Pharmacology: Special Sense

DRUGS ACTING ON EYE

OBJECTIVES  List main groups of drugs applied on the eye and their clinical applications.  Discuss the local effects of autonomic drugs on their receptor sites in the eye with relevance to their clinical applications.  Identify the lines of treatment of some eye diseases as glaucoma and conjunctivitis.

STRUCTURES OF THE EYES

Anatomically eye composed of : i) Anterior chamber ii) Posterior chamber ANTERIOR CHAMBER INCLUDE: 1. CORNEA 2. IRIS 3. LENS 4. AQUEOUS HUMOUR 1. THE CORNEA CORNEAL OR CONJUNCTIVAL REFLEX  The cornea and the sclera are supplied by sensory nerves.  When the cornea is touched the corneal reflex is initiated i.e. the eye blinks on touching the cornea with a piece of cotton DRUGS ACTING ON CORNEA Include: A. Local Anaesthetics B. Diagnostic Dyes C. Topical Anti-Inflammatory D. Topical Anti-Infective Drugs E. Tear Substitutes & Lubricating Agents A. LOCAL ANAESTHETIC DRUGS Includes: 1. Surface anaesthesia by lidocaine eye drops for : a. Tonometry: measurement of IOP b. Removal of corneal foreign bodies 2. Profound anaesthesia by tetracaine eye drops for: Removal of cataracts B. DIAGNOSTIC DYES Fluorescein 1% - Used for diagnosis of corneal ulcers - Denuded epithelium is stained bright green Rose Bengal 1% - Used for diagnosis dry eye - Dead cells are stained red

Pharmacology: Special Sense C. TOPICAL ANTI-INFLAMMATORY DRUGS Includes: 1. Steroidal anti-inflammatory drug  Used for anterior segment of eye inflammation as allergic conjunctivitis  Example: Dexamethasone 2. Non-steroidal anti-inflammatory drugs  Have anti-prostaglandins action  Example: Ketophenac sodium D. TOPICAL ANTI-INFECTIVE DRUGS Include: 1. Topical Anti-Biotics (e.g. Neomycin, Chloramphenicol, Ciprofloxacin) 2. Topical Anti-Fungi (e.g. Nystatin Solution) 3. Topical Anti-Viral Agents (e.g. Acyclovir for dendritic corneal ulcer) E. TEAR SUBSTITUTES AND LUBRICATING AGENTS Example: 1. Methyl cellulose 2. Polyvinyl alcohol Uses: 1. Formation of artificial tears in dry eye conditions as Sjogren s syndrome 2. Contact lens solution 2. THE IRIS Muscles include: 1) Sphincter Pupillae Muscle: Parasympathetic M3 Receptors 2) Dilator Pupillae Muscle: Sympathetic 1 Receptors LIGHT REFLEX PRINCIPLE  Narrowing of pupil (miosis) when the eye is stimulated by light  This miosis is due to contraction of constrictor pupillae muscle i.e. light reflex depends on integrity of parasympathetic supply of the eye  Parasympatholytics abolish light reflex 3. THE LENS ACCOMODATION REFLEX  It is the ability to increases the convexity of the crystalline lense to obtain a clear image of an object at various distances  This is mediated through the parasympathetically innervated ciliary muscle, whose contraction causes suspensory ligaments relaxation thus increasing the lense curvature and diopteric power leading to accomodation for near vision 4. THE AQUEOUS HUMOUR  It is formed of highly vascularized ciliary body processes that absorb sodium selectively via carbonic anhydrase enzyme(70%) and ATPase system  The aqueous humour circulates through the pupil and is drained in the canal of Schlemm then to episcleral veins  Normally there is balance between aqueous homour formation and outflow and this keeps intraocular pressure within normal range (10-21mmHg)

Pharmacology: Special Sense

AUTONOMIC DRUGS ACTING ON THE EYE

Includes: A. Miotics B. Mydriatics A. MIOTICS Includes: 1. Parasympathomimetics 2. Sympatholytics (e.g. Guanethidine) 3. Morphine (by stimulation of Edinger-Westphal nuclei) 1. PARASYMPATHOMIMETICS MECHANISM OF ACTION  They stimulate M3 receptors in ciliary muscle and constrictor pupillae muscle leading to: a. Miosis: constriction of the pupil b. Accomodation for near vision c. Reduce intraocular pressure: as when the pupil is constricted, the anterior chamber angle is widened and this facilitates the drainage through Canal of Schlemm INCLUDES: I) Cholinesters 1. Carbachol 1% 2. Bethenecol 1% II) Cholinomimetic Alkaloids Pilocarpine 2% III) Anticholinesterases A. Reversible i. Physostigmine 1% ii. Neostigmine 3% B. Irriversible i. AS D.F.P 0.1%

Parasymathomimetics
     Pupil Size Light Reflex Accommodation IOP Conjunctival BV : Miosis : Absent : For Near Vision : Reduced : Congested

B. MYDRIATICS CAUSE: A. Passive Mydriasis i. Parasympatholytics B. Passive Mydriasis i. Sympathomimetics ii. Cocaine

Pharmacology: Special Sense A i) PARASYMPATHOLYTICS MECHANISM OF ACTION They cause paralysis of sphincter pupillae muscle leading to: a. Passive mydriasis b. Abolish light reflex c. Increase IOP: due to narrowing of anterior chamber angle d. Loss of accomodation for near vision: as they produce cycloplegia INCLUDES: a. Atropine 1% (last for 10 days) b. Atropine Substitutes i. Homatropine 2% (for 24 hours) ii. Eucatropine 2% (for 3-4 hours) iii. Cyclopentolate 1% (2 hours) iv. Tropicamide 1% THERAPUTIC USES 1. Fundus examination and diagnosis of refractory errors 2. To break recent adhesions between the iris and the lense in anterior uveitis 3. Treatment of acute iritis and iridocyclitis as they relief pain resulting from cilliary muscle spasm

Parasympatholytics
     Pupil Size Light Reflex Accommodation IOP Conjunctival BV : Passive Mydriasis : Absent Due To Paralysis Of Constrictor Pupillae Muscle : For Far Vision : Increased : No Effect

B i) SYMPATHOMIMETICS MECHANISM OF ACTION  They produce active mydriasis by sympathetic nerve fibers that are motor to radial muscle through action on 1 receptor  They do not affect light reflex or accomodation  They are vasoconstrictors so the reduce vascular congestion of conjunctival blood vessels EXAMPLE Ephedrine sulphate, Phenylephrine and Dipivefrin B ii) COCAINE MECHANISM OF ACTION 1. It produces active mydriasis as it potentiates sympathetic response by: a. Decreasing re-uptake of released catecholamines b. Inhibits degradation of catecholamines by MAO 2. It preserves light reflex 3. Abolishes corneal reflex by its local anaesthetic action

Pharmacology: Special Sense

TREATMENT OF SOME EYE DISEASES

A. CONJUNCTIVITIS Includes: 1. Bacterial Conjunctivitis 2. Allergic Conjunctivitis 1. BACTERIAL CONJUNCTIVITIS DEFINITION It is inflammation of the conjunctiva associated with mucopurulent discharge, redness and eyelids edema. MANAGEMENT Includes: I) Eye Lotions II) Hot Foments III) Astringent Eye Drops IV) Topical Antimicrobial Agents I) EYE LOTIONS  To wash off the discharge  Example: Bland eye lotions Boric acid lotion 4% II) HOT FOMENTS  Are applied locally in order to relief edema and pain III) ASTRINGENT EYE DROPS  Precipitate proteins so decrease capillary permeability  Example: Zinc sulphate 1% IV) TOPICAL ANTIMICROBIAL AGENTS  Local eye drops every 1-2hrslday and eye ointment at night  Example: Neomycin 2. ALLERGIC CONJUNCTIVITIS DEFINITION It is acute allergy due to exposure to allergen .The patient present with redness of eyes with itching and lacrimation. MANGEMENT Includes: I) Treatment Of Acute Attack a. Anti-Histaminic Eye Drops b. Glucocorticoid Eye Drops II) Prophylactic Treatment a. Mast Cell Stabilizer

Pharmacology: Special Sense I a) ANTI-HISTAMINIC EYE DROPS y Example: Levocabastine Antazoline I b) GLUCOCORTECOIDS EYE DROPS y Example: Dexamethasone y Precaution: We must exclude viral dendritic ulcer and glaucoma II a) MAST CELL STABILIZERS Example: Na cromoglycate

B. GLAUCOMA # DEFINITION It is agroup of diseases that have in common a characteristic optic neuropathy with associated visual field loss for which the elevated intraocular pressure is one of primary risk factors. # CLASSIFICATION Includes: 1. Closed-Angle Glaucoma 2. Open-Angle Glaucoma

1. CLOSED-ANGLE GLAUCOMA  It is associated with a shallow anterior chamber, in which a dilated iris can occlude the outflow drainage pathway at the angle between cornea and cilliary body  In this type, acute and painful rise of IOP is often precipitated that must be controlled on an emergency basis with drugs or prevented by iridectomy 2. OPEN-ANGLE GLAUCOMA  The outflow of aqueous humour through the trabecular meshwork-Schlemm s canal venous system is impaired  It is a chronic condition and treated medically, aiming to slow the rate of disease progression to prevent significant visual impairment

Pharmacology: Special Sense # MEDICAL MANAGEMENT OF GLAUCOMA I) -BLOCKERS II) DIURETICS III) SYMPATHOMIMETICS IV) PROSTAGLANDIN ANALOGUES V) PARASYMPATHOMIMETICS I) - BLOCKERS Includes: A. Non-Selective -Blockers (e.g. Timolol Maleate Topical Eye Drops) B. Selective 1 Blockers (e.g. Levobunolol HCL Topical Eye Drops) Mechanism Of Action Timolol blocks beta receptors on the cilliary processes resulting in decreasing aqueous production. It is treatment of choice in open-angleglaucoma II) DIURETICS Includes: 1. Hyper Osmotic Agents a. Mannitol I.V. 2. Carbonic Anhydrase Inhibitors a. Acetazolamide Oral (I.V. in emergency) b. Dorzolamide Topical Eye Drops Mechanism Of Action Of Hyperosmotic Agents It acts by withdrawing fluid from the eye and reducing vitreous volume. Mechanism Of Action Of Carbonic Anhydrase Inhibitors They inhibit carbonic anhydrase in the cilliary body, which prevents bicarbonate synthesis resulting in a fall in Na transport and aqueous flow. III) SYMPATHOMIMETICS Includes: 1. And Agonists a. Dipiverfin HCL Topical Eye Drops 2. 2 Agonists a. Brimonidine Tartrate Topical Eye Drops Mechanism Of Action Of And Agonists It lowers the IOP by a balance between and adrenoreceptors stimulation 1. mediated VC of the cilliary BVs will decrease the aqueous flow 2. 2 mediated effect will increase trabecular meshwork drainage Contraindication Angle-closed glaucoma Mechanism Of Action Of 2 Agonist 1. It reduces aqueous humour production 2. It increases uveoscleral outflow (secondary pathway for aqueous outflow 20%)

Pharmacology: Special Sense IV) PROSTAGLANDIN ANALOGUES (F2 ) Example And Form Latanoprost solution: topical eye drops Mechanism Of Action 1. It enhances the uveoscleral outflow of the aqueous 2. It increases blood flow to the optic nerve that may contribute in retinal neuroprotection V) PARASYMPATHOMIMETICS Example And Form Pilocarpine HCL: topical eye drops or gel Mechanism Of Action It increases aqueous outflow by contracting the ciliary muscle. Which pulls the scleral spur, resulting in widening of the trabecular meshwork Side Effects Blurred vision and ache over the eye # DRUGS CONTRAINDICATED IN GLAUCOMA o Topical and systemic corticosteroids due to the possible increase in trabecular meshwork inducible glucocorticoid response (TIGR) gene expression as an assumed mechanism for outflow obstruction. o Strong vasodilators (e.g. nitrites) because they may increase aqueous humour formation. o Cycloplegic drugs as atropine.