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Ocular pharmacology
1. Ocular Pharmacology
Guided By
Dr. V.M Motghare,
Prof. and Head
Department of pharmacology
G.M.C. Nagpur
& Dr . S.A. Pimpalkhute
Dr. Kundan Nivangune
JR3
2. Overview
Overview of ocular anatomy & Physiology
Pharmacokinetics & Toxicology 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
New drug delivery systems in Ophthalmology
Conclusion
7. Pharmacokinetics of Ocular Drugs
Classical pharmacokinetic theory based on
systemically administered drugs does not fully
apply to all opthalmic drugs
Topical route – most commonly used
8. Absorption
Rate & extent of absorption of topically instilled
drugs depends upon –
1. Time the drug remains in the cul-de-sac &
precorneal tear film
“Drug penetration into the eye is
approximately 2. Elimination by linearly nasolacrimal related drainage
to its
concentration in the tear film.”
3. Drug binding to tear proteins
4. Drug metabolism by tear & tissue proteins
“”Drug penetration into the eye is approximately linearly related to
its concentration in the tear film.”
5. Diffusion across cornea & conjunctiva
9. Distribution
Transcorneal absorption
Accumulation in aqueous humor
Distribution to intraocular structures
Trabecular meshwork pathway
Distribution to systemic circulation
10. Distribution
Melanin binding of certain drugs –
- Ex:
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
11. Metabolism
Enzymatic biotransformation of ocular drugs-significant
Esterases – particular interest
Ex: Development of prodrugs for enhanced
ocular permeability
1. Dipivefrin hydrochloride
2. Latanoprost
12.
13. Ocular Routes of Drug Administration
Sr.N
o
Route Special Utility Limitations &
Precautions
1. Topical --Convenient
-- Economical
--Relatively safe
--Compliance
--Corneal & conjunctival
toxicity
--Nasal mucosal toxicity
--Systemic side effects from
nasolacrimal absorption
2. Subconjunctival,
sub-Tenon’s &
Retrobulbar
injections
-Anterior segment
infections
-Posterior uveitis
-Cystoid Macular
Edema (CME)
-Local Toxicity
-Globe perforation
-Optic nerve trauma
-Central retinal artery or
vein occlusion
3. Intraocular
Injections
Anterior segment
surgery or infections
-Corneal toxicity
-Relatively short duration of
action
4. Intravitreal
Immediate local effect Retinal toxicity
15. 1. Autonomic Drugs for Ophthalmic Use
2. Antimicrobial agents
3. Immunomodulatory & Antimitotic Drugs
4. Agents used to Assist in Ocular Diagnosis
5. Agents Used to treat Retinal
Neovascularization & Macular Degeneration
6. Drugs & Biological Agents Used in
Ophthalmic Surgery
16. Glaucoma
Definition:
Glaucoma is a chronic, progressive optic
neuropathy characterized by slow progressive
degeneration of the retinal ganglion cells and
the optic nerve axons leading to increased
deterioration of visual field.
• Parson’s.
17. History of Glaucoma
Hippocrates described "glaykoseis" as blindness
which occurs in the elderly.
The English ophthalmologist Banister - First to
establish the connection between increased
tension of the eyeball and glaucoma.
In 1862, Donders - High intraocular pressure
caused blindness and called the disease
"Glaukoma simplex.“
Drug treatment started in 1875 with the discovery
of pilocarpine.
18. Glaucoma…
IOP – Not an accurate indicator of disease
Ocular Hypertension - IOPs in mid to high 20s
with no optic nerve damage
Normal or low- tension Glaucoma – Progressive
glaucomatous optic nerve damage despite having
IOPs in normal range
19.
20. Types Of Glaucoma
Primary Glaucoma:
Primary open angle
glaucoma
Angle closure glaucoma
Secondary
Glaucomas
Congenital or
developmental
26. Mechanism of Action of β Blockers
Lower IOT by reducing aqueous formation
-- Down regulation of adenylylcyclase due to β2
receptor blockade in ciliary epithelium
-- Reduction in ocular blood flow
27. BETAXOLOL
Less efficacious than
Timolol
TIMOLOL
20-35% fall in IOT
within 1 hour & lasts for
12 hours
30% patients -
Additional medication
BETAXOLOL
Less efficacious than
Timolol
Protective effect on
retinal neurons by
blocking some calcium
channels & reducing
reducing Na2+/Ca2+
influx
28. Adverse Effects of Ocular β
Adrenergic blockers
Ocular
1. Stinging, redness &
dryness of eye
2. Corneal hypoesthesia
3. Allergic
blepharoconjunctivitis
4. Blurred vision
Systemic
1. Bronchospasm in
asthmatics & COPD
patients
2. Bradycardia &
accentuation of Heart
block
Minimization of systemic
adverse effects
29. Carbonic anhydrase Inhibitors
(CAI)
Topical CAI – Dorzolamide , Brinzolamide
MOA – Inhibit carbonic anhydrase (isoenzyme
II) on ciliary body epithelium → Reduces
formation of bicarbonate ions →
Reduces fluid transport → Reduces aqueous
formation → Decrease IOP
Use – Only as add on drug to topical β
blockers or PG analogs
Systemic CAI – Final medication option before
resorting to laser or incisional surgical treatment
30. Adrenergic Agonists
Dipivefrine
Prodrug of Adrenaline
Reduces aqueous
production
Augments uveoscleral
outflow
Ocular burning
Infrequently used for
add on therapy
Apraclonidine
Selective α2 agonist
Highly ionized at
physiological pH
Do not cross BBB
Reduces aqueous
production
Enhance uveoscleral
outflow
31. Topical Miotics
Historically important in open angle glaucoma
MOA - Ciliary muscle contraction
-Increase drainage through trabecular
meshwork
Drugs----Pilocarpine
Less useful drugs – Numerous side effects &
three to four times a day dosing
32. Stepped Medical Approach to
Treatment of Open Angle Glaucoma
Start monotherapy with Latanoprost or topical β
blocker
If target i.o.t. not attained, either change over to
alternative drug or use both the above
concurrently
Brimonidine/dorzolamide – Use only when there
are contraindications to PG analogs/ β blockers
or to supplement their action
Oral acetazolamide/Topical miotics – Last resort
43. Topical Antibacterial Agents
Commercially Available for Ophthalmic
Use
Azithromycin 1% solution H Conjunctivitis
Ciprofloxacin
0.3% solution;
H
hydrochloride
0.3% ointment
D-RCD
-Conjunctivitis
-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
44. Topical Antibacterial Agents Commercially
Available for Ophthalmic Use…..
Gentamicin
sulfate
0.3%
solution
H Conjunctivitis, Keratitis
Levofloxacin 0.5% H Conjunctivitis
Levofloxacin 1.5% H Corneal Ulcers
Moxifloxacin 0.5%
solution
H Conjunctivitis
Ofloxacin 0.3%
solution
H Conjunctivitis
Corneal Ulcers
Tobramycin
sulfate
0.3%
solution
0.3%
ointment
H External infections of the eye
49. Therapeutic Uses of Topical
Glucocorticoids
1. Significant ocular allergy
2. Anterior uveitis
3. Postoperative inflammation following
refractive, corneal & intraocular surgery
4. To reduce potential scarring of surgical site
(After Glaucoma filtering surgery )
55. Therapeutic Uses
1. In Glaucoma surgery, to improve success of
filtration surgery by limiting postoperative wound-healing
process.
2. In corneal surgery, topical mitomycin – To reduce
risk of scarring after excision of pterygium
3. Conjunctival papilloma & conjunctival tumours –
Interferon alpha- 2b
4. Uveitis & uveitic cystoid macular edema –
Intraocular Methotrexate
56. Immunomodulatory Agent
Topical Cyclosporine
– Approved for the treatment of chronic dry eye
associated with inflammation
-Decreases inflammatory markers in lacrimal gland &
increases tear production
57. Agents used to Assist in Ocular
Diagnosis
Fluorescein dye - Epithelial defects of cornea
& conjunctiva and aqueous
humor leakage
- IOP measurement
Mydriatrics - Dilated fundoscopic
Examination
58. Agents Used to treat Retinal
Neovascularization & Macular Degeneration
1. Verteporfin
2. Pegaptanib
3. Bevacizumab
4. Ranibizumab
78. LACRISERT
- Hydroxypropyl cellulose ophthalmic insert
(LACRISERT)
Patients with dry eyes (keratitis sicca)
A substitute for artificial tears
Placed in the conjunctival sac and softens within 1
h and completely dissolves within 14 to 18 h
Stabilizes and thickens the precorneal tear film and
prolongs the tear film break-up time
80. Ocusert
Pilocarpine, a parasympathomimetic agent for
glaucoma
Acts on target organs in the iris, ciliary body and
trabecular meshwork
Carrier for pilocarpine : alginic acid in core of
Ocusert
White annular border : titanium dioxide (pigment)
(easy for patient to visualize)
81.
82. Contd… Advantages
1) Drug application convenient (Once a week)
2) Stabilization of Diurnal variation in IOT.
3) Guard against dangerously high IOT due to
irregularly instilled drops.
Disadvantages
1) Foreign body sensation
2) Difficulty in retention of device
3) Increased cost
4) Detailed instruction.