Ocular Anti allergy drugs

Ocular allergy are a group of external ocular conditions resulting from one or more types of hypersensitivity reactions to allergens.
Anti Allergic eye drops are liquid medicine used to treat symptoms of eye allergies.

1. UNIVERSITY OF GONDAR college of Medicine and health sciences Department of Optometry Topic-anti allergic drugs by Group 3

2. O bjectives After complete presentation of this topic you are expected to Define ocular allergy Describe anti allergy drugs & their classification List and describe different anti allergy drugs E xplain the mechanism by which Anti allergy drugs work

3. outline I ntroduction Mechanism of action C lassification Decongestant Antihistamine Mast cell stabilizer NSAIDs Corticosteroid

4. Introduction Allergy means altered reaction A hypersensitivity to a specific substance that causes the body to react to any contact with that substance Ocular allergy are a group of external ocular conditions resulting from one or more types of hypersensitivity reactions to allergens Four types of allergic responses Type I- Immediate/anaphylactic reaction Type II- Cytotoxic reaction Type III- Immune complex reaction Type IV- cell mediated immunity

5. Con… Cross linkage of adjacent Ig E antibodies by antigen activates the mast cell and it granulates. Which cause release of mediators Histamine , protease , prostaglandin , leukotriene and cytokines. Cause vascular and smooth muscle reaction , late phase reaction and inflammation. Risk factor-Trigger by some thing like pollen , dust and pet tender

6. Symptoms include-burning -itching -red eye -Swallowed eye lid -Tearing Anti Allergic eye drops are liquid medicine used to treat symptoms of eye allergies. Avoiding object that trigger may be the best solution.

7. M echanism of action Antigen /Allergan Exposed activates immune system IgE antibodies Binds to mast cells & sensitized Calcium channel opening Degranulation of mast cell

8. Release of preformed mediators membrane phospholipid Histamine Tryptase Arachidonic acid Cytokines Chymase heparin cyclooxygenase Lipooxgenase - prostacyclin - leukotriene -prostaglandin

9. Main classes of anti-allergy drugs 1. Ocular Decongestants 2. Antihistamines 3. Mast Cell Stabilizers 4. NSAIDS 5. Corticosteroids

10. 1.Ocular Decongestants Cost effective choice for mild allergies Use with cold compresses Artificial tears necessary Mechanism of action This drugs are adrenergic agonist mainly alpha 1 receptor Local vasoconstrictor, temporarily reduces redness and swallowen blood vessel Does not treat itching and sneezing

11. CONT…. Drug available Phenylephrine 0.12% and 0.125% Naphazoline ( 0.012%, 0.05%, 0.1%) Tetrahydrozoline ( 0.05%) Imidazole derivatives Oxymetazoline ( 0.025%)

12. Phenylephrine Mechanism of action-selective alpha one agonist that weakens beta- adenergic activity. It causes vasoconstriction o f arterioles and also dilate the pupil. used to relive eye redness ,dryness , burning and irritation Dosage -0.25% to 2.5% solution

13. Side effect of Decongestion Short duration of action It may cause burning and stinging sensation Chronic use lead to conjunctiva inflammation and hyperemia Corneal opacity Papillary dilation Dry eye

14. 2.Anti-histamines- ocular Mechanism of action Blocks H1 receptors which control . Itching . Capillary dilation . Increase in capillary permeability Thus providing symptomatic relief from histamine activity histamine induced capillary dilatation, increase in capillary permeability & pain. Reduces itching caused from already released histamine from mast cells and basophils Almost always combined with ocular decongestant

15. Con… -Activation of H1 histamine receptors stimulate itching, whereas H2 receptors are involved in vasodilation. -Topical ocular antihistamines bind to H1 receptors in the conjunctiva and this reduces itching but does not reduce redness Side effect of anti histamine - topical antihistamines do not have a long duration of action. - Adverse reactions can include burning and stinging on instillation, headache, and dry mouth.

16. Drugs available Pheniramine, antazoline combined with naphazoline Levocabastine HCl ophthalmic suspension 0.5 % ( Livostin ) Emedastine difumarate 0.05% ( Emadine ) All QID dosing for 2 weeks

17. Emedastine Mechanism of Action Histamine H1 antagonist, inhibits vascular permeability Emedastine is a selective H1 receptor antagonist that also inhibits histamine release from mast cell Emedastine significantly reduces itching and redness within 10 minutes of instillation,with a duration of action of at least 4 hours. It is formulated as a 0.05% solution (Emadine),and the recommended dosage is four times per day.(QID) Emedastine is approved for use in patients 3 years of age and older.

18. 3.Chronic Care Drugs: Mast cell stabilizers These are among the newest drugs. Not effective in acute disease Must be used regularly for better performance Mechanism of action - Mast cell stabilizers work by inhibiting mast cell degranulation thereby reducing the release of inflammatory substances . - However, these agents do not eliminate inflammatory mediators that have released prior to drug instillation. Mast cell stabilizers inhibit the degeneration of sensitized mast cells when exposed to specific antigens by inhibiting the release of mediators from the mast cells. These agents block calcium ions from entering the mast cell.

19. Drug available First generation (older) • Cromolyn Sodium (Sodium cromoglycate ) 4% -BD • Lodoxaminde 0.1% • Second generation- BD dosing, same efficacy as first generation • Pemirolast potassium 0.1% ( Alamast ) • Nedocromil sodium 2% ( Alocril )

20. Cromolyn Sodium 4.0 % Mechanisms of action Traditional view was that it inhibits mast cell degranulation & release of mediators of allergic disease by preventing calcium influx. However the mast cell stabilizers containing Cromolyn may also act via other mechanisms. These include inhibition of the activation of other cell types, including neutrophils,monocytes,and eosinophils. Cromolyn may also prolong the tear breakup time in patients with chronic conjunctivitis Its main mode of action is to prevent mediator release and its subsequent clinical manifestations.

21. USE Effective in treating ocular allergic reactions like vernal conjunctivitis & keratitis, allergic keratoconjunctivitis & giant papillary conjunctivitis. Side effect -frequent-stinging - burning after in installation -Infrequently- conjunctiva injection, -watery or itchy eyes, -dryness around the eye , - puffy eyes and stys can be seen.

22. 4. Anti-histamines combined with Mast cell stabilizers Stabilizes mast cell membranes and controls immediate itching Very successful and effective Names are: Olopatadine hydrochloride 0.1% ( Patanol ) Ketotifen fumarate 0.025% ( Zaditor ) Azelastine HCl 0.05% ( Optivar )

23. Side Effects Adverse reactions for these multiaction drugs include burning, foreign body sensation, dry eye, Systemic side effects may include headache, flu-like syndrome,and rhinitis. Most common to all these drugs is headache, burning and stinging

24. Olopatadine  ( Patanol ®) Mechanism of action- Inhibit release of histamine from mast cells and histamine induced effect I ndications : treatment of the signs and symptoms of allergic conjunctivitis . Dosing : The recommended dose is one drop in each affected eye two times per day at an interval of 6 to 8 hours . Supplied : [0.1% soln,0.2%] Side effect –headache -blurred vision -dry eye -foreign body sensation

25. Azelastine Mechanism of action- : Azelastine hydrochloride is a relatively selective histamine H1 antagonist and an inhibitor of the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. INDICATIONS AND USAGE : Treatment of itching of the eye associated with allergic conjunctivitis. CONTRAINDICATIONS : Persons with known or suspected hypersensitivity to any of its components Dosage- [ Supplied : 0.05% ophthalmic solution - one drop instilled into each affected eye twice a day.   - For patients above 3 years of age.

26. Adverse Effects Transient burning/stinging Headache Bitter taste

27. Epinastine 0.05% Mechanism of Action Histamine H1 antagonist, inhibits vascular permeability and release of histamine and other mediators involved in allergic response; has affinity for H2 alpha1, alpha2 Dosage BID Onset: 3-5 min Duration: 8 hr Half Life: 12 hr Total Body Clearance: 56 L/hr Excretion: Urine 55%; feces 30%

28. 5, NSAID Used regularly in the treatment of allergic reaction Used mainly in acute allergic conjunctivitis Does not affect IOP, pupillary response or visual acuity . Mechanism of action NSAIDs inhibit prostaglandin production from arachidonic acid by blocking cyclooxygenase . which results in vasoconstriction, decrease in vascular permeability and leukocytosis In turn, this relieves itching and hyperemia. I t penetrates the cornea & reaches concentrations that reduces prostaglandin E levels in the aqueous humor. Topical NSAIDs provide good relief of ocular itching and redness.

29. Con…. Available drugs Ketorolac troethamine ( Acular )- First NSAID approved for topical ocular use in seasonal allergic reactions

30. Ketorolac tromethamine Ketorolac tromethamine is a member of the pyrrolopyrrole group of NSAIDs Mechanism of action- It inhibit prostaglandin biosynthesis Used to relive itching eyes Used to prevent and treat eye swelling due to certain type of eye surgery Work by blocking certain natural substance in your body to reduce pain and swelling Dosage -0.5%

31. Side effect -Transient stinging & burning occurs frequently -Allergic reactions & superficial keratitis rarely occurs. Contraindications - In patients wearing contact lenses. -Patient who have previously exhibited sensitivity to acetylsalicylic acid, phenylacetic acid derivatives & other NSAIDs.

32. 6.Corticosteroids Corticosteroid treatment has a role for managing inflammation Used for short term intervention in sever disease. Mechanism of action -One of anti inflammatory protein induced by corticosteroid is ( lipocorine ) which interact with and inhibit phospholipase A2 . -There by blocking release of arachidonic acid and its subsequent conversion to eicosanoids . -Inhibition of degranulation of mast cells, basophils and neutrophils -This drugs are lipophilic which can easily cross cell membrane and gain access to cytoplasm.

33. Control of inflammatory and immunologic diseases of eye. Reduction in capillary permeability and cellular exudation. Act on both early and late phase of the allergic reaction by suppressing mast cell proliferation , inhibiting the production of inflammatory mediators Available drugs Has 4 groups 1 ,hydrocortisone-contain prednisone/1%/ and hydrocortisone/0.5%/ 2,Acetonide- contain triamcinolone and actinide 3,Betamethasone –dexamethasone/0.1%/ 4,Ester betamethasone-methyl prednisolone.

34. Classification Short acting Hydrocortisone, cortisone, prednisolone Intermediate acting Triamcinolone, Fluprednisolone Long acting Dexamethasone ,betamethasone

35. Dexamethasone Dexamethasone is available as an alcohol or phosphate derivative in the form of a 0.1% ophthalmic suspension or solution. It is also formulated as dexamethasone sodium phosphate ointment,0.05% Used to treat certain eye condition due to inflammation or injury. Experimental studies indicate that dexamethasone alcohol is superior in anti-inflammatory activity to dexamethasone sodium phosphate,

36. Cont... Works by reliving symptoms such as swelling , redness and itching Comes us oral tablet , oral solution , eye drop. It’s also available us an injection solution or intraocular solution Approximately 4% patient develop high pressure >31 mm hg after 6 weeks use of this drug. Observations suggest that dexamethasone is resistant to metabolism after penetration into the aqueous humor. Peak levels occur between 90 and 120 minutes

37. Side effects Dexametasone may bring Cataract Glaucoma Exophthalmose stunning of growth in children Impaired myocardial contractility ( prolonged use of it) Osteoporosis

38. Fluorometholone 0.1% Unlike prednisolone and dexamethasone, which are structurally related to cortisol,fluorometholone is a fluorinated structural analogue of progesterone. Formulated both as an alcohol and acetate derivative,fluorometholone has proven to be an effective agent in external ocular inflammations,with relatively low potential for elevating IOP After topical application to the eye, fluorometholone alcohol penetrates and is rapidly metabolized within the aqueous humor.

39. Cont ... Clinical evaluation of patients with conjunctivitis, episcleritis, and scleritis indicates that fluorometholone acetate improves clinical signs and symptoms of inflammation significantly more than fluorometholone alcohol. Furthermore, when fluorometholone acetate 0.1% was compared with prednisolone acetate 1.0% in patientswith moderate inflammation, no difference in the antiinflammatory effects of the two steroids was observed.

40. Prednisolone A synthetic analogue of the major glucocorticoid hydrocortisone (cortisol), prednisolone has proven an effective anti-inflammatory agent in patients with external and intraocular inflammations. It is commercially formulated as an acetate and a phosphate. Prednisolone acetate is available in 0.125% and 1.0% concentration 1% prednisolone acetate is generally considered the most effective anti-inflammatory agent for anterior segment ocular inflammation.

41. SIDE EFFECT of corticosteroid Ocular -cause cataract -increasing IOP -Immune suppression -Ptosis -Scleral melting - midrasis

42. References www.webmed.com www.medscape .com Fundemental principle of opthamology Pharmacology handout

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