Pharm: Ocular pharmacology Flashcards
ocular routes of administration
- topical- eyedrops: inferior fornix of conjunctivae
- local injections
- subconjunctival: under eyelid
- retrobulbar: behind eye
- peribulbar: under the tendons
- intracameral - inject to anterior chamber
- intravitreal- inject in vitreous chamber - oral injections
- systemic injections
transcorneal absorption?
its a fat-water-fat structure: would want drug w/ both hydrophilic and hydrophobic properties
iris sphincter mm.
circular mm. of the eye - constriction of pupil in bright light
- PS innervation = miosis = M3 muscarinic receptor
PS inhibition = relaxation, large pupils, mydriasis
iris dilator mm.
radial mm. of iris - dilates pupil during flight/fight response
- symp innervation = mydriasis = alpha1 receptors
ciliary muscle
accomodation to focus on near objects
- contraction d/t M3 muscarinic mm
- inhibition of PS –> relaxation, cycloplegia
(clinically insiginificant B2 mediated relaxation)
anisocoria
unequal pupil size … but which side?
- one sided ptosis: abnormal sized pupil presumed to be on that side.
Horner’s syndrome: - testing of Horners?
Ptosis, Miosis (small pupil), anydrosis (lack of sweating)
= injury to symp tract
** can be confused w/ CN III injury b/c ptosis is common manifestation, however miosis distinguishes horner’s from CN III injury, which would cause dilated unreactive pupil!
Testing:
- Cocaine: results in no dilation d/t damage to sympathetics (pupil remains small)
- Hydroxyamphetamine
- preganglionic horner’s: pupil still responsive to local release of NE –> dilation
- postganglionic horner’s: pupil unable to respond to NE or NE not available for release
Why?
- cocaine inhibits reuptake of NE/dopa in cleft, however if the problem is that NE can’t get into the cleft, then when cocaine is added you see no dilation.
- amphetamines act on transporter and instead of blocking reuptake they reverse it
Adie’s pupil: test?
Injury to PS tract: Mydriasis (dilated pupil), loss of DTRs, excessive sweating
when mm. is deprived of PS innervation it becomes supersensitive to stimulation by muscarinic agonists such as pilocarpine – normal eye doesn’t usually respond to low doses of this (normally only 1% causes constriction), but in Adie’s 0.1% pilocarpine results in constriction of damaged eye!
** this is d/t circular sphincter mm. having denervation supersensitivity to Ach **
sympathomimetics- alpha adrenergic agonists
result in dilation = mydriasis d/t dilator radial mm. (alpha1)
parasympathomimetics
result in constriction = miosis d/t M3 and M2 receptors
Opioid agonists
morphine, heroin, etc.
- result in pinpoint pupil
- act on Mu opioid receptor that excites the PS nn.
what blocks aqueous humor production from ciliary epithelial processes?
beta blockers
carbonic anhydrase inhibitors
what enables more fluid to flow through canal of schlemm?
cholinergic agonists
- used in glaucoma therapy: result in contraction of ciliary mm. fibers resulting in enlarged openings in trabecular meshwork
what can induce angle-closure glaucoma in anatomically susceptible eyes?
antimuscarinics, sympathomimetic (alpha1 agonists), antihistaminic agents - drugs lead to partial dilation of the pupil and a change in vectors of force preventing the drainage from posterior chamber–> causes iris to be pushed against angle wall
agents used to reduce aqueous humor secretion in open-angle glaucoma?
- beta blockers
- carbonic anhydrase inhibitors
- alpha-adrenergic agonists (alpha2 selective)
agents used to tx open-angle glaucoma through increasing aqueous humor outflow?
- prostaglandin F2alpha analogs
- alpha-adrenergic agonists
- parasympathomimetics: muscarinic agonists and AChE inhibitors
topical miotic agents: cholinomimetic
ACh agonists: pilocarpine, carbachol
AChE inhibitor: physostigmine, echothiophate, demecarium
- previously first line therapy - but req. freq. dosing
cause ciliary mm. contraction –> increased outflow
USE: open angle glaucoma
SE: lots of SE’s (SLUDGE), along with dosing 3-4x/day
AE’s: visual blurring, AChE cause cataract formation, increased risk of retinal detachment
CI: Ach agonists CI for people with asthma
alpha2 adrenergic agonists?
dipivefrin (nonselective) –> increased outflow
brimonidine, apraclonidine (selective alpha2, lipophlic w/ easy corneal penetration) –> decreased aqueous secretion
USE: open angle glaucoma
AE’s: can cause vasoconstriction-vasodilation rebound phenomenon leading to red eye, dry mouth, h/a, increased BP
DI: antidepressants may alter metabolism
beta blockers?
nonselective: timolol, carteolol, levobunolol, metipranolol
selective: betaxolol (less efficacious, but B1 selective, thus no lung problems)
MOA: target ciliary epithelium and cause decreased aqueous secretion from ciliary epithelium
use: open angle glaucoma
relative CI: people w/ asthma, COPD, cardiac dysrhythmias
carbonic anhydrase inhibitors
dorzolamide, brinzolamide (topical)
acetazolamide, dichlorphenamide, methazolamide (oral)
MOA: inhibit CA in ciliary body, which cause decreased aqueous secretion d/t lack of HCO3-
Use: open angle glaucoma
SE:
- topical = stinging, redness, dry eyes, frequent dosing - not first line!
- oral = malaise, fatigue, depression, paresthesias, nephrolithiasis
Prostaglandin F2alpha?
**latanoprost
bimatoprost, travoprost
(acetazolamide and methazolamide are oral)
MOA: cause increased outflow
use: open angle glaucoma
once per day dosing, low SE’s = ** first line therapy for glaucoma!
muscarinic antagonists?
atropine, scopolamine,
- used for fundoscopic exam to cause dilation
glucocorticoids?
dexamethasone, predinsolone, fluormetholone, loteprednol, rimexolone
USE: imp. in managing ocular inflammatory diseases - anterior uveitis, allergies, infections
toxicity: can have significant toxicity in the eye - can result in increased IOP, thus CI in pt. w/ family hx of glaucoma
NSAIDs?
diclofenac, flubiprofen, ketorolac, bromfena
topical formation in eye - for allergic conjunctivitis, postop inflammation, decreasing pain after surgery
risk factors for glaucoma?
Elevated intraocular pressure (IOP) Positive family history African-American heritage Myopia (nearsightedness) Systemic Hypertension
IOP causes damage to optic disk and gradual loss of vision
ciliary epithelium
stimulated by beta receptors –> beta blockers result in less fluid
