NSAIDs are analgesic, antipyretic and anti-inflammatory drugs. Non-narcotic, non-opioid, aspirin-like drugs Primarily, acts on peripheral pain mechanism and do not depress the central nervous system Some protective role against cancer and cardiovascular diseases (e.g., aspirin, antithrombotic effects) Accounts for 5% of all drugs prescribe globally 30 million people consume NSAIDs every day Available over the counter medicine in most countries

1. Ocular NSAIDs
(Non-steroidal
Anti-
inflammatory
Drugs)
Dr Gauri Sr Shrestha
IOM, TU

2. NSAIDs in general
• NSAIDs are analgesic, antipyretic and anti-inflammatory drugs.
• Non-narcotic, non-opioid, aspirin-like drugs
• Primarily, acts on peripheral pain mechanism and do not depress
the central nervous system
• Some protective role against cancer and cardiovascular diseases
(e.g., aspirin, antithrombotic effects)
• Accounts for 5% of all drugs prescribe globally
• 30 million people consume NSAIDs every day
• Available over the counter medicine in most countries

3. Some definitions
• Analgesic = peripheral inhibition of prostaglandin production and
inhibition of pain stimuli at a subcortical site (Bradykinin)
• Antipyretic: Inhibition of prostaglandin production in the
hypothalamus, resetting thermoregulatory system, leading to
vasodilation and increased heat loss.
• Anti-inflammatory: a substance that reduces inflammation (e.g.,
redness, swelling, and pain) in the body by inhibiting certain
inflammatory mediators.
• Bradykinin: Bradykinin is a peptide that promotes inflammation. It
causes arterioles to dilate via the release of prostacyclin, nitric
oxide, and endothelium-derived hyperpolarizing factor

4. Arachidonic Acid Pathway
for NSAIDs action
• PGH2 = progtaglandin
endoperoxidase
• PGG2 = prostaglandin G2
• PGI2 = Prostaglandin I2
(prostacyclin)
• PGE2/D2 = Prstaglandin
E2 (dinoprostone)/ D2
• TXA2 = Thromboxane A2

5. Cyclo-oxygenase enzymes
• COX-1:
• a constitutive enzyme expressed in most tissues, including blood platelets
• Housekeeping role as it involves in tissue homeostasis, cytoprotection,
platelet aggregation, renal blood flow autoregulation
• COX-2:
• induced in inflammatory cells when activated (not present normally in cells).
• Produces prostaglandins that mediate inflammation, pain and fever

6. Features of COX inhibitors
(Non-selective and COX-2 selective)
Action COX-1 inhibitor COX-2 inhibitor
Analgesic + +
Antipyretic + +
Anti-inflammatory + +
Antiplatelet aggregation + -
Gastric mucosal damage + -
Renal salt/ Water retention + +
Ductus arteriosus closure + Unknown
Aspirin sensitive asthma precipitation + -

7. Role of prostaglandins in inflammation
Prostaglandins Effects
PGE1 and
PGE2, PGI2
• Increase Inflammation, IOP, capillary permeability and miosis
• Regulate rental and mucosal blood flow in the stomach
• Sensitise afferent nerve endings to pain-inducing chemical
stimulus
PGD2 • Stimulates vasodilation and chemosis
PGF2α • Decrease IOP, minimal inflammatory and miosis
• Contract uterine and cause vasodilation
Thromboxane
A2
• Vasoconstriction, platelet aggregation and platelet
degranulation

8. Adverse effect associated with inhibition of
PG synthesis
• Gastric mucosal
damage
• Bleeding: inhibition of
platelet function
• Limitation of renal
blood flow: Na+ and
water retention.
• Asthma and
anaphylactic reactions

9. Classification of NSAIDs
(this is not a complete list – mind it is just for a reference)
1. Non-selective COX inhibitors (traditional NSAIDs)
a. Salicylates. e.g., Aspirin
b. Propionic acid derivatives. e.g., Ibuprofen, Naproxe, Flurbiprofen
c. Aryl acetic acid derivative. e.g., Diclofenac, Aceclofenac
d. Pyrrolo pyrrole derivative. e.g., Ketorolac
e. Indole derivatives. e.g., Indomethacin, Sulindac
2. Preferential COX inhibitor
a. Sufonanilide derivative. Nimesulide
3. Selective COX-2 inhibitors – Celecoxib, Etoricoxib, Parecoxib
4. Analgesic- antipyratics with poor anti-inflammatory action –
a. Paracetamol, Metamizole and Nefopam

10. Ocular NSAIDs
Reduce corneal scarring and preserve vision.
DO NOT affect on IOP, induce cataracts, exacerbate eye infection and
decrease epithelization.
Limits the action of prostaglandins.

11. FDA approved Ophthalmic NSAIDs
Drug Trade name Indication Contraindication
Flurbiprofen sodium
0.03%
Flur, Ocuflur, Eyefen • Inhibition of intraoperative
miosis
• Eye surface inflammation
• Dendritic keratitis
• Hypersensitivity
• embryocidal, delays
parturition, prolongs gestation,
reduces the weight of the
fetus, and causes growth
retardation
• Lactation
Diclofenac 0.1% Diclofenac sodium
0.1% eye drop
• Post-operative inflammation
(cataract surgery)
• Relief of pain and
photophobia (corneal
refractive surgery)
• soft contact lens wearers
• Hypersensitivity
• Pregnancy: closes ductus
arteriosus of the fetus

12. FDA approved Ophthalmic NSAIDs
Drug Trade name Indication Contraindication
Bromefenac
0.09%
Megabrom,
Eynac, Bromica,
Bomefact
• Post-operative
inflammation and
pain (cataract surgery)
• Hypersensitivity
Ketorolac
tromethamine
0.5%
Acular, Ketlur • Temporary relief from
ocular itching-related
to seasonal allergic
conjunctivitis
• Post-operative
inflammation
(cataract surgery)
• soft contact lens wearers
• Hypersensitivity
• may cause dystocia with
systemic medication (difficult
or obstructed labor)
• Lactation

13. FDA approved Ophthalmic NSAIDs
Drug Trade name Indication Contraindication
Ketorolac
tromethamine
0.4%
Ketlur LS, Acular
LS, Albalon
• Reduction of ocular pain,
burning, photophobia and
stinging
• soft contact lens
wearers
• Hypersensitivity
• Lactation
Nepafenac 0.1%
suspension
Nepalact,
Nepaloc,
• Treatment of pain and
inflammation (e.g.,
cataract surgery)
• Hypersensitivity
Indomethacin
suspension
NA • episcleritis, mild anterior
uveitis
• reduce postoperative IOP
(cataract surgery)
• Hypersensitivity

14. Sample
eye
NSAIDs

15. Adverse effect of NSAIDs
https://www.ncbi.nlm.nih.gov/books/NBK547742/

16. Adverse reaction and drug interaction
Adverse reactions:
Topical: Most frequent: transient
burning, stinging upon instillation,
minor symptoms of ocular
irritation.
Drug Interactions:
Acetylcholine and carbachol are
ineffective when used with
flurbiprofen.

17. Precaution
• May delay wound healing: Diclofenac and Flurbiprofen.
• May increase bleeding tendency of ocular tissues and conjunctiva with
surgery: Diclofenac or flurbiprofen.
• Monitor patients with herpes simplex keratitis while using flurbiprofen.
• Ketorolac (Acular, Acular LS) are approved for use in children above three
years and older
• Children: Safety and efficacy unknown

18. Adverse effects of ophthalmic NSAIDs
reported as a percentage
Drug
Transient burning
and stinging
Ocular
irritation
Corneal
oedema
Vision
change
Bromfenac 0.09% 2 – 7 2 – 7 Not reported
(NR)
NR
Diclofenac 0.1% 15 <5 <5 <5
Flurbiprofen 0.03% Reported Reported NR NR
Ketorolac tromethamine
0.5%
<40 1 – 10 1 – 10 Rare
Ketorolac tromethamine
0.4%
20 – 40 1 – 10 1 – 5 NR
Nepafenac 0.1% Reported 1 – 5 1 – 5 5 - 10

19. Conditions
Aggravated
by NSAIDs
Peptic ulcer.
Hypertension.
Congestive heart failure.
Renal insufficiency.
Hemostatic (bleeding) disorder.

20. Thank you