Pharm: Ocular pharmacology

Question 1

ocular routes of administration

Answer 1

1. topical- eyedrops: inferior fornix of conjunctivae
2. local injections
   - subconjunctival: under eyelid
   - retrobulbar: behind eye
   - peribulbar: under the tendons
   - intracameral - inject to anterior chamber
   - intravitreal- inject in vitreous chamber
3. oral injections
4. systemic injections

Question 2

transcorneal absorption?

Answer 2

its a fat-water-fat structure: would want drug w/ both hydrophilic and hydrophobic properties

Question 3

iris sphincter mm.

Answer 3

circular mm. of the eye - constriction of pupil in bright light
- PS innervation = miosis = M3 muscarinic receptor

PS inhibition = relaxation, large pupils, mydriasis

Question 4

iris dilator mm.

Answer 4

radial mm. of iris - dilates pupil during flight/fight response
- symp innervation = mydriasis = alpha1 receptors

Question 5

ciliary muscle

Answer 5

accomodation to focus on near objects

• contraction d/t M3 muscarinic mm
• inhibition of PS –> relaxation, cycloplegia

(clinically insiginificant B2 mediated relaxation)

Question 6

anisocoria

Answer 6

unequal pupil size … but which side?

- one sided ptosis: abnormal sized pupil presumed to be on that side.

Question 7

Horner’s syndrome: - testing of Horners?

Answer 7

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:

1. Cocaine: results in no dilation d/t damage to sympathetics (pupil remains small)
2. 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

Question 8

Adie’s pupil: test?

Answer 8

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 **

Question 9

sympathomimetics- alpha adrenergic agonists

Answer 9

result in dilation = mydriasis d/t dilator radial mm. (alpha1)

Question 10

parasympathomimetics

Answer 10

result in constriction = miosis d/t M3 and M2 receptors

Question 11

Opioid agonists

Answer 11

morphine, heroin, etc.

• result in pinpoint pupil
• act on Mu opioid receptor that excites the PS nn.

Question 12

what blocks aqueous humor production from ciliary epithelial processes?

Answer 12

beta blockers

carbonic anhydrase inhibitors

Question 13

what enables more fluid to flow through canal of schlemm?

Answer 13

cholinergic agonists
- used in glaucoma therapy: result in contraction of ciliary mm. fibers resulting in enlarged openings in trabecular meshwork

Question 14

what can induce angle-closure glaucoma in anatomically susceptible eyes?

Answer 14

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

Question 15

agents used to reduce aqueous humor secretion in open-angle glaucoma?

Answer 15

1. beta blockers
2. carbonic anhydrase inhibitors
3. alpha-adrenergic agonists (alpha2 selective)

Question 16

agents used to tx open-angle glaucoma through increasing aqueous humor outflow?

Answer 16

1. prostaglandin F2alpha analogs
2. alpha-adrenergic agonists
3. parasympathomimetics: muscarinic agonists and AChE inhibitors

Question 17

topical miotic agents: cholinomimetic

Answer 17

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

Question 18

alpha2 adrenergic agonists?

Answer 18

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

Question 19

beta blockers?

Answer 19

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

Question 20

carbonic anhydrase inhibitors

Answer 20

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

Question 21

Prostaglandin F2alpha?

Answer 21

**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!

Question 22

muscarinic antagonists?

Answer 22

atropine, scopolamine,

- used for fundoscopic exam to cause dilation

Question 23

glucocorticoids?

Answer 23

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

Question 24

NSAIDs?

Answer 24

diclofenac, flubiprofen, ketorolac, bromfena

topical formation in eye - for allergic conjunctivitis, postop inflammation, decreasing pain after surgery

Question 25

risk factors for glaucoma?

Answer 25

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

Question 26

ciliary epithelium

Answer 26

stimulated by beta receptors –> beta blockers result in less fluid