Ocular pharmacology

Nutthiya Hanprasertpong, M.D., Ph.D.

Department of Pharmacology
Faculty of Medicine
Chiang Mai University
knutthiya@gmail.com
Objectives
You should be able to
Describe the important pharmacokinetic of
topical ophthalmic drugs
Describe the indications and adverse drug
reactions of the commonly used ophthalmic
drugs
Advise the patients how to apply the topical
ophthalmic drugs
Ocular pharmacology
Pharmacokinetics
Antimicrobial agents
Immunomodulatory drugs
Autonomic agents
Ocular hypotensive drugs
Wetting agents and tear substitutes
 Anatomy of the eye
dominant
opinion

Iiiiiiivanann

Tum

Goodman & Gilman s The Pharmacological Basis of Therapeutics, 12th ed.

 Tear drainage system

y
woman
mmmm I
Tear film
is
mmmmm

-Lipid layer i
-Aqueous layertwin varuswooing
lacrimalgland
-Mucin layer
on oobletall cmjuntivasalwwnrnrina.non

Goodman & Gilman s The Pharmacological Basis of Therapeutics, 12th ed.

 Drug Deliver Strategies (1)
Route Special Utility Limitation and Precautions
Topical* convenient compliance Unmiriosuvonourianon

solution economical Iain corneal and conjunctival toxicity

mm
suspension relatively safe nasal mucosal toxicity
ointment joruionmon systemic side effect from
gel y oinvin
nasolacrimal absorption
solid insert
soft contact lensfrontino
limisimurio

collagen shields www.t.mn

Sinmunnorm
Ivano nowoisin
*Sterile preparations (used within 1 mo after opened the vial/tube)
Whitman's
 Drug Deliver Strategies (2)
Route Special Utility Limitation and Precautions
Subconjunctival, ant. segment infections local toxicity
sub- post. uveitis tissue injury onlineme
retrobulbar cystoid macular edema globe perforation anonion
injections optic nerve trauma onfavnerve
central retinal artery and or vein
occlusion
direct retinal drug toxicity with
inadvertent globe perforation
ocular muscle trauma
prolonged drug effectWu
 Winning

onsclera
 Drug Deliver Strategies (3)
Route Special Utility Limitation and Precautions
Intraocular ant. segment surgery corneal toxicity
(intracameral) infections intraocular toxicity tantunoon
injections whointomduced
relatively short duration of action
Intravitreal endophthalmitis retinal toxicity
injection or wa retinitis Damonin
device jspin

Intraocular injection
Possible absorption pathways of an ophthalmic drug
following topical application to the eye.
Transcorneal and
transconjunctival/scleral main dunlin
am
absorption are the desired routes origin
for localized ocular drug effects
Drug with both hydrophilic and
lag time 1g-water-
composition
nun
air
rain
or
nine
lipophilic properties is best suited ants
for transcorneal absorption is
Nasolacrimal drainage
systemic absorption
Absorption from the nasal mucosa
avoids first-pass metabolism
systemic side effects,
especially when used chronically

: corneal route
: conjuctival route
: nasolacrimal route
th ed.
Pharmacokinetics: topical (1)
Most ophthalmic drugs are applied topically
Absorption: determined by
Residence time in the cul-de-sac and precorneal
tear film Wrontinodiuzan
time in cul-de-sac drug absorption
Formulation time a drug remains on eye surface
Gels, ointments, solid inserts, soft contact lens
Fanionionnitiviontudiou Flwainriounilvinoilwanmun
Elimination by nasolacrimal drainage
Drug binding to tear proteins oupr9 risparmiomid
prlunoonlurioum

Drug metabolism by tear and tissue proteins

Diffusion across the cornea and conjunctiva
me
withdraws
Pharmacokinetics: topical (2)
Distribution: undergo systemic distribution by
Nasal mucosal absorption (primary)
Transcorneal-transconjunctival absorptionKudos
Metabolism:
Local enzymatic biotransformation e.g., esterase,
lysosomal enzyme, glucuronide, MAO and COMT
Liver (after systemic absorption)
ADRs and Toxicity
All ophthalmic medications are potentially absorbed
into the systemic circulation
undesirable systemic side effects
Potential local toxic effects are due to
or
Hypersensitivity reactions
(common with neomycin, thimerosal or chlorhexidine)
Direct toxic effects on the cornea, conjunctiva,
o periocular skin, and nasal mucosa from drugs and
preservatives
Iatrogenic infection jairo
nooooo
Eye Drop Application
Moshilinodlumwiron

A smaller instilled eye drop may result in

blinking nuking
nonrandom nodular
I
retention time angarwoir
greater absorption
A large portion of an instilled drop nasolacrimal
drainage systemic absorption ADR
n042000mi ochwarm g
toonion now
Only 1 drop (30-50 l) is enough
noon2ms mission'ssmin
5 minutes interval between each eye drop
Keep eyes closed for 2-5 minutes
Chemotherapy of Microbial
Diseases in the Eye
Antibacterial agents** Joe

Antiviral agents
Antifungal agents
Antiprotozoal agents
 Antibacterial agents (1)
Hordeolum or sty ( )
An infection of the meibomian, Zeis, or Moll glands at
the eyelid margins
o
Characterized by localized red, swollen, acutely tender
area on the upper or lower lid
Typical offending bacterium is S. aureus
Treatment:
Topical ABO (gel, drops, or ointment)
t
slide2 liardaniv
 n'wimlvowiniouvuwonda

(Zeis gland)

Moll gland (sweat gland)

molto n'nipa
Antibacterial agents (2)
Blepharitis no s mo inulou

A common bilateral inflammatory process of the eyelids

characterized by irritation and burning
Typical offending bacterium is Staphylococcus species
Treatment: aulvairiomi Mariamman
Local hygiene is the mainstay of therapy
obiodun
Topical antibiotics: ointment form
Bacitracin zinc, Erythromycin,
Gentamicin sulfate, Polymyxin B,
Tobramycin
Antibacterial agents (3)
Bacterial conjunctivitis Otus
UW

Symptoms: bilateral irritation and injection, purulent exudate

with sticky lids on waking, and occasionally lids edema
Pathogens: Streptococcus pneumoniae, Hemophilus
species, S. aureus, Moraxella lacunata, Neisseria species,
and chlamydial species
Treatment: treated empirically with a broad-spectrum
topical antibiotic
Bacitracin zinc, Chloramphenicol, Ciprofloxacin,
Erythromycin, Gatifloxacin, Levofloxacin, Moxifloxacin,
Ofloxacin, Polymyxin B, Tobramycin, etc.
Antibacterial agents (4)
Bacterial keratitis ns.onmioniru Jaguars la Hoodoo.m

Corneal inflammation caused by bacteria

Symptoms: rapid onset of pain, photophobia, and vision
Mitu
Precipitating factors: contact lens wear, corneal trauma
Pathogens: P. aeruginosa, Pneumococcus, Moraxella
species, and staphylococci
Treatment: Mild, small, more peripheral infections are
treated with broad-spectrum topical antibiotic
Chloramphenicol, Ciprofloxacin, Levofloxacin, Ofloxacin,
Polymyxin B, Tobramycin, etc.
virus fungus protozoa
gulls

Antiviral agents
Viral keratitis
An infection of the cornea caused by viruses
Pathogens: HSV type I and varicella zoster viruses
Treatment:
Topical antiviral agents: epithelial disease due to herpes
simplex infection
Very narrow margin between the therapeutic topical
antiviral activity and the toxic effect on the cornea
Drugs: Trifluridine and Vidarabine
 Antifungal agents
Drugs Route Indications for use
Polyenes
Amphotericin B Topical solution Yeast and fungal keratitis and
endophthalmitis
coolupts herpes simplex
Subconjunctival linoYeast and fungal endophthalmitis
Intravitreal inj. Yeast and fungal endophthalmitis
Intravenous Yeast and fungal endophthalmitis
Natamycin Topical suspension Yeast and fungal blepharitis,
conjucntivitis, keratitis
Imidazoles
Miconazole Topical solution Yeast and fungal keratitis
Subconjunctival Yeast and fungal endophthalmitis
Intravitreal inj Yeast and fungal endophthalmitis
 rink
est
Antifungal agents
pinion Danolupt
immunocomporin

Drugs Route Indications for use

Polyenes
Amphotericin B Topical solution Yeast and fungal keratitis and
endophthalmitis
Subconjunctival Yeast and fungal endophthalmitis
Intravitreal inj. Yeast and fungal endophthalmitis
Intravenous Yeast and fungal endophthalmitis
Natamycin Topical suspension Yeast and fungal blepharitis,
conjucntivitis, keratitis
Imidazoles
Miconazole Topical solution Yeast and fungal keratitis
Subconjunctival Yeast and fungal endophthalmitis
Intravitreal inj Yeast and fungal endophthalmitis
Antiprotozoal agents
Usually manifest as a form of uveitis (less common: 9
conjunctivitis, keratitis, and retinitis) MUM
Most common: Acanthamoeba and Toxoplasma gondii
Treatment : onv'own Moon Gran
movouvilwob
Acanthamoeba
INContactlensToxoplasmosis
Combination topical antibiotics, Several regimens have been
such as recommended with concurrent use
- Polymyxin B sulfate of systemic steroids:
- Bacitracin zinc (1) pyrimethamine + sulfadiazine +
folinic acid
- Neomycin sulfate
(2) pyrimethamine + sulfadiazine,
- and sometimes an imidazole clindamycin + folinic acid
(clotrimazole, miconazole, or
ketoconazole) (3) sulfadiazine and clindamycin
Use of Immunomodulatory Drugs in
the Eye (1)
Glucocorticoids
Drugs: Dexamethasone, Prednisolone, Difluprednate, etc.
Also formulated in combination with antibacterial agents
Clinical use: ocular inflammatory diseases
significant ocular allergy
Ininuwominant
anterior uveitis
postoperative inflammation following corneal and intraocular
surgery Wimanionm

D
ADRs
posterior subcapsular cataracts
woiliminnappin

secondary infections inn

infants
secondary open-angle glaucoma Noriou's
Use of Immunomodulatory Drugs in
the Eye (2)
NSAIDs
wirinmanonionlonglap radioononrub
5 topical NSAIDs approved for ocular use:
Bromfenac: postoperative inflammation and pain
Diclofenac: postoperative inflammation and pain, cystoid
macular edema
Nepafenac: postoperative inflammation and pain following
cataract surgery
Flurbiprofen: unwanted intraoperative miosis during
cataract surgery
Ketorolac: seasonal allergic conjunctivitis, cystoid macular
edema
Mormon hiatusninny
ADRs: sterile corneal melts and perforations
 Use of Immunomodulatory Drugs in
the Eye (3)
Antihistamines
as
Drugs: Emedastine, Levocabastine (newer antihistamines)
: Pheniramine/Antazoline + Naphazoline (vasoconstrictor)
Clinical uses: allergic conjunctivitis

linorio
Mast-cell stabilizers Tig more
Allergen Drugs: Cromolyn sodium, Nedocromil

twin al Should be used prior to allergen exposure

O
season
Clinical uses: conjunctivitis that is thought
w to be allergen-mediated, such as
vernal conjunctivitis onn I
V
l 8onin
 ANS and Eye
Unionwar
Tcu

Tissue Receptor Response

Iris radial m. 1 Mydriasis shrimuno
Iris sphincter m. M3 Miosis Shuman
Ciliary epithelium Aqueous production
Accommodation
Ciliary m. M3
Aqueous drainage
 do solar

http://www.vision-and-eye-health.com/eye-exercises.html
https://mammothmemory.net/biology/organs-and-systems/the-eye/ciliary-muscles.html
Use of Autonomic Agents in the
Eyes (1) B wowluann f

Drugs Receptors Clinical uses

adrenergic agonists
Apraclonidine tproduction Glaucoma
Brimonidine Glaucoma
unuidium
Phenylephrine 1,
Mydriasis
& adrenergic antagonists
Dapiprazole I 1,
o -selective
Reverse mydriasis
Betaxolol 1
Glaucoma
Carteolol 1, 2
Glaucoma
Timolol 1, 2
Glaucoma
 Use of Autonomic Agents in the
Eyes (2)
Drugs Receptors Clinical uses
Chlinergic agonists Muscarinic Miosis in surgery
(Acetylcholine, Carbachol, Glaucoma
Pilocarpine) L Ciliary Adrainage
Anticholinesterase Muscarinic Glaucoma minus
(Physostigmine) AChd Accommodative esotropia
Muscarinic antagonist Muscarinic Mydriasis saturnine
(Atropine, Scopolamine, Cycloplegia* ArrowCiliarymus
wa
Homatropine, Tropicamide) Cycloplegic retinoscopy tray
d
*Paralysis of ciliary muscle loss of accommodation suit
Guacoma
Other Ocular Hypotensive Drugs
Prostaglandin F2 analogues
Altered ciliary muscle tension + trabecular meshwork cells
MMP digest extracellular matrix drainage
Once-daily dosing, good safety profile and potent IOP lowering
effect first line therapy for glaucoma
Drugs: Latanoprost, Travoprost, Bimatoprost, Tafluprost
ADRs: blurred vision, burning/itching/redness of the eye, lash growth
Tamas
Carbonic anhydrase inhibitor lavamins
Inhibit carbonic anhydrase isoenzyme II (ciliary epithelium)
aqueous humor production
Drugs: dorzolamide, brinzolamide
ADRs: burning and stinging of the eye, a metallic taste
 Glaucoma
Pathophysiology: a progressive optic nerve cupping
and visual field loss
Intraocular pressure reduction is a helpful treatment
Pharmacotherapy are targeted to
outflow through the trabecular meshwork and
uveoscleral pathways
Prostaglandin analogues** safe driven
Prostaglandin analogues
Cholinergic agonistdirect
(direct
andand
AntiAntiChE)
go Cholinergicagonist che
production of aqueous humor at the ciliary body
-blockers
Bblocker
Carbonic
carbonic anhydrase inhibtiors
anhydrase inhibitor
 Hominis
Wetting Agents and Tear Substitutes

Used for dry eyes management

Tear substitutes: hypotonic or isotonic solutions
Is
composed of electrolytes, surfactants, preservatives and
some viscosity-increasing agent
available as preservative-containing or preservative-free
viscosity range from watery to gel-like an
Lubricants
n
composed of white petrolatum, mineral oil, liquid or
alcohol lanolin, and sometimes a preservative
high viscous formulation blurred vision bedtime use
use only in critically ill patients, or in severe dry eye
Topical Antibacterial Agents Commercially Available for Ophthalmic Use
Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13e, 2018

Agent Formulation Toxicity Indication for use

Azithromycin Solution H Conjunctivitis
Bacitracin Ointment H Conjunctivitis, blepharitis,
keratitis, corneal ulcers,
Mos
meibomianitis, nowwinor
dacryocystitis
Chloramphenicol Ointment, solution H, BD Conjunctivitis, keratitis
Ciprofloxacin Ointment, solution H, D-RCD Conjunctivitis, keratitis, corneal
ulcers, blepharitis,
meibomianitis, dacryocystitis
Erythromycin Ointment H Superficial ocular infections
involving the conjunctiva or
cornea; prophylaxis of
ophthalmia neonatorum
Gatifloxacin Solution H Conjunctivitis

BD, blood dyscrasia; D-RCD, drug-related corneal deposits; H, hypersensitivity.

Agent Formulation Toxicity Indication for use
Gentamicin Ointment, solution H Conjunctivitis, blepharitis,
keratitis, corneal ulcers,
meibomianitis, dacryocystitis
Levofloxacin Solution H Conjunctivitis
Moxifloxacin Solution H Conjunctivitis
Ofloxacin Solution H Conjunctivitis, corneal ulcers
Sulfacetamide Ointment, solution H, BD Conjunctivitis, other superficial
ocular infections

Polymyxin B Ointment, solution Conjunctivitis, blepharitis,

keratitis
Tobramycin Ointment, solution H External infections of the eye
and its adnexa

BD, blood dyscrasia; D-RCD, drug-related corneal deposits; H, hypersensitivity.