ANTI GLAUCOMA DRUGS

PRESENTATION BY DR.ASIF, HOUSE OFFICER IN EYE UNIT 2, MAYO HOSPITAL, LAHORE

1. Anti-Glaucoma Drugs Dr. Muhammad Asif Ismail House Officer EYE Unit-2 Mayo Hospital, Lahore

2. Presentation Layout What is Glaucoma? Anti-Glaucoma Drugs Classification Indications Contraindications Summary

3. Glaucoma Glaucoma is a chronic, progressive optic neuropathy caused by a group of ocular conditions which leads to damage of optic nerve with loss of visual function . The most common risk factor known is raised intraocular pressure. Normal intraocular pressure = 10–20 mm Hg Suspicious case = 20–25 mm Hg Glaucoma = Above 25 mm Hg Hypotony = Below 10 mm Hg

4. Aqueous Production and its Drainage Secreted by ciliary body ( posterior chamber ) Drainage Route Primary (90%): Trabacular meshwork Uveoscleral outflow (10%)

5. Purpose of initiating Glaucoma Therapy The ultimate goal of glaucoma treatment is To preserve enough vision during patient’s lifetime to meet their functional needs To delay glaucomatous process

6. Medical Aspects of Glaucoma Therapy When to treat? When glaucomatous damage is documented or future damage is likely What to prescribe? Start with one drug having least ocular and systemic side effects Use least amount of medication In emergency, use two drugs

7. MOA of Anti-Glaucoma Drugs Aim is to lower IOP to the target level either by Reducing aqueous production from ciliary body Promoting aqueous humor outflow through trabecular meshwork Promoting aqueous humor outflow via uveoscleral pathway

8. Classification Topical Drugs Beta Blockers Adrenergic agonists Prostaglandins analogues Cholinergic agents Carbonic anhydrase inhibitors Systemic Drugs Carbonic Anhydrase inhibitors Osmotic Agents

9. Beta Blockers First drug of choice for POAG Lowers IOP by reducing aqueous secretion by acting on Beta-2 receptors Non-Selective Selective Timolol Betaxolol Levobunolol Pindolol Metipranolol Metaprolol Carteolol

10. Mechanism of Action Antagonize the effect of catecholamines Reduction in Aqueous secretion Beta blockers reduce aqueous formation by 24-48 %

11. Beta Blockers

12. Beta Blockers Additive to Miotics Adrenergic agonists CA inhibitors PG analogues Good synergistic effect with miotics , used in POAG unresponsive to single drug Timolol and latanoprost combination results in an additional IOP reduction of 13-37% Betaxolol is the beta blocker of choice in patients at risk for pulmonary disease

13. Side Effects and Contraindications

14. Prostaglandin Analogues ( Mechanism of Action )

15. Drugs

16. Parasympathomimetics ( Cholinergics ) Mechanism of Action Contractionof the iris sphincter: constricts the pupil( miosis ) mechanically moves the iris away from trabecular meshwork Contraction of longitudinal fibres of ciliary muscle tension on the scleral spur (opening the trabecular meshwork facilitation in aqueous outflow

17. Reversible e.g., Physostigmine Irreversible e.g., Demecarium

18. Pilocarpine

19. Blue eyes show maximal ocular hypotensive response Darkely pigmented eyes demonstrate a relative resistance to IOP reduction Miotics better tolerated in Aphakic eye than in Phakic eyes

20. Available Preparations Eyedrops Available in 1%, 2% and 4% strengths The onset of action - 20 minutes Peak in – 2 hours Duration of effect – 4 to 6 hours Prescribed every 6 or 8 hourly Pilocarpine Gel (4%) Causes 18 to 25% fall in IOP

21. Side Effects Ocular Posterior synechiae Keratitis Myopia RD Blurred vision Cataract growth Miosis Color vision changes Systemic Increased sweating and salivation Urinary frequency Diarrhea bronchospasm

22. Carbachol Indications Alternative to Pilocarpine in resistant or tolerant cases Preparations 0.75% and 3% Duration of onset 40 minutes Duration of effect 12 hours Dosage 2 to 3 times per day

23. Sympathomimetics (Adrenergic Agonists)

24. Classification

25. Non-Selective Epinephrine Preparations 0.5%, 1%, 2% eyedrops Dosage the action starts within 1 hour and lasts upto 12-24 hours Dipivefrine Prodrug converted to epinephrine after its absorption into the eye More lipophilic than epinephrine (corneal penetration increased by 17 times) Preparations 0.1% eyedrops Dosage Twice daily action and efficacy similar to 1% epinephrine

26. Clonidine Decreases Aqueous production Increases both trabecular and uveoscleral outflow (lesser extent) Preparations 0.06%, 0.125% Dosage 6 to 8 hourly Side effects Conjunctively blanching Sedation Dry mouth hypotension

27. Apraclonidine Decreases aqueous production Decreases episcleral venous pressure Improves trabecular outflow Peak action 2 hours Duration of action 12 hours Preparations 0.50 and 1% Dosage 8 hourly Uses Post-laser trabeculoplasty Post-lase iridotomy Post-posterior capsulotomy Post-cataract extraction Side effects Allergic reactions Tachyphylaxis Conjunctival blanching Follicular conjunctivitis

28. Brimonidine More selective alpha-2 action Less ocular allergic reactions, Less tachyphylaxis Peak IOP reduction 26% (2 hours post-dose) Conta -indications Infants Yonug children (due to risk of respiratory depression, somnolence, hypotension and seizures)

29. CA Inhibitors Potent and most commonly used systemic anti-glaucoma drugs Mechanism of Action >90% of ciliary enzyme activity must be abolished to decrease aqueous production and IOP

30. Drugs Systemic Actazolamide Methazolamide Dichlorphenamide Ethoxzolamide Topical Dorzolamide Brinzolamide Lodoxamide

31. Acetazolamide Reduces aqueous production by 30 to 40% Uses control of very high IOP in acute angle closure Refusal of surgery Dosage Oral 125 mg and 250 mg tablets 6 hourly 500 mg Sustained release capsules B.D IV Preparations 500 mg (lowers IOP within 20 minutes) Side effects (Dose related) Altered taste Loss of appetite Paesthesia of hands, feet Sulfa allergy Hypokalemia Metabolic acidosis Renal stones Blood dyscariasis Acetazolamide Not metabolized, Excreted in urine. Safe in hepatic failure Methazolamide Metabolized by liver, Decrease risk of systemic adverse effects

32. CA Inhibitors Dorzolamide Topical agent Preparation 2% Fall in IOP 13 to 24% Side effects Punctate keratitis bitter taste Allergic reactions transient burning due to decrease in pH Brinzolamide Preparation 1% Suspension causes white deposits in tera film

33. Hyperosmotics IV : Mannitol Oral : Glycerol Mechanism of Action

34. Mannitol Concentration 20% Dose 0.5 – 2.0 g/kg body weight Side effects IOP rebound Increased aqueous flare Headache Mental confusion Backache CHF, MI Subdural, Subarachnoid haemorrhage Glycerol Concentration 50% Dose 1 – 1.5 g/kg Side effects It precipitates hyperglycaemia Ketoacidosis in Diabetics

35. Hyperosmotics are contraindicated in patients with renal failure or on dialysis Rarely administered for longer duration, cause effects are transient, result of rapid reequilibration or osmotic gradient. Less effective overtime, rebound increase in IOP may occur Larger the dose, more rapid the administration, greater decrease in IOP

36. COMPOUNDS CONCENTRATION DOSING TIMOLOL/BRINZOLAMIDE 0.5% / 1% BD TIMOLOL/DORZOLAMIDE 0.5% / 2% BD TIMOLOL/LATANOPROST 0.5% / 0.005% OD, AT NIGHT TIME TIMOLOL/TRAVOPROST 0.5% / 0.004% OD, AT NIGHT TIME TIMOLOL/BIMATOPROST 0.5% / 0.03% OD, AT NIGHT TIME TIMOLOL/BRIMONIDINE TARTARATE 0.5% / 0.2% BD

37. Primary Open Angle Glaucoma A. Single Drug Therapy Topical beta blockers : DOC, 1 st line Timolol maleate, Betaxolol , Levobunolol , Carteolol Latanoprost : 1 st line Dorzolamide: 2 nd line Pilocarpine : 2 nd line Adrenergic Drugs: Dipivefrine hydrochloride (combined with beta-blockers in patients where other drugs are contraindicated) B. Combination Topical Therapy If one drug is not effective, then a combination of two drugs – one drug which decreases aqueous production ( timolol or other beta-blocker, or brimonidine or dorzolamide ) and other drug which increases aqueous outflow ( latanoprost or brimonidine or pilocarpine ) may be used

38. Acute Primary Angle-Closure Glaucoma Medical therapy is instituted as an emergency and temporary measure before the eye is ready for operation; Systemic hyperosmotic agent intravenous mannitol (1gm/kg body weight) Acetazolamide 500 mg intravenous injection followed by 250 mg tablet should be given 3 times a day Analgesics and anti-emetics Pilocarpine eyedrops 2 % pilocarpine should be administered every 30 minutes for 1-2 hours and then 6 hourly Beta blocker eyedrops like 0.5% Timolol maleate or 0.5% Betaxolol should also be administered twice a day to reduce the IOP Corticosteroid eyedrops like Dexamethasone or Betamethasone should be administered 3-4 times a day to reduce the inflammation

39. THANK YOU