OPTHALMOPHARMACOLOGY

M.Djamaludin dr,SpFK,M.Kes
Lab.Farmakologi
FK-UNJANI

Introduction
Some of the the many diseases of the eye

are listed below.

Despite claims to the contrary, there is no
clear clinical evidence that drug treatment,
or viitamin supplementation, prevent or
cure cataracts, or genetic retinal dystrophy

although possible useful responses are

seen in age-related macular degeneration

where diet supplementation with vitamins
C and E as well as carotene has been
claimed to reduce the risk of progression of
the disease although the evidence is
limited

Drug therapy of glaucoma, inflamation of

the eye age-related macular degenaration,

ocular disorders, tear deficiency and
inflamation of the eye are varyingly
effective and all are discused.

Disease

N
O-A Glaucoma
C-A Glaucoma
Inflamation + Allergic
Squint & oculom.disorder
Tear deficiency
-

D
N
Detached retina
Cataracts
Retinal pigmentation

Amblopia

Retinopathy

A.ANESTHESIA
TOPICAL ANESTHETICS
The efficacy of TA usually detemined

by ability to suppress corneal

sensitivy
Conentration of each drug is obtained
beyond which no further increas in
activity occurs

Maximum effective
concentration
The concentration at which this

maximum efficacy occurs

Increasing the concentratio of the
anesthetic beyond the MEC serves no
useful purpose but increases the risk
of local and systemic toxicity

MEC of Procaine,Tetracaine,and

Coacaine are 0.5%,1% and 2.0%

In clinical practice however the OEC
(Optimum Effective Concentration)
may be less than MEC

For instance,0.5% tetracaine is less

irritating to the eye than the MEC 1%

and thus is better suited for clinical
use
Contribution of two or more local
anesthetics dose not produce and
additive effect,but it dose increase
the risk of side effects so is
contraindicated

TOXICITY
It is uncommon for topically applied

anesthetics,benoxinate and tetracaine,to

cause mild local stingging or burning after
installation
In some patients,especially who over 50
years old a diffuse desquamation of corneal
epithelium may be occurs : Punctate
keratitis

Typical manifestation of
systemic intoxication
CNS

Excitement,restlesness,headache,delirium,c
onvul sion
CVS::Rapid and irregular pulse
(tachyarritmia)
Ocular :Dilated pupils
GIT::Nausea,vomitus,and abdominal pain
Note: Acute systemic (10 drps of a 4%
solution)

Hypersensitivity
Ocular

Allergi episode occur mainly with use of

the ester group of anesthetics,that is the
commonly for topical
Lidocaine,mepivacaine,and bupivacaine is
less frequently than the ester other group
Systemic anaphylactic reaction topical
anesthetics are extremely rare

Psycomotor Reaction
Psycomotor reaction such as vasovagal

syncope may usually occur from anxiety

related to the office visit
Respiration and cardivascular status should

be monitored to eliminate drug induced

anaphylacxis as a possible cause of he
collapse

Prevention of Adverse Systemic

ReactionsAdverse
Adverse reactions to locl anesthetic drugs

usually occur depend on dose

Limit the dosage of drugs to those

comparable with effective anesthesia
without substantial risk of systemic toxicity

Indications
1.Operative
2.Remove corpus alienum

Route of Administration
1.Injected
2.Topical

Contraindications
Hypersensitivity
Liver disease
Concommitans medications
Dry Eye
Perporatory ocular Injury
Self Administration of Topical Anesrherics

Tasting

Mechanism of Pain and

Analgesia
Primary eye care practitioners often

encounter patients who experiencing

substantial pain from an underlying ocular
disease
For example patients with corneal or
conjunctival foreign bodies,abrasions of
traumatic hyperaemias usully complain of
pain as their primary complain

Cocaine
Cocaine exhibits both anesthetic and

adrenergic activity
The usual concentration for ocular topical
1% to 4% but the 10% solution is often
used of diagnosis of Horners syndrome.
One drop of 2% solution produde exellent
corneal anesthesia within 5 to 10 minutes

Cocaine is used as a nasal spray or in

dacrocystorhinostomy
Cocainogenic due to its adrenergic effects

i.e blocks reuptake of norephinephrine

Cocaine contraindicated
to
Systemc hypertension
Retinal detachment surgery
Routine opthalmoscopy
Gonioscopy
Angle-close glaucoma (mydriatic effec)

Tetracine
Ester PABA
Intensity,DOA comparable with

propaeracaine and benoxinate

1% sol. Successfully to provide anesthesia
during phacoemulsification cataract
surgery and intraocular lens implantation

Benoxinate (Flurasafe)
Is most commonly combined with sodium

fluoescein of 0.25%,but recently it was

combined with 0.35% disodium flurexon
Indication:Primary used for implantation
tonometry
Side Effects:
Stingging,burning,increase or decrease
corneal thikness and allergic reaction

Proparacaine
Concentration solution,both with or without

sodium of 0.25% - 0.5% fluoescein

OOA,intensity and DOA of anesthesia
are similar with tetracaine and
beionnoxinate
It produce little or no irritation on
instillation and therefore readly accepted
by more patient
Allergic reaction: Characterized
conjunctival hypeemia and
edema,edematous eyelids,and
lacrimation.Corneal thickness instally can

B.OCULAR HYPOTENSION
DRUGS
Overview.
Glaucoma can often lead to visual

impairment and even blindess

Management of these disorders is almost
always directed at the existing intraocular
pressue (IOP) lowering
This can accomplished either
pharmacologicaly or surgically be
decreasing aqeous production or by
increasing aqeous outflow

1.Prostaglandine
Analogues
Latanaprost
Travoprost
Bimatroprost
Prostaglandin Combination

Compounds
Prostaglandin and -blocker

2.Beta-Adrenergik
Antagonist
Timolol
Levobunolol
Betaxolol
Metipranolol
Carteolol

3.Adrenergic Agonist.
Adrenalin
Noradrenalin

Cholinergic agonist
Carbacchol

Prostaglandin Analogues
Latanaprost (Xalatan)
Prostaglandin were originally discovered in

the eye as mediators of the ocular

inflamatory response and most of the
preliminary research focused on their
potential role in uveitis and other
inflamatory disease
Latanaprost demonstrates sufficient
hypotensive activity with minimal side
effect

Latanaprost is analogue of prodrug

prostaglandin PGE2-isoprophyl ester.When

installed topically into human eye it will be
converted by corneal esterase into
lanataprost acid,which exerts its biological
activity at the the FP receptor on the cilliary
muscle (FP is receptor for PGF2).

Corneal esterase

PGE2-isoprophyl ester

Lanataprost

Latanaprost appears to exert its ocular

hypotensive effect exclusively by
increasing uveoscleral flow.
In long term clinical trial,latanaprost has
been shown to be at least as effective as
timolol in reducing IOP
Latanaprost should be dosed only once
daily in the evening or bed time

The additive ocular hypotensive effect

Lanataprost and timolol are greater than

when brimonidine,dorsolamide,or
pilocarpine is used with timolol.
The effect achived with miotis and
pilocarpine seems to be most effective the
bed time dosed is administered an hour
after latanaprost
Latanaprost available in concentration
0.005% preserved with 0.02 benzalkonium
chloride (BAC)

Side Effects
Iris color darking
Increased eyelid pigmentation
Hypertrichosis
Conjunctival hyperemia
Allergy
CME (Crystaloid macular edema)
Anterior uveitis
Punctate corneal erosion
Corneal pseudodendrites

Contraindications
Relative contraindicated to patient wih a

history of uveitis or prior incisional ocular

surgery
Previous episodes of herpes simplex virus
keratitis
Should be used cautously after cataract
surgery in patients who have risk favouring
the development of CME (crystaloid
macular edema).

Travoprost (Travatan).
Travoprost is a PGF2 analog used for

treatment of patients with open-angle

glaucoma or ocular hypertension.Its
mechanism of action is similar with
latanaprost.
The drugs is formulated as aquous solution
in a concentration of 0.004% prserved with
0.015 benzakonium chloride (BAC)

Bimaprost (Lumigan)
Bimatoprost is generally considered to be

part of the prostaglandin family of ocular

hypotensive analogues.
Bimatoprost is formulated as a 0.03%
solution incitratephophate buffer preserved
with BAC (0.005%)

Bimatroprost dosed once dayly provider

lower mean IOP than doses timolol used

twice daily
Side Effect.
Similar to latanaprost and
travoprost,bimatoprsot reported to cause
changes to pigmented tissues
Contraindications:
Similar with lanataprost

Prostaglandin Combination
Compound
Prostaglandin and -blocker
These product include a combin ation of

latanaprost or travanost with timolol.

Studies have demonstrated comparable
eeficacy and in the case of travoprostimolol
combination ,a favourable IOP reduction
product and the separate compounds
administered concommitantly

2.-Adrenergi Antagonist
Timolol
MOA: Block 1 receptor on cilliary

body
Given topically induced a significant and
long lasting ocular hypotension.Mean
decreases in IOP approximataly 25%.
The ocular effect hypotensive of timolol is
greater than of pilocarpine.
Drug tolerance of timolol has been
described

Clinical Uses.

1.Primary open-angle glaucoma

2.Ocular hypotension
3.Secondary glaucoma
4.Prophylactic in IOP after laser
iridotomy,posterior capsulotomy,and
cataract surgery.
Timolol is supplied as 0.25 and 0.5%
solution
Given once or twice installation

Side Effects:
CVS:

Bradycardia,arrythmias,hypotension,Reyna
uds phenomenon,fluid retentiom.
Pulmonary:
Bronchocontriction,asthma,dyspnea
CNS:
Depression,confusion,headache,insomnia
and myasthenia gravis

GIT: Nausea,diarrhea
Dermatologic: Alopecia and nail

hyperpigmentation
Metrabolic effect : Hypoglymia
Ocular:
Allergic
Blepharitis
Dry eye
Corneal anesthetic
Macular edema

Uveitis
Cataract progression
Contraindications:
Bronchial asthma
Bradycardia
Severe heart blok
Overt cardiac failure
Hypersensitivity

Levobunolol

Similar with timolol is a non-selective blocker

Clinical Uses:
IOP in ocular hypotension
Open-angle glaucoma
Prophylactic after cataract surgery
Anterior segment laser procedure
Contraindications: Bronchial
asthma,COPD

Betaxolol:
Less potent than timolol.
Clinical Uses:
Chronic ocular hypertension
Open-angle glaucoma
Side Effects:
Ocular discomportwith 0.25% :
Contraimdications:
Bradycardia,severe heart block,Overt
cardiac
failure,hypersensitivity

Metipranolol
Used worlwide both orally in the treatment

of systemic hypertension and topically for

the treatment of elevated IOP.
Clinical Uses:

Chronis treatment of IOP and open-angle

glaucoma

Carteolol
Carteolol is as a noncardioselective -

blocker similar to timolol,levobutolol,and

metipranolol
In general carteolo, 1$ an ocular
hypotensive effect similar so that of timolol
maleat of 5% solution
Clijical Uses:
Carteolol is used for chronic treatment of

elevated IOP in patients with ocular

hypertension and open-angle glaucoma.

3.Adrenergic Agonist
Apraclonidine

A relative selective 2-adrenoceptor

agonist,derived as a derivate of clonidine
Clinical Uses:
Prevention of post surgery
Initial treatment of acute-angle
glaucomas

Prevention of postcycloplegic apikes in IOP

Side Effects:

After topically installation can occurs

:Blanching,eyelids retaction and mydriasis
Contraindications:
Patient sensitive to clonidine and taking
MAOI

Brimonidine
A relative potent and highly selective 2adrenoceptor agonist
Like apraclonidine is additive to other
glaucoma medications
Side Effects:
Hyperemia,burning,stingging,blurred
vision,and foreign body senstion

Contraindications:

Patients receiving MAOI

It is not contraindicated in cardiopulmunaly
disease but must used with caution I
patients with severe cardiovascular disease
Side Effects:
Sleepness
Lerthargy
Fatigue
Youn children , 20 kg

4.Carbonic Anhydrase Inhibitors

M O A:
Block CA and reduce bicarbonate

formation
Bicarbonate formation is an essential
compounent of aqeous production.
A relatively high concentration of
bicarbonate can found in the aqeous
humor

The presence of CA in cilliary processes can

be also be demosntrated in both human

and animal
The earliest reported ocular hypotensive
properties of acetazolamide,a CAI
demonstrated a decrease in IOP induced
from inhibition of AH production.
Clinical Uses:

All type of glaucomas

Oral acetazolamide is often preserved for

short term IOP reduction only

Additional decrease in IOP when added to
miotics, -blocker and prostaglandin is
occurs.
Acute angle-glaucoma is often
administered soon after the diagnosis is
made

Systemic Effects
Numbless
Tingling of the fingers,toes and perioral

region are most common events

Malaise
Fatigue
Weight loss
Depression
Anorexia
Libido decreasing
Diarhea

Ocular Effects
Drug induced transient myopia
Myopia probably results cilliary body

edema that produces a forward

displacement of the lens-iris diaphragma
The myaopia subside on reduction or
discontinuation of acetazolamide therapy

Contraindications
1.Liver diseases
2.Severe COPD
3.Certain secondary edema
4.Renal disease including renal stone
5.Pregnancy
6.History hypersensitivity to sulphonamide

Pharmacokinetic of CAI
DRUG
DOA
Acetz tab
6h
Acetz cap
18 h
Acetz inj
h
Mtzl
14 h
Dichp
12 h

DOSE

OOA

65-250 mg/qid

0.5-1 h

500 mg bid

0.5-1 h

500 ng

40-

1 min

25-100 mgb/tid

1h

10-

25-50 mgb/t/qid

50 min

6-

Methazolamide
Structurally similar with acetazolamide
Decrease ionization and thereby improve

intraocular penetration
Well absorbed after oral adiministtration

Clinical Uses
Methamizole like other CAIs may be addded

to treat patients with primary open-angle

glaucoma and secondary glaucoma when
topical ocular hypotensive agents alone
provide inadequate pressure control
It is the first CAI usedfor systemic
glaucoma therapy

Side Effects
Compared with acetamizole it produces

less acidosisi and less effect on urinary

level and less causes paresthesia but often
cause more drowsiness.
Skin eruption can also occur

Contraindications
Are the same as those associated with the

use of acetazolamide
Merhamizole is more safty in patient with
history of kidney stones or renal
impairment

TOPICAL CAI
Dorzolamide (Trusopt)
The first commercially available CAI show

significant ocular hypotensive activity in

human
Indications: IOP ,OAG
SE: Local irritation
(Stingging,burning,blurring)
Contraindications: Allergic,renal
impairment (CrCl,30 ml/min).

Brinzolamide (Azopt)
Indications: IOP and OAG
SE : Taste abnormalities
Contraindications : Similar with

d0rzolamide
Timolol 0.5% +Dorzolamide 2%
Cosopt
Twice daily
The mean reduction in IOP 22.2% - 27.4%

Clinical adventage of CAI

CAIs reduced nocturnal aqeous flow by

25%

Carbachol
Increase drainage of aqeous hu,or

MIOTIC
Cholinergic agonis
Direct acting : Acethylcholine

Metacholine
Pilocarpine
Carbachol
Indirect acting: (Choliesterase inhibitors).
Physostigmine
Neostigmine
Edrophonium
Demecarium

Irreversible :

Echothipate
Diisoprophylflourophosphate

Pilocarpine
Its activity at muscarinic receptor sited on

the iris sphincter cilliary muscle,pilocarpine

causes pupillary constriction and varying
degrees of accomodative spasm depending
on patients age
Clinical Uses:

Primary open-angle glaucoma

Acute angle closure glaucoma
Many secondary glaucoma

Ocular Effects

Accomodative spasm
Systemic Effects:
Weakness
Nausea,vomitus,diarrhea
Salivation
Lacrimatiom
Headache
Browache (Aggressive)

Pulmonary edema
Systemic hypertension
Bradycardia
Generalized muscle eweakness
Increased tone and motility of git
(Abdiominal pain,diarrhea)
Respiratory paralysis

Contraindications
Cataract (Nuclear sclerotic,posterior

subcapsular cataract)
To prevent retinal detachment
Retinal detachment
Patient with myopia
Peripheral retinal dieas
Aphakia or pseudoaphakia

Pilocarpine should be avoided in patients

with asthma or a history of asthma

Carbachol and Echotiphate

Due to their side effects these drugs are

rarely used for treatment of glaucoma

MYDRITIC
Atropine
Adrenaline
Nor-adrenaline

Mydritic indications

TREATMENT OF
ABNORMALITY FILM
Introduction
The tear film on cornea contains 3 layers
The thin

The goal of ocular surface disease (OSD)

therapy are:
1.To relieve symptoms of oSD
2.To prevent serious complications of OSD

The catagories of dry eye

treatment
1.Tear supplementation
2.Tear conservation
3.Tear stimulation

3 option treatment for dry

eye
Tear supplement (artificial tears):Lacrisert

(Lactic acid)
Tear conservation ointment:Punctat
occlusion
Tear stimulation:
Secretogogues,antiinflamatories
or imunomodulators

Tear supplementation
Polymer-based artificial tear most

common tear supplement product used dry

eye treatment:
Ocular lubricant are used to treat:
1.Corneal abration
2.UV keratitis
3.Herpes simplex keratitis
4.Herpes zoster keratitis

The ideal artificial tear

.Produced the metabolic optic and

physical characteristic of nature tear

Have a long residence time
Contain therapeutical additive to treat
primary and secondary damage to eye
Supplement of natural tear with a
substanced that prolongs residence
time,improve tear film break up
(TBUP) and suoerior to tear
replacement fluids of flow retention

Most artificial tear

formulation
Water based
Polymer to enhance:

Viscosioty
Lubricant
Retention time to promote tear film
ability

Other viscosity increasing

agents
Gelatin
Glycerin
Polyethyleneglycol
Poloxamer 407
Polysorbate 80

NaCl
KCl
Boric acid
Help to maintain tonicity and pH
simlar to normal tear
ROHTO TEARS (Rohto Lab)
Tetrahydozoline HCl
Mg-L-aspartate,K-L-aspartate (1:1)

Polysacharides and vinyl

derivates
Not produce constantly

1.The sustitutes should have properties to

enhance retention in the tear film
2.Addition of polymer to artificial tear
improve:
Retention
Increase corneal surface wetability
Decrease blink friction
Minimize surface tension.

Natural tear contain

Glycoprotein & Surfactant macromole

Decrease surface tennsion

Others substitutes
cellulose
Hydroxy ethylene cellulose
Hydroxyprophyl cellulose
Methyl cellulose
Carboxymethyl cellulose
These cellulose have been:

1.Used in artificial formulation

2.Dissolve in water to produce colories solution
of varying visvcocity
3.Having proper optical clarity reflective similar
to
cornea

Vicoelastic agents
Na hyaluronat
Na chondroiti sulfate=Mucopolysach in

extracell
Such as:Vitreous,cornea,and aqeous humor
Used for:Intraocular surgery
Severe dry eye disorders
Concentration : 0.1 0.5%
Subjective and objective
improvement (itching)

Sodium hyaluronate
Hydrophylic
High molecular weight
Polysacharide polyrmer
Subjective and objective symptoms in dry
eye patients

Chondroitin sulfate
Hyaluronic acid 0.1%
Chondroitin sulfate 1%
Mixture: ChS (0.38%) and HA (0.3%)
Effective in patients with:

Itching
Burning
Foregn body sensation

Polyvinyl alcohol
OPTIFRESH (Konimex).
Enhance contact time of ophthalmic

medication
As wetting agent for contact lens
Concentration 1 4%
Has good retention time due to adsorptive
properties
Can be easily sterilized
Indication: Lubricant ,prevent
irritaion on dry eye

Viscocity enhance agents

Others vinyl derivates:

!.PVP: Non ionic surfactant

To increase viscicity
Concentration: 3- 5%
2.HPA- guar (Hydroxyprophyl-guar)
High mollecular weight
A gallable lubricant,to mimic the mucin
layer of tears

Preservatives
Added to ophthalmic sol.
To kill or inhibit growth of microorganism

Nutrients
Necessary for corneal and conjucntival
meabolim
>>>> mucin synthrsis
Vit A deficiency effect a variety of epitheliallined
organ,including eye

Other ingredients
Electrolyt

>> NaCl

Buffers
Normal pH 7.5 depend on
Bicarbonate,protein,phosphate ion and
substance

Mucolytic agents
Soften mucus and make it more fluid
Acetylcystein
Available as mucomyst in a 10% or 20%

solution of the sodium salt acetylcystein

Artificial tear insert

LACRISERT
Watersoluble
Contain hydroxyprophylcellulose

Indications:
Blurred vision

Autologos serum
A source of tears replacement in serve dry

eye
Improved ocular surface staining

Ointment
Indicated for moderate to severe dry eye
Retain longer than other ophthalmic

vechicles
Patient acceptance ointment preparation
highly variable

Lacrimal occlusive device

Used to preserved existing tears
Absorble insert made with hydroxyprophyl

cellulose,collagen and silicone

Topical anesthetics may be used to
minimize eyelids reaction.

Th/.RED EYE
ROHTO (Rohto Lab)
VISINE (Pfizer)
Contain: Tetrahydrozoline

ANTIINFECTIVES AGENTS
ALBUCETINE drops contained:
Sulphacetamide 10%
Chlorapnenicol
Thimerosal

1%
0.02%

ALBUCETINE ZALF contained

Sulphacetamide 10%
Chlorapnenicol

1%

ANALGESIC/ANTIINFLAMATION
VOLTAREN OPHTHA
Contain: Diclofenac Na
Indication:
Prevent myosis during cataract lens

operation,prrevent inflamation after

cataract surgery

ALBUCID & ALBUVIT contained;

Sulphacetamide Na

Blepharitis,
Blepharoconjunctivitis
Chronicconjunctivitis
Dacryocystitis
Trachoma
Corneal abration,laceration,ulcers

BAQUINOR
Cyproploxacin drops (3 mg/ml) @ 5

ml:
Indication:
Corneal ulcers
Conjunctivitis
TARIVID OPTHALMIC SOLUTION
Contained
Ofoxacin
Use for patient with hypersensitivity to

ciprofloxacin

CENDOMYCETINE (Cendo)
Zalf contained:
Chloraphenicol 1%
Polymixin B sulphate 5000 IU/g
Indications:
Tracoma
Blepharitis
Conjunctivitis
Keratitis
Dacryocystitis

CORTICOSTEROIDS
CENDOMYCOS

Hidrocortisone acetate 0.5%

Chloramphenicol 0.2%
Indications: Conjunctivitis non-purulent
Dose: 3dd gtt 1-2

CENDOXITROL drops
Dexamethasone

0.1%
Neomycin sulphate 3.5 mg
Polynixin B sulphate 6000 IU

Indications:
Bacterial Conjunctivitis,keratititis,
Keratoconjunctivitis,
Blepharoconjunctivitis

ANTIVIRAL
ZOVIRAX (Glaxo Smith Kline)
Contained :Ayclovir
Indications: Herpes viral infection.

OTOPHARMACOLOGY
ANTIINFECTIVE & ANTISEPTIC
Antibiotics effective to Gram

negatif

OTOLIN drops
Contained:
Polymixin B sulfate 10.000 IU
Chloramphenicol 5%
Benzocaine 1%
Nipagin 1%

SOFRADEX drops
Contained
Framiceti sulfate 5 mg
Gramicidine
0,05 mg
Dexamethasone 0,5 mg
Indication: External otitis
Contraindication: Perforation of
tymphanic
membrane

OTOPAIN drops
Contained
Polymixin B50.000 IU
Neomycin sulfate 25 mg
Fludrocortisone acetate 5 mg
Lidocaine HCl 40 mg

SEROMUNOLYTIC
WAXSOL
Contained Docusate Na
Desintegration Cerumen prop
Using:Drop into internal ear 2 day/night
before
cleaning

Contraiindication:
Perforation of tymphanic
membrane or internal ear infection
PEROXIDE (H2O2) Solution 1-3%

Drug induced ototoxic

Aminoglycocides
Amikacin
Gentamycin
Kanamycin
D-streptomycindeafness
L-Streptomycinequilibrium

 END
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