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‫سم اـهلل لرـاـحمن لرـاـحيم‬

‫بــ‬

Ocular Pharmacology
By
Dr. Muhammad Imran Ali
Learning objectives
By the end of this session, the student should be able to:
1. Describe the basic principles of ocular therapeutics.
2. Revise various routes for ocular administration of drugs
3. Recall mechanism of action and discuss clinical indications for
 mydriatics/ cycloplegics,
 miotics,
 topical steroids,
 topical anesthetics,
 anti-glaucoma drugs,
 anti-allergic drugs
 topical NSAIDs
and review their common side effects (both systemic and local)
Ocular pharmacology:
Basic principles
 Ocular pharmacology
 Due to a number of anatomical and biological factors that exist to protect the eye,
the intraocular bioavailability of topically administered medications is typically
only 1-10%
 A smaller instilled eye drop may result in decreased blinking, increased retention
time, and greater absorption
 A large portion of a topically instilled drop results in nasolacrimal drainage and
systemic absorption, which may lead to adverse side effects
 The cornea is a potent barrier to drug absorption due to its small surface area
and its low permeability to both lipophilic and hydrophilic drugs
 Some aspects of drug formulation that affect bioavailability include
hydrophilicity/lipophilicity, concentration, osmoticity, pH, and viscosity
 a
 Pharmacokinetics
 Topical drop size = app 50 µL (1ml = 20 drops)
 Only 10 µL is retained by the conjunctiva ( remaining flows over cheek and lids or drained by
lacrimal drainage system into nose)
 The tear turn over is about 15 % per minute. So the drug that remains in conjunctival sac is
washed away by tears in approximately five minutes.
 During this time the drug is absorbed by the conjunctiva or and cornea.
 Drug absorbed by conjunctiva goes either to systemic circulation or enters the sclera and
reaches ciliary body but faces tight junctions of retinal pigment epithelium so can not enter
posterior segment.
 Cornea has three barriers: surface epithelium and endothelium have tight junctions so force
drug to pass through cellular membranes thus allowing only lipophilic drugs to pass.
 Corneal stroma is water rich and resists the passage of lipophilic drugs while facilitating
hydrophilic drugs to pass.
Methods to increase bioavailability of
Topical drugs
 Punctal occlusion
 By finger pressure on the medial corner of eye
 Eyelid closure to avoid blinking (some authorities consider it more effective than
finger pressure)
 Silicone plugs
 Increase the concentration of the drug ( limited by toxicity and tonicity)
 Increased dosing frequency
 Changing the characteristics of the drug or its vehicle
 Increasing lipid solubility
 Adding surfactant
 Increasing viscosity
 others
Different formulations of Topical
Medications
Eye drops:
 Solutions
 Contact time is minimal so need more frequent dosing
 Suspensions
 More contact time
 Particulate nature stimulates reflex tearing
 Suspensions tend to settle in the bottom so need to be shaken before usage

Ointments :
 Increase the contact time further so need less frequent dosing
 Leave a film over eye causing blurring of vision
Routes of ocular drug administration
 Topical (into conjunctival cul-de-sac)
 Periocular
 Subconjunctival
 Sub tenon
 Anterior
 posterior
 Peribulbar
 Retrobulbar
 Intraocular
 Intracameral ( into the anterior chamber)
 intravitreal
 Systemic
 Commonly Prescribed
Drugs in Ophthalmology
Commonly Prescribed Drugs in
Ophthalmology
1. Mydriatics/cycloplegics
2. Miotics
3. Topical steroids
4. Topical anesthetics
5. Anti-glaucoma drugs
6. Anti-allergic drugs
7. Topical NSAIDs.
1. MYDRIATICS/CYCLOPLEGICS

 Mydriatics – dilate the pupil

 Cycloplegics – relax ciliary muscle
 Two groups of autonomic drugs
 Parasympatholytics ( have both mydriatics and cycloplegics effects)
 Sympathomimetics (have only mydriatic effect)
 Parasympatholytics (mydriatic and cycloplegic
 effects)
Anti-muscarinic anticholinergics
 Block muscarinic receptors of sphincter pupillae and ciliary muscles leading to dilation of the
pupil and relaxation of ciliary muscle. So abolishing accommodation.
 Commonly used drugs are
1. Atropine (long duration of action, about 10 - 14 days)
2. Cyclopentolate (intermediate duration of action, about 24 hours)
3. Tropicamide (shortest duration of action, about 6 hours)
 Indications
 Pupil dilation for funduscopy (Tropicamide)
 Pupil dilation for cataract surgery (Tropicamide +/- Cyclopentolate)
 In uveitis to prevent the formation of posterior synechia by dilating pupil, and to relive ocular pain by
relxing ciliary muscle (Tropicamide/ Cyclopentolate)
 In young children to do objective refraction cycloplegic retinoscopy (Cyclopentolate/ atropine)
Side effects of Parasympatholytics

 Increase heart rate

 Flushing of face
 Fever
 Dry mouth
 Dry eye
 Urinary retention
 Constipation
 Confusional psychosis
Phenylephrine hydrochloride (mydriatic
only)
 Sympathomimetic
 Selective α-1 receptor agonist
 Stimulates dilator pupillae muscle to cause dilation of the pupil
 No effect on ciliary muscle
 Used
 To dilate the pupil for fundus examination
 To dilate the pupil for cataract surgery
 Side effects
 Marked increase in blood pressure
 Tachycardia
 Cardiac arrhythmia
 Risk of MI
2. Miotics
 Parasympathomimetics
 Pilocarpine, Carbachol
 Stimulate sphincter pupillae to cause miosis
 By contracting the longitudinal muscle of the ciliary body and
mechanically pulling on the trabecular meshwork, thereby opening
it
 By contraction of radial ciliary muscle leading to increase in
refractive power of lens
 Indications:
 Treatment Of Angle Closure Glaucoma
 Treatment of Primary Open Angle Glaucoma
Side effects of Miotics (Pilocarpine)

 Brow ache
 Blood aqueous breakdown
 Angle closure
 Decreased night vision
 Variable myopia
 Retinal tears / retinal detachment
 Cataract
 Diarrhoea, cramps, enuresis
3. TOPICAL CORTICOSTEROIDS

 PREDNISOLONE
 FLUOROMETHOLONE
 DEXAMETHASONE
 RIMEXOLONE
 Mechanism of action of steroids

 Anti-inflammatory
 ACT BY SUPPRESSING THE FORMATION
OF ARACHIDONIC ACID AND OTHER
MEDIATORS OF INFLAMMATION
Common indications of topical Steroids

 Uveitis
 Allergic conjunctivitis
 VKC
 Scleritis
 Episcleritis
 Post operative ( after cataract surgery)
 MUST NOT BE PRESCRIBED AS INITIAL TREATMENT OF
BACTERIAL KERATITIS/ CORNEAL ULCER
Side Effects Of Topical Steroids
 OCULAR
 Steroid induced glaucoma
 Posterior sub-capsular cataract
 Corneal thinning
 Delayed wound healing
 Predisposition to infections

 SYSTEMIC
Peptic Ulcer, GI Hemorrhage, GI Perforation, Osteoporosis, Diabetes, Electrolyte
Imbalance, Hypertension, Avascular Bone Necrosis Of Head Of Femur, Weight Gain,
Acne, Hirsutism
4. TOPICAL ANESTHETICS
 Proparacaine (Alcaine) most commonly used
 Tetracaine
 Procaine
 Benoxinate
 Uses (indications)
 To anesthetize cornea for
1. Removal of superficial corneal foreign bodies
2. To measure IOP with contact (Goldmann, Perkins, Schiotz) tonometers
3. Gonioscopy
4. Removal of corneal sutures
5. Cataract surgery under topical anesthesia
6. Refractive surgery
7. Biometry ( to measure axial length using A-scan)
Side effects of topical anesthetics

 Delay corneal wound healing and regeneration of epithelium

 Patients with corneal ulcer sometimes demand to prescribe them
topical anesthetic but these should never be prescribed
5. ANTI GLAUCOMA DRUGS

1.Hyperosmotic Agents
2.Carbonic Anhydrase Inhibitors
3.Prostaglandin Derivatives
4.Beta-blockers
5.Alpha2-agonists
6.Miotics (Parasympathomimetics)
HYPEROSMOTIC AGENTS

 Mannitol (for intravenous administration)

 Glycerol ( for oral administration)
 Osmotic diuretics
 Draw fluid out of vitreous into choroidal /retinal circulation
 Lower IOP immediately
 Used in acute congestive glaucoma (acute angle closure
glaucoma)
 Also used to lower IOP before cataract surgery in patients with
lens induced glaucoma
Side effects of Hyperosmotic Agents
 Cardio vascular over load
 Due to increase extra cellular volume
 Caution in patients with cardiac or renal disease
 Urinary retention
 In elderly patients with I/V administration.
 Catheterization may be necessary in those with prostatism
 Miscellaneous
 Headache
 Backache
 Nausea
 Confusion
 CARBONIC ANHYDRASE INHIBITORS
 Sulphur compounds related to sulphonamides
 Inhibitors of carbonic anhydrase enzyme so reduce aqueous
production/secretion
 Systemic: Acetazolamide (oral and injectable)
 Topical: Dorzolamide, Brinzolamide
 Systemic Side Effects
 Common
 Paresthesia
 Malaise complex
 Hypokalemia
 Metabolic acidosis
 Uncommon
 GI upset, renal stone formation, stevens-johnson syndrome, blood dyscrasias
β-BLOCKERS

 Reduce aqueous secretion form ciliary processes

 Timolol – non selective β-blocker
 Betaxolol – β1 selective
 Used as first line treatment of primary open angle
glaucoma
 Major side effects are
 Bradycardia , hypotension
 Heat block
 Precipitation of asthmatic attack in asthmatics
α2-AGONISTS

 These agents decrease IOP by both decreasing aqueous secretion

and enhancing uveoscleral outflow
 Brimonidine
 Apraclonodine
 Their IOP lowering effect is less than beta blockers
 Side effects
 Topical: toxicity, irritation,
 Systemic : xerostomia, fatigue etc
 Tachyphylaxis : loss of effect with time
Prostaglandin analogs
They reduce IOP by enhancing uveoscleral outflow
 LATANOPROST
(Prostaglandin F2-alpha analogue)
 Convenient dosage
 Better patient compliance
 Efficacy is superior to timolol
 Side effects (ocular)
 Conjunctival hyperemia
 Hyper pigmentation and lengthening of eye lashes
 Anterior uveitis
 Cystoid macular edema
 Systemic side effects
 Headache
 Upper respiratory tract symptoms
Anti glaucoma therapy for Primary open angle
glaucoma
 First line drugs are prostaglandin analogs or beta blockers or both
 If the above regimen does not control IOP then topical carbonic
anhydrase inhibitor is added
 Other options are alpha agonists, miotics etc. used in patients
intolerant or sensitive to above drugs.
6. ANTI-ALLERGIC DRUGS
 Antihistamines (H1 antagonists)
 Levocabastine
 Emedastine
 Antihistamine/ decongestants
 Naphazoline/pheniramine (riazolin) should not be used long term
 Mast cell stabilizers
 Cromolyn sodium
 lodoxamide
 Combined mast cell stabilizers/ antihistamines
 Olopatadine
 Ketotifen
ANTI-ALLERGIC DRUGS

 Used for seasonal, perennial allergic conjunctivitis

 Vernal kertoconjunctivitis
 Giant papillary conjunctivitis
 Newer drugs like olopatadine with convenient Once a day or twice
a day dosage in good for long term usage as it improves patient
compliance
 No significant side effects
7. TOPICAL NSAIDs
 Anti inflammatory drugs
 Diclofenac sodium, flurbiprofen, Nepfenac, Ketorolac
 Uses
 To control inflammation after cataract surgery, in scleritis, episcleritis,
 To maintain mydriasis during cataract surgery
 To treat cystoid macular edema
 To treat allergic conjunctivitis (Ketorolac)
 Side effects
 Topical irritation, discomfort
 Corneal thinning with long term use of diclofenac
Thank You