Ocular Cholinergic Agonists and Antagonists PDF

Ocular Cholinergic Agonists (Parasympathomimetics) and Antagonists (Parasympatholytics/Cycloplegics/ Cyclomydriatics) Jose M De Jesus, OD, MD, MA, FAAO Efferent Oculo-parasympathetic Pathway Originates in the E-W nucleus Preganglionic fibers Ciliary ganglion Cholinergic Innervation Acetylcholine is...

Ocular Cholinergic Agonists (Parasympathomimetics) and Antagonists (Parasympatholytics/Cycloplegics/ Cyclomydriatics) Jose M De Jesus, OD, MD, MA, FAAO Efferent Oculo-parasympathetic Pathway Originates in the E-W nucleus Preganglionic fibers Ciliary ganglion Cholinergic Innervation Acetylcholine is the neurotransmitter for both pre and post-ganglionic synapse is acetylcholine Post-Ganglionic Effector Structures Iris Sphincter Ciliary muscle * M3 receptors Ocular Cholinergic Agonists Direct Parasympathomimetics Indirect Parasympathomimetics (Cholinesterase Inhibitors) Direct Parasympathomimetics Direct Parasympathomimetics Pilocarpine 1) Pharmacology 2) Conc. 3) Ocusert - Membrane-bound device - Ocusert pilo-20 - Ocusert pilo-40 4) IOP reduction mechanism 5) Side effects Indirect Parasympathomimetics (Cholinesterase Inhibitors) MOA Edrophonium Chloride (Tensilon) MG - Dx - Ocular Signs - Treatment options and dosage Side effects Lambert-Eaton Myasthenic Syndrome (LEMS) Rare autoimmune disorder that affects voltage-gated calcium channels on the pre-synaptic membrane of the nerve-muscle neuromuscular The inhibition of the voltage-gated calcium channels prevents acetylcholine from being released from the presynaptic terminal and the subsequent stimulation of the post-synaptic terminal which would lead to muscle contraction TX - steroids Ocular Cholinergic Antagonists (Parasympatholytics/Cycloplegics/ Cyclomydriatics) Parasympatholitics Atropine a. Naturally occurring alkaloid from a plant called atropa belladona b. Clinical uses - Cycloplegic refraction – refractive accommodative esotropia - Iridocyclitis Parasympatholitics Atropine b. Clinical uses - Treatment of myopia - Amblyopia – cycloplegic blur - Provocative for narrow angle c. Ocular side effects - Irritation – chlorobutanol - Keratitis - Contact dermatitis - Angle apposition/closure in pts. with narrow angles - Increase IOP in pts. with open angle glaucoma Parasympatholitics Atropine d. systemic side effects - Dosage dependent - Lethal dosage in adult is 100mg - Lethal dosage in children 6-12 years old is 10 mg - Deaths have been reported in pts. 3 y/o or less 1) Majority had mental or motor retardation 2) Extreme caution should be taken in pts 1-5 years old 3) Premature infants not administered Parasympatholitics Atropine d. Systemic side effects (cont) - Initial signs 1) Decrease salivation 2) Dryness of mouth and skin - Other signs 1) Facial flushing 2) Fever due to inhibited sweating - Cardiac affection - blockage of vagus tone - Central nervous system 1) Delirium and halucinations 2) Irritability 3) Coma Parasympatholitics Atropine d. Systemic side effects - Specific antidote - physostigmine (antilirium) 1) 0.25mg in children by sub-cutaneous administration, 1-2mg in adults 2) Given every 15 min. until pt. starts responding (salivation) 3) Physostigmine has the ability to pass through the blood brain barrier Parasympatholitics Homatropine a. 2% and 5% b. 1/10 as potent as atropine c. Has shorter duration of mydriatic and cycloplegic action than atropine d. Clinical uses - Adjunct treatment of iridocyclitis - It’s only used as an alternative in cycloplegic refraction not involving accommodative esotropia e. adverse effects similar to atropine Parasympatholitics Scopolamine (hyocine) a. On a molecular weight basis, its anti-cholinergic potency is greater than that of atropine b. Its mydriatic and cycloplegic effect are of shorter duration because of the conc. (0.25%) c. Clinical uses - Its toxicity makes it not a drug of choice - It is primarily used has an alternative tx when allergic reaction to atropine occurs d. Side effects similar to atropine Parasympatholitics Cyclopentolate a. Commercially available in 0.5%, 1.0%, 2.0% b. Less mydriatic and cycloplegic effect on dark iridis c. Full recovery within 24 hrs. d. Average residual accommodation is approximately 1.25 diopters e. Clinical uses - Drug of choice for cycloplegic refraction - Alternative adjunct treatment for iridocyclitis Parasympatholitics Cyclopentolate f. Ocular side effects - Superficial punctate keratitis - Contact dermatitis - Increase iop in pts. w/ POAG - Angle apposition / closure in pts. with narrow angles - Iris pigment dispersion g. Central nervous system effects - More common in children - Drowsiness, Restlessness, Disorientation - Incoherent speech - Cerebellar dysfunctions Parasympatholitics Tropicamide a. 0.5% and 1.0% b. The cycloplegic that cause the most amount of mydriasis with the weakest cycloplegia (> 4D) c. Clinical uses - Dilated fundus examination - Provocative in narrow angles d. Ocular side effects - Angle apposition/closure in pts. with narrow angles - Increase in IOP in patients with POAG e. Systemic adverse effects are almost non-existent since is metabolized quickly