Pharmacology of the eye

Question 1

ANS control over pupil

Answer 1

• When the PsNS is activated there is Ach released on the sphincter muscles, the Ach binds to muscarinic receptors and the muscles contract
• This leads to pupil constriction (miosis)
• When the SNS is activated there is NE released which binds to a1 receptors on the dilator muscles and the muscles contract
• This leads to pupil dilation (mydriasis)

Question 2

Stimulating miosis

Answer 2

• Miosis can be stimulated thru 2 ways: by blocking the a1 receptors (a1 antagonist like phentolamine, or surgical sympathectomy)
• Or by administering muscarinic agonists/CEIs (must use tertiary to cross the cornea)

Question 3

Stimulating mydriasis

Answer 3

• Also thru 2 ways: by blocking the muscarinic receptors (such as atropine or surgical parasympathectomy)
• Or by activating the a1 receptors by a1 adrenergic agonists

Question 4

Pharmacology of accommodation 1

Answer 4

• Contraction of the ciliary muscles causes the ciliary body to move closer to the lens, relieving the tension on the lens fiber
• The lens relaxes and becomes more convex, allowing near vision

Question 5

Pharmacology of accommodation 2

Answer 5

• The contraction of the ciliary muscles is under PsNS control
• Decreasing PsNS output on the ciliary muscle results in an increased tension on the lens, lens flattening, and far vision
• SNS plays no role in accommodation
• Preventing PsNS activity on the ciliary muscle results in inability to focus on close objects (cycloplegia)

Question 6

The light reflex

Answer 6

• Light striking one retina results in activation of the PsNS and constriction of both pupils
• SNS plays no role in the light reflex, thus a loss of light reflex demonstrates a loss of PsNS activity

Question 7

Horner’s syndrome

Answer 7

• Due to damaged sympathetic innervation to the eye, creating a functional sympathectomy
• Since PsNS activity is unopposed the pupil constricts
• There is also loss of SNS innervation to the superior tarsal muscle of the eye lid and this there is ptosis and lid lag

Question 8

Differences in a1 agonists vs muscarinic blockers

Answer 8

• Giving an a1 agonist (phenylephrine) results in mydriasis, but has no effect on accommodation or the light reflex
• Giving a muscarinic blocker (atropine) results in mydriasis, and prevents the light reflex and accommodation

Question 9

Uses of mydriatic and antimydriatic drugs

Answer 9

• Dilating the pupil so that physicians can see the eye more clearly
• Since atropine has a long T1/2, tropicamide is used since it has a much shorter T1/2
• Muscarinic antagonists can be revised by using muscarinic agonists (pilocarpine) or CEIs (tertiary ones like physostigmine)
• Must be tertiary (lipophilic) b/c will be applied to the surface of the eye and will have to pass cornea to get to the iris

Question 10

Flow of aqueous humor

Answer 10

• Aqueous humor is made in the ciliary body, flows behind the iris and thru the pupil into the anterior chamber
• Once in the anterior chamber the fluid flows out thru the trabecular meshwork and drains thru the canal of schlemm

Question 11

Angle closure glaucoma

Answer 11

• In angle closure glaucoma the angle btwn iris and cornea is small
• When the pupil is dilated (SNS activation) the iris is pushed forward against the trabecular meshwork btwn the iris and the cornea
• This closes off the trabecular meshwork and prevents drainage of the aqueous humor
• Pressure builds up in the anterior chamber and its transmitted back thru the lens and vitreous to the retina, causing damage to the optic nerve and subsequent vision loss

Question 12

Open angle glaucoma

Answer 12

• The trabecular meshwork becomes clogged so the fluid in the anterior chamber cannot drain into the canal of schlemm
• This also leads to build up of aqueous, increased IOP, and damage to the optic nerve

Question 13

Rx of angle closure glaucoma

Answer 13

• Miotics such as pilocarpine (muscarinic agonist) and physostigmine (3o CEI) constrict the pupil by enlarging the iris
• Enlarging the iris flattens it against the lens thus unblocking the meshwork and canal of schlemm by increasing the angle of the iris with the cornea
• This alleviates the pressure in the eye

Question 14

Rx of open angle glaucoma 1

Answer 14

• It is important to decrease the aqueous formation and increase aqueous outflow
• Direct and indirect muscarinic agonists (PSPMs) will stimulate contraction of the ciliary muscles
• Contraction of the ciliary muscles produces traction on the scleral spur and this in turn increases the probity of the trabecular network (opens the meshwork)
• Must be aware of the possibility of systemic aborption thru the tear duct

Question 15

Rx of open angle glaucoma 2

Answer 15

• There are a variety of ways to decrease the formation of aqueous humor, many are not well understood
• Carbonic anhydrase inhibitors do this, and thus slow the buildup of pressure
• Beta blockers (b1 antagonists or a2 agonists) will also decrease the formation of aqueous humor and also allow more PsNS effect on the ciliary muscles, further opening the trabecular meshwork
• Prostaglandin agonists (latanoprost): increases the % of aqueous humor through the uveoscleral outflow (normally only 10-20%), further decreasing the amount of aqueous humor and IOP
• The side effect of latanoprost is growth of eyelashes and iris pigmentation (darker)