OCCULAR PHARMACOLOGY:

DRUGS ACTING ON THE EYE.

The eye is a specialized sensory organ that is relatively secluded from

systemic access by the blood-retinal, blood – aqueous, and blood-
vitreous barriers; as a consequence, the eye exhibits some unusual
pharmacodynamic and pharmacokinetic properties. No other organ in
the body is so readily accessible or as visible for observation, however,
it also presents some unique challenges as well as opportunities for drug
delivery.

Fig 1.
TEARS

Corneal CONJUNCTIVA
Route

Conjuctival/
CORNEA SCLERA
Sclera/Route

AQUEOUS
HUMOUR

Nasolacrimal
CILIARY absorption
IRIS
BODY pathway

SYSTEMIC CIRCULATION

Fig:1 Absorption pathways of an ophthalmic drug following topical

application to the eye.

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Receptors of the Eye and Related structures

Structure Receptors

Adrenergic – subtype/Response Cholinergic – subtype/Response

Corneal epithelium 𝛽2 /unknown M a /unknown

Corneal endothelium 𝛽2 /unknown undefined/unknown

Iris Radial Muscle 𝛼1 /Mydriasis − / −

Iris Sphincter Muscle − / − M3 /miosis

Trabecular Meshwork 𝛽2 /unknown − / −

Ciliary epithelium 𝛼2 , 𝛽2 /𝑎𝑞𝑢𝑒𝑜𝑢𝑠 production − / −

Ciliary muscle 𝛽2 /𝑅𝑒𝑙𝑎𝑥𝑎𝑡𝑖𝑜𝑛 M3 /Accomodation

Lacrimal gland 𝛼1 /secretion M2 M3 /secretion

Retinal pigment epithelium 𝛼1 , 𝛽2 𝑤𝑎𝑡𝑒𝑟 𝑡𝑟𝑎𝑛𝑠𝑝𝑜𝑟𝑡 − / −

Sympathetic drugs on the pupils lead to dilation (mydriasis),

parasympathetic drugs on pupillary response is constriction (miosis),
cocaine 4-10% causes no dilation, Hydroxyamphetamine 1%
(preganglionic) – dilation; post ganglionic – no dilation, pilocarpine 0.05-
0.1% - constriction, and opiods (oral or intravenous) – pinpoint pupils.

Ophthalmic Topical Antibacterial Agents

- Azithromycin (1% solution) for conjunctivitis
Toxicity ⎯ Hypersensitivity

- Bacitracin (500units/g ointment) - conjunctivitis, blepharitis, keratitis, corneal ulcers,

- keratoconjuctivitis, meibomianitis, dacryocustitis.
Toxicity ⎯ Hypersensitivity

- Besifloxacin (0.6% suspension) ⎯ Conjuctivitis

- Chloramphenical (1% ointment) ⎯ conjunctivitis, keratitis

Toxicity ⎯ Hypersensitivity, Blood dyscrasia
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- Ciprofloxacin Hydrochloride (0.3% solution/ointment) - conjunctivitis, keratitis,
kerato conjunctivitis, meibomianitis, dacryocustitis,
corneal ulcers, blepharitis, blepharoconjunctivitis
Toxicity ⎯ Hypersensitivity, Drug – related corneal deposits.

- Erythromycin (0.5% ointment) – superficial ocular infections involving the conjuctiva

or cornea, prophylaxis of ophthalmic neonatorium.
Toxicity ⎯ Hypersensitivity

- Gatifloxacin (0.3% solution) ⎯ Conjuctivitis

Toxicity ⎯ Hypersensitivity

- Gentamicin sulfate (0.3% solution/ointment) - conjunctivitis, blepharitis, keratitis,

keratoconjunctivitis, corneal ulcers, blepharoconjunctivitis,
meibomianitis, dacryocystitis.
Toxicity ⎯ Hyper sensitivity

- Levofloxacin (0.5%) solution ⎯ Conjuctivitis

Toxicity ⎯ Hypersensitivity

- Levofloxacin (1.5% solution) ⎯ Corneal ulcers.

Toxicity ⎯ Hypersensitivity

- Moxifloxacin (0.5% solution) ⎯ Conjuctivitis

Toxicity ⎯ Hypersensitivity

- Ofloxacin (0.3% solution) ⎯ Conjuctivitis, corneal ulcers.

Toxicity ⎯ Hypersensitivity

- Sulfacetamide sodium (1%, 10%, 15% and 30% solution; 10% ointment)
⎯ Conjuctivitis, other superficial ocular infections.
Toxicity ⎯ Hypersensitivity, blood Dyscrasia.

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- Polymyxin B combinations (various solutions and ointments)- conjunctivitis
blepharitis, Keratitis.

- Tobramycin sulfate (0.3% solution, 0.3% ointment) ⎯ External infections of

The eye and its adnexa.
Toxicity ⎯ Hypersensitivity

ANTIVIRAL OPHTHALMIC AGENTS

- Trifluridine: Topical 1% solution - herpes simplex keratitis and keratoconjunctivitis
Toxicity ⎯ Punctate Keratopathy, Hypersensitivity

- Acyclovir: - Oral, IV
- 200mg capsule, 400mg and 800mg tablets - Herpes zoster ophthalmicus
- Herps simplex iridocyclitis

- Valacyclovir: Oral – 500mg and 1000mg tablets - Herps simplex Keratitis

- Herpes zoster ophthalmicus

- Famciclovir: Oral – 125-, 250-, and 500mg tablets - Herps simplex Keratitis
- Herpes zoster ophthalmicus

- Foscarnet: Intravenous, Intravitreal – Cytomegalovirus retinitis

- Ganciclovir: Intravenous, Oral, intravitreal implant – Cytomegalovirus retinitis

- Valganciclovir: Oral ⎯ Cytomegalovirus retinitis

- Cidofovir: IV ⎯ Cytomegalovirus retinitis.

ANTIFUNGAL OPHTHALMIC AGENTS

(1) Polyenes:
(a) Amphotericin B; 0.1 -0.5% (0.15%) Topical solution – yeast and fungal
Keratitis and endophthalmitis.

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 - 0.8mg – 1.0mg subconjunctival – yeast and fungal endophthalmitis
- 5g intravitreal injection – ,, ,, ,, ,,
- Intravenous – ,, ,, ,, ,,

(b) Natamycin: 5% Topical suspension ⎯ yeast and fungal blepharitis

⎯ Conjunctivitis
⎯ Keratitis.

(2) Imidazoles:
(a) Fluconazole: Oral, IV - yeast keratitis and endophthalmitis
(b) Itraconazole: Oral - yeast and fungal keratitis and endophthalmitis
(c) Ketoconazole: Oral - yeast keratitis and endophthalmitis
(d) Miconazole: 1% Topical solution - yeast and fungal keratitis
5 – 10mg subconjunctival - yeast and fungal endophthalmitis
10g intravitreal injection – yeast ,, ,, ,,

Autonomic Ophthalmic Drugs

(1) Cholinergic Agonist Indications Ocular Side Effects
(a) Acetylcholine – 1% solution Miosis in surgery- Corneal Edema

(b) Carbachol – 0.01-3% solution - Miosis in surgery- Corneal edema, miosis,

- Glaucoma induced myopia decreased
Vision, brow, ache, retinal
Detachment

(c) Pilocarpine: 0.5,1 2, 4 and 6% % solution – Glaucoma same as carbachol

4% gel

(2) Anticholinesterase Agent

(a) Echothiophate: 0.125% solution : Cycloplegia Revival Detachment
- Accomodative miosis, cataract, Pupillary
esotropia block glaucoma iris cysts,
Brow ache, punctal stenosis
of the nasolacrimal system.
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(3) Muscarinic Antagonists
(a) Antropine: 0.5%, 1% and 2% solution: Cycloplegia Photosensitivity
1% ointment Mydriasis Blurred vision
Cycloplegic Retinoscopy
Dilated funduscopic
Examination

(b)i. Scopolamine – 0.25% solution

ii. Homatropine – 2% and 5% solution Cycloplegia Photosensitivity
iii. Cyclopentolate – 0.5%, 1% and 2% solution Mydriasis Blurred Vision
iv. Tropicamide – 0.5% and 1% solution

(4) Sympathomimetic Agents

(a) Dipivefrin: 0.1% solution Glaucoma Photosensitivity, Conjuctival
hyperemia hypersensitivity

(b) Phenylephrine: 0.12, 2.5 and 10% solution: Mydriasis

Vasoconstriction
Decongestion

(c) Apraclonidine: 0.5% and 1% solution: Occular Hypertension

(d) Brimonidine: 0.1, 0.15 and 0.2% solution: Glaucoma The same
Occular Hypertension as
Dipivefrin

(e) Naphazoline: 0.012%, 0.03 and 0.1% solution: Decongestant

(f) Tetrahydrozoline: 0.05% solution: : Decongestant

(5) Adrenergic Antagonists

(a) Betaxolol (β1 selective): 0.25% and 0.5 % susp.
(b) Carteolol (β): 1% solution
(c) Levobunolol (β): 0.25% and 0.5% solution Glaucoma, Ocular
(d) Metipranolol (β): 0.3% solution: Hypertension
(e) Timolol (β): 0.25% and 0.5% solution and gel

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(6) Immunomodulatory and Antimitotic Ophthalmic Agents
(a) Glucocorticoids for ocular inflammatory diseases.
The topical agents here include: Dexamethasone, Prednisolone,
Fluorometholone, Loteprednol, Rimexolone and Difluprednate. They are
used in managing ocular allergy, anterior uveitis, external eye
inflammatory diseases associated with some infections and ocular
cicatricial pemphigoid and post operative inflammation following
refractive, corneal and intra-ocular surgery.
Toxicity - Ocular problems include:

- Development of posterior sub capsular cataracts

- Secondary infections

- Secondary open – angle glaucoma

- Raised intraocular pressure (IOP).

(b) NSAIDs
Five topical NSAIDS in use in ocular diseases include:

- Flurbiprofen – counter unwanted intraoperative miosis in cataract surgery.

- Ketorolac –for seasonal allergic conjunctivitis also for cystoids macular edema
and
- Dictofenac for post – op inflammation post cataract surgery

- Bromfenac
- Nepafenac for post - op pain and inflammation after cataract surgery

(c) Antihistamines and Mast – Cell Stabilizers

Pheniramine and Antazoline, both H1 receptor antagonists, are formed in
combination with naphazoline, a vasoconstrictor, for relief of allergic
conjunctivitis; as well as emedastine difumarate.

Cromolyn sodium have limited use in treatment of conjunctivitis that is

allergen mediated e.g. vernal conjunctivitis. Lodoxamide tromethamine and
pemirolast mast cell stabilizers are also available. Nedocromil is a mast cell
stabilizer with some antihistamine properties. Olopatadine hydrochloride,

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Ketotifen fumarate, bepotastine and azelastine are H1 antagonists with
mast – cell – stabilizing property.

Epinastine antagonizes both H1 and H2 receptors and exhibits mast cell-

stabilizing activity.