Glaucoma Part 2: beta blockers

Examples of beta blockers

timolol, levobunolol, metepranolol, betaxolol

Mechanism of beta blockers

dec aq humor production

Efficacy of beta blockers

20-30%, dec pm efficacy

Dosing of beta blockers

QD and BID

Common side effects of beta blockers

systemic effects (bradycardia, bronchospasm), local stinging

Intrinsic sympathetic activity in beta blockers

Partial agonist

Clinical benefits of intrinsic sympathetic activity

Less impact on HR or CO at rest, less metabolic effect

Membrane-stabilizing activity in beta blockers

Structural similarity to local anesthetics

Clinical benefits of membrane-stabilizing activity

Dec corneal sensitivity -> less stinging, anti-arrhythmic at high dose

Difference of betaxolol as a beta blocker

Moderate efficacy and only B1-selectivity versus high efficacy and non-selectivity in the rest

MSA or ISA of betaxolol

MSA - betaxolol

ISA of carteolol

Carteolol = ISA

Examples of carbonic anhydrase inhibitors (CAIs)

dorzolamide, brinzolamide, acetazolamide, methazolamide

Mechanism of CAIs

dec aqueous humor production

Efficacy of CAIs

15-20% (topical) 20-40% (oral)

Dosing of CAIs

BID and TID

Common side effects of CAIs

stinging, bitter taste; metabolic acidosis, kidney stones, tingling in fingers

Mechanism of action for CAIs

AH secretion by NPE (nonpigmented epithelial cells in iris) (catalyzed by carbonic anhydrase)

Oral CAI side effects

paresthesia, fatigue (systemic acidosis); kidney stone (inc Ca2+ precipitation); hypokalemia (forced H+/K+ exchange -> K+ loss)

Contraindication for CAIs

Contraindicated if sulfa allergy bc sulfa in CAI

Examples of rho kinase inhibitors

Netarsudil, ripasudil (expensive)

Mechanism of rho kinase inhibitors

Inc trabecular meshwork outflow, dec episcleral venous pressure, dec aqueous production (minor)

Efficacy of rho kinase inhibitors

20-25% even in low baseline IOP

Dosing of rho kinase inhibitors

QD

Common side effects of rho kinase inhibitors

conjunctival hyperemia, corneal verticillata (deposits)

Mechanism of action for ROCK inhibitors

ROCK regulates actin cytoskeleton dynamics and SM contraction

Clinical effects of ROCK inhibition

Relax actin stress fibers, dec cell stiffness, loosens adhesions, and inc pore formation, inc conventional outflow, slightly dec AH production

Examples of parasympathomimetics (miotics)

Eg. pilocarpine

Mechanism of parasympathomimetics

inc TM outflow

Efficacy of parasympathomimetics

15-25%

Dosing of parasympathomimetics

TID or QID

Common side effects of parasympathomimetics

brow ache, miosis, poor night vision, RD

Common combo formulations

CAI + B blocker, CAI + a2 agonist, a2 agonist + B blocker, PGA + ROCK inhibitor, PGA + B blocker