Download MBBS Ophthalmology PPT 35 Ocular Pharmacology I Lecture Notes

Ocular Pharmacology-I

Learning Objectives

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At the end of this class students shall have a

basic understanding of :

?pharmacokinetics and pharmacodynamics of

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ocular drugs

?Ocular routes of drug administration

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?Topical antibiotic and cycloplegic agents

2

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Overview

Overview of ocular anatomy & physiology
Pharmacodynamics and Pharmacokinetics of ocular therapeutic agents
Ocular Routes of Drug Administration

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Therapeutic & Diagnostic applications of Drugs in Ophthalmology
Ophthalmic Effects of Selected Vitamin Deficiencies & Zinc Deficiency
Systemic Agents with Ocular Side Effects
Conclusion

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Anatomy of Eye

4

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Tear Film

5

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Pharmacodynamics

?It is the biological and therapeutic effect of the drug

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(mechanism of action)

?Most drugs act by binding to regulatory

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macromolecules, usually neurotransmitters or

hormone receptors or enzymes

?If the drug is working at the receptor level, it can be

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agonist or antagonist

?If the drug is working at the enzyme level, it can be

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activator or inhibitor

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Pharmacokinetics

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?It is the absorption, distribution, metabolism, and

excretion of the drug

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?A drug can be delivered to ocular tissue as:

? Locally:

? Eye drop

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? Ointment

? Periocular injection

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? Intraocular injection

? Systemically:

? Orally

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? IV

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Pharmacokinetics of Ocular Drugs

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? Classical pharmacokinetic theory based on
systemically administered drugs does not fully
apply to all ophthalmic drugs

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?Topical route ? most commonly used

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Absorption

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Rate & extent of absorption of topically instilled drugs depends upon ?
"Drug penetration into the eye is approximately linearly related to its

concentration in the tear film."

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1. Time the drug remains in the cul-de-sac &

precorneal tear film

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2. Elimination by nasolacrimal drainage

3. Drug binding to tear proteins

4. Drug metabolism by tear & tissue proteins

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5. Diffusion across cornea & conjunctiva

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Distribution

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Transcorneal absorption


Accumulation in aqueous humor

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Distribution to intraocular structures

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Trabecular meshwork pathway

Distribution to systemic circulation

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Distribution

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?Melanin binding of certain drugs ?
- Eg:
1. Mydriatic effect of alpha adrenergic agonists
slower in onset - darkly pigmented irides compared to

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those with lightly pigmented irides

2. Atropine's mydriatic effect ? long lasting in non-albino
rabbits than in albino rabbits

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3. Accumulation of chloroquine in retinal pigment
epithelium ? Bull's eye maculopathy

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Metabolism

?Enzymatic biotransformation of ocular drugs

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- significant

?Esterases ? particular interest

Eg: Development of prodrugs for enhanced

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ocular permeability

1. Dipivefrin hydrochloride

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2. Latanoprost

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Drug Delivery in Eyes

Topical

Periocular Intraocular

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Systemic

drop

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Subconjunctival

Intracameral

Oral

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ointment

Subtenon

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Intravitreal

intravenous

gel

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Peribulbar

Intramuscular

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Soft contact lens

Retrobulbar

Ocular Routes of Drug Administration

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Sr.N Route

Special Utility

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Limitations &

o

Precautions

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1.

Topical

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--Convenient

--Compliance

-- Economical

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--Corneal & conjunctival

--Relatively safe

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toxicity

--Nasal mucosal toxicity

--Systemic side effects from

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nasolacrimal absorption

2.

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Subconjunctival, -Anterior segment

-Local Toxicity

sub-Tenon's &

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infections

-Globe perforation

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Retrobulbar

-Posterior uveitis

-Optic nerve trauma

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injections

-Cystoid Macular

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-Central retinal artery or

Edema (CME)

vein occlusion

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3.

Intraocular

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Anterior segment

-Corneal toxicity

Injections

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surgery or infections

-Relatively short duration of

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action

4.

Intravitreal

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Immediate local effect Retinal toxicity

Injection

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Factors influencing local drug penetration into ocular tissue

?Drug concentration and solubility:

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higher concentration -- better penetration

e.g pilocarpine 1-4% but limited by reflex tearing

?Viscosity: addition of methylcellulose and polyvinyl

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alcohol increases drug penetration by increasing

contact time with cornea and altering corneal

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epithelium

?Lipid solubility: higher lipid solubility- more

penetration

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Factors influencing local drug penetration into ocular tissue

? Surfactants: preservatives alter cell membrane in cornea

and increase drug permeability e.g. benzylkonium and

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thiomersal

? pH: the normal tear pH is 7.4

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If drug pH is much different, this will cause reflex tearing

? Drug tonicity: when an alkaloid drug is put in relatively

alkaloid medium, the proportion of the uncharged form

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will increase, thus more penetration

? Molecular weight and size

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TOPICAL

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Drop (Gutta)- simplest and most convenient

mainly for day time use

1 drop=50 microlitre

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Conjuctival sac capacity=7-13 micro liter

so, even 1 drop is more than enough

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Method

hold the skin below the lower eye lid

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pul it forward slightly

INSTILL 1 drop

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? measures to increase drop absorption:

-wait 5-10 minutes between drops

-compress lacrimal sac

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-keep lids closed for 5 minutes after instil ation

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Ointments

?Increase the contact time of ocular medication to ocular

surface, thus better effect

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?It has the disadvantage of

blurring vision

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?The drug has to be highly lipid soluble with some water

solubility to have maximum effect as ointment

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Peri-ocular injections
?They reach behind iris-

lens diaphragm better

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than topical application

?E.g. subconjunctival,

subtenon, peribulbar, or

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retrobulbar

?This route bypass the

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conjunctival and corneal

epithelium which is good

for drugs with low lipid

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solubility (e.g. penicillins)

?Also steroids and local

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anesthetics can be

applied this way

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Periocular
Subconjunctival - To achieve higher concentration

Drugs which cannot penetrate cornea due to large

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size

Penetrate via sclera

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Subtenon--Ant. Subtenon? diseases anterior to the lens

Post. Subtenon? disease posterior to the lens

Retrobulbar- Optic neuritis

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Papil itis

Posterior uveitis

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Anesthesia

Peribulbar-- anesthesia

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Intraocular injections

? Intracameral or intravitreal

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? E.g.

? Intracameral acetylcholine

(miochol) during cataract

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surgery

? Intravitreal antibiotics in

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cases of endophthalmitis

? Intravitreal steroids in

macular edema

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? Intravitreal Anti-VEGF for

DR

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Sustained-release devices

?These are devices that

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deliver an adequate

supply of medication at a

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steady-state level

?E.g.

?Ocusert delivering

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pilocarpine

?Timoptic XE delivering

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timolol

?Ganciclovir sustained-

release intraocular

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device

?Collagen shields

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Systemic drugs

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?Oral or IV

?Factor influencing systemic drug penetration

into ocular tissue:

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?lipid solubility of the drug: more

penetration with high lipid solubility

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?Protein binding: more effect with low

protein binding

?Ocular inflammation: more penetration

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with ocular inflammation

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Therapeutic applications of

Drugs in Ophthalmology

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Common ocular drugs

?Antibacterials (antibiotics)

?Antivirals

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?Antifungals

?Mydriatics and cycloplegics

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?Antiglaucoma medications

?Anti-inflammatory agents

Corticosteroids

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?Ocular Lubricants

NSAID's

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?Local anesthetics

?Ocular diagnostic drugs

?Ocular Toxicology

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Topical Antibacterial Agents

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Commercially Available for Ophthalmic

Use

Azithromycin

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1% solution

H

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Conjunctivitis

Ciprofloxacin

0.3% solution;

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H

-Conjunctivitis

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hydrochloride

0.3% ointment

D-RCD -Keratitis

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-Keratoconjunctivitis

-Corneal Ulcers

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-Blepharitis

-Dacryocystitis

Erythromycin

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0.5% ointment

H

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-Superficial Ocular Infections

involving cornea or conjunctiva

Gatifloxacin

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0.3% solution

H

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Conjunctivitis

H- Hypersensitivity ; D-RCD ? Drug Related Corneal Deposits

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Topical Antibacterial Agents Commercially

Available for Ophthalmic Use.....

Gentamicin

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0.3%

H

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Conjunctivitis, Keratitis

sulfate

solution

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Levofloxacin

0.5%

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H

Conjunctivitis

Levofloxacin

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1.5%

H

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Corneal Ulcers

Moxifloxacin

0.5%

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H

Conjunctivitis

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solution

Ofloxacin

0.3%

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H

Conjunctivitis

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solution

Corneal Ulcers

Tobramycin

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0.3%

H

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External infections of the eye

sulfate

solution

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0.3%

ointment

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Antibacterials( antibiotics)

? Penicillins

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? Cephalosporins
? Sulfonamides
? Tetracyclines
? Chloramphenicol
? Aminoglycosides

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? Fluoroquinolones
? Vancomycin
? Macrolides

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Antibiotics

? Used topically in prophylaxis

(pre and postoperatively) and

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treatment of ocular bacterial

infections.

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? Used orally for the treatment

of preseptal cellulitis

e.g. amoxycillin with

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clavulanate, cefaclor

? Used intravenously for the

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treatment of orbital cellulitis

e.g. gentamicin, cephalosporin,

vancomycin,

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? Can be injected intravitrally for

the treatment of

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endophthalmitis

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? Specific antibiotic for almost each organisms

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? Sulfonamides- Chlamydial infections like TRACHOMA
INCLUSION CONJUNCTIVITIS
TOXOPLAMOSIS
Bacterial cell wall synthesis inhibitors-
Penicil in

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Cephalosporins
I) First generation- Gram + cocci eg cephazoline
i ) Second generation --Gram ? ve and antistaphylococcal--
cefuroxime
i i) Third generation? Gram ?ve bacilli --ceftriaxones

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? Side effects- allergic reaction
neutropenia

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thrombocytopenia

Amino glycosides
Mainly against gram negative bacilli
Bacterial protein synthesis inhibitors

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Gentamycin- 0.3% eye drops
Tobramycin- 0.3% eye drop
Neomycin-- 0.3-0.5% eye drops
Amikacin ----- 1% eye drops

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Tetracycline

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Inhibit protein synthesis

active against both gram+ and gram -ve, some

fungi and Chlamydia

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Chloramphenicol

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Broad spectrum ,bacteriostatic,

gram+/gram-ve, Chlamydia

0.5% Eye drops, ointment

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Fluoroqinolones

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?Most frequently used topical broad spectrum

antibiotics

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?Ciprofloxacin ? 0.3% eye drops

?Ofloxacin - 0.3% eye drops

?Moxifloxacin - 0.5 % eye drops

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?Levofloxacin and Besifloxacin eye drops

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Antibiotics

? Trachoma can be treated by

topical and systemic

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tetracycline or erythromycin,

or systemic azithromycin.

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? Bacterial keratitis (bacterial

corneal ulcers) can be treated

by topical fortified

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cephalosporins,

aminoglycosides,

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vancomycin, or

fluoroquinolones.

? Bacterial conjunctivitis is

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usually self limited but topical

erythromycin,

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aminoglycosides,

fluoroquinolones, or

chloramphenicol can be used

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Dacryocystitis - Infection of the lacrimal

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sac

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Hordeolum/ Stye ? Infection of the meibomian, Zeis

or Moll gland

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Conjunctivitis ? Inflammatory process of

the conjunctiva

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Blepharitis ? Bilateral inflammatory process of the

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eyelids

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Antiviral Agents for Ophthalmic Use

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GENERIC NAME

ROUTE OF

OCULAR

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INDICATIONS FOR USE

ADMINISTRATION

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TOXICITY

Trifluridine

Topical (1% solution) PK, H

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-Herpes simplex keratitis

- Keratoconjuctivitis

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Acyclovir

Oral (200 mg

-Herpes zoster

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capsules, 800 mg

ophthalmicus

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tablets)

- Herpes simplex

Intravenous

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iridocyclitis

Valacyclovir

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Oral (500- & 1000

-Herpes simplex keratitis

mg)

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-Herpes zoster

ophthalmicus

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Famciclovir

Oral (125-,250 mg

-Herpes simplex keratitis

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tablets)

-Herpes zoster

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ophthalmicus

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PK ? Punctate Keratopathy ; H - Hypersensitivity

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Antiviral Agents for Ophthalmic Use...

GENERIC NAME

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ROUTE OF

OCULAR

INDICATIONS FOR

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ADMINISTRATION

TOXICITY

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USE

Foscarnet

Intravenous

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-----

Cytomegalovirus

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Intravitreal

Retinitis

Ganciclovir

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Intravenous, Oral

-----

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Cytomegalovirus

Intravitreal implant

Retinitis

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Valganciclovir

Oral

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-------

Cytomegalovirus

Retinitis

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Cidofovir

Intravenous

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------

Cytomegalovirus

Retinitis

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Antivirals

?Acyclovir- Most commonly used anti-viral

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3% ointment 5 times-10-14 days
800mg oral 5 times 10-14 days
Intravenous for Herpes zoster retinitis
Others

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Idoxuridine

INDICATIONS

Vidarabine

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HZ keratitis

Cytarabine

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Viral uveitis

Triflurothymidine
Gancyclovir

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VIRAL DENTRITIC ULCER

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CMV Retinitis

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Antifungal Agents for Ophthalmic Use

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Drug

Method of Administration

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Indications for Use

Amphotericin B

0.1-0.5% solution

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Yeast & fungal keratitis &

endophthalmitis

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0.8-1 mg Subconjunctival

- Yeast & fungal endophthalmitis

5 microgram intravitreal

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- Yeast & fungal endophthalmitis

injection

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- Yeast & fungal endophthalmitis

Natamycin

5% topical suspension

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-Yeast & fungal blepharitis

-Conjunctivitis ; keratitis

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Fluconazole

Topical, Oral & Intravenous

Yeast keratitis & endophthalmitis

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Itraconazole

Topical ,Oral

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Yeast & fungal keratitis &

endophthalmitis

Ketoconazole

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Oral

Yeast keratitis & endophthalmitis

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Miconazole

1% topical solution

Yeast & fungal keratitis

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ANTIFUNGAL

INDICATIONS

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Fungal corneal ulcer

Fungal retinitis/ Endophthalmitis

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Commonly used drugs are

? Polyenes

? damage cel membrane of susceptible fungi

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? e.g. amphotericin B, natamycin, nystatin

? side ef ect: nephrotoxicity

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? Imidazoles

? increase fungal cel membrane permeability

? e.g. miconazole, ketoconazole,fluconazole

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? Flucytocine

? act by inhibiting DNA synthesis

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Mydriatics and cycloplegics

? Dilate the pupil, ciliary muscle paralysis

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? CLASSIFICATION

Short acting- Tropicamide (4-6 hours)
Intermediate- homatropine ( 24 hours)
Long acting- atropine (2 weeks)

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Indications

corneal ulcer
uveitis

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cycloplegic refraction

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SR. DRUG

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FORMULATIO INDICATIONS FOR USE OCULAR SIDE

NO.

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N

EFFECTS

1

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Atropine

0.5%, 1% & 2% -Cycloplegia

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-Photosensitivity

solution; 1%

-Mydriasis

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-Blurred vision

ointment

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-Cycloplegic retinoscopy

-Dilated fundoscopic

Exam

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2

Scopolamine 0.25% solution Cycloplegia

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Photosensitivity

-Mydriasis

-Blurred vision

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3

Homatropine 2% & 5%

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Cycloplegia

Photosensitivity

solution

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-Mydriasis

-Blurred vision

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4

Cyclopentolat 0.5% 1%

Cycloplegia

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Photosensitivity

e

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solution

-Mydriasis

-Blurred vision

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5

Tropicamide

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0.5% & 1%

Cycloplegia

Photosensitivity

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solution

-Mydriasis

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-Blurred vision

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Thank you

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