4 - Anti-inflammatory Drugs Flashcards
List 4 corticosteroids and 3 NSAIDs
- Funding for each?
- Penetration of steroids?
Corticosteroids:
- Prednisolone acetate (best penetrate)
- Dexamethasone (good penetrate)
- Prednisolone sodium acetate (okay penetrate)
- Fluorometholone acetate (worse penetrate)
NSAIDS:
- Diclofenac 0.1%
- Ketorolac (unfunded)
- Nepafenac
Between pred forte and prenisolone, which requires shaking and why?
Pred Forte needs to be shaken otherwise only saline is in drops.
Corticosteroid:
- Normal cortisol regulation
- Mechanism of action
Normally,
- Hypothalamus -> corticotropin-releasing hormone (CRH)
- Anterior pituitary -> Adrenocorticotrophic hormone (ACTH)
- Adrenal cortex -> cortisol (-ve feedback to hypothalamus)
Cortisol responds to stress
- Increase BP
- Regulate T-cell proliferation
- Regulate metabolsim of proteins, carbs, and fats
- Promote glucose in blood (antagonises insulin)
Corticosteroids block Phospholipase A2 which otherwise converted phospholipids into arachidonic acid. This ends up blocking both COX1 and Lipogenase pathway. Prevents releasing histamine, prostaglandin, leukotrienes, thrombaxane… which causes inflammation.
General considerations when prescribing corticosteroids (6 total)
- Which route of administration has worse side effects?
- How much do we prescribe?
- Who could have worse side effects?
- Why taper?
- Side effects depends on route of administration (systemic worse than topical)
- Duration of Tx
_________ - Use as little as required.
_________ - Familial tendencies for steroid-induced complications
- Diabetics (blood sugar can rise)
_________ - Body may not be producing cortisol on own after long/excessive corticosteroid use. Will have to taper drugs. Realistically, won’t happen w/ eyedrops as not potent systemically.
Note: Drops can also have preservatives which can cause allergic response.
Factors affecting bioavailability of steroids
- Ointment vs drop?
- Which derivatives penetrate better?
- What condition can increase penetration?
- Drops give a big spike in drug absorbtion and falls out over time whilst ointments slowly release the drug over time. This means less ointment is needed per day whilst drops require multiple per day to maintain steady volume.
- Acetate/alcohol derivatives = lipophilic = better penetration
- Phosphate derivatives = hydrophilic
- Non-contact cornea significantly increases penetration
When HSV infection, how do we prescribe steroids?
- Not when epithelial HSV
- Only when stromal HSV (allergic mediated)
- Use anti-virals alongside
Describe the main side effect of corticosteroids
- Effect among population?
- Risk factors for effect?
- Mechanism of action
- Recovery?
Higher IOP
- 4-6% >15mmHg (high responders)
- 30% 6-15mmHg
- 66% <6mmHg
- 46% of glaucoma Pxs high responders
- Children can respond significantly
- Impossible to predict who will respond (even w/ known risk factors or previous unresponsiveness)
Risk factors:
- Family history
- POAG
- High myope
- Diabetes
- CT disease (e.g. RA)
- Reduces outflow and related to TIGR (Trab Meshwork-induced Glucocorticoid response protein) causes ECM at TM to change.
- 1 – 4 weeks recovery
Other side effects of corticosteroids?
Cataract (PSC)
- Possibly within 4 months, but usually 18 months
- VA slightly reduces
- Due to drug binding to lens proteins + oxidation
- Immunosuppressed
- Infections increased (Don’t use on herpes keratitis if epithelial)
- Poor corneal healing (Punctate Epithelial Erosions can occur)
- Wound strength poor
- Dilation + ptosis possible
Complications of local ocular corticosteroid? (16 total)
- Epithelial toxicity
- Delayed epithelial healing + decreased wound strength
- Keratocyte apoptosis
- Corneal deposits
- Worsening infection or reactivation of HSK
- Crystalline keratopathy
- Hypertension/glaucoma
- PSC
- Ptosis
- Dilation
- EOM imbalance
- Orbital fat atrophy
- Intraocular vascular occulusion/haemorrhage
- Accidental intraocular penetration
- Systemic absorption
- Systemic glucocorticoid suppression
Systemic side effects of corticosteroids?
Cushing’s syndrome
- Round face
- neck fat
- weak bones
- slow growth rates…
- Osteoporosis
- Muscle wasting
- Mood swings, confusion
- Diabetes
NSAID mechanism
Inhibits COX (later pathway of inflammation)
- Prevent platelet aggregation (avoid if Px is bleeding)
- Reduces inflammation via blocking prostaglandin (not as strong as steroid but less side effects)
Side effects of NSAID
- CV disease w/ some COX-2 drugs
- Smooth muscle contraction
- Dilation of ocular BVs
- IOP increase possible
Main benefit compared w/ steroids is how much safer it is
NSAID ocular drug
- Side effects
- Contraindications
Main benefit compared w/ steroids is how much safer it is
- Burns/stings on instill
- Conjunctivia hyperaemia (redness worse first before getting better)
- Allergies poss
- SPK
- Steile corneal infiltrates
- Corneal healing delayed?
- Corneal ulceration/perforation (rare)
Systemically,
- GI toxicity due to COX-1 inhibit
AVOID IN:
- Pxs w/ bleed (increase bleed time)
- Soft CLs wear
Note: No tapering needed.
