3 - Anti-Inflammatory Flashcards
Overview of arachadonic acid pathway
First step: phospholipase A2 (steroids, plaquenil)
Arachidonic acid splits:
-lipoxygenase -> leukotrienes: rhinitis, bronchoconstriction (leukast)
-COX (NSAIDs) -> prostacyclines, prostaglandins, thromboxanes
—PGs: cox1 gastic (inhibits secr, incr motility), cox2 inflammation (pain, fever, swelling)
—TXA: cox1 platelet aggregation (make “sticky” for clotting)
Hydroxychloroquine
- MOA
- clinical indications
1) inhibits phospholipase A2 (anti-inflammation, first step)
2) build-up of heme (anti-malarial (toxic to plasmodium parasite))
Lupus, rheumatoid arthritis, malaria
Hydroxychloroquine
- adverse effects
- incr risk factors
Whorl keratopathy
Bull’s eye maculopathy (greatest threat to vision)
-risk significantly lower than chloro
Dose: 5mg/kg real body weight/day or 400mg/day
Weight: <135lbs
Duration: 5 years
Abnormal renal function, liver dz, concomitant retinal disease
Age >60
High body fat
AAO standards for hydroxy/chloroquine exams
Baseline exam with DFE within 1 year of beginning
Annual screening after 5 years: 10-2 HVF, SD-OCT
If greater risk of developing bull’s eye, exams every 6 mo-1 year after baseline
-primary risk factors are the same, tho chloroquine (2.3mg/kg/day) is much higher than hydroxy (5mg/kg/day)
Steroids (general)
- MOA
- clinical indications
- adverse effects
Inhibit phospholipase A2 -> decr inflammatory mediators
Systemic concerns: HTN, DM, peptic ulcer dz, poor healing/immunity, bones/cartilage
-DM/insulin resistance:
—increases BS
—decr fibroblast func (poor healing), poor bones/cartilage -> osteoporosis
Ocular concerns: PSC, glaucoma, secondary infections, CSCR
Hydrocortisone
- MOA
- clinical indications
Inhibit phospholipase A2 -> decr inflammatory mediators
Adrenal insufficiency, potent anti-inflammatory
Triamcinolone
- MOA
- clinical indications
- adverse effects
Inhibit phospholipase A2 -> decr inflammatory mediators
Ophthalmic: administered via injection for inflammation
- DME, Grave’s, intermediate/non-resolving post uveitis, chalazia, Irvine-Gass, CME assoc with non-infectious post uveitis (PG-induced), mac edema secondary to CRVO
Systemic: dermatoses, asthma, MS exacerbations, arthritis
SE:
- decr TM outflow -> incr IOP
- endophthalmitis (injected)
- permanent depigmentation of lid skin in dark-skinned pts (when used for chalazia)
Fluticasone
- MOA
- clinical indications
- adverse effects
Inhibit phospholipase A2 -> decr inflammatory mediators
Intranasal corticosteroid: allergic rhinitis
PSC, incr IOP, conj-itis, dry eye dz, CSCR
Aspirin
- MOA
- clinical indications
- adverse effects
Irreversible COX1+2 inhibitor -> inhib synth of PGs and TXAs
Antipyresis (fever), anti-inflammatory, analgesia
81mg proven to red risk of recurrent heart attacks in pts with heart dz
GI (cox1 decr)
Antiplatelet (TXA decr) -> retinal/subconj heme
Reye syndrome in children: rapidly progressive brain dz, confusion -> seizures -> multi-organ failure
Indomethacin, Ibuprofen, Naproxen sodium, Piroxicam
- MOA
- clinical indications
- adverse effects
Reversible COX1+2 inhibitor (cleared much more quickly than aspirin)
Epi/scleritis (oral)
Relatively contraindicated in pts with heart dz
Incr risk of bleeding complications in eye
Boxed warning for GI bleeding
Unlike aspirin, contraindicated in pts with hx of CAD and/or stroke: can incr BP
-do not cause Reye’s - ibuprofen approved for 6mo and up
Take with food to reduce GI effects
Indomethacin
- clinical indications
- unique SE vs other NSAIDs
Gout (also allopurinol)
Whorl keratopathy
Retinal pigmentary changes: mottling (esp macular)
Drug that protects stomach from NSAIDs
Misoprostol: synthetic PGE1
- protects stomach lining
- prevention/tx of NSAID-induced ulcers
- main SE: miscarriage, premature labor
Celecoxib
- MOA
- clinical indications
- adverse effects
Selective COX2 inhibitor
Spares cox1 = protects stomach
Reversible conj-itis
Blurry vision
Steven-Johnson syndrome
