Ocular

Pharmacology
Anatomy of Eye

2
Tear Film

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4
 Pharmacodynamics
• It is the biological and therapeutic effect of the drug
(mechanism of action)
• Most drugs act by binding to regulatory
macromolecules, usually neurotransmitters or hormone
receptors or enzymes.
• If the drug is working at the receptor level, it can be
agonist or antagonist
• If the drug is working at the enzyme level, it can be
activator or inhibitor

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 Pharmacokinetics

• It is the absorption, distribution, metabolism, and excretion of

the drug
• A drug can be delivered to ocular tissue as:
• Locally:
• Eye drop
• Ointment
• Periocular injection
• Intraocular injection
• Systemically:
• Orally
• IV

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 Pharmacokinetics of Ocular
Drugs
➢ Classical pharmacokinetic theory based on
systemically administered drugs does not
fully
apply to all ophthalmic drugs

➢Topical route – most commonly used

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 Absorption
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.”
1. Time the drug remains in the cul-de-sac & precorneal tear
film

2. Elimination by nasolacrimal drainage

3. Drug binding to tear proteins

4. Drug metabolism by tear & tissue proteins

5. Diffusion across cornea & conjunctiva

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 Distribution
Transcorneal absorption

Accumulation in aqueous humor

Distribution to intraocular structures

Trabecular meshwork pathway

Distribution to systemic circulation 9

 Distribution
➢ Melanin binding of certain drugs –
- Eg:
1. Mydriatic effect of alpha adrenergic agonists
slower in onset - darkly pigmented irides compared to
those with lightly pigmented irides

2. Atropine’s mydriatic effect – long lasting in non-albino

rabbits than in albino rabbits

3. Accumulation of chloroquine in retinal pigment

epithelium – Bull’s eye maculopathy 10
 Metabolism

➢Enzymatic biotransformation of ocular drugs-

significant
➢Esterases – particular interest
Eg: Development of prodrugs for enhanced
ocular permeability
1. Dipivefrin hydrochloride
2. Latanoprost
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12
 Drug Delivery in Eyes
Topical Periocular Intraocula Systemic
r
drop Subconjunctival Intracameral Oral

ointment Subtenon Intravitreal intravenous

gel Peribulbar Intramuscular

Soft contact lens Retrobulbar

Ocular Routes of Drug Administration
Sr.N Route Special Utility Limitations &
o Precautions
1. Topical --Convenient --Compliance
-- Economical --Corneal & conjunctival
--Relatively safe toxicity
--Nasal mucosal toxicity
--Systemic side effects from
nasolacrimal absorption
2. Subconjunctival, -Anterior segment -Local Toxicity
sub-Tenon’s & infections -Globe perforation
Retrobulbar -Posterior uveitis -Optic nerve trauma
injections -Cystoid Macular -Central retinal artery or
Edema (CME) vein occlusion
3. Intraocular Anterior segment -Corneal toxicity
Injections surgery or infections -Relatively short duration
of action
4. Intravitreal Immediate local effect Retinal toxicity
Injection 14
Factors influencing local drug penetration into ocular tissue
• Drug concentration and solubility:
higher concentration -- better penetration
e.g pilocarpine 1-4% but limited by reflex tearing

• Viscosity: addition of methylcellulose and polyvinyl

alcohol increases drug penetration by increasing contact
time with cornea and altering corneal 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
thiomersal

• pH: the normal tear pH is 7.4

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
will increase, thus more penetration
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• Molecular weight and size

 TOPICAL
Drop (Gutta)- simplest and most convenient
mainly for day time use
1 drop=50 microlitre

Conjuctival sac capacity=7-13 micro liter

so, even 1 drop is more than enough

Method
hold the skin below the lower eye lid

pull it forward slightly

INSTILL 1 drop
• measures to increase drop absorption:
-wait 5-10 minutes between drops
-compress lacrimal sac
-keep lids closed for 5 minutes after instillation 17
 Ointments
• Increase the contact time of ocular medication to ocular
surface, thus better effect

• It has the disadvantage of

blurring vision

• 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
than topical application
• E.g. subconjunctival,
subtenon, peribulbar, or
retrobulbar
• This route bypass the
conjunctival and corneal
epithelium which is good
for drugs with low lipid
solubility (e.g. penicillins)
• Also steroids and local
anesthetics can be applied
this way 19
 Periocular
Subconjunctival - To achieve higher concentration
Drugs which cannot penetrate cornea due to large
size
Penetrate via sclera

Subtenon—Ant. Subtenon– diseases anterior to the lens

Post. Subtenon– disease posterior to the lens

Retrobulbar- Optic neuritis

Papillitis
Posterior uveitis
Anesthesia

Peribulbar-- anesthesia 20
 Intraocular injections
• Intracameral or intravitreal
• E.g.
• Intracameral acetylcholine
(miochol) during cataract
surgery
• Intravitreal antibiotics in
cases of endophthalmitis
• Intravitreal steroids in
macular edema
• Intravitreal Anti-VEGF
for DR
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 Sustained-release devices
• These are devices that deliver
an adequate supply of
medication at a steady-state
level
• E.g.
• Ocusert delivering
pilocarpine
• Timoptic XE delivering
timolol
• Ganciclovir sustained-
release intraocular device
• Collagen shields
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 Systemic drugs

• Oral or IV
• Factor influencing systemic drug penetration
into ocular tissue:
• lipid solubility of the drug: more
penetration with high lipid solubility
• Protein binding: more effect with low
protein binding
• Ocular inflammation: more penetration
with ocular inflammation
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Therapeutic applications
of Drugs in
Ophthalmology

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• Common
Antibacterials (antibiotics) ocular drugs
• Antivirals
• Antifungals
• Mydriatics and cycloplegics
• Antiglaucoma medications Corticosteroids
• Anti-inflammatory agents NSAID’s
• Ocular Lubricants
• Local anesthetics
• Ocular diagnostic drugs
• Ocular Toxicology 25
 Topical Antibacterial Agents
Commercially Available for Ophthalmic
Use

Azithromycin 1% solution H Conjunctivitis

Ciprofloxacin 0.3% solution; H -Conjunctivitis
hydrochloride 0.3% ointment D- -Keratitis
RCD -Keratoconjunctivitis
-Corneal Ulcers
-Blepharitis
-Dacryocystitis

Erythromycin 0.5% ointment H -Superficial Ocular Infections

involving cornea or conjunctiva

Gatifloxacin 0.3% solution H Conjunctivitis 26

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

 Topical Antibacterial Agents Commercially
Available for Ophthalmic Use…..

Gentamicin 0.3% H Conjunctivitis, Keratitis

sulfate solution
Levofloxacin 0.5% H Conjunctivitis
Levofloxacin 1.5% H Corneal Ulcers

Moxifloxacin 0.5% H Conjunctivitis

solution
Ofloxacin 0.3% H Conjunctivitis
solution Corneal Ulcers

Tobramycin 0.3% H External infections of the eye

sulfate solution 27

0.3%
ointment
 Antibacterials( antibiotics)
• Penicillins
• Cephalosporins
• Sulfonamides
• Tetracyclines
• Chloramphenicol
• Aminoglycosides
• Fluoroquinolones
• Vancomycin
• Macrolides

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 Antibiotics
• Used topically in prophylaxis
(pre and postoperatively) and
treatment of ocular bacterial
infections.
• Used orally for the treatment of
preseptal cellulitis
e.g. amoxycillin with
clavulanate, cefaclor
• Used intravenously for the
treatment of orbital cellulitis
e.g. gentamicin, cephalosporin,
vancomycin,
• Can be injected intravitrally for
the treatment of
endophthalmitis 29
• Specific antibiotic for almost each organisms
• Sulfonamides- Chlamydial infections like TRACHOMA
INCLUSION CONJUNCTIVITIS
TOXOPLAMOSIS
Bacterial cell wall synthesis inhibitors-
Penicillin
Cephalosporins
I) First generation- Gram + cocci eg cephazoline
ii) Second generation —Gram – ve and antistaphylococcal—
cefuroxime
iii) Third generation– Gram –ve bacilli --ceftriaxones
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• Side effects- allergic reaction
neutropenia
thrombocytopenia

Amino glycosides
Mainly against gram negative bacilli
Bacterial protein synthesis inhibitors
Gentamycin- 0.3% eye drops
Tobramycin- 0.3% eye drop
Neomycin— 0.3-0.5% eye drops
Amikacin ----- 1% eye drops 31
Tetracycline
Inhibit protein synthesis
active against both gram+ and gram -ve, some
fungi and Chlamydia

Chloramphenicol
Broad spectrum ,bacteriostatic,
gram+/gram-ve, Chlamydia
0.5% Eye drops, ointment
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 Fluoroqinolones

• Most frequently used topical broad spectrum

antibiotics
• Ciprofloxacin – 0.3% eye drops
• Ofloxacin - 0.3% eye drops
• Moxifloxacin - 0.5 % eye drops
• Levofloxacin and Besifloxacin eye drops
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 Antibiotics
• Trachoma can be treated by
topical and systemic
tetracycline or erythromycin,
or systemic azithromycin.

• Bacterial keratitis (bacterial

corneal ulcers) can be treated
by topical fortified
cephalosporins,
aminoglycosides, vancomycin,
or fluoroquinolones.

• Bacterial conjunctivitis is
usually self limited but topical
erythromycin,
aminoglycosides,
fluoroquinolones, or
chloramphenicol can be used
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Dacryocystitis - Infection of the
lacrimal 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
eyelids

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 Antiviral Agents for Ophthalmic Use

Trifluridine Topical (1% PK, H -Herpes simplex keratitis

solution) - Keratoconjuctivitis
Acyclovir Oral (200 mg -Herpes zoster
capsules, 800 mg ophthalmicus
tablets) - Herpes simplex
Intravenous iridocyclitis
Valacyclovir Oral (500- & 1000 -Herpes simplex keratitis
mg) -Herpes zoster
ophthalmicus
Famciclovir Oral (125-,250 mg -Herpes simplex keratitis
tablets) -Herpes zoster 39
ophthalmicus
PK – Punctate Keratopathy ; H - Hypersensitivity
 Antiviral Agents for Ophthalmic
Use…

Foscarnet Intravenous ----- Cytomegalovirus

Intravitreal Retinitis
Ganciclovir Intravenous, Oral ----- Cytomegalovirus
Intravitreal implant Retinitis

Valganciclovir Oral ------- Cytomegalovirus

Retinitis

Cidofovir Intravenous ------ Cytomegalovirus

Retinitis 40
 Antivirals
• Acyclovir- Most commonly used anti-viral
3% ointment 5 times-10-14 days
800mg oral 5 times 10-14 days
Intravenous for Herpes zoster
retinitis
Others
Idoxuridine
INDICATIONS
Vidarabine
HZ keratitis
Cytarabine
Viral uveitis
Triflurothymidine
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Gancyclovir
VIRAL DENTRITIC ULCER
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CMV Retinitis

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 Antifungal Agents for Ophthalmic Use

Amphotericin B 0.1-0.5% solution Yeast & fungal keratitis &

endophthalmitis
0.8-1 mg Subconjunctival - Yeast & fungal endophthalmitis
5 microgram intravitreal - Yeast & fungal endophthalmitis
injection - Yeast & fungal endophthalmitis

Natamycin 5% topical suspension -Yeast & fungal blepharitis

-Conjunctivitis ; keratitis
Fluconazole Topical, Oral & Intravenous Yeast keratitis & endophthalmitis

Itraconazole Topical ,Oral Yeast & fungal keratitis &

endophthalmitis

Ketoconazole Oral Yeast keratitis & endophthalmitis

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Miconazole 1% topical solution Yeast & fungal keratitis

 INDICATIONS
ANTIFUNGAL
Fungal corneal ulcer
Fungal retinitis/ Endophthalmitis

Commonly used drugs are

• Polyenes
• damage cell membrane of susceptible fungi
• e.g. amphotericin B, natamycin, nystatin
• side effect: nephrotoxicity
• Imidazoles
• increase fungal cell membrane permeability
• e.g. miconazole, ketoconazole,fluconazole
• Flucytocine
• act by inhibiting DNA synthesis 45
46
 Mydriatics and cycloplegics
• Dilate the pupil, ciliary muscle paralysis
• CLASSIFICATION
Short acting- Tropicamide (4-6 hours)
Intermediate- homatropine ( 24 hours)
Long acting- atropine (2 weeks)

Indications
corneal ulcer
uveitis
cycloplegic refraction 47
1 Atropine 0.5%, 1% & -Cycloplegia -Photosensitivity
2% solution; -Mydriasis -Blurred vision
1% ointment -Cycloplegic retinoscopy
-Dilated fundoscopic
Exam
2 Scopolamine 0.25% solution Cycloplegia Photosensitivity
-Mydriasis -Blurred vision

3 Homatropine 2% & 5% Cycloplegia Photosensitivity

solution -Mydriasis -Blurred vision

4 Cyclopentolate 0.5% 1% Cycloplegia Photosensitivity

solution -Mydriasis -Blurred vision

5 Tropicamide 0.5% & 1% Cycloplegia Photosensitivity

solution -Mydriasis -Blurred vision
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