The document is a comprehensive overview of ocular therapeutics, detailing pharmacodynamics, pharmacokinetics, mechanisms of drug action, and various drug classifications including ocular anaesthetics, anti-glaucoma medications, antibiotics, antifungals, antivirals, and diagnostic agents. It also discusses routes of administration, therapeutic indices, adverse effects, and complications related to ocular procedures. A significant focus is on drug formulations, their mechanisms, indications, and side effects associated with treatment for various ocular conditions.

1. Ocular Therapeutics Ocular Therapeutics Dr Rajvin Samuel Ponraj

2. Pharmacodynamics Study of mechanisms of drug effects Receptor - special types based on transduction of signal Regulation of receptors – Down regulation Up regulation Therapeutic index

3. Pharmacokinetics Quantitative study of drug movement in, through and out of the body

4. Transport across cell membrane Passive transport Specialized transport First Pass metabolism Bioavailabilty

5. Distribution Barriers concerned with distribution Blood aqueous barrier Blood retinal barrier Corneal barrier Tissue binding Tissue perfusion

6. Biotransformation Phase 1 reactions Phase 2 reactions

7. Excretion of drugs Elimination kinetics - First order kinetics Zero order kinetics Clearance Half life

8. ADVERSE DRUG EFFECTS SIDE EFFECTS TOXIC EFFECTS INTOLERANCE TERATOGENICITY

9. Routes of administration Local topical Periocular Intraocular Systemic oral injection

10. Topical drug methods Eye drops Eye ointment Gels Ocuserts Soft contact lens

11. Drug penetration Topically : -Lipid and water solubility -Contact time , viscosity , - isotonicity Systemically : - Lipid solubility - eye inflammation - protein binding -molecular weight

12. Ocular anaesthetics MOA :- Reduce nerve impulse conduction by reducing membrane to sodium ions. Common local anaestheitics :- Ester type = Tetracaine 0.5 % , propacaine 0.75 % Amide type = Lidocaine 2 % , Bupivacaine 0.75 %

13. Topical anaesthetic Aim :- To block nerves of superficial cornea Advantages :- No needle insertion No haemorrage Systemic anticoagulants can use Patient alert Disadvantages :- No akinesia Not adequate anaesthesia Adv effects :- Corneal stinging ,epithelial & endothelial toxicity Allergy & contact dermatitis Contraindications :- Nystagmus , uncooperative patients

14. Retrobulbar block Aim :- To block 3 rd cranial nerve in posterior intraconal space Site of injection :- Above inferior orbital rim midway of lateral canthus & temporal limbus Advantages :- Excellent akinesia quick onset of block Disadvantages:- High complication rate Complications :- Retrobulbar Haemorrhage Globe perforation Optic nerve contusion Oculocardiac reflex Respiratory depression

16. Peribulbar block Aim :- To block extraconally the nerves Site of injection :- midway b/w temporal limbus & lateral canthus -Inferomedial to superior orbital notch Advantages :- All that of retrobulbar block Less complications Disadvantages :- More than one injection needed Only good akinesia , anesthesia Longer time for anesthesia Chemosis

18. Sub tenon’s block At 1 or 2 ‘0’ clock positions from corneal limbus [7-8 mm away] Using a 30 mm radius flexible cannula after perforating conjunctiva Passed beyond equator b/w tenon’s capsule & sclera Most frequent site is inferotemporal .

19. Intraocular injections Intracameral or intravitreal E.g. Intracameral acetylcholine (miochol) during cataract surgery Intravitreal antibiotics in cases of endophthalmitis Intravitreal steroid in macular edema Intravitreal Anti-VEGF for DR INTRA-OCULAR INJECTIONS

20. Mydriatics & Cycloplegics Anticholinergic drugs :- Atropine 1 % - 1 week Homatropine 2 % - 24 hrs Cyclopentolate 1 % - 24 hrs Tropicamide 0.5 % - 4 hrs Indications :- corneal ulcer , uveitis , cycloplegic refraction Side effects :- blurry vision , photophobia ,precipitates angle closure glaucoma Sympathomimetics :- Phenylephrine 5 % I ndications - Along with mydriatic in Preoperative cataract preparation , fundus examination Side effects - Stinging , rise in Blood pressure

21. Anti glaucoma drugs - B adrenergic blockers : MOA - Reduce aqueous production – down regulation of Adenylcyclase Advan : NO pupil change, induced myopia No headache, nor IOT fluctuation Side eff : Stinging,burning ,allergy,.. Bronchospasm,Heart block Timolol – Non selective 0.5 % Betaxolol - B 1 selective

22. MIOTICS : Pilocarpine –cholinomimetic drug MOA : increases tone of ciliary muscles -pull trabecular meshwork - outflow of aqueous Advant : Rapid but short acting Disadv : IOT fluctuation ,dim visual loss Side eff : Spasm of accomadation ,brow ache, git disturbances 0.5 % - drops , ocuserts, gel

23. Adrenergic agonists Epinephrine MOA - On alpha , beta receptors – reduce aqueous formation increases aqueous outflow Side effects : Burning , stinging , Conjunctival blanching , CME , Endothelial toxicity follicular conjunctivitis [0.5 -2 %] tachycardia , hypertension Contradicted in aphakic & Closed angle glaucoma Apraclonidine MOA- On alpha 1,2 receptors –reduce aqueous formation Side eff : Itching ,dryness in mouth, follicular conjunctivitis, mydriasis Use : to reduce IOT after laser trabeculoplasty [0.25 – 1 %] Brimonidine – alpha 2 selective Side eff :- dryness in mouth ,fall in Bp,

24. Carbonic anhydrase inhibitors ACETAZOLAMIDE MOA - inhibits bicarbonate ion production , osmotic gradient reduce aqueous formation Side effects – Paraesthesia, anorexia, malaise ,Gi irritation Oral 0.25 gms BD DORZOLAMIDE – 2 % DROPS PROSTOGLANDINS LATANOPROST MOA – On prostanoid FB receptors Increase uveoscleral flow & permeability of CBM Side effects – eye irritation , pain, blurry vision 0.005 % drops

25. Hypertonic agents MOA - Raises the osmotic pressure to reduce intra ocular pressure Glycerol [ 10 % infusion / 1 gm /kg oral ] Side effects : nauseating sweet taste ,diarrhoea,headache Mannitol [ 20 % infusion ] Side effects : Hypervolemia , pulmunory edema

26. Drugs during glaucoma surgery ANTIFIBROBLASTIC AGENTS – 5 FU & MITOMYCIN C MOA -Inhibit collagen and protein synthesis by interfering with DNA transcription and replication Side effects : 5 FU – keratopathy Mitomycin - scleral ulcer & iritis Administration : 5 FU - 50 mg/ml Sponge / sub conjunctival mitomycin – 0.5 mg/ml topically

27. Antibacterials PENICILLINS MOA :- Bactericidal Destroys cell wall [gram + , gram – cocci,spirochetes] - penicillin G [1 lakh U/ml topical] [0.5 M U/ ml sub conj inj ] [5 M U / 4 hrs IV] - Cloxacillin [penicillinase resistant] [50-100 mg/kg] 6 hrly oral [staphylococci] - Amoxycillin [25-50 mg/kg] 6 hrly oral [ gram +,- bacteria] Adverse eff :- Hypersensitivity reactions , rash ,..

28. QUINOLONES MOA :- [ Bacterial ] Anti DNA gyrase – inhibits division & supercoiling [gram -- bacteria , gram + bacteria ,chlamydia, mycoplasma] - Ciprofloxacin :- 0.3 % topical , 500 mg BD oral , 5-10 mg/kg IV 200 mg /ml intravitreal Uses :- Keratoconjunctivitis, ulcers,blepharitis, dacryocystitis , infectious endoophthalmitis S/E :- Arthropathy in children ,GIT irritation, Photosensitivity ,rash, liver damage - Gatifloxacin :-

29. CEPHALOSPORINS MOA :- Bactericidal – destroys cell wall 1 st generation :- gram + cocci & gram – bacilli Cephazolin – 0.5 – 1 g/ml 8 hrly IM /IV 2000 ug Intravitreal , 100 mg S/C Cefadroxil – 0.5 -1 g BD oral S/E :- GIT disturbances ,hypoprothrombinemia 2 nd generation :- gram – bacteria ,some anaerobes Cefuroxime axetil – 250-500 mg BD oral Cefoxitin – 1-2 gm 8 hrly IM/IV S/E :- GIT disturbances , migraines, headache 3 rd generation :- gram – bacteria Cefixim – 200-400 mg bd oral ceftazidim -1-2 gm 8 hrly IM/IV S/E: diarrhoea , neutropenia, thrombocytopenia

30. 4 th generation :- against many bacteria ,highly resistant to B –lactamases Cefepime & cefpirome :- 1-2 gm 8 hrly IM/IV S/E : allergic reactions , breathing difficulty, swelling of face ,.. Uses :- along with aminoglycosides In endoophthalmitis and bacterial corneal ulcers,..

31. Chloramphenicol MOA :- Bacteriostatic , Inhibits Protein synthesis by binding to 50 S ribosomal subunit [gram +,- aerobes , chlamydia,ricketssia,mycoplasma] 0.5 % ointment, 50 mg /kg 4 times oral 2 mg/ml intravitreal Uses :- Intraocular infections Conjunctivitis Side eff :- Bone marrow depression Aplastic anemia , agranulocytosis

32. Tetracycline MOA :- Bacteriostatic - inhibits protein synthesis by binding to 30 S Ribosome - 250-500 mg 4 hrly oral - 1 % topical Uses :- Chlamydial diseases phlyctenular conjunctivitis Toxoplasmosis ocular rosacea Side eff :- GIT disturbances discolouration of teeth photosensitivity , rashes nephrotoxicity

33. AMINOGLYCOSIDES MOA :- Bacteriocidal - inhibits protein synthesis ,binding 30 S ribosome sub unit [gram negative bacteria & staph aureus ADR : Ototoxicity , nephrotoxicity ,corneal , retinotoxicity,.. Gentamycin :- 0.3 % drops, 20 mg sub conjunctival inj 200 ug/ml intravitreal inj Uses :- Endoophthalmitis , ocular injuries ,retained FB conjunctival necrosis Amikacin :- 0.3 % drops , 15 mg / kg 8 hrly IV , 0.4 mg intravitreal Uses :- along vancomycin in post op endophthalmitis Tobramycin :- including proteus,pseudomonas 0.3 % drops , 3 - 5 mg /kg /day IV , 150-200 ug /ml

34. SULPHONAMIDES MOA :- Bacteriostatic - Inhibits folate synthesis [PABA folic acid ] [gram - ,+ bacteria] Sulfacetamide , Sulfamethoxazole , sulfadiazine Topically 10% ,20 % ,30 % drops Oral 2-4 gm/day TDS COTRIMOXAZOLE MOA :- Inhibits Dihydro folate reductase in conversion of DHF THF Sulfamethoxazole [400 mg ] + trimethoprim [80 mg]

35. USES :- In trachoma along with pyrimethamine in toxoplasmosis S/E :- GIT disturbances , Hypersensitivity reactions , urticaria , renal toxicity-crystalluria.

36. Antifungals Polyene antibiotics :- MOA - Selective action on ergosterol of fungal cell membrane forming micropores – increase permeability Amphotericin B – Against yeast ,filamental fungi [0.25 % topical ] [ 0.25 mg/kg oral] Nystatin - against candida [ 1 lakh u/gm oint] Natamycin – against candida , aspergillus ,fusarium [ 5 % suspension] Uses in keratomycosis and endophthalmitis[5-10 ug intravitreal] Common side effects : allergic hypersensitivity reactions

37. Imidazoles :- MOA - Block fungal cytochrome P-450 enzyme in ergosterol [increase permeability tru membrane] Clotrimazole :- [1 % topical] Miconazole :- [ 1 % drops,2 % oint, 5-10 mg sub conj ] Ketoconazole :- [200-800 mg oral daily , 0.5 mg intravitreal] Uses :- candida,fungal , endoophthalmitis Side effect:- liver toxicity Triazoles :- Fluconazole - [100-200 mg oral] [0.2% topical] [0.1 mg intravitreal] Uses :- Candida,cryptococcus

38. Anti virals PYRIMIDINE DERIVATIVES Idoxuridine :- 0.1 % drops hrly / 0.5 % ointment TRIFLUOROTHYMIDINE :- 1 % drops MOA : By incorporation - inhibition of viral DNA synthesis Uses :- Dendritic ulcer , herpes simplex keratoconjunctivitis Side effects :- with corticosteroids – SPK, follicular conjunctivitis,..

39. PURINE DERIVATIVES ADENINE ARABINOSIDE MOA :- Blocking DNA synthesis of virus Acyclovir - 3 % ointment , 400-800 mg 5 times/day a week Uses :- EB virus, CMV ,Herpes zoster virus,.. S/E :- Allergic reactions,.. Valacyclovir - 1000 mg TDS Famciclovir - 500 mg TDS S/E :- GIT disturbances Ganciclovir - 5-6 mg intravitreal inj , 5 mg IV S/E :- bone marrow depression , rashes

40. Ocular antiallergics MOA – Competitive antagonist of H1 receptors Uses - vernal keratoconjunctivitis , Giant papillary conjunctivitis Allergic conjunctivitis CPM – 4 times /day topical Azelastine - 2 times/day Loratadine/ cetrizine – at bed time Mast cell stabilizers MOA – Stabilizes mast cells and prevent release of histmaine Cromolyn sodium [2-4 % ] 6 hrly Olapatadine [0.1 % ] 12 hrly

41. Corticosteroids MOA :

42. In general : Anti inflammatory action - fibroblast formation reduce capillary permeable Topical steroids : 1 % prednisolone 0.1 % FML 0.1 % dexamethasone in conjunction to antibiotic Uses : Allergic conjunctivitis , iritis, keratitis ,episcleritis Injection steroids : 40 mg Triamcinolone acetate - periocular 1 mg dexamethasone - intravitreal Uses : Endoophthalmitis, Cysotid macular edema ,…

43. Oral steroids : 1 - 2 mg /kg /wt - orbital inflammation post operative inflammation panuveitis Adverse drug reaction : Prolonged use - posterior sub capsular cataract glaucoma

44. NSAID E.g. ketorolac 0.5 % , flurbiprofen 0.03 %,.. Mechanism: inactivation of cyclo-oxygenase Uses: postoperatively mild allergic conjunctivitis episcleritis, mild uveitis, cystoid macular edema Side effects: stinging , burning

45. Anti VEGF MOA : Inhibits vascular EGF in retinal ischaemia Uses : Diabetic retinopathy , macular edema , ROP ARMD - Intravitreal inj - Pegaptanib [macugen ] Ranibizumab [ lucentis ]

46. Drugs for dry eye Characteristics of ideal tear drops : - Soothing effect - proper wetting agent , viscious - No epithelial toxicity - Alkaline p H MOA : mucomimetic - bind to corneal epithelium form hydrophilic layer to stabilize tear film . Hydroxy propyl methyl cellulose – 0.5 - 1 % Polyvinyl alcohol -- 1.4 % Carboxy methyl cellulose -- 0.5 %

47. Viscoelastics Properties - optical - cohesive [ space maintaining tissue manipulation in surgery] - dispersive [ Coating ocular surface protecting corneal endothelium lower surface tension] - Elasticity Sodium hyaluronate 1 % Sodium hyaluronate 3 % & chondroitin sulphate 4 % Hydroxy propyl methyl cellulose 3 % Uses :- - In gonioscopy - in intra ocular surgeries

48. IRRIGATING SOLUTIONS Characteristics of an ideal solution : -- Maintain moisture of & cleanse ocular tissues -- Isotonicity electrolyte and p H same as aqueous -- Maintain pressure of globe -- Protect delicate ocular structures -- Endothelial nourishment Available preparations :- Balanced salt solution[BSS] BSS plus Dextran containing soln Glucose fortified BSS plus USES :- Intraocular – in cataract surgery Extraocular – FB removal,tonometry,gonioscopy

49. Ocular diagnostic drugs Fluorescein dye Available as drops or strips Uses : stain corneal abrasions, applanation tonometry, detecting wound leak, NLD obstruction, fluorescein angiography Caution: stains soft contact lens Fluorescein drops can be contaminated by Pseudomonas sp. Ocular Diagnositic Drugs

50. Rose bengal stain Stains devitalized epithelium Uses: severe dry eye, herpetic keratitis

51. Ocular toxicology : Amiodarone :- Vortex keratopathy Digitalis :- Chromatopsia [seeing yellow colour ] Chloroquine :- Bull’s eye maculopathy Ethambutol :- Optic neuropathy , colour vision disturbed Corticosteroids :- Posterior sub capsular cataracts Thioridazine :- Pigmentary retinopathy Copper, Gold :- Lenticular opacities Rifabutin :- Anterior uveitis

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