Ocular Pharm/Glaucoma Flashcards
Contraction of the iris radial muscle (α1 receptor) has what effect on the outflow of aqueous humor?
Mydriasis —> decreased outflow (conventional outflow)
What is the MOA of timolol in the treatment of glaucoma?
Reduces production of aqueous humor by the ciliary body by blocking β receptors
β-blockers should be used with caution in patients with what underlying conditions?
- Bradycardia
- AV block
- Heart failure
- Atherosclerosis
- Diabetes
*As well as receiving oral β-blocking therapy
What are the two topical carbonic anhydrase inhibitors used in the treatment of glaucoma?
- Brinzolamide
- Dorzolamide
Which drug-drug interaction must be considered when treating glaucoma with a β-blocker?
Increases risk for what?
- May interact with orally given verapamil
- Increases risk of cardiac depression and heart block
What is the MOA of α2-agonists in tx of glaucoma?
Decrease the rate of aqueous humor production
Which α2-agonist is the first line agent for the treatment of glaucoma?
Brimonidine
What is the function of the ciliary muscle of the eye and via which receptor?
- 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
Why is the α2-agonist, Apraclonidine, not preferred for the treatment of glaucoma?
Frequent allergic reactions, development of tachyphylaxis
What is the algorithm for pharmacotherapy of open angle glaucoma?
- 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
Of the prostaglandin analogs, which is the most effective at lowering IOP for treatment of glaucoma?
Bimatoprost
Function of the ciliary epithelium of the eye and via which receptor?
- Produces (secretes) aqueous humor
- β receptor activation increases humor production
Why is the β-blocker, timolol, favored for the treatment of glaucoma?
- Lacks local anesthetic effects
- Available as generic
- Full antagonist
- Shown to be as effective as pilocarpine
Current pharmacotherapy of glaucoma is directed at producing what effect?
Reduction of IOP
What are the two muscarinic agonists (aka direct acting cholinergic agonists) used in the treatment of glaucoma?
- Carbachol
- Pilocarpine
What are the 3 first line agents for the treatment of open angle glaucoma?
- Prostaglandin analogues
- β-blockers - timolol is favored
- Brimonidine (α2-adrenergic agonist)
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?
- 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
Activation of which sympathetic receptor will increase production of aqueous humor?
Which receptors will cause a decrease?
- β-receptor activation will increase production
- α-receptor activation will decrease production
What are some of the benefits of using prostaglandin analogs in the treatment of glaucoma?
- More efficiently reduce IOP than β-blockers
- Systemic side effects are not significant
Function of iris circular muscle and via which receptor?
- Constricts pupil to cause miosis
- Effect is due to activation of M3 receptor
Increased ________ is though to play an important role in the pathogenesis of glaucoma
Intraocular pressure
Which anatomical changes may predispose someone to developing closed-angle glaucoma?
- Shallow anterior chamber
- Narrow angle between cornea and iris
- Tight contact between iris and the lens
Why are β-blockers commonly used in the treatment of glaucoma?
- Convenience of dosing
- Relative lack of adverse effects
What are the two α2-adrenergic agonists used in the treatment of glaucoma?
- Apraclonidine
- Brimonidine
What are the three prostaglandin analogs used in the treatment of glaucoma?
- Latanoprost
- Bimatoprost
- Travoprost
What is the cholinesterase inhibitor used in the treatment of glaucoma?
- Echothiophate
What are the adverse systemic and local effects of α2-agonists used in the treatment of glaucoma?
- Systemic: dizziness, fatigue, dry mouth, bradycardia, reduced BP
- Local: allergic reaction (eyelid edema, itching, hyperemia)
With closed angle glaucoma the goal is a rapid reduction of IOP, what drugs are used in preparation for surgery?
- 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)
What are the two systemic carbonic anhydrase inhibitors used in the treatment of glaucoma?
- Acetazolamide
- Methazolamide
Which muscles of the eye are involved in improving the outflow of aqueous humor; which receptor mediates this?
- Contraction of ciliary musle - muscarinic receptor
- Contraction of iris circular muscle - muscarinic receptor
Which drugs are contraindicated with closed angle glaucoma due to their ability to cause mydriasis and possible angle closure?
- Antimuscarinic drugs (topical, systemic)
- Drugs w/ alpha-adrenomimetic activity (topical)
- Tricyclic antidepressants and Serotonin-norepinephrine reuptake inhibitors (due to potent antimuscarinic action)
Function of iris radial muscle and via which receptor?
- Dilates pupil to cause mydriasis
- Effect is due to activation of α1 adrenergic receptor
Adverse systemic effects of β-blockers when treating glaucoma (i.e., heart, airways, and metabolically)?
- Heart: negative inotropic effect
- Airways: bronchospasm
- Hyperlipidemia
- Exacerbation of hypoglycemia (in patients on insulin)
List the 5 β-blocking drugs that are used in glaucoma?
- Betaxolol
- Timolol
- Metipranolol
- Levobunolol
- Carteolol
Adverse local effects of β-blockers when treating glaucoma?
- Stinging
- Dry eyes
- Blurred vision
- Blepharitis, and (rarely) keratitis and conjunctivitis
