caused by sympathetic innervation
3 muscles: pupillary dilator (alpha1 receptor) constriction and superior tarsal constriction; ciliary muscle (beta2 receptor) relaxation
2 muscles: ciliary muscle contraction, pupillary sphincter contraction
All work through muscarinic receptors
(also...Enhance drainage of aqueous humor (trabecular meshwork & canal of Schlemm))
An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response.
Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.
. Whereas an agonist causes an action, an antagonist blocks the action of the agonist (and an inverse agonist causes an action opposite to that of the agonist.)
aqueous humor production
Enhance aqueous humor formation (ß receptors)
Inhibit aqueous humor formation (alpha2 receptors)
Enhance drainage of aqueous humor (trabecular meshwork & canal of Schlemm) via muscarinic receptors
Drugs promoting mydriasis
A. sympathetic activation or B. inhibition of the parasympathetic pathway!!
A = phenylephrine, epinephrine, amphetamine (promotes NE release from postganglionic cell) or cocaine (blocks Na+ dependent NE reuptake transporter)
B= Inhibitors of parasympathetic nervous system (Atropine—muscarinic antagonist. Literally translates as “pretty women”)
alpha1 adrenergic stimulants
PHENYLEPHRINE (selective) (mydrifrin) is a drug used in eye drops to dilate pupil. Also reverses ptosis in Horner’s Syndrome.
Epinephrine (Epitrate) 0.5 to 2% solution to treat glaucoma (nonselective!!!)-- promotes humor outflow and inhibits formation
No eye response to cocaine or amphetamine means what?
postganglionic Horner’s Syndrome
Agents releaseing NE
amphetamine -- reverses axoplasmic pump
hydroxyamphetamine (0.1% solution) used to diagnose post-ganglionic nerve damage vs. a defect prior to the postganglionic nerve
no reaction means postganglionic nerve defect
response to amphetamine indicates normal post-ganglionic nerve
If eye responds to pilocarpine with miosis, then problem...
is with the nerve (third nerve palsy)
pilocarpine is a muscarinic agonist
If eye does not respond to pilocarpine, then problem...
is with the eye itself (Atropinic mydriasis)
pilocarpine is a muscarinic agonist
Drugs producing miosis
Nicotine activates parasympathetic nerves
Muscarinic agonists such as Pilocarpine (Pilocar), acetylcholine (Miochol)
Pilocarpine used as 2% solution
1% solution to differentiate IIIrd nerve palsy from “Atropinic” mydriasis
If pilocarpine is active (produces miosis) then the defect must be in the nerve.
Agents preventing acetylcholine degradation...
increase in ACh will cause miosis... pupil constriction... via parasympathetic activation (sort of)
Physostigmine (Isopto eserine), Ecothiophate (phospholine iodide), demecarium (Humorsol), isofluorophate (floropryl)
Norepinephrine depleting agents...
NE release from postganglionic terminal on smooth muscle prevented
Reserpine -- not normally used for eye treatment, but can have ocular side effects.
Drugs for Treatment of Glaucoma
ß Blockers: Timolol (Timoptic); Betaxolol (Betoptic); Carteolol (Ocupress); Levobunolol (Betagan); Metipranolol (Optipranolol)- they decrease aqueous humor formation
Muscarinic Receptor Agonists-
Pilocarpine (Pilocar)- enhances aqueous humor drainage through trabecular meshwork & canal of Schlemm
Physostigmine (Isopto eserine), Ecothiophate (Phospholine iodide)- enhances aqueous humor drainage through trabecular meshwork & canal of Schlemm
Ptosis and treatment
drooping of the upper eyelid due to paralysis or disease,
Characteristic of sympathetic nerve disruption;
Superior tarsalis muscle holds eyelid open
treate wth botulinum toxin (inhibits acetylcholine release)
alpha1 agonist, Phenylephrine
Muscarinic antagonist, Atropine
Agents releasing norepinephine, Amphetamine
Agents preventing norepinephrine uptake into the nerve (Cocaine)
These can all precipitate closed angle gluacoma
Muscarinic agonist (Pilocarpine, Acetylcholine)
a1 adrenergic antagonists (Terazosin)
Treatments for Glaucoma
Agents enhancing aqueous humor outflow (by trabecular meshwork and Canal of Schlemm)
Muscarinic agonists (pilocarpine)
Agents suppressing aqueous humor production (by ciliary processes)
ß adrenergic antagonists (Timolol)
a2 adrenergic agonists (Aproclonidine)
Carbonic anhydrase inhibitors (Acetazolamide)