Pharmacology of the Eye Flashcards
Phase I metabolism
Hydrolysis, oxidation, reduction
Phase II metabolism
Conjugation (methylation, etc)
Absorption of drugs in eye determined by?
Length of time drug stays in the inferior fornix and precorneal tear film
How to ocular drugs enter systemic circulation?
Via the nasal mucosa
How do ocular drugs get to interior ocular structures?
Via aqueous humor by trabecular meshwork.
Metabolism?
tear and tissue proteins, diffusion. Hepatic if enters systemically
Does first pass metabolism occur if absorbed by nasal mucosa?
No.
Pupillary constriction
Parasympathetic inputs contract circular muscle (miosis)
Pupillary dilation
Sympathetic stimulation of radial muscles (mydriasis)
Ciliary body consists of
Ciliary muscle and ciliary epithelium
Parasympathetic stimulation to ciliary muscle
Causes contraction, accommodation (near focus), zonule fibers relax
Cyclospasm
Severe ciliary muscle contraction. Can be caused by AChE inhibitors
Cycloplegia
Block of accommodation by cholinergic antagonists
Effect of parasympathetic stimulation on trabecular meshwork?
Tension opens pores and facilitates outflow of aqueous humor into canal of Schlemm. This decreases interocular pressure
Where does drainage from canal of schlemm go?
Into superchoroidal space
Effect of sympathetic stimulation on aqueous humor secretion?
Promotes secretion by stimulating beta receptors.
Predominant beta receptor in eye?
B2
Predominant beta receptor in heart?
B1
Predominant beta receptor in lungs?
B2
How to treat open-angle glaucoma?
Decrease production of aqueous humor, increase outflow at canal of schlemm or in sclera
Latanoprost
Prostaglandin agonist which is 1st line for glaucoma. Works by increasing aqueous humor outflow via uveoscleral pathway. Unclear how
Creation of prostaglandins
From arachidonic acid (usually in membranes), COX oxygenizes to create prostaglandins, thromboxane, and prostacyclin
Effect of prostaglandins
Targets all over body including smooth muscle and eye
Prostaglandin agonist side effects
Blurred vision, burning sensation in eye, punctate keratopathy (keratitis)
Punctate keratopathy
Cornification of cornea thought to be due to irritation from prostaglandin agonists or from a preservative.
Timolol
B1 and B2 antagonist, second line for glaucoma. Prevents creation of aqueous humor by ciliary epithelium
Mechanism of action of B receptor mediated creation of aqueous humor
Linked to Gs, so produces cAMP, which is thought to increase aqueous humor.
Side effects of B antagonists
Blurred vision, burning sensation in eye, dry eyes, cough, bradycardia, hypotension. Systemic side effects unlikely.
Why do beta blockers cause hypotension?
Because they slow heart rate, which decreases CO, which decreases MAP.
Brimonidine
Alpha2 agonist. This works in 2 ways. 1) Binding to presynaptic A2 receptor, which decreases the amount of NE in synapse. 2) Binding to postsynaptic A2 receptor (Gi) decreasing cAMP and preventing aqueous humor production
How does brimonidine cause hypotension
Because it works more strongly at the autoreceptor in vascular musculature, which prevents alpha mediated constriction.
Dorzolamide
Carbonic anhydrase inhibitor. Works by preventing secretion of HCO3 into aqueous humor.
Carbachol/pilocarpine
Cholinergic agonists, these cause muscarinic induced ciliary muscle contraction, increasing outflow at trabecular mesh.
