Ocular Pharmacology

Question 1

Beta blocking drugs used in glaucoma

Answer 1

Betaxolol
Timolol
Metipranolol
Levobunolol
Carteolol

Question 2

Alpha2-adrenergic agonists used in glaucoma

Answer 2

Apraclonidine

Brimonodine

Question 3

Prostaglandin analogs used in glaucoma

Answer 3

Latanoprost
Bimatoprost
Travoprost

Question 4

Topical carbonic anhydrase inhibitors used in glaucoma

Answer 4

Brinzolamide

Dorzolamide

Question 5

Systemic carbonic anhydrase inhibitors used in glaucoma

Answer 5

Acetazolamide

Methazolamide

Question 6

Muscarinic agonists used in glaucoma

Answer 6

Carbachol

Pilocarpine

Question 7

Cholinesterase inhibitors used in glaucoma

Answer 7

Demecarium

Echothiophate

Question 8

In general, what classes of drugs are used to treat glaucoma?

Answer 8

Beta-blockers
Alpha2-adrenergic agonists
Prostaglandin analogs
Carbonic anhydrase inhibitors (topical and systemic)
Muscarinic agonists
Cholinesterase inhibitors

Question 9

The iris circular muscle constricts the pupil to cause miosis; its effect is due to the activation of ____ receptors

Answer 9

M3

Question 10

The iris radial muscle dilates the pupil to cause mydriasis; its effect is due to the activation of _______ receptors

Answer 10

Alpha1-adrenergic

Question 11

The ciliary muscle causes accommodation of the eye to near vision; it also opens the trabecular meshwork, improving the outflow of aqueous humor into the canal of schlemm, decreasing IOP; its action is due to the activation of ___ receptors

Answer 11

M3

Question 12

The ciliary epithelium secretes the aqueous humor on activation of _____ receptors

Answer 12

Beta

Question 13

What is the role of the sympathetic nervous system (i.e., what receptors) in production of aqueous humor?

Answer 13

Beta receptor activation —> increased production

Alpha-2 receptor activation —> decreased production

Question 14

Role of ciliary muscle and iris circular muscle on aqueous humor outflow

Answer 14

Contraction of these muscles leads to improved outflow (under the control of M3 receptors)

Question 15

_______ improves uveoscleral (or unconventional) outflow of aqueous humor

Answer 15

Prostaglandin F2a

Question 16

What effect does contraction of the iris radial muscle have on aqueous humor outflow?

Answer 16

Contraction of iris radial muscle (alpha 1 receptor) —> mydriasis —> decreased outflow

Question 17

2 types of primary glaucoma

Answer 17

Open angle: chronic progressive disease with no apparent mechanical blockage for humor outflow [95% of cases; second leading cause of blindness]

Closed angle: acute intermittent partial or complete blockage of the outflow, may have to be treated as an emergency to avoid vision loss

Question 18

What are some anatomical predisposing factors to developing closed angle glaucoma?

Answer 18

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

Question 19

What are the 2 types of classic primary closed angle glaucoma?

Answer 19

With pupillary block: tight contact between iris and lens, the flow of humor into anterior chamber is blocked, iris moves forward and blocks outflow

Without pupillary block: the ciliary processes are located in such a way that they push the iris forward and the iris blocks the outflow, especially during mydriasis

Question 20

T/F: increased IOP is a good diagnostic indicator for glaucoma

Answer 20

False, 20-30% with visual field loss have normal IOP

Optic disk exam and visual field evaluation is most conclusive method for diagnosis

Question 21

A ____ is an area of vision loss or decreased visual acuity surrounded by the field of normal vision

Answer 21

Scotoma

Question 22

First line agents for treatment of open angle glaucoma

Answer 22

Prostaglandin analogues
Beta-blockers (timolol)
Brimonidine

Question 23

Second line therapy for open angle glaucoma

Answer 23

Pilocarpine
Apraclonidine
Topical carbonic anhydrase inhibitors

Question 24

Last line therapy choices for open angle glaucoma

Answer 24

Carbachol
Cholinesterase inhibitors
Oral carbonic anhydrase inhibitors

Question 25

Beta-blockers are commonly used for open angle glaucoma due to convenience of dosing and relative lack of adverse effects. Why is timolol the favored agent?

Answer 25

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

Question 26

MOA of timolol in open angle glaucoma

Answer 26

Reduces production of aqueous humor by the ciliary body by blocking beta-receptors

Question 27

Adverse effects of beta blockers used in glaucoma

Answer 27

Local: stinging, dry eyes, blurred vision, blepharitis (rarely keratitis and conjunctivitis) — often due to agents in formulation Systemic: negative cardiac ionotropic effect, bradycardia, bronchospasm, hyperlipidemia, exacerbation of hypoglycemia in pts on insulin

Question 28

Beta blockers may interact with orally given ______, increasing the risk of cardiac depression and heart block

Answer 28

Verapamil

Question 29

In what patients should beta blockers be avoided/used with caution?

Answer 29

Patients with bradycardia, AV block, heart failure, atherosclerosis, diabetes, as well as receiving oral beta blocking therapy

Question 30

What are some of the prostaglandin analogues used in glaucoma, and which one is most effective in lowering IOP?

Answer 30

Latanoprost Bimatoprost - most effective at lowering IOP Travoprost

Question 31

T/F: prostaglandin analogues more efficiently reduce IOP than beta blockers

Answer 31

True

Question 32

Systemic side effects of prostaglandin analogues are not significant. What are some local side effects of these drugs?

Answer 32

Corneal erosions Conjunctival hyperemia Iris hyperpigmentation (irreversible) Hypertrichosis and hyperpigmentation around eyelashes and eyelids (reversible)

Question 33

In terms of alpha2-agonists used to treat glaucoma, ______ is the first line agent of choice. ________ is associated with frequent allergic reactions including development of tachyphylaxis. Both are effective at decreasing the rate of aq.humor production

Answer 33

Brimonidine; apraclonidine

Question 34

Adverse effects associated with alpha2-agonists used for glaucoma

Answer 34

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

Question 35

What is the algorithm used for pharmacotherapy of open angle glaucoma?

Answer 35

1. Start with a beta blocker 2. If intolerance to specific beta-blocker, use class alternative 3. If contraindications to beta-blockers, switch to alternative first line agent (prostaglandins or brimonidine) 4. If intolerance to prostaglandin agent, switch to class alternative 5. If contraindications to all first line agents, use topical CA inhibitors 6. If monotherapy fails, use combo therapy 7. If all else fails, use laser or surgical procedure

Question 36

Describe treatment of closed angle glaucoma in terms of treatment goals and drugs used

Answer 36

Goal is rapid reduction of IOP Acute: use systemic osmotic diuretics in preparation for surgery [IV Mannitol] Drug of choice before surgery = pilocarpine — induces miosis Surgical or laser iridectomy — produce a hole in iris facilitating humor outflow

Question 37

Drugs contraindicated in open angle glaucoma

Answer 37

Glucocorticoids Fenoldopam Topical antimuscarinic drugs

Question 38

Drugs contraindicated in closed angle glaucoma

Answer 38

[angle closure may be triggered by any drug that causes mydriasis] Antimuscarinic drugs Drugs with alpha-adrenomimmetic activity Tricyclic antidepressants and serotonin-NE reuptake inhibitors (because of their potent antimuscarinic activity)