Ocular Pharmacology

Anatomy of Eye

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Tear Film

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 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

Ø Classical pharmacokinetic theory based on

systemically administered drugs does not fully

apply to all ophthalmic drugs

Ø Topical route – most commonly used

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 Absorption
Rate & extent of absorption of topically instilled drugs
depends upon –
1. Time
“Drug the druginto
penetration remains in the
the eye cul-de-sac &
is approximately
precorneal
linearly related tear
to itsfilm
concentration in the 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
9 circulation
 Distribution
Ø 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

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 Metabolism
Ø Enzymatic biotransformation of ocular
drugs- significant
Ø Esterases – particular interest
Eg: Development of prodrugs for enhanced
ocular permeability
1. Dipivefrin hydrochloride
2. Latanoprost

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 Drug Delivery in Eyes
Topical Periocular Intraocular Systemic

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
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Injection
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
• Molecular weight and size

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 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

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-keep lids closed for 5 minutes after instillation
 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
t h a n t o p i c a l
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) 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 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 22
 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 ocular drugs
• Antibacterials (antibiotics)

• 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-RCD -Keratitis
-Keratoconjunctivitis
-Corneal Ulcers
-Blepharitis
-Dacryocystitis

Erythromycin 0.5% ointment H -Superficial Ocular Infections

involving cornea or conjunctiva

Gatifloxacin 0.3% solution H Conjunctivitis

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

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 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
0.3% 27
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 29
endophthalmitis
• 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

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iii) Third generation– Gram –ve bacilli --ceftriaxones
• 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 32

 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% solution) PK, H -Herpes simplex keratitis

- 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
ophthalmicus
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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

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 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
INDICATIONS
Idoxuridine HZ keratitis
Viral uveitis
Vidarabine

Cytarabine 41
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

Miconazole 1% topical solution 44 Yeast & fungal keratitis

 ANTIFUNGAL
INDICATIONS

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
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 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

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cycloplegic refraction
1 Atropine 0.5%, 1% & 2% -Cycloplegia -Photosensitivity
solution; 1% -Mydriasis -Blurred vision
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% solution Cycloplegia Photosensitivity

-Mydriasis -Blurred vision

5 Tropicamide 0.5% & 1% Cycloplegia Photosensitivity

solution -Mydriasis -Blurred vision
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Obat Anti Glaukoma
 OBAT
BERPENGARUH
PADA
PENGLIHATAN
Acne Isotretinoin dry eyes and a sudden decrease
Medication in night vision
Antihistamines CTM Narrow angle glaucoma
!sudden vision changes,
headache pain around the eyes,
blurred vision, or double vision

Antimalaria chloroquine retinal toxicity, leading to

permanent vision loss
Corticosteroid prednison cataract or glaucoma
Erectile sildenafil blurred vision, sensitivity to
Dysfunction light, and seeing a temporary
Drugs
blue tinge
Ethambutol visual acuity, or clarity, and
difficulty seeing certain colors
Phenothiazines chlorpromazine sensitivity to light, changes
in color vision, blurred
vision, and problems seeing
at night
Tamoxifen crystalline retinopathy,
include blurred vision,
corneal changes, and an
increased risk for cataracts

Topiramate Narrow angle glaucoma

!sudden vision changes,
headache pain around the
eyes, blurred vision, or
double vision
 PUPIL

Ukuran pupil
dipengaruhi:
– Cahaya
– Parasimpatis
– Simpatis
MIDRIASIS MIOSIS
• Cahaya redup++ • Cahaya terang++
• Parasimpatomimetik++
• Anti-muskarinik++
• Muskarinik agonis++
• Simpatomimetik+
• Stimulasi reseptor
• Alfa1-adrenoseptor opioid++
agonis+ • Alfa1-adrenoseptor
antagonis+
CATATAN:

• Obat tetes mata dapat sebabkan efek samping sistemik

• Pigmen iris dapat menyerap obat (mis. Atropin)

• Hitam > coklat > hijau > abu-abu > biru
• Onset lambat, durasi memanjang

• Beberapa obat dapat merubah warna mata

• Epinefrin, latanoprost

• Zat pengawet / tambahan pada tetes mata dapat

sebabkan alergi
 EFEK SAMPING
ETAMBUTOL
1. neuritis retrobular

" Buta warna merah-hijau (etambutol 25 mg/kg selama

beberapa bulan) ! Reversibel

"penurunan ketajaman penglihatan

2. Otto-toksisitas (jarang), nervedeafness (biasanya

irreversible) pada terapi klorokuin dosis tinggi jangka
panjang

Tinitus dan berkurangnya pendengaran "500 mg

klorokuin 1x seminggu dalam beberapa bulan
 EFEK SAMPING
KLOROKUIN
• Kerusakan retina yang ireversibel, penglihatan
kabur, kesulitan untuk memfokuskan pandangan dan
penglihatan berkabut.

• Gangguan penglihatan parah bisa terjadi jika

klorokuin digunakan jangka panjang dengan dosis
lebih dari 150 mg perhari

• Pengobatan jangka panjang dengan dosis tinggi

menyebabkan: keratopathy, transient edema
Thank you

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