1. Pharmacology of drugs acting on the eye
Prof. Hanan Hagar
Pharmacology Unit
Physiology Department
College of Medicine
King Saud University

2. Routes of drug administration into the eye
Drugs can be delivered to ocular tissue as:
Locally (Topically): more common
Eye drop
Ointment
Injection :
Periocular injection
e.g. subconjunctival, peribulbar, or retrobulbar
Intraocular injection
e.g. Intracameral or intravitreal
Systemically:
Orally IV

3. Eye drops Ointment Eye drops- most common one drop = 50 µl
volume of conjunctival cul-de-sac 7-10 µl
Increase the contact time of ocular medication to ocular surface thus better effect
Disadvantages
The drug has to be high lipid soluble with some water solubility to have the maximum effect as ointment

4. Intraocular injections
Peri-ocular injections
Intraocular injections
Intracameral or intravitreal
E.g.
Intracameral acetylcholine (miochol) during cataract surgery
Intravitreal antibiotics in cases of endophthalmitis
Intravitreal steroid in macular edema
subconjunctival, peribulbar, or retrobulbar
reach behind iris-lens diaphragm better than topical application
bypass the conjunctival and corneal epithelium which is good for drugs with low lipid solubility (e.g. penicillins)
steroid and local anesthetics can be applied this way

5. Systemic drugs Oral or IV
Factor influencing systemic drug penetration into ocular tissue:
lipid solubility of the drug: more penetration with high lipid solubility
Protein binding: more effect with low protein binding
Eye inflammation: more penetration with ocular inflammation

6. Physiological Anatomy of the Eye

7. Pharmacology of drugs acting on the eye
Drugs used for the treatment of eye
Drugs that can produce harmful effects on the eye

8. Ophthalamic Uses of Drugs
Autonomic drugs:
Affect the size of the pupil:
Miotics
Mydriatics
Affect accommodation (Cycloplegics).
Anti-inflammatory drugs:
Glucocorticoids
NSAIDs
Chemotherapeutics (antibacterial, antifungal and antiviral agents).
Local Anesthetic drugs

9. Drugs used for treatment of the eye
Chemotherapeutic agents
Local anesthetics
Anti-inflammatory drugs
Miotics
Mydriatics
Cycloplegics
Autonomic drugs

10. Autonomic Nerve supply of the Eye
Parasympathetic N.S.
Constriction of the pupillary sphincter muscle (miosis)
Contraction of the ciliary muscle (accommodation for near vision).
Decrease in intraocular pressure ↓ IOP.
increases aqueous outflow through the trabecular meshwork into canal of Schlemm by ciliary muscle contraction
Increased lacrimation
Conjunctival Vasodilatation

12. The aqueous humor is secreted by the ciliary body
The aqueous humor is secreted by the ciliary body. Produced by a combination of active transport of ions and ultrafiltration of interstitial fluid. The fluid flows over the surface of the lens, out through the pupil into the anterior chamber. Flows through the trabecular meshwork into Schlemm’s canal and is collected in the scleral veins.

14. Autonomic
control
of pupil (A)
and site
of action of
mydriatics (B)
and
miotics (C)

15. Accomodation

16. Sympathetic N.S.
Contraction of dilator Pupillae ( Mydriasis) α1
Relaxation of ciliary muscles (accommodation for far vision) β receptors
Increase in intraocular pressure
Lacrimation α1
Vasoconstriction of conjunctival blood vessels α1
β receptors in the blood vessels of the ciliary processes →production of aqueous humour.
β antagonists reduces the production of aqueous humor
α agonists increase outflow of aqueous humor and ↓ IOP

17. Sympathetic N.S. Parasympathetic N.S.
Eye
Contraction (Mydriasis) α1
No effect
Contraction (miosis) M3
Iris
radial muscle
circular muscle
Relaxation β2
Contraction M3
Ciliary muscle
accommodation for far vision
for near vision
Accommodation
Conjunctival Vasoconstriction
Conjunctival Vasodilatation
Conjunctival blood vessels
Narrow filtration angle
Decrease
Intraocular pressure(IOP)

18. Pupillary Muscles
Miosis
Mydriasis

19. Drugs acting on parasympathetic system
Cholinergic agonists
Direct agonists
Methacholine, carbachol, pilocarpine
Indirect acting agonists (anticholinesterases)
Reversible :Physostigmine
Irreversible: Ecothiophate
USES:
-Glaucoma (open angle glaucoma)
-Counteract action of mydriatics
To break adhesions
in accommodative esotropia (ecothiophate)

20. bronchial constriction vomiting and diarrhea
 Adverse Effects of cholinergic agonists:
Miosis
Salivation
Sweating
bronchial constriction
vomiting and diarrhea
CNS effects: high doses (physostigmine & pilocarpine)
Ocular side effects: diminished vision (myopia), headache,
Contraindications of cholinergic agonists:
Bronchial asthma.
Peptic ulcer.
Angina pectoris
Incontinence
Intestinal obstruction

21. Cholinergic drugs Ocular uses Drugs Induction of miosis in surgery
Glaucoma
Acetycholine
Carbachol
Methacholine
In open angle glaucoma
Pilocarpine
Glaucoma, accommodative esotropia
Physostigmine
Ecothiophate

22. Cholinergic antagonists (Muscarininc antagonists)
Passive mydriasis
due to relaxation of circular muscles
Cycloplegia (loss of near accommodation) due to relaxation of ciliary muscles
Loss of light reflex.
increased I.O.P # glaucoma.
 Lacrimal secretion  sandy eye
Duration of effect
Drugs
7-10 days
3-7 days
Natural alkaloids
Atropine
Scopolamine (hyoscine)
1-3 days
24 hour
6 hour
Synthetic atropine substitutes
Homatropine
Cyclopentolate
Tropicamide

23. To prevent adhesion in uveitis & iritis
USES:
To prevent adhesion in uveitis & iritis
Funduscopic examination of the eye
Measurement of refractive error
Side effects: blurred vision, tachycardia, constipation,
urinary retention, dryness of mouth , dry sandy eyes, fever
CNS effects: sedation, hallucination, excitation (toxic dose).
Contraindications of antimuscarinic drugs
Glaucoma (angle closure glaucoma)
Tachycardia, Prostate hypertrophy in old patients.
Constipation, paralytic ileus.

24. Drugs acting on sympathetic system
Adrenergic agonists
Non-selective agonists (α1, α2, β1, β2), eye drops
e.g. epinephrine, depevefrin (pro-drug of epinephrine)
Uses: open angle glaucoma
Mechanism:  uveoscleral outflow of aqueous humor
Side Effects: cardiovascular arrhythmia, tachycardia
C/I in closed angle glaucoma in patients with narrow angles
α1 agonists e.g. phenylepherine
mydriasis (without cycloplegia), decongestant
Uses:
Funduscopic examination of the eye
To prevent adhesion in uveitis & iritis
Decongestant in minor allergic hyperemia of eye
Can cause significant increase in blood pressure

25. α2 agonists e.g. apraclonidine (eye drops)
Uses: glaucoma treatment, prophylaxis against IOP spiking after
glaucoma laser procedures
Mechanism:  production of aqueous humor
Side Effects: Lethargy, fatigue, dry mouth
[apraclonidine is a derivative of clonidine (antihypertensive)
which cannot cross BBB to cause systemic hypotension.

26. β blockers selective: betaxolol (beta 1 “cardioselective”)
non-selective: timolol, carteolol
selective: betaxolol (beta 1 “cardioselective”)
Given topically as eye drops
Uses: open angle glaucoma
Mechanism: Act on ciliary body to  production of aqueous humor
Advantages can be used in patients with hypertension/ischemic heart disease
Contraindications
Bronchospasm (less with betaxolol)
Cardiovascular (bradycardia, hypotension, asystole, syncope)
Depression
C/I in asthmatic patients or patients with pacemaker.

27. Treatment of open angle glaucoma (chronic)
The main goal is to decrease IOP and this can be obtained by:
Decreasing production of aqueous humor
Beta blockers
Alpha-2 agonists
Carbonic anhydrase inhibitors
Increasing outflow of aqueous humor
Prostaglandins
Adrenergic agonists, nonspecific
Parasympathomimetics
Prostaglandins and Beta blockers are the most popular drugs.

28. Carbonic anhydrase inhibitors
e.g. acetazolamide (oral), dorzolamide (topical)
Mechanism:  production of aqueous humor by blocks carbonic anhydrase enzyme required for production of bicarbonate ions (transported to posterior chamber, carrying osmotic water flow).
Side Effects:
myopia, malaise, anorexia, GI upset, headache
metabolic acidosis, renal stone
bone marrow suppression “aplastic anemia”
Contraindication:
sulpha allergy

29. Prostaglandins Latanoprost, travoprost Are prostaglandins F2α analogs
Mechanism:
uveoscleral outflow by relaxing ciliary body muscle
Uses: open angle glaucoma
Administration: Topical drops
Side Effects: Iris color change

30. Drug Therapy of acute angle closed glaucoma (narrow angle)
Is associated with occlusion of the outflow drainage pathway
Acute, painful increases of pressure
emergency situation that require treatment before surgery (Iridectomy)
The use of drugs is limited to :
Oral Acetazolamide
Topical cholinomimetics e.g.: pilocarpine
Dehydrating agents: IV infusion Of hypertonic solution ( Mannitol, Glycerol)
Analgesics: pethidine or morphine (for pain)

31. Dehydrate vitreous body which reduce IOP significantly E.G.
Osmotic agents
Dehydrate vitreous body which reduce IOP significantly
E.G.
glycerol 50% syrup (cause nausea, hyperglycemia)
Mannitol 20% IV (cause fluid overload and not used in heart failure)

34. Corticosteroids Topical Systemic:
Mechanism: inhibition of arachidonic acid release from phospholipids by inhibiting phosphlipase A2
Topical
E.g. prednisolone, dexamethasone, hydrocortisone
Uses: postoperatively, anterior uveitis, severe allergic conjunctivitis, scleritis, prevention and suppression of corneal graft rejection
Systemic:
E.g. prednisolone, cortisone
Uses: posterior uveitis, optic neuritis

35. Corticosteroids Side effects: Glaucoma, cataract, mydriasis
Suppression of pituitary-adrenal axis
Hyperglycemia, Osteoporosis
Peptic ulcer, Psychosis, susceptibility to infections

36. NSAID E.g. ketorolac, diclofenac
Mechanism: inhibition of cyclo-oxygenase
Uses: postoperatively, mild allergic conjunctivitis, episcleritis, mild uveitis, cystoid macular edema, preoperatively to prevent miosis during surgery
Side effects: stinging

37. Harmful drugs for the Eye
Drugs that ↑ IOP:
Mydriatic cycloplegics, tricyclic antidepressants
Chronic steroid use
Cataractogenic drugs:
steroids, phenothiazines, heavy metals…

38. Drugs causing corneal deposits:
chloroquine, amiodarone,
Amiodarone , a cardiac arrhythmia drug
causes optic neuropathy (mild decreased vision, visual field defects)
causes corneal keratopathy which is pigmented deposits in the corneal epithelium.
Digitalis , cardiac failure drug
Causes chromatopsia (objects appear yellow) with overdose

39. Other agents methanol – optic atrophy and blindness
Ethambutol – optic neuropathy
Hypervitaminosis A – yellow skin and conjunctiva, retinal hemorrhage.
Hypovitaminosis A – night blindness (nyctalopia).