Download MBBS Ophthalmology PPT 39 Ocular Pharmacology II Lecture Notes

Ocular Pharmacology -II

h

--- Content provided by FirstRanker.com ---

Learning Objectives

At the end of this class students shall have a basic

understanding of :

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

surgery

? Ocular toxicology

--- Content provided by FirstRanker.com ---

--- Content provided by FirstRanker.com ---

Overview

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

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Agents used for treatment of

Open angle Glaucoma

1. Prostaglandin analogues

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Prostaglandin Analogs

First- line medical therapy for Glaucoma

PGF2 analogs -

--- Content provided by FirstRanker.com ---

Good efficacy

Once daily application

--- Content provided by FirstRanker.com ---

Absence of systemic side effects

1.Latanoprost 2. Travoprost 3.Bimatoprost

Facilitate aqueous outflow through uveoscleral outflow

--- Content provided by FirstRanker.com ---

pathway

Prostaglandin Analogs

--- Content provided by FirstRanker.com ---

Side effects

Ocular irritation & pain
Blurring of vision
Increased iris pigmentation

--- Content provided by FirstRanker.com ---

Macular edema
Adrenergic blockers

?Nonselective blockers ? Timolol maleate
- Levobunolol

--- Content provided by FirstRanker.com ---

- Metipranolol
- Carteolol

? -1 antagonist - Betaxolol

--- Content provided by FirstRanker.com ---

Mechanism of Action of Blockers

?Lower IOP by reducing aqueous formation

- Down regulation of adenylylcyclase due to 2

--- Content provided by FirstRanker.com ---

receptor blockade in ciliary epithelium

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

--- Content provided by FirstRanker.com ---

blockers

Ocular

--- Content provided by FirstRanker.com ---

Systemic

1. Stinging, redness &

1. Bronchospasm in

--- Content provided by FirstRanker.com ---

dryness of eye

asthmatics & COPD

--- Content provided by FirstRanker.com ---

2. Corneal hypoesthesia

patients

3. Allergic

--- Content provided by FirstRanker.com ---

2. Bradycardia &

blepharoconjunctivitis

--- Content provided by FirstRanker.com ---

accentuation of Heart

4. Blurred vision

block

--- Content provided by FirstRanker.com ---

Minimization of systemic

adverse ef ects

--- Content provided by FirstRanker.com ---

Alpha Adrenergic agonists

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

--- Content provided by FirstRanker.com ---

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

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

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

body epithelium Reduces formation of bicarbonate

ions Reduces fluid transport Reduces aqueous

formation Decrease IOP

--- Content provided by FirstRanker.com ---

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

analogs

--- Content provided by FirstRanker.com ---

Systemic CAI ? Final medication option before resorting to laser or

incisional surgical treatment

Carbonic anhydrase Inhibitors (CAI)

--- Content provided by FirstRanker.com ---

Side effects

--- Content provided by FirstRanker.com ---

Paresthesia

Frequent urination

GI disturbances

--- Content provided by FirstRanker.com ---

Hypokalemia
Topical Miotics

?Only of historical importance in open angle

--- Content provided by FirstRanker.com ---

glaucoma

?- Ciliary muscle contraction
- Increase drainage through trabecular meshwork

--- Content provided by FirstRanker.com ---

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

?Less useful drug ? Numerous side effects & three to

four times a day dosing

--- Content provided by FirstRanker.com ---

Stepped Medical Approach to Treatment of Open

Angle Glaucoma

--- Content provided by FirstRanker.com ---

Start monotherapy with Latanoprost or

topical blocker

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

--- Content provided by FirstRanker.com ---

alternative drug or use both the above concurrently

Brimonidine/dorzolamide ? Use only when there

--- Content provided by FirstRanker.com ---

are contraindications to PG analogs/ blockers

or to supplement their action

Oral acetazolamide/Topical miotics ? Last

--- Content provided by FirstRanker.com ---

resort
Angle closure Glaucoma

1. Hypertonic Mannitol ( 20%)

--- Content provided by FirstRanker.com ---

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.

--- Content provided by FirstRanker.com ---

Definitive treatment ? Surgical/

Laser iridotomy

Anti-

--- Content provided by FirstRanker.com ---

inflammatory

Corticosteroid

--- Content provided by FirstRanker.com ---

NSAID
stimulus

Steroids

--- Content provided by FirstRanker.com ---

Phospholipase A2

NSAIDS

Lipoxygenases

--- Content provided by FirstRanker.com ---

Leukotrienes

Corticosteroids

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Long acting
Dexamethasone ,Betamethasone
Therapeutic Uses of Topical steroids

1. Significant ocular allergy

--- Content provided by FirstRanker.com ---

2. Anterior uveitis
3. Postoperative inflammation following refractive,

corneal & intraocular surgery

--- Content provided by FirstRanker.com ---

4. To reduce potential scarring of surgical site (After

Glaucoma filtering surgery )

NEVER GIVE STEROIDS IF YOU ARE SUSPECTING ACTIVE INFECTION

--- Content provided by FirstRanker.com ---

Steroids in ocular conditions......

? Systemic steroids & by sub-Tenon's capsule

--- Content provided by FirstRanker.com ---

injection ? Posterior Uveitis

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

--- Content provided by FirstRanker.com ---

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

? Optic Neuritis

--- Content provided by FirstRanker.com ---

ALLERGIC CONJUNCTIVITIS

SCLERITIS
ANTERIOR UVEITIS

--- Content provided by FirstRanker.com ---

OPTIC NEURITIS


Toxicity of Steroids

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

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

SYSTEMIC side effects of steroids

--- Content provided by FirstRanker.com ---

Peptic ulcer
Hypertension
Increased blood sugar
Osteoporosis
Mental changes

--- Content provided by FirstRanker.com ---

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

Sr. No. Topical NSAID

--- Content provided by FirstRanker.com ---

Ocular Use

1

Flurbiprofen

--- Content provided by FirstRanker.com ---

To counter unwanted intraoperative miosis during cataract

surgery

--- Content provided by FirstRanker.com ---

2

Ketorolac

-Seasonal al ergic conjunctivitis

--- Content provided by FirstRanker.com ---

-Cystoid Macular Edema (CME ) occuring after cataract

surgery

--- Content provided by FirstRanker.com ---

3

Diclofenac

-Postoperative inflammation

--- Content provided by FirstRanker.com ---

-Cystoid Macular Edema (CME ) occuring after cataract

surgery

--- Content provided by FirstRanker.com ---

4

Bromfenac

Postoperative pain & inflammation after cataract surgery

--- Content provided by FirstRanker.com ---

5

Nepafenac

--- Content provided by FirstRanker.com ---

Postoperative pain & inflammation after cataract surgery

Tear Substitutes

?Hypotonic or isotonic solutions ?

--- Content provided by FirstRanker.com ---

Eg: Carboxymethylcellulose
Polyvinyl alcohol
Polyethylene and propylene glycol

? Indications

--- Content provided by FirstRanker.com ---

Ocular irritation in various diseases
Dry eye disease

--- Content provided by FirstRanker.com ---

Therapeutic Uses of Tear Substitutes

?Ocular diseases ? Al ergic conjunctivitis

- Blepharitis

--- Content provided by FirstRanker.com ---

- Corneal dystrophies

- Chemical Burns

--- Content provided by FirstRanker.com ---

?Systemic diseases ? Sjogren's syndrome

- Rheumatoid arthritis

- Vitamin A deficiency

--- Content provided by FirstRanker.com ---

- Stevens-Johnson syndrome

Immunosuppressive & Antimitotic Agents

--- Content provided by FirstRanker.com ---

Agents commonly used ?

1. 5-fluorouracil

2. Mitomycin C

--- Content provided by FirstRanker.com ---

Used

? In Glaucoma surgery, to

--- Content provided by FirstRanker.com ---

improve success of filtration

surgery by limiting

postoperative wound-healing

--- Content provided by FirstRanker.com ---

process.

? In corneal surgery, to reduce

--- Content provided by FirstRanker.com ---

risk of scar ing after excision of

pterygium
Immunomodulatory Agent

--- Content provided by FirstRanker.com ---

Topical Cyclosporine

? Approved for the treatment of chronic dry

eye associated with inflammation

--- Content provided by FirstRanker.com ---

-Decreases inflammatory markers in lacrimal

gland & increases tear production

--- Content provided by FirstRanker.com ---

Ocular diagnostic drugs

? Fluorescein dye

? Available as drops or strips

--- Content provided by FirstRanker.com ---

? Uses:

? To stain corneal abrasions

--- Content provided by FirstRanker.com ---

applanation tonometry

detecting wound leak

fluorescein angiography

--- Content provided by FirstRanker.com ---

? Caution:

? Stains soft contact lens

--- Content provided by FirstRanker.com ---

? Fluorescein drops can be

contaminated by Pseudomonas sp.
Ocular diagnostic drugs

--- Content provided by FirstRanker.com ---

? Rose bengal stain

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

--- Content provided by FirstRanker.com ---

Anaesthetics In Ophthalmic Procedures

? Proparacaine & tetracaine drops ?

Uses ? Tonometry

--- Content provided by FirstRanker.com ---

Gonioscopy

Removal of foreign bodies, sutures

--- Content provided by FirstRanker.com ---

on conjunctiva and cornea


? Adverse effects: toxic to corneal epithelium

--- Content provided by FirstRanker.com ---

allergic reaction (rarely)
Drugs & Biological Agents

Used in Ophthalmic Surgery

--- Content provided by FirstRanker.com ---

Sr. Drugs & Biological

Use in Ophthalmic Surgery

No. Agents

--- Content provided by FirstRanker.com ---

1

Povidone iodine (5% solution)

To prepare periocular skin & to ir igate cornea,

--- Content provided by FirstRanker.com ---

conjunctiva & palpebral fornices

2

--- Content provided by FirstRanker.com ---

Viscoelastic substances

Maintain spaces & protects surfaces during

(chondroitin sulphate,

--- Content provided by FirstRanker.com ---

anterior segment surgery

hydroxypropylmethylcel ulose)

--- Content provided by FirstRanker.com ---

3

Ophthalmic Glue-

a) Cyanoacrylate tissue adhesive Corneal ulcerations & Perforations

--- Content provided by FirstRanker.com ---

b) Fibrinogen Glue

To secure conjunctiva & corneal grafts.

--- Content provided by FirstRanker.com ---

4

Anterior Segment Gases

Reat achment of Descemet's membrane to stroma

--- Content provided by FirstRanker.com ---

a) Sulfur Hexafluoride (SF6)

of Cornea

--- Content provided by FirstRanker.com ---

b) Perfluoropropane

5

Vitreous Substitutes

--- Content provided by FirstRanker.com ---

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

FDA approved - Strabismus & Blepharospasm

--- Content provided by FirstRanker.com ---

associated with dystonia, facial wrinkles (glabellar

lines), axillary hyperhydrosis & spasmodic Torticolis

--- Content provided by FirstRanker.com ---

MOA ? Prevention of acetyl choline release at

neuromascular junction ? temporary paralysis of

locally injected muscle

--- Content provided by FirstRanker.com ---

Ophthalmic Effects of Selected

Vitamin Deficiencies & Zinc Deficiency

--- Content provided by FirstRanker.com ---

Deficiency Effects in Anterior

Effects in Posterior Segment

Segment

--- Content provided by FirstRanker.com ---

Vitamin A

Conjunctiva(Bitot's spot,

--- Content provided by FirstRanker.com ---

Retina(Nyctalopia)

xerosis)

Retinal pigment epithelium

--- Content provided by FirstRanker.com ---

Cornea (Keratomalacia ,

(hypopigmentation)

--- Content provided by FirstRanker.com ---

Punctate keratopathy)

Vitamin B1 - -

Optic nerve (Visual field

--- Content provided by FirstRanker.com ---

defects)

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

--- Content provided by FirstRanker.com ---

Optic nerve (Visual field

defects)

--- Content provided by FirstRanker.com ---

Vitamin C

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

--- Content provided by FirstRanker.com ---

Deficiencies & Zinc Deficiency

Deficiency

Ef ects in Anterior

--- Content provided by FirstRanker.com ---

Ef ects in Posterior Segment

Segment

--- Content provided by FirstRanker.com ---

Vitamin E

- - - -

Retina & retinal pigment

--- Content provided by FirstRanker.com ---

epithelium (? Macular

degeneration)

--- Content provided by FirstRanker.com ---

Folic acid

- - - -

Vein occlusion

--- Content provided by FirstRanker.com ---

Vitamin K

Conjunctiva

--- Content provided by FirstRanker.com ---

Retina (Hemor hage)

(Hemor hage)

Zinc

--- Content provided by FirstRanker.com ---

- - -

Retina & retinal pigment

--- Content provided by FirstRanker.com ---

epithelium (? Macular

degeneration)

--- Content provided by FirstRanker.com ---

Ocular

Toxicology
Toxicology

--- Content provided by FirstRanker.com ---

?Al opthalmic medications ? Potentially absorbed into

systemic circulation ? Undesirable systemic side effects

?Eg. Timolol (single eye drop) - Death

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Complications of topical administration

? Mechanical injury from the

bottle e.g. corneal abrasion

--- Content provided by FirstRanker.com ---

? Pigmentation: epinephrine-

adrenochrome

--- Content provided by FirstRanker.com ---

? Ocular damage: e.g.

topical anesthetics,

benzylkonium

--- Content provided by FirstRanker.com ---

? Hypersensitivity: e.g.

atropine, neomycin,

--- Content provided by FirstRanker.com ---

gentamicin

? Systemic effect: topical

phenylephrine can

--- Content provided by FirstRanker.com ---

increase BP


Amiodarone

--- Content provided by FirstRanker.com ---

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

defects, bilateral optic disc swelling)

--- Content provided by FirstRanker.com ---

? Also causes corneal vortex keratopathy (corneal verticillata)

which is whorl-shaped pigmented deposits in the corneal

--- Content provided by FirstRanker.com ---

epithelium

Digitalis

? A drug for treating cardiac failure

--- Content provided by FirstRanker.com ---

? Causes chromatopsia (objects appear yellow) with

overdose

--- Content provided by FirstRanker.com ---

Chloroquines

? E.g. chloroquine,

hydroxychloroquine

--- Content provided by FirstRanker.com ---

? Used in malaria,

rheumatoid arthritis, SLE

--- Content provided by FirstRanker.com ---

? Cause vortex keratopathy

(corneal verticillata) which

is usually asymptomatic

--- Content provided by FirstRanker.com ---

but can present with glare

and photophobia

--- Content provided by FirstRanker.com ---

? Also cause retinopathy

(bull's eye maculopathy)

Chorpromazine

--- Content provided by FirstRanker.com ---

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

surface opacities

--- Content provided by FirstRanker.com ---

? Rarely symptomatic
? Reversible with drug discontinuation

--- Content provided by FirstRanker.com ---

Thioridazine

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

--- Content provided by FirstRanker.com ---

Diphenylhydantoin

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

--- Content provided by FirstRanker.com ---

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

? Reversible with discontinuation of the drug

--- Content provided by FirstRanker.com ---

Topiramate

? A drug for epilepsy

--- Content provided by FirstRanker.com ---

? Causes acute angle-closure glaucoma (acute eye

pain, redness, blurred vision, haloes).

? Treatment is by cycloplegia and topical steroids

--- Content provided by FirstRanker.com ---

(rather than iridectomy) with the discontinuation of

the drug

--- Content provided by FirstRanker.com ---

HMG-CoA reductase inhibitors (statins)

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

--- Content provided by FirstRanker.com ---

atorvastatin, rosuvastatin

? Can cause cataract in high dosages specially if

used with erythromycin

--- Content provided by FirstRanker.com ---

Ethambutol

? An anti-tubercular drug

--- Content provided by FirstRanker.com ---

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

visual damage might occur

--- Content provided by FirstRanker.com ---

Systemic Agents with Ocular Side Ef ects

Sr. Name of Drug

Ocular Side Effect

--- Content provided by FirstRanker.com ---

No.

1. Topiramate

--- Content provided by FirstRanker.com ---

Angle Closure Glaucoma

2.

Hydroxychloroquine/Chloroquine

--- Content provided by FirstRanker.com ---

Chloroquine amblyopia ( Bul 's Eye

Maculopathy )

--- Content provided by FirstRanker.com ---

3.

Tamoxifen

Crystal ine Maculopathy

--- Content provided by FirstRanker.com ---

4.

Vigabatrin

--- Content provided by FirstRanker.com ---

Progressive & Permanent bilateral concentric

visual field constriction

5.

--- Content provided by FirstRanker.com ---

Sildenafil/Vardenafil/tadalafil

Nonarteritic Ischemic Optic Neuropathy

--- Content provided by FirstRanker.com ---

(NAION )

6.

Ethambutol, Chloramphenicol ,

--- Content provided by FirstRanker.com ---

Toxic Optic Neuropathy (Progressive bilateral

Rifampin

--- Content provided by FirstRanker.com ---

central scotomas & vision loss )

7.

Ocular Steroids

--- Content provided by FirstRanker.com ---

Elevated IOP & Glaucoma

8.

--- Content provided by FirstRanker.com ---

Steroids

Cataract

--- Content provided by FirstRanker.com ---

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

Sr. Name of Drug

Ocular Side Effect

--- Content provided by FirstRanker.com ---

No.
9.

Rifabutin + Clarithromycin /

--- Content provided by FirstRanker.com ---

Iridocyclitis & Hypopyon

Fluconazole

--- Content provided by FirstRanker.com ---

10.

Isotretinoin

Dry eye & meibomian gland dysfunction

--- Content provided by FirstRanker.com ---

11.

Amiodarone

--- Content provided by FirstRanker.com ---

Drug deposits in cornea ( Cornea

verticil ata )

12.

--- Content provided by FirstRanker.com ---

Chlorpromazine & Thioridazine

Brown pigmentary deposits in the

--- Content provided by FirstRanker.com ---

cornea

13.

Gold

--- Content provided by FirstRanker.com ---

Chrysiasis ( gold deposits in cornea &

conjunctiva )

--- Content provided by FirstRanker.com ---

14.

Tetracyclines

Yel ow discoloration of light-exposed

--- Content provided by FirstRanker.com ---

conjunctiva

Visual field constriction

--- Content provided by FirstRanker.com ---

Cataract
Thank you