pharmacology of eye Flashcards
routes of administration in eye
extraocular - topical the most common
intraocular
peri-oculat
what does the extraocular route target
anterior segment
cornea sclera conjunctiva iris ciliary body
the major route of absorption of the eye when given extraocular
cornea
examples of intraocular route meds
Intravitreal injections e.g. Anti-VEGF injections (ranibizumab) for proliferative diabetic neuropathy and wet AMD.
peri-ocular route targets
peri-bulbar
retrobulbar injections
subtenons block
which medications in opthamology take the systemic route
steroids
carbonic anhydrase inhibitors
ABx
Pts presenting with papilloedema
secondary to raised ICP or acute angle
closure glaucoma are treated with
IV acetozolamide to reduce IOP
Patients with severe active thyroid eye
disease can be treated with
IV methylprednisolone to reduce inflammation and prevent optic neuritis
advantages of ABx
- Less invasive mode of delivery
- More pleasant for patient
- Reduced infection risk compared
to injections
Disadvantages of ABx
- Needs to penetrate blood-retinal
and blood-aqueous barrier - High doses can cause systemic side effects
most common route of administration
into the inferior fornix
foreign bodies may be hid in the superior fornix
bioavailability of drug is affected by what
corneal and precorneal factors
what are the precorneal factors and how does it affect the bioavailability
solution drainage - Once in the fornix the drugs drain through the
nasolacrimal duct to enter the inferior meatus through
the valve of Hasner. Here a substantial amount is
absorbed by the nasal mucosa into the blood stream:
blink rate 15p per minute
tear volume adn tear turnouver rate -> 7/8uL
can be altered by - blink rate and lacrimation
induced lacrimation - inflammation - Light • Temperature • Additional environmental factors
tear film
- structure of tear film is altered ie meiobian gland dysfunction - reduced drug residency time in fornix
- pH of tear film ->6.5-7.6 - altered can affect diffusion
- might bind to tear film proteins - albumin and lysozyme
layers of the cornea are bound by
desmosomes
which layer of cornea is hydrophobic and which layer allows ionised water soluble drugs
epithelium is hydrophobic - lipid soluble drugs
stroma - type 1 collagen, permites ionised water soluble drugs
endothelium allows aqueous humour how
gap junctions
2 major ocular barriers to drugs
blood - aqueous barrier
blood - retinal barrier
what is the blood - aqueous barrier
Two discrete
cell layers located in the anterior segment of
the eye:
- The vascular endothelium of the iris/ciliary
vessels - The non-pigmented ciliary epithelium
prevent the entry of soutes into the anterior segment
what is the blood-retinal barrier
(BRB) restricts the entry of
the drugs from blood into the posterior segment.
It is composed of two types of cells :
- The retinal capillary endothelial cells (inner BRB)
- The retinal pigment epithelium cells (outer BRB)
what is the outer BRB (RPE)
RPE: The outer retinal layers
are nourished by the choroid.
• Nutrients/drugs enter the systemic
circulation and eventually reach the
vascular choroid.
• RPE tight junctions restrict diffusion from
choroid to the outer retinal layers.
what is inner BRB
The inner retinal layers are
nourished by the retinal vessels.
• Diffusion from the retinal vessels is
restricted by tight junctions in the
endothelium.
which receptor do acetylcholine bind to in PS Ns
Muscarinic receptors located on post-
ganglionic effector organ
Nicotinic receptors located on ganglion
synapses and NMJ
The ocular receptor are found where
EOM
Levator palpabrae superioris
Iris sphincter
Iris sphincter muscle
Ciliary Body
Lacrimal gland
what is choline acetyltrasferase and where is it found
responsible for degrading Ach
- Corneal epithelium
- Ciliary body
- Inner plexiform layer of the retina
actions of cholinergic agonists
reduce IOP - opening trabecular meshwork to allow aqueous drainage
accomodation - stimulate ciliary muscle and open outflow pathway
miosis (pupil constriction) - stimulates iris sphincter muscle
examples of direct parasympathomimetic and indirect parasympathomimetic
Direct parasympathomimetic: Pilocarpine. Used frequently in the treatment of glaucoma.
Indirect Parasympathomimetic (Inhibit Acetylcholinesterase and prevent breakdown of Ach): Edrophonium, Physostigmine.
how to test for ocular myasthenia
made using the Tensilon
Test. IV is edrophonium is administered. Any improvement in ptosis or
diplopia confirms a positive diagnosis.
Longer acting neostigmine can be used for treatment
SEs of parasympathomimetics
Systemic –salivation, bradycardia
Ocular – cataracts iris cysts, conjunctival toxicity
actions of cholinergic antagonists
mydriasis (pupil dilatation) - inhibits sphincter pupillae)
cycloplegia - inhibits ciliary muscle contraction - NO ACCOMMODATION
slightly decreased lacrimal secretions
how are sympathomimetics used in uveitis and iritis
prevent the formation of posterior synaechiae - adhesions between the posterior iris and anterior lens surface
uses of cholinergic antagonists
Prevent posterior synechiae
• Routine fundal exam
• Provocation of glaucoma (test)
types of cholinergic antagonist
time to onset of action
time of effect
Atropine
40 mins
7-10 dyas
Cyclopentolate
30 mins
12-24 hours
Tropicamide
20 mins
3-4 hours
SEs of cholinergic agonists
Systemic – sweating, flushing, tachycardia
Ocular - blurred vision, photophobia, glaucoma,
what is the sympathetic outflow trunk
T1-L2
what is the role of alpha agonists
Smooth muscle contraction
• Dilator pupillae muscle
• Ciliary muscle
• Constriction of conjunctival
and episcleral vessels
role of beta blockers
- increase aqueous outflow
- decreased aqueous production
types of topical alpha agonists
apraclonidine
brimonidine
clonidine
SEs of alpha agonists
Common: allergic conjunctivitis,
conjunctival blanching
Systemic: hypotension, dry mouth
types of beta blockers
timolol
betacolo
levobunolol
where are Beta 2 receptors found
ciliary processes
trabecular meshwork
MOA of carbonic anhydrase inhibitor
Inhibit carbonic anhydrase which is
found in ciliary body epithelium.
It is a key enzyme in aqueous production
types of topical CAIS
acteozolamide (IV/PO)
dorzolamiode
brinzolamide
topically as have adequate corneal penetration
SEs of CAIs
Systemic: renal stones, malaise, fatigue
Ocular: stinging, allergic reactions
function of the aqueous
- supply nutrition to the lens, corneal endothelium, corneal stroma BUT NOT CORNEAL ENDOTHELIUM
- Maintain IOP -determined bu the rate of aqueous secretion and rate of aqueous outflow 10-21 mmHg
- remain transparent
aqueous humor pathway
secreted by ciliary body epithelium into the posterior chamber
Aqueous flows through the pupil
into the anterior chamber
• Aqueous can be drained through
the trabecular outflow (90%) or
uveoscleral outflow (10%)
• Trabecular: trabecular meshwork,
Schlemm’s canal, episcleral veins
• Uveoscleral: Drained by the
venous circulation in the ciliary
body, choroid and sclera
tear film layer and role
lipid layer - • Smooth surface for lids to glide over
• Reduces surface tension and draws water into the tear
film
• Prevents evaporation of the
aqueous layer
Antibacterial IgA and lysozyme
• Transfers oxygen to the avascular corneal epithelium
• Abolishes surface irregularities of the cornea
mucous layer
‘Wets’ the cornea and lubricates it. Essentially attaches
the aqueous to the corneal epithelium.
epithelial layer
role of orbicularis oculi pump
• 70% tears drained by the lower canaliculus. Remainder drained by the
upper.
• With each blink fibres of orbicularis shorten the canaliculi and move the
puncta medially. The lacrimal sac expands creating negative pressure
and drawing in the tears
• When the eyes open and the muscles relax, the sac collapses and tears drain
down the ducts
light stimulus pathway
• Light stimulus
• EDW nucleus is the
PNS preganglionic
nucleus.
• Fibres travel in CN III
and synapse in the
ciliary ganglion
- Short ciliary nerve
- Sphincter pupillae
what is accomodation
Accommodation occurs when the eyes are directed from a distant object to a near object
accommodation reflex
- Convergence of the eyes
- Pupillary constriction
- Increased biconvexity of the lens
when does accommodation develop and when does ones ability decrease
develops at 2 months and is well developed at 8 months
decrease with age and by 60 years is extrememly poor presbyopia
how is convergence obtained in accommodation
contraction of medial rectus via innervation
by oculomotor nerve
how is pupillary constriction achieved in accommodation
contraction of sphincter pupillae
how is increased lens biconvexity achieved
Circular ciliary muscle contracts, decreasing tension in zonular fibres, and allowing the lens capsule to contact and change the shape of he lens. The anterior pole moves forward, the axial width increases and the diameter of the lens decreases.
