delayed healing ◦ If removal necessary: irrigation or manual expression Diane T. Adamczyk, OD Copyright © 2024 79 -if you have to remove it you can manually express it or remove by irrigation 79