1. DR: Mahmoud Saeed Lecturer Of Clinical Pharmacy BMC
OCULAR PHARMACOLOGY
DR: Mahmoud Saeed Lecturer Of Clinical Pharmacy BMC

2. & Physiological considerations
Anatomical
& Physiological considerations

4. 1. Iris and Pupil A-Constrictor pupillae muscle :
Parasympathetic supply.
Muscarinic M3 receptors.
Miosis (constriction of pupil).

5. 1. Iris and Pupil B-Dilator pupillae muscle: Sympathetic supply.
α1 receptors.
Mydriasis (dilation of pupil).

6. 2.Ciliary body Functions:
Secretion of aqueous humor by ciliary epithelium ( mainly β2 & some β1 receptors).
Accommodation of the vision by contraction of ciliary muscle ( loss of accommodation = Cycloplegia ).
Uveoscleral outflow.

7. Intraocular pressure(IOP)
Normal IOP: mm Hg.
Glaucoma = ↑ IOP.
To ↓ IOP :
1- ↓ Formation of aqueous humor.
2- ↑ Drainage of aqueous humor.

8. Miotic Drugs Drugs that constrict the pupil .
A – Parasympathomimetics:
1. Direct acting :
e.g. pilocarbine , carbachol & bethanecol .
2. Indirect acting :
e.g. physostigmine .

9. Miotic Drugs Actions of Parasympathomimetics : Miosis :
Through M3 receptors → contraction of Constrictor Pupillae Muscle
2. Accommodation for near vision .
3. ↓ IOP due to opening of canal of Schlemm.

10. Miotic Drugs B – Sympatholytics: e.g. Guanethidine .
C – Central acting :
e.g. Morphine .

11. Mydriatic Drugs Drugs which produce dilation of the pupil.
A- Active Mydriatics :
Stimulate dilator pupillae muscle via α1 R.
1- Sympathomimetics :
Direct effect : e.g. Phenylephrine.
Indirect effect : e.g. Amphetamine .
Dual action : e.g. Ephedrine .

12. Mydriatic Drugs A- Active Mydriatics : 1- Sympathomimetics : Actions :
1. Contraction of dilator pupillae muscle. (Light & corneal reflexes are present).
2. Vasoconstriction of blood vessels→ eye decongestant .
3. No cycloplegia .
4. Contra-indicated in closed angle glaucoma .

13. Mydriatic Drugs A- Active Mydriatics : 2. Cocaine :
Local anesthetic for the cornea & conjunctiva.
Corneal & conjunctiva reflex are absent .
Light reflex is present.

14. Mydriatic Drugs B – Passive Mydriatics :
Parasympatholytics → M3 blocker → Paralysis of ciliary muscle → cycloplegia .
e.g. Atropine & homatropine.

15. Mydriatic Drugs B – Passive Mydriatics : Parasympatholytics: Actions :
1-Cycloplegia (accommodation for far vision).
2-↑ IOP .
3- Absolutely contraindicated in glaucoma .

16. Glaucoma

17. What is glaucoma?
Optic neuropathy that is the leading cause of irreversible blindness in the world
Major types are open angle and closed angle
Differences among various types of glaucoma complicate the nomenclature
Glaucoma is commonly associated with elevated intraocular pressure (IOP), but the disease can occur in the context of normal IOP
Our understanding and treatment of the disease is very focused on IOP
The diversity of diseases that fall under the name ‘glaucoma’ make a precise definition of the disease hard to come by. Most clinicians call any condition in which the intraocular pressure is elevated glaucoma. But, this is not a sufficient definition of the disease. Glaucoma is not a single entity.
Glaucoma is the leading cause of irreversible blindness in this country
However, our understanding of the disease and approach to treatment is very centered around the intraocular pressure. As such, it is important that we understand the dynamics of aqueous humor flow.

18. In order to understand the two subtypes of the disease that are the focus of today’s case, we must understand the dynamics of aqueous humor production and flow. Disruption of this process can result in elevated IOP and contribute to the pathogenesis of glaucoma.
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.
Seeing this flow pattern, you can imagine how problems can occur and result in accumulation of fluid and elevated pressure.

19. Open Angle Glaucoma
Obstruction at the level of the trabecular meshwork.
Progressive loss of visual field over time from periphery to center.
Majority of patients have IOP > 21 mmHg, asymptomatic.
Treatment:
1-β-Blockers.
2-α2 Agonist.
3-Prostaglandin analogues.
4-Miotic drops.
5-Non specific adrenergic agonist.
6-Carbonic anhydrase inhibitors.
In open angle glaucoma, there is an obstruction at the level of the trabecular meshwork obstructing flow.
In closed angle, the lens pushes forward impeding flow through the pupil. This creates a pressure gradient across the iris pushing the iris forward mechanically blocking the trabecular meshwork resulting in a block of aqueous humor flow and elevated intraocular pressure.
Although patients with open angle glaucoma may have elevated pressure, they generally do not perceive it- likely because this elevated pressure has developed slowly over time rather acutely, as is the case in closed angle

20. Closed Angle Glaucoma Apposition of iris and trabecular meshwork
Parasympatholytics (pupillary dilation) can precipitate attack
Increase risk with age, increase in volume of lens
Acute onset, patient complains of nausea, headache (rather than eye ache), malaise, general distress
Requires surgery .
We must decrease IOP before surgery by: 1- Osmotic agents.
2- Miotic drops.
3-Carbonic anhydrase inhibitors.
4-α2 agonist.
There is a lifelong increase in the volume of the lens. In our case, dilation of the pupil caused the iris to dilate and resulted in angle closure. This person already had a predisposition. Acute angle closure attacks can also occur with the administration of systemic parasympatholytic agents. These agents dilate the pupil and induce iridotrabecular contact
The patient appears to be generally in distre

21. REVIEW: Autonomic NS Effect on the Eye
RECEPTOR ACTIVATION WILL:
TO LOWER IOP, AIM FOR:
IRIS, Circular Fibers
mAchR : Constrict Pupil
 Activity
IRIS, Radial Fibers
1 R : Dilate Pupil
 Activity
CILIARY MUSCLES
mAchR : Contract for Accomodation
2 R : Relax for Far Vision
Activity
Activity

22. TREATMENT RATIONALE LOWER IOP BY:
Decreasing Production of Aqueous Humor
Increasing Outflow of Aqueous Humor

23. DRUGS THAT DECREASE AQUEOUS PRODUCTION
Beta-Blockers [levobunolol, timolol, carteolol, betaxolol]
-Mechanism: Act on ciliary body to  production of aqueous humor
-Administration: Topical drops to avoid systemic effects
-Side Effects: Cardiovascular (bradycardia, asystole, syncope), bronchoconstriction (avoided by b1-selective betaxolol), depression
Alpha-2 Adrenergic Agonists [apraclonidine, brimonidine]
-Mechanism:  production of aqueous humor
-Administration: Topical drops
-Side Effects: Lethargy, fatigue, dry mouth [apraclonidine is a derivative of clonidine (antihypertensive) which cannot cross BBB to cause systemic hypotension]
Carbonic Anhydrase Inhibitors [acetazolamide, dorzolamide]
-Mechanism: Blocks CAII enzyme production of bicarbonate ions (transported to posterior chamber, carrying osmotic water flow), thus  production of aqueous humor
-Administration: Oral, topical
-Side Effects: malaise, kidney stones, possible (rare) aplastic anemia

24. DRUGS THAT INCREASE AQUEOUS OUTFLOW
Nonspecific Adrenergic Agonists [epinephrine, dipivefrin]
-Mechanism:  uveoscleral outflow of aqueous humor
-Administration: Topical drops
-Side Effects: Can precipitate acute attack in patients with narrow iris-corneal angle, headaches, cardiovascular arrhythmia, tachycardia
Parasympathomimetics [pilocarpine, carbachol, echothiophate]
-Mechanism:  contractile force of ciliary body muscle,  outflow via TM
-Administration: Topical drops or gel, (slow-release plastic insert)
-Side Effects: Headache, induced miopia. Few systemic SE for direct-acting agonists vs. AchE inhibitors (diarrhea, cramps, prolonged paralysis in setting of succinylcholine). Why isn’t Ach used?
Prostaglandins [latanoprost]
-Mechanism: May  uveoscleral outflow by relaxing ciliary body muscle
-Side Effects: Iris color change

25. Rx GLAUCOMA: ADDITIONAL CONSIDERATIONS
No single medication can be used in all patients
Compliance
Critical: Rx often requires several agents,
multiple times a day, everyday
Role of slow-release drug delivery devices (Langer)
Non-pharmacologic ways to lower IOP:
Laser (argon laser trabeculoplasty)
 aqueous outflow, loses effectiveness over time
Surgical (trabeculectomy)
Creates alternative path for aqueous outflow
Only definitive therapy for closed angle
Effectiveness of Rx measured by ability to lower IOP, but other factors may be (more) important:
Neuroprotection/increased blood flow to optic nerve

26. GLAUCOMA: Key Points • Glaucoma: -Visual loss from optic neuropathy
-Open angle chronic, Closed angle acute
-Final common pathway:  IOP (usually)
Drug Rx: All directed towardsIOP either via:
-  aqueous production: Beta blockers
Alpha-2 agonists
Carbonic anhydrase inhibitors
-  aqueous outflow: (Adrenergic agonists, nonspecific)
Parasympathomimetics
Prostaglandins
Treatment slows progression
Understanding ANS effect on the eye is critical for reasoning through drug mechanisms of action
Understanding ANS effect on the whole body is critical for predicting and avoiding dangerous side effects

27. Thank You