Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Ophthalmology PPT 35 Ocular Pharmacology I Lecture Notes
Ocular Pharmacology-I
Learning Objectives
At the end of this class students shall have a
basic understanding of :
?pharmacokinetics and pharmacodynamics of
ocular drugs
?Ocular routes of drug administration
?Topical antibiotic and cycloplegic agents
2
Overview
Overview of ocular anatomy & physiology
Pharmacodynamics and Pharmacokinetics of ocular therapeutic agents
Ocular Routes of Drug Administration
Therapeutic & Diagnostic applications of Drugs in Ophthalmology
Ophthalmic Effects of Selected Vitamin Deficiencies & Zinc Deficiency
Systemic Agents with Ocular Side Effects
Conclusion
3
Anatomy of Eye
4
Tear Film
5
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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
? 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
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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
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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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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
Injection
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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
pul 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 instil ation
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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
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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
Papil itis
Posterior uveitis
Anesthesia
Peribulbar-- anesthesia
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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
23
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 ocular drugs
?Antibacterials (antibiotics)
?Antivirals
?Antifungals
?Mydriatics and cycloplegics
?Antiglaucoma medications
?Anti-inflammatory agents
Corticosteroids
?Ocular Lubricants
NSAID's
?Local anesthetics
?Ocular diagnostic drugs
?Ocular Toxicology
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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%
ointment
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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
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? Specific antibiotic for almost each organisms
? Sulfonamides- Chlamydial infections like TRACHOMA
INCLUSION CONJUNCTIVITIS
TOXOPLAMOSIS
Bacterial cell wall synthesis inhibitors-
Penicil in
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
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
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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
37
Hordeolum/ Stye ? Infection of the meibomian, Zeis
or Moll gland
38
Conjunctivitis ? Inflammatory process of
the conjunctiva
39
Blepharitis ? Bilateral inflammatory process of the
eyelids
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Antiviral Agents for Ophthalmic Use
GENERIC NAME
ROUTE OF
OCULAR
INDICATIONS FOR USE
ADMINISTRATION
TOXICITY
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...
GENERIC NAME
ROUTE OF
OCULAR
INDICATIONS FOR
ADMINISTRATION
TOXICITY
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
Idoxuridine
INDICATIONS
Vidarabine
HZ keratitis
Cytarabine
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
Drug
Method of Administration
Indications for 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
Yeast & fungal keratitis
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ANTIFUNGAL
INDICATIONS
Fungal corneal ulcer
Fungal retinitis/ Endophthalmitis
Commonly used drugs are
? Polyenes
? damage cel membrane of susceptible fungi
? e.g. amphotericin B, natamycin, nystatin
? side ef ect: nephrotoxicity
? Imidazoles
? increase fungal cel membrane permeability
? e.g. miconazole, ketoconazole,fluconazole
? Flucytocine
? act by inhibiting DNA synthesis
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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
cycloplegic refraction
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SR. DRUG
FORMULATIO INDICATIONS FOR USE OCULAR SIDE
NO.
N
EFFECTS
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
Cyclopentolat 0.5% 1%
Cycloplegia
Photosensitivity
e
solution
-Mydriasis
-Blurred vision
5
Tropicamide
0.5% & 1%
Cycloplegia
Photosensitivity
solution
-Mydriasis
-Blurred vision
50
Thank you
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This post was last modified on 07 April 2022