OCULAR PHARMACOLOGY

DR: Mahmoud Saeed

Lecturer Of Clinical Pharmacy

BMC

Anatomical & Physiological considerations

1. IRIS AND PUPIL A-Constrictor pupillae muscle :

Parasympathetic supply.

Muscarinic M3 receptors.

Miosis (constriction of pupil).

1. IRIS AND PUPIL B-Dilator pupillae muscle: Sympathetic supply.

α1 receptors.

Mydriasis (dilation of pupil).

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.

INTRAOCULAR PRESSURE(IOP)

Normal IOP: 15-25 mm Hg.

Glaucoma = ↑ IOP.

To ↓ IOP : 1- ↓ Formation of aqueous humor. 2- ↑ Drainage of aqueous humor.

MIOTIC DRUGS• Drugs that constrict the pupil . A – Parasympathomimetics: 1. Direct acting : e.g. pilocarbine , carbachol &

bethanecol .

2. Indirect acting : e.g. physostigmine .

MIOTIC DRUGS Actions of Parasympathomimetics :1. Miosis : Through M3 receptors → contraction of

Constrictor Pupillae Muscle

2. Accommodation for near vision .

3. ↓ IOP due to opening of canal of Schlemm.

MIOTIC DRUGS B – Sympatholytics: e.g. Guanethidine .

C – Central acting : e.g. Morphine .

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 .

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 .

MYDRIATIC DRUGS A- Active Mydriatics : 2. Cocaine :o Local anesthetic for the cornea &

conjunctiva.o Corneal & conjunctiva reflex are absent .o Light reflex is present.

MYDRIATIC DRUGS B – Passive Mydriatics :

Parasympatholytics → M3 blocker → Paralysis of ciliary muscle → cycloplegia .

e.g. Atropine & homatropine.

MYDRIATIC DRUGS B – Passive Mydriatics :

Parasympatholytics:

Actions :

1-Cycloplegia (accommodation for far vision).

2-↑ IOP .

3- Absolutely contraindicated in glaucoma .

GLAUCOMA

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

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.

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.

REVIEW: Autonomic NS Effect on the EyeRECEPTOR ACTIVATION WILL: TO LOWER IOP, AIM FOR:

IRIS, Circular Fibers mAchR : Constrict Pupil ActivityIRIS, Radial Fibers 1 R : Dilate Pupil ActivityCILIARY MUSCLES mAchR : Contract for Accomodation

2 R : Relax for Far Vision ActivityActivity

TREATMENT RATIONALE

LOWER IOP BY:(1)Decreasing Production of

Aqueous Humor(2)Increasing Outflow of Aqueous

Humor

DRUGS THAT DECREASE AQUEOUS PRODUCTION

I. 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), depressionII. 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]

III. 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

DRUGS THAT INCREASE AQUEOUS OUTFLOWI. 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

II. 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?

III. Prostaglandins [latanoprost] -Mechanism: May uveoscleral outflow by relaxing ciliary

body muscle -Administration: Topical drops -Side Effects: Iris color change

Rx GLAUCOMA: ADDITIONAL CONSIDERATIONS1. No single medication can be used in all patients

2. Compliance • Critical: Rx often requires several agents,

multiple times a day, everyday• Role of slow-release drug delivery devices (Langer)

3. 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

4. Effectiveness of Rx measured by ability to lower IOP, but other factors may be (more) important:

Neuroprotection/increased blood flow to optic nerve

GLAUCOMA: Key Points• Glaucoma: -Visual loss from optic neuropathy

-Open angle chronic, Closed angle acute -Final common pathway: IOP (usually)

• Drug Rx: All directed towardsIOP either via: - aqueous production: Beta blockers

Alpha-2 agonistsCarbonic 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

THANK YOU