This document discusses ocular NSAIDs (non-steroidal anti-inflammatory drugs). It begins by outlining the inflammatory response and pharmacologic principles of NSAIDs. It then discusses the classification of NSAIDs and common ophthalmic NSAIDs used. The main indications for ocular NSAIDs are reducing inflammation and pain from conditions like conjunctivitis, corneal injuries, episcleritis, and uveitis. Side effects can include gastric irritation and bleeding risks.

1. OCULAR NSAIDS
Sabina Poudel
16th Batch
B.Optometry
MMC, IOM

2. PRESENTATION LAYOUT
Inflammatory response
Pharmacologic principle of NSAIDs
Classification of NSAIDs
Common ophthalmic NSAIDs
Indications , contraindications and their side
effects

3. INFLAMMATION
Protective response by the body to variety of
infectious or non-infectious agents in order to
eliminate or limit the spread of the injurious agent
Mechanism of acute early response
• Release of mediators
• Vascular changes
• Leucocyte activity

4. source Mediator Main action
Cell derived Mast cells, basophils,
platelets
Histamine Increase permeability
Platelets Serotonin Increase permeability
Inflammatory cells prostaglandins vasodilatation
leukotrienes Increase permeability
Lysosomal enzymes Tissue damage
Platelet activating factor Increase permeability
Cytokines Fever
Nitric oxide & oxygen
metabolites
Tissue damage
Plasma derived Clotting & fibrinolytic
system
Fibrin split products Increase permeability
Kinin system kinin/bradykinin Increase permeability
Complement system Anaphylatoxins
C3a, c4a ,c5a ,c5b –c9
Increase permeability

6. 1. Redness (rubor): vasodilation of capillaries to increase
blood flow
2. Heat (calor): due to transfer of internal heat to the
tissue by increased blood flow
3. Pain (dolor): due to sensitization of sensory nerve
endings
4. Swelling (tumor): due to increased vascular
permeability and escape of plasma proteins from the
bloodstream
Cardinal signs of
inflammation

8. NSAIDS
Non steroidal anti-inflammatory drugs
All NSAIDs have three major therapeutic effects:
NSAIDs
Anti-
inflammatory
Analges
ic
Anti-pyretic
Cause suppression of signs and symptoms of
inflammation but do not eliminate the cause

9. Developed as an alternative to steroids in treatment of
inflammatory disease
Most are the organic acid derivatives
Aka non narcotic, non opoid, aspirin like drugs
Do not depress CNS
Act primarily on peripheral pain mechanism

10. HISTORY
Sodium salicylate was used for pain & fever in 1875 AD.
It’s great success led to the introduction of aspirin in 1899
AD.
Indomethacin was introduced in 1963 AD.
 After the discovery of ibuprofen the mechanism involving
cycloxygenase inhibition was revealed.

11. Membrane phospholipid
Arachidonic acid
Chemical and
mechanical
stimuli
Phospholipase A
cyclooxygenase lipooxygenase
endoperoxidases leukotrienes
Prostacyclin
PGI2
PGE2 , PGD2 ,
PGF2a
Thromboxane A2
glucocorticoids
NSAIDs

12. Phospholipids : major component of all cell membranes, forms
bilipid layer
Arachidonic acid: polyunsaturated carboxylic acid present in
phospholipids of cell membrane, freed from phospholipid by
phospholipase A2
Prostaglandins: hormone like lipid compounds derived from
fatty acids produced in almost all nucleated cells
Few terminologies

13. Prostacyclin(PGI2): induces vasodilatation,
bronchodilation and inhibits platelet aggregation
Leukotrienes: inflammatory mediators first isolated from
leucocytes.
In body PGs, TXs and LTs are all derived from eicosa
(referring to 20 C-atom) tri/tetra/penta enoic acids. So they
are collectively called eicosanoids.

14. CYCLOOXYGENASE
Enzyme responsible for the formation of prostanoids i.e
prostaglandins, prostacyclin and thromboxane
Two main form of cyclooxygenase
Cyclooxygenase-1 (COX-
1)
Cyclooxygenase -2 (COX-
2)
Produces prostaglandins
that mediate homeostatic
functions
Produces prostaglandins
that mediate
inflammation, pain and
fever
Constitutively expressed
in most tissues like GI,
Induced mainly in sites of
inflammation by

15. FUNCTIONS OF PROSTAGLANDINS
(a) PGE2:
•Vasodilation
•Regulate renal and mucosal blood flow in stomach
•Sensitize afferent nerve endings to pain inducing
chemical stimulus
•Powerful bronchodilator
•Mediate fever
(b) PGF2a:
•Uterine contraction and vasodilation.

16. (d) PGI2:
•Vasodilation
•Inhibition of platelet aggregation
•Regulate renal and mucosal blood flow in stomach
•Sensitize afferent nerve endings to pain inducing
chemical stimuli.
Thromboxane A2: active in platelet aggregation
besides its role as a vasoconstrictor and
bronchoconstrictor

17. 5/22/2016 17
OCULAR EFFECT OF PROSTAGLANDIN
PROSTAGLANDI
N
EFFECT
PGD2 STIMULATES VASODILATATION AND CHEMOSIS
PGE1,PGE2 INFLAMATION , IOP , CAPILLARY PERMEABILITY,
STIMULATES VASODILATION, STIMULATES MIOSIS
PGF2 IOP, MINIMAL EFFECT ON INFLAMATION, MINIMAL EFFECT
ON MIOSIS

18. PROSTAGLANDIN (PGE1, PGE2)
AND MIOSIS
 Researcher isolated a substance called “ Irin” from
extracts of the iris tissue, later found to be
prostaglandin
 Cause miosis when introduced into the anterior
chamber
 Mechanism: not known
 Inhibitors: Topical Cycloxygenase blocker

19. MECHANISM OF ACTION OF NSAIDS
1) Anti-inflammatory effect:
 due to the inhibition of the enzymes cyclooxygenase
that converts arachidonic acid into prostaglandin,
prostacyclin and thromboxane A2
 all NSAIDs reversibly inhibit cyclooxygenase except
Aspirin which inhibit it irreversibly

20. Membrane phospholipid
Arachidonic acid
Chemical and
mechanical
stimuli
Phospholipase A
cyclooxygenase lipooxygenase
endoperoxidases leukotrienes
Prostacyclin
PGI2
PGE2 , PGD2 ,
PGF2a
Thromboxane A2
glucocorticoids
NSAIDs

21. 2) Analgesic effect:
The analgesic effect of NSAIDs is thought to be related
to
• Pripheral inhibition of
prostaglandin synthesis
• Prevent the potentiating action of
prostaglandin on endogenous
mediators of peripheral nerve
stimulation (e.g. bradykinin)

22. 3) Antipyretic effect:
The antipyretic effect of NSAIDs is related to
• Inhibition of production of
prostaglandins induced by
interleukin-1 and IL-6 in the
hypothalamus• Resetting of
themoregulatory system,
leading to vasodilatation and
increased heat loss

23. BENEFICIAL ACTIONS DUE TO PG
SYNTHESIS INHIBITION
Anti-inflammatory effect
Analgesic effect
Anti-pyretic effect
Anti thrombotic effect
Closure of ductus arteriosus in
new born

24. ADVERSE EFFECT OF PG SYNTHESIS
INHIBITION
Gastric mucosal damage
Bleeding: Inhibition of platelet
function
Limitation of renal blood flow
Asthma and anaphylactoid reaction

25. Enchance
acid
secretion
Inhibition of cox-1mediated
synthesis of gastroprotective
PGs (PGE2, PGI2)
Diffusion of H+ ions in
the gastric mucosa
Deficiency of PGs reduces mucus and
HCO3- secretion
Gastric mucosal
damage
Gastric
mucosal
erosion/ulcerat
ion

26. Bleeding
NSAIDs inhibit
synthesis of
proaggregatory
Inhibit
synthesis of
antiaggregator
y PGI2
Inhibit
platelet
aggregation
Bleeding time
prolonged

27. Hypovolumeia, decreased renal perfusion, Na+ loss
Limitation of renal blood flow
induce
Renal PG synthesis which brings intrarenal adjustments by
Promoting vasodilatation
Inhibiting tubular Cl- reabsorption
Opposing ADH action
NSAIDs cause:
1) COX1 dependent impairment of renal blood flow and
reduction of G.F.R
2) Juxtaglomerular COX2 dependent Na+ and water retention

28.  Certain NSAIDs precipitates:
Anaphylactoid reactions
Asthma Angioneurotic
swelling
Urticaria Rhinitis

29. CLASSIFICATION OF NSAIDS
A) Non selective COX inhibitors
1. Salicylates: Aspirin
2. Propionic acid derivatives: Ibuprofen, Naproxen,
Ketoprofen, Flurbiprofen
3. Anthranilic acid derivatives: mephenamic acid
4. Aryl-acetic acid derivatives: Diclofenac, Aceclofenac
5. Oxicam derivative: Piroxicam, Tenoxicam
6. pyrrolo-pyrrole derivative: Ketorolac
7. Indole derivative: Indomethacin, Sulindac
8. Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone

30. B) Preferential COX2 inhibitors: Nimesulide, Meloxicam,
Nabumetone
C) Selective COX2 inhibitors: Celecoxib, Etoricoxib,
Parecoxib
D) Analgesic- antipyretic with poor anti-inflammatory
action: Paracetamol, Metamizol, Propiphenazone, Nefopam

31. FEATURES OF NONSELECTIVE COX INHIBITORS &
SELECTIVE COX 2 INHIBITORS
Action COX-1/COX2
COX-2
inhibitors
inhibitors
1.Analgesic + +
2.Antipyretic +
+
3.Antiinflammatory +
+
4.Antiplatelet aggregation +
-
5.Gastric mucosal damage +
-

32. Ophthalmic
NSAIDs

33. ROUTES OF ADMINISTRATION
TOPICAL ORAL

34. Diclofenac
Flurbiprofen
Indomethacin
Ketorolac
Suprofen
Nepafenac
Topical Ophthalmic
NSAIDs

35. COMMON TOPICAL OPHTHALMIC
NSAIDS
Generic name Trade name Formulation Concentratio
n
Diclofenac Voltaren Solution 0.1%
Flurbiprofen Ocufen Solution 0.03%
Ketorolac Acular Solution 0.5%
Acular PF Solution 0.5%
Acular LS Solution 0.4%
Suprofen Profenal Suspension 1.0%
Indomethacin Indocid Solution 0.5%
Nepafenac Nevanac Suspension 0.1%

36. Topical NSAIDs in Preoperative Period
Topical NSAIDs in Anterior Segment
Inflammation
INDICATIONS

37. TOPICAL NSAIDS IN PREOPERATIVE
PERIOD
1. Intraoperative miosis:
topical NSAIDs reduce pupillary constriction that occurs
during cataract extraction and other intraocular surgeries

38. 2. Post operative inflammation:
• use of NSAIDs before surery prevent the synthesis of
prostaglandin and provide prophylaxis for expected
inflammation
• NSAIDs also prevent blood aqueous barrier
breakdown and reduce cells and flare in AC

39. 3. Cystoid macular edema:
• prevention of acute aphakic and pseudophakic CME
and treatment of chronic CME
• peak incidence of CME occurs between 4 and 8 weeks
after surgery

40. TOPICAL NSAIDS FOR ANTERIOR
SEGMENT INFLAMMATION
1. Allergic and non
bacterial conjunctivitis
- most ocular allergies
are type I hypersensitivity
reaction mediated by
mast cells
- degranulation releases
preformed mediators
such as histamine and
initiates synthesis of
newly formed mediators

41. 2. Corneal pain
- injury to corneal tissues stimulates prostaglandin
synthesis
- corneal pain following abrasions, trauma or
epithelial erosions, PRK treated with topical NSAIDs

42. 3. Episcleritis
- topical NSAIDs may be useful
- oral NSAIDs may be required in recurrent cases
Tab Flurbiprofen 100 mg TDS
Tab Indomethacin 25 mg TDS

43. Non necrotising scleritis
Tab Indomethacin 75 mg BD until inflammation
resolves
Given in conjunction with topical steroids
Other Indications

44. Anterior Uveitis
- Systemic Aspirin can be used where steroids are
contraindicated
- Phenylbutazone and oxyphenbutazone potent in
uveitis associated with rheumatoid disease
- Naproxen is useful in ankylosing spondylitis

45. DICLOFENAC SODIUM
 Trade Name: Voltaren
 available as
Indications:
-Postoperative inflammation
-Temporary relief of pain and
photophobia in patients undergoing
corneal refractive surgery
0.1% ophthalmic
solution

46. FLURBIPROFEN SODIUM
Trade name: Ocufen
Available as
Indications:
-Inhibition of intraoperative miosis
-Post operative inflammation
0.03% ophthalmic
solution

47. KETOROLAC TROMETHAMINE
Trade name: Acular, Acular PF, Acular LS
Available as
Good penetrative properties
Indications:
-Allergic conjunctivitis
-post cataract surgery inflammation
-post operative pain and photophobia in radial
keratotomy
-ketorolac 0.5% in treatment of chronic CME
0.5% and 0.4% ophthalmic
solution

48. INDOMETHACIN
Trade name: Indocid
Available as
Indications:
Treatment of cystoid macular edema
0.1% ophthalmic
solution

49. SUPROFEN
Trade name: Profenal
Available as
1% ophthalmic
suspension
Indications
Prevention of intraoperative miosis

50. NEPAFENAC
Trade name: Nevanac
Available as
0.1% ophthalmic
suspension
Indications:
For pain and inflammation after cataract
surgery

51. DOSING REGIMENS OF TOPICAL
NSAIDSIndication Drug Regimen
Intraoperative miosis
prevention
Flurbiprofen 1 drop every 30 min, 4 times before surgery
Ketorolac 1 drop every 30 min, 4 times before surgery
suprofen 1 drop every 30 min, 4 times before surgery
Postoperative
inflammation
Diclofenac 1 drop q.i.d for at least 1-2 weeks after
surgery
Ketorolac 1 drop q.i.d for at least 1-2 weeks after
surgery
Cystoid macular edema Ketorolac 1 drop q.i.d for at least 3 months
Indomethacin 1 drop q.i.d
Allergic conjunctivitis Ketorolac 1 drop q.i.d for relief of ocular itch during
allergy season
Corneal pain Diclofenac 1 drop preoperatively and 1 drop q.i.d
postoperatively for 3 days

52. ORAL NSAIDS IN OPHTHALMIC
USES
Ibuprofen
-0ral
-trade name: flexon, brufen
Indications:
As analgesic in stye, chemical injury
Flexon: ibuprofen 400mg +
paracetamol 500mg
Brufen: ibuprofen 400mg
1 tab PO
TDS

53. As oral NSAIDs has more systemic side effects (esp.
Gastric mucosal damage), drugs for peptic ulcer is
used
1) H2 antihistamines: cimetidine, ranitidine
2) proton pump inhibitors: omeprazole, pantoprazole,
rabeprazole
Tab Ranitidine 300 mg OD or 150
mg BD
Tab Pantoprazole 40 mg
OD

54. CONDITIONS AGGRAVATED BY
NSAIDS
Peptic ulcer
Hypertension
Congestive heart failure
Renal insufficiency
Hemostatic disorder

55. DRUG INTERACTIONS WITH NSAIDS
β blockers Decrease antihypertensive effect
ACE inhibitors Decrease antihypertensive effect
Anticoagulants Increase risk of G.I bleeding
Cyclosporine Increase nephrotoxicity
Corticosteroids Increase risk of G.I bleeding

56. WARNINGS/PRECAUTIONS
1. Increased bleeding of ocular tissues, including
hyphemas in conjunction with ocular surgery
2. Slow or delayed wound healing
3. Cross sensitivity with acetylsalicylic acid

57. 4. Topical NSAIDs may cause keratitis: Continued
treatment with ophthalmic NSAIDs may result in
epithelial breakdown, corneal thinning, corneal
infiltrates, corneal erosion in certain susceptible
patients.
5. Pregnancy: Due to known effect of NSAIDs on fetal
cardiovascular system including closure of ductus
arteriosus, use of ophthalmic NSAIDs during late
pregnancy should be avoided

58. CONTRAINDICATIONS
A) Hypersensitivity to any component of formulations
B) Nepafenac and Ketorolac: contact lens wearers
C) Flurbiprofen and Suprofen: patients with dendritic
keratitis

59. Adverse Effects:
Systemic absorption minimal in topical NSAIDs
Local effects:
-burning sensation
-stinging sensation upon instillation
-conjunctival hyperemia

60. REFERENCES
1) Essential Of Medical Pharmacology- K.D. Tripathi
2) Clinical ocular Pharmacology- Jimmy D Barlett
3) Ophthalmic Drugs- Graham Hopkins , Richard Pearson
4) Comprehensive Ophthalmology- A.K. Khurana
5) Internet sources
6) Previous presentations