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


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