O , my sustainer! Open my Heart

andmake my task easy for me

and loosen the knot from my tongueso that, they might understand my speech

Surah Taha (16:25-290)____Al Quran

Dr. Faizur RahmanProfessor of OphthalmolgyPeshawar Medical College

Peshawar

ANTIBOITICS , STEROIDS USED IN OPHTHALMIC PRACTICE

AND DRUG TREATMENT OF CERTAIN DISEASES

At the end of the session the students wouldbe able to:

Know various antibiotics and steroids used in Ophthalmic practice. Describe the rationale of using various drugs. Mechanism of action , effects and side effects of these drugs. Know drug treatment of certain diseases

Learning objectives

A chemical substance produced by one organism causing the death of other bacterial cells i.e penecillin and streptomycin.

After the introduction of synthetic agents these are now called antibacterials.

As newer agents came up now a wide spectrum of drugs are available called antimicrobials.

What is antibiotic?

Difference between humans and microbes isexploited to produce substances toxic to microbesand harmless to humans.

The selective toxicity may be relative than absolute.

Concentration of antimicrobials must be carefully controlled.

Mechanism of action.

INHIBIT BACTERIAL CELL WALL OR ACTIVATE ENZYMES THAT DESTROY BACTERIAL CELL WALL:◦ PENICILLINS◦CEPHALOSPORINS◦BACITRACIN◦VANCOMYCIN◦KETOCONAZOLE◦MICONAZOLE

Mechanism of action...Cont.

ALTER CELL WALL PERMEABILITY AND LEAKAGE OF INTRACELLULAR CONTENTS◦ POLYMYXINS◦NYSTATIN◦AMPHOTERICIN B◦COLISTIMETHATE

Mechanism of action...Cont.

INHIBIT PROTEIN SYNTHESIS◦Tetracyclines◦Aminoglycosides◦Macrolides/Ketolides◦Clindamycin◦Chloramphenicol

Mechanism of action...Cont.

DRUGS THAT BLOCK SPECIFIC METABOLIC STEPS (Foleate inhibitors)◦ SULFONAMIDES◦TRIMETHOPRIM

INHIBIT DNA DEPENDENT RNA POLYMERASE◦RIFAMPICIN

Mechanism of action...Cont.

INHIBIT DNA DEPENDENT DNA SYNTHESIS◦QUINOLONES

ACT AS NUCLEIC ACID ANALOGUES◦ANTIVIRALS

Mechanism of action...Cont.

Identify the infecting organism Empiric therapy prior to identification Determination of susceptibility Barriers Patient factors. Safety of agent Cost of therapy.

Selection.

Chloramphenicol (Topical) Anti-mycotics(Systemic and topical) Aminoglycosides(Systemic and topical) Sulphonamides(Systemic and topical) Anti-virals (Systemic and topical) Macrolides(Systemic) Quinilones (Systemic and topical) Cephalosporines (Systemic and topical)

Common Antimicrobials used in Ophthalmology

Ophthalmic Antibiotics

STEROIDS

Mineralo corticoids Glucocorticoids

Androgens

Types

Beciomethasone Betamethasone Cortisone Des oxy cortico sterone Dexamethasone Fludro cortisone Hydrocortisone Methyl prednisolone Para methasone Prednisolone Prednisone Triamcinolone

Some Corticosteroids

Promote normal intermediary metabolism:GluconeogenesisStimulate protein catabolismStimulate lipolysis

Increase resistance to stress by:Raising blood glucose levelModest rise in BP

Alter blood cell levels in plasma:Decrease in eosinophils, basophils, monocytes and lymphocytes by redistribution from circulation to lymphoid tissueIncrease in the number of RBC, platelets, neutrophils

Actions

Anti inflammatory action: (Complex mechanism)Suppression of immunityIndirect inhibition of phospholipase A2

Alter other endocrine systems:Decrease in ACTH and TSHIncrease in GH

Effects on other systems:Increased production of gastric acid, pepsinEffects on CNSBone lossMyopathy

Actions…Cont.

In the treatment of ocular inflammations and immune related ocular diseases.

Act by suppressing the formation of arachidonic acid and other mediators by induction mediators like phospholipaze A2 and inhibitory protein Lipocorteins

Prevent edema, Fibrin deposition, capillary dilatation and proliferation, Leukocyte infiltration and subsequent scarring.

Indications

Antibiotic + Steroid Preparations

Long acting/ Short acting/ Depot Very potent Potent Moderately potent Mild

Properties and Duration of action

Impaired wound healing/ Easy Bruising Negative calcium balance/ Osteoporosis Increased appetite/ Hyperglycemia/ Diabetes Mellitus Euphoria/ Depression/ Psychosis Hypertension Edema (Sodium and water retension)/ Weight Gain Peptic ulcers/ GI Hemorrhage/ GI Perforation Hypokalaemia (Potassium depletion) Hirsutism /Acne/ Coetaneous striae/ Amenorrhea Myopathy (Gluconeogenesis) Avascular Bone necrosis (Neck of femur) Decreased Immunity

Side effects-Systemic

Cataract (PSC) Steroid induced Glaucoma Retinal Micro-Aneurysms Papilloedema Delayed Wound Healing Mild Blephroptosis Immune Suppression-Secondary Infections◦CANDIDA, TOXOPLASMOSIS, CMV, HSV,

Side effects- Eye

Topical Intralesional Subconjunctival Subtenon Periocular Intravitral Intracameral Systemic

oraliv

Routes of administration

Prenisolone (Topical and systemic) Dexamethasone (Topical and systemic) Betamethasone (Topical and systemic) Hydrocortisone (Systemic only) Loteprednol (Topical only) ( No IOP Rise) Flouromethalone (Topical only) ( No IOP Rise)

Commonly used Steroids

Intra lesional in hemangioma and chalazion Iv in optic neurirtis Oral in dysthyroid ophthalmopathy. Corneal

transplant Intravitreal in CRVO Topical postoperative, uveitis, corneal transplant Intracameral Per-op in children

Steroid use in ophthalmology

Strong Steroids

Weak Steroids

Dexamethasone Injectios and Prednisole Tablets

Hydrocortisone and Prednisolone Injections

Steroid Drops

The patient with orbital cellulitis should be promptly hospitalized for treatment. Hospitalization should be continued until the patient is afebrile and is clearly improved clinically.

Symptomatic; antipyretic, NSAIDS Antimicrobials ; ◦ Ceftazidime 1 g tds , I/M◦ Metronidazole 500mg tds, PO ◦ Vancomycin in case of allergy to the above mentioned

Surgical intervention in case of local abscess or unresponsive cases Consultation with ENT specialist, neurosurgeon & paediatrician if

required

Treatment of Orbital Cellulitis

Specifically identified pathogens identified on cultures.

Intravenous antibiotic therapy should be continued for 1-2 weeks and then followed by oral antibiotics for an additional 2-3 weeks.

Fungal infection requires intravenous antifungal therapy along with surgical debridement.

Treatment of Orbital Cellulitis

Surgical drainage of an orbital abscess is indicatedif any of the following occurs:

A decrease in vision occurs. An afferent pupillary defect develops. Proptosis progresses despite appropriate antibiotic

therapy. The size of the abscess does not reduce on CT scan within

48-72 hours after appropriate antibiotics have been administered.

If brain abscesses develop and do not respond to antibiotic therapy, craniotomy is indicated.

Treatment of Orbital Cellulitis

SAFE strategy developed by WHO for trachoma: Surgery:◦To prevent blindness & limits progression of corneal

scarring.◦Can improve vision.

Antibiotics:◦Azithromycin—1 G single dose (adults).◦Children: 20mg/kg single dose

Treatment of Trachomatous Conjunctivitis

Erythromycin 250 mg QID for 4 weeks. (children 125mg/kg).

Tetracycline 250 mg QID for 4 weeks. Topical tetracycline 1% 0.5 inch ribbon BD for 6 weeks. Facial cleanliness:◦ Reduces risk & severity of trachoma.

Environmental change:◦ Improved water supply & household sanitation.◦ Personal & community hygiene.◦ Adequate housing & water & sewage system.

Treatment of Trachomatous Conjunctivitis

Topical Tetracycline.

Oral Erythromycin 25mg/kg body weight 12

hourly for 14 days.

Caution:

Examine mother & father for chlamydial urethritis/

cervicitis and treat.

Ophthalmia neonatorum

Broad spectrum antibiotics Analgesics Drainage if abscess formation

Acute Dacrocystitis

Initial treatment: Broad spectrum topical antibiotics (Fortified)

Dual therapy: Aminoglycoside & cephalosporin. Mono therapy: Fluoroquinolone. Oral antibiotics: Atropine. Systemic analgesics.

Treatment of Corneal Ulcer (Bacterial)

• Acyclovir 3% ointment x 5 times daily• Trifluorothymidine 1% drops 2-hourly• Debridement if non-compliance or no response

Treatment of Corneal Ulcer (Viral)

Polyenes: Natamycin 5%: Filamentous fungi.

Amphotericin B: Filamentous fungi. Imidazole:

Miconazole 1%: Candida, Aspergillus.Systemic: Itraconazole, Ketoconazole.

Pyramidine: Flucytosine 1%: Candida.

Treatment of Corneal Ulcer (Fungal)

Antifungal (Natamycin)

Topical: Propamidine Isothionate 0.1% (Brolene), Dibromopropamidine Isothionate 0.15%, Miconazole 1%.

Systemic: Ketoconazole.

Treatment of Corneal Ulcer (Acantamoebal)

• Intravitreal antiboitics• Subconjuntival antibiotics.• Topical antibiotics.• Role of systemic antibiotics. • Role of steroids.• Role of vitrectomy.• Cycloplegics and analgesics.

Treatment of Endophthalmitis

Drug Treatment of Glaucoma

To prevent further damage to the eye by lowering IOP & to ultimately prevent

blindness

PRIMARY GOAL

Plasma Expanders Urea

Mannitol 20% IV solution.

Dose: 1-2g/kg or 5 ml/kg body weight.

Up-to 60 drops/min over 20-30 min.

Peak of action: within 30 min.

Duration of action: up-to 6 hrs. Diuretics IV Acetazolimide

Systemic-Used in Emergency

50% solution. Oral agent with a sweet & sickly taste. Pure lemon should be added to avoid nausea. Dose:1-2g/kg or 2-4ml/kg body weight. Peak of action: Within 1 hr. Duration of action: Upto 3 hrs. Metabolized to glucose in the body.

Glycerol-Oral

Oral agent with a minty taste.

Dose: Same as for glycerol.

Metabolically inert & can be given to diabetics

without insulin cover.

Isosorbide-Oral

Mechanism Of Action:1- POAG: Stimulation of longitudinal muscle of ciliary body---pull on scleral spur---widening of trabecular spaces---lowering of IOP.2- PACG: Opening the angle by pulling the peripheral iris away from the trabeculum.

Parasympatomimatics

Indications: POAG. Acute ACG. Many secondary glaucomas. Good additive effect with beta blockers.

Response:Blue eyes: Max. response.Dark eyes: Relatively low response.

Pilocarpine

Pilocarpine(1%,2%,3%,4%):One-half inch ribon at bed time.

Induced myopia & miosis lasts only during sleep.Corneal haze in 20%, rarely affects VA.

Pilocarpine sustained-release (Ocusert Pilo-20 & Pilo-40): Polymer containing adsorbed pilocarpine.Inserted in upper fornix---7 days.Pilo-20: Equivalent to pilocarpine 1% drops.Pilo-40: Equivalent to pilcarpine 2-4% drops.

Preparations

Parasympathomimetic muscarinic agonist, also a weak chloinesterase inhibitor.Onset of action: Within 40 min.Duration: 12 hrs.Dose: 8 hourly.Good alternative to pilocarpine in resistant cases.0.01% intraocular solution for miosis during surgery.

Carbachol (3%)

EpinephrineDipivefrinClonidineApraclonidineBrimonidine

Sympathomimetics

Epinephrine 0.5, 1%, 2% Mechanism Of Action: Increases both trabecular &

uveoscleral outflow via beta agonist activity mediated by cyclic AMP.

Tripple response: Conj. decongestion, slight mydriasis & reduction of IOP.

Onset of action: Within 1 hr. Duration of action:12 - 24 hr. Indications: POAG, ocular hypertension.

Sympathomimetics (Alpha Agonists)

Dipivefrin (0.1%)—(Propine) Prodrug: Converted to adrenaline after absorption. Penetration 17 times greater than adrenaline. Duration of action same. IOP lowering effect is comparable with 1%

adrenaline. Fewer side effects.

Alpha Agonists…Cont.

Twice daily dose. Wash out period: 3.3 wks. Peak effect at 2 hrs. Duration of action 12 hrs. Comparable to Timolol. Nonresponder: Less than 10%. No tachyphylaxis. Good additivity to beta blockers, CAIs & miotics. No vasoconstrictive effect in retinal tissues.

Brimonidine-0.2%(Alphagan)

Prophylaxis of post-laser IOP spike. Property of neuroprotection in animal models. SIDE EFFECTS:

Ocular: Follicular conj., contact dermatitis, ocular irritation & hyperemia.

Systemic: Bradycardia, hypotension, apnea in neonates.

Brimonidine (0.2%)

Pharmacokinetics: Highly selective alpha-2 agonist. Easy penetration to cornea. Lower access to CNS: Less lipophilic, rapid

metabolism, short plasma half life. Reduce allergic reaction: Not produce hapten. Mechanism Of Action: Reduce IOP by initial

decreasing aqueous production followed by increase in uveoscleral flow.

Brimonidine (0.2%)

OCULAR Irritation. Lacrimation. Allergic BC. Adrenochrome

pigmentations. Cystoid macular

edema. Pupillary dilatation.

SYSTEMIC Headache. Palpitations. Tachycardia. Hypertensive crisis. Anxiety.

Side Effects

Mechanism Of Action: Decrease aqueous secretion with little effect on

episcleral venous pressure. 10% unresponsive. First choice medication for POAG. Non-selective or cardioselective. Contralateral effect.

Beta Blockers

0.25% and 0.50% BD.

Timolol LA 0.25% and 0.50%.

Digital pressure over eyes after medication

(3minutes) to reduce systemic absorption.

TIMOLOL(Betalol)

Beta Blocker drops

0.5% BD. Cardio-selective. Ocular hypotension < Timolol & Levobunolol &

similar to Carteolol. IOP reduction 6 mm Hg. Less effective than Timolol in post-cataract surgery

increase in IOP. Increases retinal blood flow. Superior visual fields protection.

BETAXOLOL—(Betaxol, Betoptic-S)

Non selective. Onset of action: Within 1 hr. Peak of action: 2-6 hr. Duration: 24 hr. Dose: Usually OD. Potent as Timolol.

Levobunolol--0.5%--(Betagan)

Levobunolol--0.5%--(Betagan)

Non-selective. More selective action on the eye than cardiopulmonary

system. (less bradycardia than Timolol). Efficacy similar to Timolol.Metipronolol (0.1%, 0.3%) Non-selective. Similar properties to Timolol.

Carteolol (1% & 2%)

Latonoprost (Latep) Travoprost (Travatan) Unoprostone (UF-021) Bimatoprost (Lumigan)

Arachidonic Acid Analogues

Prodrug derived from pulmonary metabolite of PGF2 alpha.

Efficacy:14-17% less than Latanoprost & comparable to Timolol.

Dose: 0.15% BD.Inhibit activity of endothelin-1 & may improve ocular blood flow.

Side effects: Conj. hyperemia, corneal epithelial defects.

Unoprostone (UF-021)

Synthetic PGF2 alpha analog. Dose: 0.004% OD. Widest temperature storage range. Efficacy:

7-8mm Hg IOP reduction (upto 33%)—start after 2 hr, peak at 12hr.6-7mm Hg IOP reduction with Timolol.Higher mean IOP reduction & responder rate than Latanoprost.

Travoprost (Travatan)

Synthetic analog of endogenous prostamides. Receptor profile: Controversial---no prodrug?

no binding to PG receptors? Mechanism Of Action: Increase trabecular outflow

(35%) & uveoscleral outflow (50%). Dose: 0.03% OD. Efficacy:

33% (7-8mm Hg) IOP reduction.Better diurnal control & less PG-like side effects than Latanoprost.

Bimatoprost (Lumigan)

Topical as well as systemicAcetazolamide 250mg Tablets (AZM)Brinzolamide Drops (Azopt)Dichlorphenamide 50 mgMethazolamide 50 mg

Carbonic Anhydrase Inhibitors

1) Timolol/ Dorzolamide (Cosopt)2% dorzolamide & 0.5% timolol maleate.Efficacy: 25-30% IOP reduction (less than separate therapies).

2) Latanoprost/ Timolol (Xalacom)

0.005% latanoprost & 0.5% timolol,OD 3) Timolol/ Brimonidine (Combigan) 4) Timolol/ Pilocarpine.

Fixed combination agents

THANK YOU