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Download MBBS Ophthalmology PPT 39 Ocular Pharmacology II Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Ophthalmology PPT 39 Ocular Pharmacology II Lecture Notes

This post was last modified on 07 April 2022

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Learning Objectives

At the end of this class students shall have a basic

understanding of :

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? Therapeutic agents for glaucoma
? Anti-inflammatory agents
? Tear substitutes
? Drugs and biological agents used in Ophthalmic

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surgery

? Ocular toxicology

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Overview

Overview of ocular anatomy & physiology
Pharmacodynamics and Pharmacokinetics of ocular therapeutic agents
Ocular Routes of Drug Administration

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Therapeutic & Diagnostic applications of Drugs in Ophthalmology
Ophthalmic Effects of Selected Vitamin Deficiencies
Systemic Agents with Ocular Side Effects
Conclusion

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Agents used for treatment of

Open angle Glaucoma

1. Prostaglandin analogues

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2. Beta receptor antagonists
3. Alpha receptor agonists
4. Carbonic anhydrase inhibitors


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Prostaglandin Analogs

First- line medical therapy for Glaucoma

PGF2 analogs -

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Good efficacy

Once daily application

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Absence of systemic side effects

1.Latanoprost 2. Travoprost 3.Bimatoprost

Facilitate aqueous outflow through uveoscleral outflow

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pathway

Prostaglandin Analogs

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Side effects

Ocular irritation & pain
Blurring of vision
Increased iris pigmentation

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Macular edema
Adrenergic blockers

?Nonselective blockers ? Timolol maleate
- Levobunolol

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- Metipranolol
- Carteolol

? -1 antagonist - Betaxolol

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Mechanism of Action of Blockers

?Lower IOP by reducing aqueous formation

- Down regulation of adenylylcyclase due to 2

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receptor blockade in ciliary epithelium

- Reduction in ocular blood flow
Adverse Ef ects of Ocular Adrenergic

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blockers

Ocular

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Systemic

1. Stinging, redness &

1. Bronchospasm in

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dryness of eye

asthmatics & COPD

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2. Corneal hypoesthesia

patients

3. Allergic

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2. Bradycardia &

blepharoconjunctivitis

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accentuation of Heart

4. Blurred vision

block

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Minimization of systemic

adverse ef ects

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Alpha Adrenergic agonists

? Brimonidine (Alpha-2 agonist)(0.1%,0.2%)
? Usually used as an add on agent
? Mainly reduces aqueous production

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? Also increases uveoscleral outflow
? To be used cautiously in children and elderly as it

may cause fatigue and drowsiness.
Carbonic anhydrase Inhibitors (CAI)

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?Systemic -Acetazolamide
?Topical CAI ? Dorzolamide , Brinzolamide
?Inhibits carbonic anhydrase (isoenzyme II) on ciliary

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body epithelium Reduces formation of bicarbonate

ions Reduces fluid transport Reduces aqueous

formation Decrease IOP

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?Use ? Only as add on drug to topical blockers or PG

analogs

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Systemic CAI ? Final medication option before resorting to laser or

incisional surgical treatment

Carbonic anhydrase Inhibitors (CAI)

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Side effects

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Paresthesia

Frequent urination

GI disturbances

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Hypokalemia
Topical Miotics

?Only of historical importance in open angle

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glaucoma

?- Ciliary muscle contraction
- Increase drainage through trabecular meshwork

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?Drug-- -Pilocarpine 1,2,4%.

?Less useful drug ? Numerous side effects & three to

four times a day dosing

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Stepped Medical Approach to Treatment of Open

Angle Glaucoma

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Start monotherapy with Latanoprost or

topical blocker

If target I.O.P. not at ained, either change over to

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alternative drug or use both the above concurrently

Brimonidine/dorzolamide ? Use only when there

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are contraindications to PG analogs/ blockers

or to supplement their action

Oral acetazolamide/Topical miotics ? Last

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resort
Angle closure Glaucoma

1. Hypertonic Mannitol ( 20%)

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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.

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Definitive treatment ? Surgical/

Laser iridotomy

Anti-

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inflammatory

Corticosteroid

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NSAID
stimulus

Steroids

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Phospholipase A2

NSAIDS

Lipoxygenases

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Leukotrienes

Corticosteroids

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CLASSIFICATION
Short acting
Hydrocortisone, Cortisone, Prednisolone
Intermediate acting
Triamcinolone, Fluprednisolone

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Long acting
Dexamethasone ,Betamethasone
Therapeutic Uses of Topical steroids

1. Significant ocular allergy

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2. Anterior uveitis
3. Postoperative inflammation following refractive,

corneal & intraocular surgery

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4. To reduce potential scarring of surgical site (After

Glaucoma filtering surgery )

NEVER GIVE STEROIDS IF YOU ARE SUSPECTING ACTIVE INFECTION

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Steroids in ocular conditions......

? Systemic steroids & by sub-Tenon's capsule

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injection ? Posterior Uveitis

?Intravitreal injection ?
- Age-related Macular degeneration (ARMD)
- Diabetic Retinopathy

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- Cystoid Macular Edema (CME)
?Parenteral steroids followed by tapering oral doses

? Optic Neuritis

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ALLERGIC CONJUNCTIVITIS

SCLERITIS
ANTERIOR UVEITIS

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OPTIC NEURITIS


Toxicity of Steroids

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1. Posterior subcapsular cataracts
2. Secondary infections
3. Secondary open-angle glaucoma
4. Delayed wound healing

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" Soft steroids (e.g., Loteprednol )
reduce the risk of elevated IOP "

SYSTEMIC side effects of steroids

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Peptic ulcer
Hypertension
Increased blood sugar
Osteoporosis
Mental changes

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Activation of tuberculosis and other infections
Topical NSAIDs & their Ocular Uses

Sr. No. Topical NSAID

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Ocular Use

1

Flurbiprofen

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To counter unwanted intraoperative miosis during cataract

surgery

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2

Ketorolac

-Seasonal al ergic conjunctivitis

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-Cystoid Macular Edema (CME ) occuring after cataract

surgery

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3

Diclofenac

-Postoperative inflammation

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-Cystoid Macular Edema (CME ) occuring after cataract

surgery

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4

Bromfenac

Postoperative pain & inflammation after cataract surgery

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5

Nepafenac

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Postoperative pain & inflammation after cataract surgery

Tear Substitutes

?Hypotonic or isotonic solutions ?

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Eg: Carboxymethylcellulose
Polyvinyl alcohol
Polyethylene and propylene glycol

? Indications

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Ocular irritation in various diseases
Dry eye disease



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Therapeutic Uses of Tear Substitutes

?Ocular diseases ? Al ergic conjunctivitis

- Blepharitis

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- Corneal dystrophies

- Chemical Burns

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?Systemic diseases ? Sjogren's syndrome

- Rheumatoid arthritis

- Vitamin A deficiency

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- Stevens-Johnson syndrome

Immunosuppressive & Antimitotic Agents

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Agents commonly used ?

1. 5-fluorouracil

2. Mitomycin C

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Used

? In Glaucoma surgery, to

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improve success of filtration

surgery by limiting

postoperative wound-healing

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process.

? In corneal surgery, to reduce

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risk of scar ing after excision of

pterygium
Immunomodulatory Agent

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Topical Cyclosporine

? Approved for the treatment of chronic dry

eye associated with inflammation

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-Decreases inflammatory markers in lacrimal

gland & increases tear production

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Ocular diagnostic drugs

? Fluorescein dye

? Available as drops or strips

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? Uses:

? To stain corneal abrasions

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applanation tonometry

detecting wound leak

fluorescein angiography

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? Caution:

? Stains soft contact lens

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? Fluorescein drops can be

contaminated by Pseudomonas sp.
Ocular diagnostic drugs

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? Rose bengal stain

? Stains devitalized epithelium
? Uses: severe dry eye, herpetic keratitis

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Anaesthetics In Ophthalmic Procedures

? Proparacaine & tetracaine drops ?

Uses ? Tonometry

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Gonioscopy

Removal of foreign bodies, sutures

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on conjunctiva and cornea


? Adverse effects: toxic to corneal epithelium

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allergic reaction (rarely)
Drugs & Biological Agents

Used in Ophthalmic Surgery

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Sr. Drugs & Biological

Use in Ophthalmic Surgery

No. Agents

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1

Povidone iodine (5% solution)

To prepare periocular skin & to ir igate cornea,

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conjunctiva & palpebral fornices

2

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Viscoelastic substances

Maintain spaces & protects surfaces during

(chondroitin sulphate,

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anterior segment surgery

hydroxypropylmethylcel ulose)

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3

Ophthalmic Glue-

a) Cyanoacrylate tissue adhesive Corneal ulcerations & Perforations

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b) Fibrinogen Glue

To secure conjunctiva & corneal grafts.

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4

Anterior Segment Gases

Reat achment of Descemet's membrane to stroma

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a) Sulfur Hexafluoride (SF6)

of Cornea

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b) Perfluoropropane

5

Vitreous Substitutes

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Reat achment of retina fol owing Vitrectomy.
Botulinum Toxin Type A

FDA approved - Strabismus & Blepharospasm

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associated with dystonia, facial wrinkles (glabellar

lines), axillary hyperhydrosis & spasmodic Torticolis

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MOA ? Prevention of acetyl choline release at

neuromascular junction ? temporary paralysis of

locally injected muscle

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Ophthalmic Effects of Selected

Vitamin Deficiencies & Zinc Deficiency

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Deficiency Effects in Anterior

Effects in Posterior Segment

Segment

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Vitamin A

Conjunctiva(Bitot's spot,

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Retina(Nyctalopia)

xerosis)

Retinal pigment epithelium

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Cornea (Keratomalacia ,

(hypopigmentation)

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Punctate keratopathy)

Vitamin B1 - -

Optic nerve (Visual field

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defects)

Vitamin B6 Cornea(Neovascularization) Retina (Atrophy)
Vitamin B12 - - -

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Optic nerve (Visual field

defects)

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Vitamin C

Lens (? Cataract formation) - - - -
Ophthalmic Ef ects of Selected Vitamin

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Deficiencies & Zinc Deficiency

Deficiency

Ef ects in Anterior

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Ef ects in Posterior Segment

Segment

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Vitamin E

- - - -

Retina & retinal pigment

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epithelium (? Macular

degeneration)

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Folic acid

- - - -

Vein occlusion

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Vitamin K

Conjunctiva

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Retina (Hemor hage)

(Hemor hage)

Zinc

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- - -

Retina & retinal pigment

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epithelium (? Macular

degeneration)


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Ocular

Toxicology
Toxicology

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?Al opthalmic medications ? Potentially absorbed into

systemic circulation ? Undesirable systemic side effects

?Eg. Timolol (single eye drop) - Death

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? Local toxic effects ? Hypersensitivity reactions
- Preservatives in eye drops & contact lens solutions ?
1. Benzalkonium chloride ? Punctate Keratopathy
2. Thimerosal ? Hypersensitivity reactions

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Complications of topical administration

? Mechanical injury from the

bottle e.g. corneal abrasion

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? Pigmentation: epinephrine-

adrenochrome

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? Ocular damage: e.g.

topical anesthetics,

benzylkonium

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? Hypersensitivity: e.g.

atropine, neomycin,

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gentamicin

? Systemic effect: topical

phenylephrine can

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increase BP


Amiodarone

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? A drug for treatment of cardiac arrhythmia
? Causes optic neuropathy (mild decreased vision, visual field

defects, bilateral optic disc swelling)

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? Also causes corneal vortex keratopathy (corneal verticillata)

which is whorl-shaped pigmented deposits in the corneal

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epithelium

Digitalis

? A drug for treating cardiac failure

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? Causes chromatopsia (objects appear yellow) with

overdose


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Chloroquines

? E.g. chloroquine,

hydroxychloroquine

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? Used in malaria,

rheumatoid arthritis, SLE

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? Cause vortex keratopathy

(corneal verticillata) which

is usually asymptomatic

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but can present with glare

and photophobia

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? Also cause retinopathy

(bull's eye maculopathy)

Chorpromazine

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? An antipsychotic drug
? Causes corneal punctate epithelial opacities, lens

surface opacities

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? Rarely symptomatic
? Reversible with drug discontinuation


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Thioridazine

? A psychiatric drug
? Causes a pigmentary retinopathy after high dosage

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Diphenylhydantoin

? An epilepsy drug
? Causes dosage-related cerebellar-vestibular effects:

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? Horizontal nystagmus in lateral gaze
? Diplopia, ophthalmoplegia
? Vertigo, ataxia

? Reversible with discontinuation of the drug

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Topiramate

? A drug for epilepsy

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? Causes acute angle-closure glaucoma (acute eye

pain, redness, blurred vision, haloes).

? Treatment is by cycloplegia and topical steroids

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(rather than iridectomy) with the discontinuation of

the drug

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HMG-CoA reductase inhibitors (statins)

? Cholesterol lowering agents
? E.g. pravastatin, lovastatin, simvastatin, fluvastatin,

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atorvastatin, rosuvastatin

? Can cause cataract in high dosages specially if

used with erythromycin

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Ethambutol

? An anti-tubercular drug

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? Causes a dose-related optic neuropathy
? Usually reversible but occasionally permanent

visual damage might occur

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Systemic Agents with Ocular Side Ef ects

Sr. Name of Drug

Ocular Side Effect

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No.

1. Topiramate

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Angle Closure Glaucoma

2.

Hydroxychloroquine/Chloroquine

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Chloroquine amblyopia ( Bul 's Eye

Maculopathy )

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3.

Tamoxifen

Crystal ine Maculopathy

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4.

Vigabatrin

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Progressive & Permanent bilateral concentric

visual field constriction

5.

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Sildenafil/Vardenafil/tadalafil

Nonarteritic Ischemic Optic Neuropathy

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(NAION )

6.

Ethambutol, Chloramphenicol ,

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Toxic Optic Neuropathy (Progressive bilateral

Rifampin

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central scotomas & vision loss )

7.

Ocular Steroids

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Elevated IOP & Glaucoma

8.

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Steroids

Cataract


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Systemic Agents with Ocular Side Ef ects.......

Sr. Name of Drug

Ocular Side Effect

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No.
9.

Rifabutin + Clarithromycin /

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Iridocyclitis & Hypopyon

Fluconazole

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10.

Isotretinoin

Dry eye & meibomian gland dysfunction

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11.

Amiodarone

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Drug deposits in cornea ( Cornea

verticil ata )

12.

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Chlorpromazine & Thioridazine

Brown pigmentary deposits in the

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cornea

13.

Gold

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Chrysiasis ( gold deposits in cornea &

conjunctiva )

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14.

Tetracyclines

Yel ow discoloration of light-exposed

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conjunctiva

Visual field constriction

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Cataract
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