Ocular Pharm/Glaucoma

Question 1

Contraction of the iris radial muscle (α1 receptor) has what effect on the outflow of aqueous humor?

Answer 1

Mydriasis —> decreased outflow (conventional outflow)

Question 2

What is the MOA of timolol in the treatment of glaucoma?

Answer 2

Reduces production of aqueous humor by the ciliary body by blocking β receptors

Question 3

β-blockers should be used with caution in patients with what underlying conditions?

Answer 3

• Bradycardia
• AV block
• Heart failure
• Atherosclerosis
• Diabetes

*As well as receiving oral β-blocking therapy

Question 4

What are the two topical carbonic anhydrase inhibitors used in the treatment of glaucoma?

Answer 4

• Brinzolamide
• Dorzolamide

Question 5

Which drug-drug interaction must be considered when treating glaucoma with a β-blocker?

Increases risk for what?

Answer 5

• May interact with orally given verapamil
• Increases risk of cardiac depression and heart block

Question 6

What is the MOA of α₂-agonists in tx of glaucoma?

Answer 6

Decrease the rate of aqueous humor production

Question 7

Which α₂-agonist is the first line agent for the treatment of glaucoma?

Answer 7

Brimonidine

Question 8

What is the function of the ciliary muscle of the eye and via which receptor?

Answer 8

• Causes accomodation of the eye to near vision
• Opens up trabecular meshwork, improving outflow of aqueous humor into canal of Shlemm, decreasing intraocular pressure
• M₃ receptors contract the muscle

Question 9

Why is the α₂-agonist, Apraclonidine, not preferred for the treatment of glaucoma?

Answer 9

Frequent allergic reactions, development of tachyphylaxis

Question 10

What is the algorithm for pharmacotherapy of open angle glaucoma?

Answer 10

• Start with β-blocker; if intolerance to specific β-blocker, use class alternative
• β-blockers contraindicated, use alternative 1st line agent (prostaglandins)
• If intolerance to beta blocker or prostaglandin agent, use class alternative
• If contraindications to both beta blockers and prostaglandins, switch to alternative first line agents, brimonidine or topical carbonic anhydrase inhibitors
• If monotherapy fails, use a combination therapy
• If intolerance or inadequate response to the combo therapy, use laser or a surgical procedure

Question 11

Of the prostaglandin analogs, which is the most effective at lowering IOP for treatment of glaucoma?

Answer 11

Bimatoprost

Question 12

Function of the ciliary epithelium of the eye and via which receptor?

Answer 12

• Produces (secretes) aqueous humor
• β receptor activation increases humor production

Question 13

Why is the β-blocker, timolol, favored for the treatment of glaucoma?

Answer 13

• Lacks local anesthetic effects
• Available as generic
• Full antagonist
• Shown to be as effective as pilocarpine

Question 14

Current pharmacotherapy of glaucoma is directed at producing what effect?

Answer 14

Reduction of IOP

Question 15

What are the two muscarinic agonists (aka direct acting cholinergic agonists) used in the treatment of glaucoma?

Answer 15

• Carbachol
• Pilocarpine

Question 16

What are the 3 first line agents for the treatment of open angle glaucoma?

Answer 16

• Prostaglandin analogues
• β-blockers - timolol is favored
• Brimonidine (α₂-adrenergic agonist)

Question 17

What are 4 local side effects that may result from using prostaglandin analogs for the treatment of glaucoma?

Which effects are irreversible and which are reversible?

Answer 17

• Corneal erosions
• Conjunctival hyperemia
• Iris hyperpigmentation (occurs after several months of therapy and is irreversible)
• Hypertrichosis, hyperpigmentation around eye lashes and eyelids are reversible upon discontinuation of therapy

Question 18

Activation of which sympathetic receptor will increase production of aqueous humor?

Which receptors will cause a decrease?

Answer 18

• β-receptor activation will increase production
• α-receptor activation will decrease production

Question 19

What are some of the benefits of using prostaglandin analogs in the treatment of glaucoma?

Answer 19

• More efficiently reduce IOP than β-blockers
• Systemic side effects are not significant

Question 20

Function of iris circular muscle and via which receptor?

Answer 20

• Constricts pupil to cause miosis
• Effect is due to activation of M₃ receptor

Question 21

Increased ________ is though to play an important role in the pathogenesis of glaucoma

Answer 21

Intraocular pressure

Question 22

Which anatomical changes may predispose someone to developing closed-angle glaucoma?

Answer 22

• Shallow anterior chamber
• Narrow angle between cornea and iris
• Tight contact between iris and the lens

Question 23

Why are β-blockers commonly used in the treatment of glaucoma?

Answer 23

• Convenience of dosing
• Relative lack of adverse effects

Question 24

What are the two α₂-adrenergic agonists used in the treatment of glaucoma?

Answer 24

• Apraclonidine
• Brimonidine

Question 25

What are the three prostaglandin analogs used in the treatment of glaucoma?

Answer 25

- Latano**prost** - Bimato**prost** - Travo**prost**

Question 26

What is the cholinesterase inhibitor used in the treatment of glaucoma?

Answer 26

- Echothiophate

Question 27

What are the adverse systemic and local effects of α₂-agonists used in the treatment of glaucoma?

Answer 27

- **Systemic:** dizziness, fatigue, dry mouth, bradycardia, reduced BP - **Local:** allergic reaction (eyelid edema, itching, hyperemia)

Question 28

With closed angle glaucoma the goal is a rapid reduction of IOP, what drugs are used in preparation for surgery?

Answer 28

- Systemic osmotic diuretics: **IV Mannitol (1-2 g/kg) or oral glycerin** - **Pilocarpine** = drug of choice before surgery - induces **miosis** **-Agents that reduce humor production (b-blockers, alpha 2- agonists, carbonic anhydrase inhibitors)**

Question 29

What are the two **systemic** carbonic anhydrase inhibitors used in the treatment of glaucoma?

Answer 29

- Acetazolamide - Methazolamide

Question 30

Which muscles of the eye are involved in improving the outflow of aqueous humor; which receptor mediates this?

Answer 30

- Contraction of **ciliary musle** - **muscarinic** receptor - Contraction of **iris circular muscle** - **muscarinic** receptor

Question 31

Which drugs are contraindicated with closed angle glaucoma due to their ability to cause mydriasis and possible angle closure?

Answer 31

- **Antimuscarinic drugs** (topical, systemic) - Drugs w/ **alpha-adrenomimetic activity** (topical) - **Tricyclic antidepressants** and **Serotonin-norepinephrine reuptake inhibitors** (due to potent antimuscarinic action)

Question 32

Function of iris radial muscle and via which receptor?

Answer 32

- **Dilates** pupil to cause **mydriasis** - Effect is due to activation of **α1 adrenergic receptor**

Question 33

Adverse **systemic** effects of β-blockers when treating glaucoma (i.e., heart, airways, and metabolically)?

Answer 33

- **Heart:** negative inotropic effect - **Airways:** bronchospasm - Hyperlipidemia - Exacerbation of hypoglycemia (in patients on insulin)

Question 34

List the 5 β-blocking drugs that are used in glaucoma?

Answer 34

- Betaxolol - Timolol - Metipranolol - Levobunolol - Carteolol

Question 35

Adverse **local** effects of β-blockers when treating glaucoma?

Answer 35

- Stinging - Dry eyes - Blurred vision - Blepharitis, and (rarely) keratitis and conjunctivitis