Ocular Therapeutics

Ocular Therapeutics

Dr Rajvin Samuel Ponraj

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

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

Transport across cell membrane

Passive transport Specialized transport

First Pass metabolism Bioavailabilty

Distribution
Barriers concerned with distribution  Blood aqueous barrier  Blood retinal barrier Corneal barrier

Tissue binding Tissue perfusion

Biotransformation

Phase 1 reactions Phase 2 reactions

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

ADVERSE DRUG EFFECTS

 SIDE EFFECTS  TOXIC EFFECTS  INTOLERANCE  TERATOGENICITY

Routes of administration
Local topical Periocular Intraocular

Systemic

oral injection

Topical drug methods

Eye drops Eye ointment Gels Ocuserts Soft contact lens

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

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 %

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

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

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

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 .

INTRA-OCULAR INJECTIONS 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

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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 % Indications - Along with mydriatic in Preoperative cataract preparation , fundus examination Side effects - Stinging , rise in Blood pressure

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

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

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,

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
Increase uveoscleral flow & permeability of CBM Side effects eye irritation , pain, blurry vision 0.005 % drops LATANOPROST MOA On prostanoid FB receptors

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

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

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 ,..

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 :-

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

 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,..

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

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

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

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]

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

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

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

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

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

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

Corticosteroids
MOA :

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 ,

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

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

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

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 %

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

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

Ocular Diagnositic drugs 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.

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 Rose bengal stain

Stains devitalized epithelium Uses: severe dry eye, herpetic keratitis

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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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