Pharmacology Flashcards
Muscarinic receptors in the eye
Sphincter and ciliary mm
Adrenergic receptors in the eye
Dilator (alpha) and ciliary epithelium (beta)
Sphincter pupillae
- Contraction causes MIOSIS
- Contraction mediated by ligand/agonist at M3 receptors (Gq»IP3»Ca2+)
Ciliary muscle
- M3 induced contraction causes:
- Accomodation
- Cyclospasm
- Increased tension on trabecular meshwork
Dilator pupillae
- Alpha1 receptors induce contraction causing MYDRIASIS
- Gq»IP3»Ca2+
Increased production of aqueous humor secretion
B-adrenergic receptors (Gs)»increased cAMP»increased secretion
Decreased production of aqueous humor secretion
Alpha2-adrenergic receptors (Gi)»decreased cAMP»decreased secretion
Carbonic anhydrase
- Mediates the transport of bicarbonate across the ciliary epithelium by the reversible hydration of CO2to form HCO3- and protons
- Influences fluid transport by affecting Na+
Open-Angle glaucoma
- Optic neuropathy characterized by progressive peripheral visual loss followed by central visual field loss
- ↑ IOP is common, but not always present
Angle-closure glaucoma
-Narrowing or closure of the anterior chamber angle
-Impairment of drainage»_space; increased IOP and damage to optic nerve
(Normal anterior chamber angle provides drainage for aqueous humor)
Symptoms of open-angle glaucoma
Symptoms rare and often diagnosed during eye exams
Symptoms of angle-closure glaucoma
Redness, pain (mild»severe), blurred vision, tearing, photophobia, N/V, headache, halos around light
Open-angle glaucoma treatment
- Topical
- -Increase aqueous outflow
- –Prostaglandins
- –Muscarinic agonists
- –Alpha-2 adrenergic agonists
- –rho kinase inhibitor
- -Decreasing aqueous production
- –Alpha-2 adrenergic agonists
- –Beta blockers
- –Carbonic anhydrase inhibitors (less effective therapy)
- Systemic
- -Decreasing aqueous production
- –Carbonic anhydrase inhibitors
Angle-closure glaucoma treatment
Acute setting:
- Treated initially with drugs to reverse or reduce IOP
- -Topical pressure lowering agents
- –Beta-blockers
- –Alpha-2 agonists
- –Muscarinic agonists
- -Systemic medications
- –Carbonic anhydrase inhibitors
Modifying autonomic signaling for treatment of glaucoma
- Cholinergic agonists and AChE inhibitors enhance aqueous outflow
- Beta-adrenergic antagonists and alpha-adrenergic agonists decrease aqueous inflow
PGDs
Latanoprost
Bimatoprost
-increase outflow of aqueous humor
-topical use for treatment of open angle glaucoma (more effective than beta-blockers)
Beta-blockers
Betaxolol (beta-1) Carteolol (non) Levobunolol (non) Metipranolol (non) Timolol (non) -Decrease aqueous humor production
Alpha-2 adrenergic agonists
Apraclonidine
Brimonidine
-Topical agents with similar effectiveness to beta blockers in lowering IOP in open-angle glaucoma (useful for treating normal pressure glaucoma)
MOA: Inhibiting release of catecholamine»_space; decreasing aqueous humor production
-Brimonidine may also increase outflow
Muscarinic agonists
Pilocarpine
- topical
- Causes contraction of the sphincter pupillae (miosis) and ciliary muscle (loss of accommodation)
- Lowers IOP - decreases resistance to aqueous humor outflow
- Used in open-angle and angle-closure glaucoma
Carbonic anhydrase inhibitors
Acetazolamide
Dorzolamide
-Both agents decrease production of aqueous humor by inhibiting carbonic anhydrase
Netarsudil
-Topical agent
-Mechanism:
rho kinase inhibitor
-believed to reduce IOP by increasing the outflow of aqueous humor through the trabecular meshwork
Adverse effects of beta-blockers
Stinging of eyes
Conjunctival hyperemia
Limited – asthma, nodal issues
Adverse effects of beta-blockers
Stinging of eyes
Conjunctival hyperemia
Limited – asthma, nodal issues
Alpha-agonists adverse effects
Allergic conjunctivitis, hyperemia, ocular pruritus
