Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Ophthalmology PPT 39 Ocular Pharmacology II Lecture Notes
Ocular Pharmacology -II
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Learning Objectives
At the end of this class students shall have a basic
understanding of :
? Therapeutic agents for glaucoma
? Anti-inflammatory agents
? Tear substitutes
? Drugs and biological agents used in Ophthalmic
surgery
? Ocular toxicology
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
Systemic Agents with Ocular Side Effects
Conclusion
Agents used for treatment of
Open angle Glaucoma
1. Prostaglandin analogues
2. Beta receptor antagonists
3. Alpha receptor agonists
4. Carbonic anhydrase inhibitors
Prostaglandin Analogs
First- line medical therapy for Glaucoma
PGF2 analogs -
Good efficacy
Once daily application
Absence of systemic side effects
1.Latanoprost 2. Travoprost 3.Bimatoprost
Facilitate aqueous outflow through uveoscleral outflow
pathway
Prostaglandin Analogs
Side effects
Ocular irritation & pain
Blurring of vision
Increased iris pigmentation
Macular edema
Adrenergic blockers
?Nonselective blockers ? Timolol maleate
- Levobunolol
- Metipranolol
- Carteolol
? -1 antagonist - Betaxolol
Mechanism of Action of Blockers
?Lower IOP by reducing aqueous formation
- Down regulation of adenylylcyclase due to 2
receptor blockade in ciliary epithelium
- Reduction in ocular blood flow
Adverse Ef ects of Ocular Adrenergic
blockers
Ocular
Systemic
1. Stinging, redness &
1. Bronchospasm in
dryness of eye
asthmatics & COPD
2. Corneal hypoesthesia
patients
3. Allergic
2. Bradycardia &
blepharoconjunctivitis
accentuation of Heart
4. Blurred vision
block
Minimization of systemic
adverse ef ects
Alpha Adrenergic agonists
? Brimonidine (Alpha-2 agonist)(0.1%,0.2%)
? Usually used as an add on agent
? Mainly reduces aqueous production
? Also increases uveoscleral outflow
? To be used cautiously in children and elderly as it
may cause fatigue and drowsiness.
Carbonic anhydrase Inhibitors (CAI)
?Systemic -Acetazolamide
?Topical CAI ? Dorzolamide , Brinzolamide
?Inhibits 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 blockers or PG
analogs
Systemic CAI ? Final medication option before resorting to laser or
incisional surgical treatment
Carbonic anhydrase Inhibitors (CAI)
Side effects
Paresthesia
Frequent urination
GI disturbances
Hypokalemia
Topical Miotics
?Only of historical importance in open angle
glaucoma
?- Ciliary muscle contraction
- Increase drainage through trabecular meshwork
?Drug-- -Pilocarpine 1,2,4%.
?Less useful drug ? Numerous side effects & three to
four times a day dosing
Stepped Medical Approach to Treatment of Open
Angle Glaucoma
Start monotherapy with Latanoprost or
topical blocker
If target I.O.P. not at ained, either change over to
alternative drug or use both the above concurrently
Brimonidine/dorzolamide ? Use only when there
are contraindications to PG analogs/ blockers
or to supplement their action
Oral acetazolamide/Topical miotics ? Last
resort
Angle closure Glaucoma
1. Hypertonic Mannitol ( 20%)
IV infusion 1.5 -2 g/kg
2. Acetazolamide - 0.5 g oral
3. Miotic - Pilocarpine (1-4%)
4. Timolol 0.5 % - instil ed 12 hourly.
Definitive treatment ? Surgical/
Laser iridotomy
Anti-
inflammatory
Corticosteroid
NSAID
stimulus
Steroids
Phospholipase A2
NSAIDS
Lipoxygenases
Leukotrienes
Corticosteroids
CLASSIFICATION
Short acting
Hydrocortisone, Cortisone, Prednisolone
Intermediate acting
Triamcinolone, Fluprednisolone
Long acting
Dexamethasone ,Betamethasone
Therapeutic Uses of Topical steroids
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 )
NEVER GIVE STEROIDS IF YOU ARE SUSPECTING ACTIVE INFECTION
Steroids in ocular conditions......
? Systemic steroids & by sub-Tenon's capsule
injection ? Posterior Uveitis
?Intravitreal injection ?
- Age-related Macular degeneration (ARMD)
- Diabetic Retinopathy
- Cystoid Macular Edema (CME)
?Parenteral steroids followed by tapering oral doses
? Optic Neuritis
ALLERGIC CONJUNCTIVITIS
SCLERITIS
ANTERIOR UVEITIS
OPTIC NEURITIS
Toxicity of Steroids
1. Posterior subcapsular cataracts
2. Secondary infections
3. Secondary open-angle glaucoma
4. Delayed wound healing
" Soft steroids (e.g., Loteprednol )
reduce the risk of elevated IOP "
SYSTEMIC side effects of steroids
Peptic ulcer
Hypertension
Increased blood sugar
Osteoporosis
Mental changes
Activation of tuberculosis and other infections
Topical NSAIDs & their Ocular Uses
Sr. No. Topical NSAID
Ocular Use
1
Flurbiprofen
To counter unwanted intraoperative miosis during cataract
surgery
2
Ketorolac
-Seasonal al ergic conjunctivitis
-Cystoid Macular Edema (CME ) occuring after cataract
surgery
3
Diclofenac
-Postoperative inflammation
-Cystoid Macular Edema (CME ) occuring after cataract
surgery
4
Bromfenac
Postoperative pain & inflammation after cataract surgery
5
Nepafenac
Postoperative pain & inflammation after cataract surgery
Tear Substitutes
?Hypotonic or isotonic solutions ?
Eg: Carboxymethylcellulose
Polyvinyl alcohol
Polyethylene and propylene glycol
? Indications
Ocular irritation in various diseases
Dry eye disease
Therapeutic Uses of Tear Substitutes
?Ocular diseases ? Al ergic conjunctivitis
- Blepharitis
- Corneal dystrophies
- Chemical Burns
?Systemic diseases ? Sjogren's syndrome
- Rheumatoid arthritis
- Vitamin A deficiency
- Stevens-Johnson syndrome
Immunosuppressive & Antimitotic Agents
Agents commonly used ?
1. 5-fluorouracil
2. Mitomycin C
Used
? In Glaucoma surgery, to
improve success of filtration
surgery by limiting
postoperative wound-healing
process.
? In corneal surgery, to reduce
risk of scar ing after excision of
pterygium
Immunomodulatory Agent
Topical Cyclosporine
? Approved for the treatment of chronic dry
eye associated with inflammation
-Decreases inflammatory markers in lacrimal
gland & increases tear production
Ocular diagnostic drugs
? Fluorescein dye
? Available as drops or strips
? Uses:
? To stain corneal abrasions
applanation tonometry
detecting wound leak
fluorescein angiography
? Caution:
? Stains soft contact lens
? Fluorescein drops can be
contaminated by Pseudomonas sp.
Ocular diagnostic drugs
? Rose bengal stain
? Stains devitalized epithelium
? Uses: severe dry eye, herpetic keratitis
Anaesthetics In Ophthalmic Procedures
? Proparacaine & tetracaine drops ?
Uses ? Tonometry
Gonioscopy
Removal of foreign bodies, sutures
on conjunctiva and cornea
? Adverse effects: toxic to corneal epithelium
allergic reaction (rarely)
Drugs & Biological Agents
Used in Ophthalmic Surgery
Sr. Drugs & Biological
Use in Ophthalmic Surgery
No. Agents
1
Povidone iodine (5% solution)
To prepare periocular skin & to ir igate cornea,
conjunctiva & palpebral fornices
2
Viscoelastic substances
Maintain spaces & protects surfaces during
(chondroitin sulphate,
anterior segment surgery
hydroxypropylmethylcel ulose)
3
Ophthalmic Glue-
a) Cyanoacrylate tissue adhesive Corneal ulcerations & Perforations
b) Fibrinogen Glue
To secure conjunctiva & corneal grafts.
4
Anterior Segment Gases
Reat achment of Descemet's membrane to stroma
a) Sulfur Hexafluoride (SF6)
of Cornea
b) Perfluoropropane
5
Vitreous Substitutes
Reat achment of retina fol owing Vitrectomy.
Botulinum Toxin Type A
FDA approved - Strabismus & Blepharospasm
associated with dystonia, facial wrinkles (glabellar
lines), axillary hyperhydrosis & spasmodic Torticolis
MOA ? Prevention of acetyl choline release at
neuromascular junction ? temporary paralysis of
locally injected muscle
Ophthalmic Effects of Selected
Vitamin Deficiencies & Zinc Deficiency
Deficiency Effects in Anterior
Effects in Posterior Segment
Segment
Vitamin A
Conjunctiva(Bitot's spot,
Retina(Nyctalopia)
xerosis)
Retinal pigment epithelium
Cornea (Keratomalacia ,
(hypopigmentation)
Punctate keratopathy)
Vitamin B1 - -
Optic nerve (Visual field
defects)
Vitamin B6 Cornea(Neovascularization) Retina (Atrophy)
Vitamin B12 - - -
Optic nerve (Visual field
defects)
Vitamin C
Lens (? Cataract formation) - - - -
Ophthalmic Ef ects of Selected Vitamin
Deficiencies & Zinc Deficiency
Deficiency
Ef ects in Anterior
Ef ects in Posterior Segment
Segment
Vitamin E
- - - -
Retina & retinal pigment
epithelium (? Macular
degeneration)
Folic acid
- - - -
Vein occlusion
Vitamin K
Conjunctiva
Retina (Hemor hage)
(Hemor hage)
Zinc
- - -
Retina & retinal pigment
epithelium (? Macular
degeneration)
Ocular
Toxicology
Toxicology
?Al opthalmic medications ? Potentially absorbed into
systemic circulation ? Undesirable systemic side effects
?Eg. Timolol (single eye drop) - Death
? Local toxic effects ? Hypersensitivity reactions
- Preservatives in eye drops & contact lens solutions ?
1. Benzalkonium chloride ? Punctate Keratopathy
2. Thimerosal ? Hypersensitivity reactions
Complications of topical administration
? Mechanical injury from the
bottle e.g. corneal abrasion
? Pigmentation: epinephrine-
adrenochrome
? Ocular damage: e.g.
topical anesthetics,
benzylkonium
? Hypersensitivity: e.g.
atropine, neomycin,
gentamicin
? Systemic effect: topical
phenylephrine can
increase BP
Amiodarone
? A drug for treatment of cardiac arrhythmia
? Causes optic neuropathy (mild decreased vision, visual field
defects, bilateral optic disc swelling)
? Also causes corneal vortex keratopathy (corneal verticillata)
which is whorl-shaped pigmented deposits in the corneal
epithelium
Digitalis
? A drug for treating cardiac failure
? Causes chromatopsia (objects appear yellow) with
overdose
Chloroquines
? E.g. chloroquine,
hydroxychloroquine
? Used in malaria,
rheumatoid arthritis, SLE
? Cause vortex keratopathy
(corneal verticillata) which
is usually asymptomatic
but can present with glare
and photophobia
? Also cause retinopathy
(bull's eye maculopathy)
Chorpromazine
? An antipsychotic drug
? Causes corneal punctate epithelial opacities, lens
surface opacities
? Rarely symptomatic
? Reversible with drug discontinuation
Thioridazine
? A psychiatric drug
? Causes a pigmentary retinopathy after high dosage
Diphenylhydantoin
? An epilepsy drug
? Causes dosage-related cerebellar-vestibular effects:
? Horizontal nystagmus in lateral gaze
? Diplopia, ophthalmoplegia
? Vertigo, ataxia
? Reversible with discontinuation of the drug
Topiramate
? A drug for epilepsy
? Causes acute angle-closure glaucoma (acute eye
pain, redness, blurred vision, haloes).
? Treatment is by cycloplegia and topical steroids
(rather than iridectomy) with the discontinuation of
the drug
HMG-CoA reductase inhibitors (statins)
? Cholesterol lowering agents
? E.g. pravastatin, lovastatin, simvastatin, fluvastatin,
atorvastatin, rosuvastatin
? Can cause cataract in high dosages specially if
used with erythromycin
Ethambutol
? An anti-tubercular drug
? Causes a dose-related optic neuropathy
? Usually reversible but occasionally permanent
visual damage might occur
Systemic Agents with Ocular Side Ef ects
Sr. Name of Drug
Ocular Side Effect
No.
1. Topiramate
Angle Closure Glaucoma
2.
Hydroxychloroquine/Chloroquine
Chloroquine amblyopia ( Bul 's Eye
Maculopathy )
3.
Tamoxifen
Crystal ine Maculopathy
4.
Vigabatrin
Progressive & Permanent bilateral concentric
visual field constriction
5.
Sildenafil/Vardenafil/tadalafil
Nonarteritic Ischemic Optic Neuropathy
(NAION )
6.
Ethambutol, Chloramphenicol ,
Toxic Optic Neuropathy (Progressive bilateral
Rifampin
central scotomas & vision loss )
7.
Ocular Steroids
Elevated IOP & Glaucoma
8.
Steroids
Cataract
Systemic Agents with Ocular Side Ef ects.......
Sr. Name of Drug
Ocular Side Effect
No.
9.
Rifabutin + Clarithromycin /
Iridocyclitis & Hypopyon
Fluconazole
10.
Isotretinoin
Dry eye & meibomian gland dysfunction
11.
Amiodarone
Drug deposits in cornea ( Cornea
verticil ata )
12.
Chlorpromazine & Thioridazine
Brown pigmentary deposits in the
cornea
13.
Gold
Chrysiasis ( gold deposits in cornea &
conjunctiva )
14.
Tetracyclines
Yel ow discoloration of light-exposed
conjunctiva
Visual field constriction
Cataract
Thank you
This post was last modified on 07 April 2022