NSAIDs

analgesic, anti-inflammatory, anti-pyretic, anti-platelet

what are the 4 uses NSAIDs are “known for”?

1. reduce miosis during cataract surgery

2. tx for post-op pain & inflammation after cataract surgery

3. tx of post-op pain & photophobia following corneal refractive surgery

what are the FDA approved uses for topical NSAIDs?

1. prevent & tx CME after cataract surgery

2. decrease pain & photophobia after corneal abrasion or removal of FB

3. decrease pain & photophobia w/ betadine EKC tx

4. occasionally supplemental for episcleritis, scleritis, anterior uveitis, pingueculitis

5. alleviating itching from allergic conjunctivitis

what are the non-FDA approved uses for topical NSAIDs?

1. occasionally supplemental for episcleritis, scleritis, uveitis, pingueculitis

2. reduction of pain in ocular trauma

what are some uses of oral NSAIDs?

baseline homeostatic regulator of prostaglandins (protect stomach lining from harsh acids, help maintain kidney/uterine/CV function)

what is COX-1 responsible for?

produces prostaglandins through stimulation (ex: injury)

what is COX-2 responsible for?

thromboxanes

• produced from prostaglandin H2

• stimulates thrombosis

• inhibited by NSAIDs

leukotrienes

• produced from arachidonic acid

• produced in areas of inflammation in blood vessels as part of atherosclerosis

• implicated in asthmatic constriction of bronchioles

arachidonic acid

when cell membranes are damaged, phospholipase A2 becomes activated, resulting in the production of ________

leukotrienes, thromboxane, prostaglandins

arachidonic acid uses LOX & COX to produce eicosanoids: _______

1. vasodilation

2. increased gastric acid & mucous secretion

3. increased pain sensitivity

4. renal blood flow

5. uterine blood flow

6. platelet aggregation

7. atherosclerosis, asthma bronchoconstriction

systemic actions of eicosanoids

1. miosis (acts on iris smooth muscle

2. vasodilation promotion

3. disruption of blood aqueous barrier

4. increased leukocyte migration

5. pain stimulation

6. facilitation of allergic response

7. decreased IOP

what are the ocular actions of prostglandins?

inhibition of COX enzymes → inhibition of prostaglandins & thromboxane A2 → reduce pain, fever, sign/sx of inflammation

describe the MoA of NSAIDs

1. flurbiprofen sodium

2. ketorolac tromethamine

3. diclofenac sodium

4. bromfenac

5. nepafenac

list the topical NSAIDs

phenylephrine & ketorolac

list the NSAIDs used as intraocular injection during surgery?

1. aspirin

2. ibuprofen

3. flurbiprofen

4. indomethacin

5. piroxicam

6. ketolorac

7. diclofenac

8. celecoxib

list the oral NSAIDs

acetaminophen

list the oral NSAID that is not anti-inflammatory

irreversibly inhibits COX1&2 → reduces production of thromboxane A2 & prostaglandins

what is the MoA of aspirin?

reduce prostaglandins in peripheral pain receptors & relieve pain w/o sedation

how do NSAIDs work as analgesics?

reduce prostaglandins which decreases inflammatory response (need a higher dose than with just treating pain)

how do oral NSAIDs work as anti-inflammatories?

reduce prostaglandins in the hypothalamus to decrease temp

how do oral NSAIDs work as anti-pyretics?

inhibit thromboxane A2 which reduce platelet aggregation to reduce clot formation in MI & CVA prevention

how do oral NSAIDs work as anti-platelets?

naproxen sodium

which oral NSAID is preferred for acute pain?

naproxen sodium

which oral NSAID may be safer if the pt is higher CV risk?

naproxen sodium, naproxen, celecoxib

which oral NSAIDs have less GI side effects?

indomethacin

which oral NSAID has more GI side effects?

easy bleeding/bruising

what is a common SE of all anti-platelet drugs? (includes all NSAIDs except acetaminophen)

1. coughing up blood

2. blood in urine or stool/feces

3. coffee ground vomit

4. dark tar like stool

what are some signs of serious internal/GI bleeding?

1. increased risk of GI ulcerations, bleeding, perforations

2. increased risk of CV (MI, CVA)

3. contraindicated in peri-operative period of CABG surgery

what are the FDA boxed warnings of all NSAIDs?

all NSAIDs

if a pt is allergic to one NSAID, they are allergic to _____

acetaminophen

which “NSAID” can patients that are allergic to another NSAID take?

1. stuffy nose

2. chest tightness

3. wheezing

4. SOB

what respiratory rxns can occur when taking NSAIDs?

aspirin exacerbated respiratory disease (AERD)

• chronic medical condition w/ 3 clinical features:

  • asthma

  • aspirin or other NSAID allergy

  • chronic sinusitis/urticaria w/ recurrent nasal polyps

• develops suddenly in adulthood (20-50yo)

• no clear pathophysiology mechanism

1. decreased appetite

2. GI upset

3. rash

4. SOB in asthmatic pt

5. HA

6. drowsiness

7. dizziness

8. kidney failure

9. renal failure

10. fluid retention

side effects of systemic NSAIDs?

1. allergic

2. AERD triad

3. peri-operative CABG surgery

4. known bleeding disorder

5. active/complicated GI disorders

6. >20weeks pregnant

7. kidney or liver disease

what are the contraindications of systemic NSAIDs?

1. take with food

2. hydrate

3. avoid alcohol

4. use PPI

what are some strategies to reduce systemic NSAID GI & kidney side effects?

aspirin

NSAID used mainly for anti-platelet therapy to reduce risk of blood clots, not recommended for anti-pain, anti-fever, anti-inflammation

1. tinnitus

2. reye syndrome

what are special SE of aspirin?

reversibly inhibits COX1&2 → reduces production of prostaglandins & some thromboxane A2

what is the MoA of indomethacin, ibuprofen, flurbiprofen, naproxen, piroxicam, ketorolac, & diclofenac?

1. whorl keratopathy

2. RPE disruption

what are the ocular SE of indomethacin?

reversible, selective inhibitor of COX2 → reduces production of prostaglandin

what is the MoA of celecoxib?

increased risk of CV problems

what are the specific SE of celecoxib?

high risk of GI complications

celecoxib is reserved for pt w/ _________

inhibits COX3 enzymes → inhibits prostaglandin synthesis

what is the MoA of acetaminophen?

pain & fever

what can acetaminophen be used for?

irreversible liver damage

what is the adverse effect of acetaminophen?

1. liver disease (reduced dose)

2. alcoholism

what are the contraindications of acetaminophen?

nepafenac

which topical NSAID is a suspension?

sulfite

bromfenac should be avoided in pt with _______ allergies

C

what is the pregnancy category of all topical NSAIDs?

1. decreased cost

2. more discomfort

3. increased dosing

what are some factors to consider when choosing an older topical NSAID?

1. improved comfort

2. convenient/improved compliance w/ less frequent dosing

3. comparable efficacy

4. increased cost

what are some factors to consider when choosing a newer topical NSAID?

1. burning/stinging

2. subconj heme

3. increase in IOP (rare)

4. delayed wound healing (rare)

5. corneal epithelial breakdown → SPK → corneal melt (rare)

what are the ocular SE of topical NSAIDs?

1. dry eye

2. ocular surgery

3. diabetes

4. herpetic eye disease

5. RA

6. CL wear

what factors increase the risk for corneal epithelial compromise w/ topical NSAIDs?

intracameral injection

dosage form of phenylephrine/ketorolac?

maintaining pupil size by preventing intraoperative miosis & reducing post-op pain

what is phenylephrine/ketorolac FDA approved for?

alpha adrenergic agonist at iris dilator

MoA of phenylephrine in phenylephrine/ketorolac?

inhibition of COX1&2 → decreased prostaglandins (reduces pain & prevents surgically induced miosis by inhibiting prostaglandins secondary to ocular surgical insult)

what is the MoA of ketorolac in phenylephrine/ketorolac?

10

nepafenac topical NSAID is approved down to ____yo

2-3

ketorolac topical NSAID is approved down to ____yo

birth

acetaminophen is approved down to _____

12weeks

acetaminophen should not be used in children under ______

6mo

ibuprofen is approved down to ____ of age

18

aspirin is approved down to ____yo

reversible COX1&2 inhibitors

what is the MoA of all topical NSAIDs?

bromfenac (Bromday), bromfenac (Prolensa), nepafenac (Ilevro)

which topical NSAIDs are 1x per day (QD) dosing?