Block 5 - Optho Drugs

Front 1

stimulates alpha 1 receptors, postsynaptic, dilating the iris

Back 1

phenylephrine

Front 2

stimulates alpha 2 receptors, pre and postsynaptic, acting on the CP and ESVs

Back 2

Apriclonidine
Brimonidine

Front 3

releases NE from presynaptic vesicles, dilates the iris

Back 3

hydroxymethamphetamine

Front 4

Nonspecific blockade of alpha receptors, postsynaptic, dilates the iris

Back 4

dapiprazole

Front 5

blocks the beta 1 receptor, postsynaptic, acts on the CP

Back 5

betaxolol

Front 6

blocks beta 1 and 2 receptors, postsynaptic, acts at the ciliary process

Back 6

timolol

Front 7

blockade of the beta 1 and 2 receptors, postsynaptic, acts at the CP

Back 7

timolol
levobunolol
metipranolol
carteolol

Front 8

stimulates the muscarinic cholinergic receptor, postsynaptic, acts on the IS and CP

Back 8

pilocarpine

carbachol

Front 9

Inhibition of AchE, acting at the synaptic cleft, affecting the CP and IS

Back 9

Physostigmine
neostigmine
echothiophate
isoflurophate

Front 10

Blockade of the cholinergic receptor, postsynaptic, affecting the IS and CP

Back 10

atropine
scopoloamine
homatropine
cyclopentolate
tropicaminde

Front 11

What is a drug that works indirectly at the alpha 2 adrenergic receptors?

Back 11

hydroxymethamphetamine

Front 12

What are two AchE's that act irreversibly?

Back 12

Echothiphate, Isoflurophate

Front 13

What are the primary adrenergic receptors on the CP?

Back 13

primarily beta 2, some beta 1

Front 14

What is the adrenergic receptor distribution on the IS?

Back 14

alpha = beta

Front 15

What is main distribution of adrenergic receptors on the ID and radial muscle?

Back 15

mainly alpha 1

Front 16

What is main distribution of adrenergic receptors on the CM?

Back 16

mainly beta 1

Front 17

WHat is the cholinergic recptor distribution on the IS?

Back 17

M

Front 18

What is the cholinergic receptor distribution on the CM?

Back 18

M3

Front 19

What is the cholinergic receptor distribution on the CPs?

Back 19

M1

Front 20

What is the t1/2 of strogly lipophilic drugs in the cornea?

Back 20

long

Front 21

What is the ideal octanol/water ratio for an ophthalmic drug?

Back 21

1

Front 22

Agent must be biphasic

-Agents with too low a partition coefficient (hydrophilic) do not penetrate well through the outer epithelial barrier.

-Those with too high a partition coefficient (lipophilic) tend to remain in the epithelium and move into the anterior chamber slowly, resulting in low but prolonged aqueous humor levels.

Back 22

Corneal barrier summary

Front 23

90% of corneal thickness

Mostly keratocytes

Main ocular depot for topically applied hydrophilic drugs

Due to the relatively large size, it also serves as a significant lipophilic storage depot as well.

Back 23

Corneal Stroma

Front 24

Monolayer of polygonal cells 3 microns thick.

Acts as a semi-permeable membrane but with active transport characteristics maintaining the proper water content in the corneal stroma.

Not a major reservoir for drugs
Passes all molecules less than 1 million daltons.

Back 24

Corneal Endothelium

Front 25

Drugs are primarily removed by the ......... vasculature.

Back 25

Uveal

Front 26

aqueous humor –> trabecular meshwork –> canal of Schlemm –> episcleral vessels – >systemic circulation – >renal/liver excretion.

Back 26

steps of drug removal for primary route

Front 27

What is a secondary route of drug removal, especially in the inflamed eye?

Back 27

Iris and ciliary body vasculature also serve as a secondary source of drug removal to the systemic circulation, especially in an inflamed eye

Front 28

This is mechanism by which ophthalmic medications can create systemic toxicity

Back 28

Drugs that are not absorbed into the eye are removed from (puncta – lacrimal system - nose – pharynx – GI).

Front 29

Does the ID (radial) or Muellers muscle have cholinergic receptors?

Back 29

No

Front 30

Active secretion (transport) of sodium by the nonpigmented epithelial cells of the ciliary processes via Na+, K+-ATPase and carbonic anhydrase II (via decreased bicarbonate formation): auto-regulation and neural regulation

Back 30

Aqueous Production

Front 31

In the normal human eye, about...........% of aqueous outflow exits through the trabecular meshwork into Schlemm's canal and enters the systemic circulation by way of intrascleral and episcleral veins

Back 31

90%

Front 32

direct alpha1 agonist


- Primary Effector Site: Radial Muscle of the iris and vascular Smooth Muscle

-Contracts iris dilator muscle
G protein coupled receptor Gq – Phosopholipase C – Incr in Phosphotidyl Inosotol and Ca++

Back 32

Phenylephrine

Front 33

Recommended for pupil dilation and as a decongestant and vasoconstrictor

in uveitis – (posterior synechiae breaks)

open angle neovascular glaucoma

prior to surgery

diagnostic procedures during general eye exams.

refraction

ophthalmoscopic examination

Back 33

Uses of Phenylephrine

Front 34

Side Effects, Drug Interactions

Exaggerated sympathomimetic effects can occur in the presence of MAO Inhibitors.

Contraindicated in Narrow Angle Glaucoma.

Back 34

Phenylephrine

Front 35

Why doe mydriatics such as PE not cause cycloplegia?

Back 35

Mydriatics do not result in cycloplegia in normal dosages since pharmacologically they do not interact significantly with the receptors of the ciliary body.

Front 36

Onset of dilation in 10 minutes

Maximum dilation 45 minutes

Recovery from dilation 4-6 hours

Range based on iris pigmentation
-Iris and conjunctival melanin binds most ophthalmic medication resulting in reduced physiologic effect in patients with darker irises.

Back 36

PE

Front 37

Why is PE not used for routine mydriasis for exam?

Back 37

Harder to reverse dilation (intended miosis) from phenylephrine than from the anticholinergics, therefore not used for routine narrow angle dilation.

Front 38

What will enhance the pharmacological effect of PE?

Back 38

corneal abrasion

Front 39

What happens to aqueous production upon stimulation of alpha 2 receptors in the CP?

Back 39

decrease

Front 40

-Stimulation of the presynaptic ciliary process alpha2 terminal inhibits NE release from the presynaptic terminal leaving less available for post synaptic stimulation

-minimal IOP lowering effect)

Back 40

First mechanism of alpha 2 agonism at the CP

Front 41

Alpha2 direct stimulation of the ciliary process nonpigmented epithelial cell membrane receptor reduces levels of cAMP along with other poorly identified secondary messenger actions ultimately resulting in decreased aqueous production. (8 days)

Back 41

Second mechanism of alpha 2 agonism

Front 42

-Decreases episcleral venous pressure due to effects on alpha2 stimulation of presynaptic receptor (decr. NE)

-increasing uveoscleral outflow and decreasing IOP. (Chronic)

Back 42

Third mechanism of alpha agonism

Front 43

-Minimal: presynaptic

-Acute: ciliary processes,

-Chronic: uveoscleral outflow

-IOP reduction ~ 26%

Back 43

Summary of alpha 2 agonism in the eye

Front 44

Can mildly affect blood pressure through systemic absorption.
Punctal occlude

Decr. CNS penetration with c4 amide group

Back 44

Apraclonidine

Front 45

Reduces IOP through decreased aqueous formation and increased uveoscleral outflow

No effect on trabecular outflow

Thought to potentially aid optic disc blood flow but found not to definitively occur by flow photometry studies.
-CNS extends to retina, and ............. acts centrally by reducing sympathetic outflow – reasoning to suggest long term optic disc vasculature vasodilation.

Back 45

Apraclonidine

Front 46

Peak effect at 3-5 hours with 30-40% reduction in IOP.

Long term – significant drift

Strong hx of ocular allergy

Clinically used for post surgical IOP control only

Best agent for post surgical IOP spikes from Glaucoma

--Laser Surgery when compared with timolol, CAI’s.

--Drops IOP and prevents inflammation of iris (some alpha1 properties)

Back 46

Apraclonidine

Front 47

One of the most frequently prescribed glaucoma medications due to lack of pupillary effects, unique class, and good physiologic response.

Back 47

Brimonidine

Front 48

Usually not a first line treatment, but often a second line treatment

Different classes of glaucoma medications are usually additive.

Drug of choice for normal tension glaucoma
--May improve optic nerve blood supply

Back 48

Brimonidine

Front 49

Almost as effective as Timolol at lowering IOP(~ 25%)

Major side effect: red eyes – dilation of episcleral vessels long term

Contraindicated with MAOI

Back 49

Brimonidine

Front 50

More receptor affinity than apraclonidine

Highly selective for alpha2 (30 x)

Binds to ocular melanin

Acts as a drug reservoir

Back 50

Brimonidine

Front 51

Mechanism: Causes release of NE from the presynaptic membrane after stimulation of α1 and α2 nerve terminal.

Use: mild mydriatic

No cycloplegia (not enough α1 in ciliary muscle)

Mild vasoconstriction

45-60 minutes to maximal mydriasis

Clinically not considered as potent a dilator as phenylephrine and not in great clinical favor

Back 51

Hydroxymethamphetamine

Front 52

No pupillary dilation with hydroxyamphetamine administration

Back 52

3rd order damage

Front 53

Pupillary dilation with hydroxyamphetamine administration

Back 53

1st or 2nd order damage

Front 54

Competitively binds to the postsynaptic adrenergic receptor at radial muscle.

Nonspecific Alpha antagonist

Used to produce miosis after diagnostic phenylephrine induced mydriasis at the radial muscle of the iris

--Minor IOP lowering effect through enhanced cholinergic effects
--Minor increase in ciliary muscle amplitude of accommodation (unopposed cholinergic tone)

Back 54

Dapiprazole

Front 55

reduces intraocular pressure through decreased aqueous production without significantly affecting the pupil or ciliary muscle tonus or aqueous outflow

All used in eye care used for glaucoma (IOP) control

Back 55

Beta Blockers

Front 56

increases IOP production through adenylate cyclase/cAMP (probably)

Back 56

Beta 2 stimulation in the eye

Front 57

First beta blocker on the market

Hailed as a great drug because it did not involve the pupil in glaucoma management and did not have the side effects of epinephrine (conjunctival cysts)

More potent than epinephrine at lowering IOP

Back 57

Timolol

Front 58

Noncardioselective beta blocker without ISA

Similar to propranolol

Produces approx. 35% reduction in IOP

Ocular hypotensive effect of timolol more potent than pilocarpine

Only experiences mild to moderate drift.

Additive with other classes

Back 58

Timolol

Front 59

Which other Beta 1 specific BB will cause a 3mmHg reduction in desired IOp lowering effect via timolol?

Back 59

metoprolol

Front 60

Beta1 selective blocker

Reduces IOP at the ciliary process by decreasing aqueous production

Not as potent as timolol due to the reduced number of beta1 receptors at the ciliary processes.

Indicated in patients with COPD if you must prescribe a beta blocker, but still should be used with caution

Contraindicated with sinus bradycardia

Not useful if pt. is on a systemic beta blocker

Back 60

Betaxolol

Front 61

No significant difference from timolol

Back 61

metipranolol

Front 62

Possesses ISA

Less irritating than timolol

More potent, but same IOP lowering effect

Back 62

carteolol

Front 63

BB with a local anesthetic effect?

Back 63

Betaxolol

Front 64

Best BB for least effect on lipids?

Back 64

carteolol

Front 65

BB with the shortest t 1/2

Back 65

metipranolol

Front 66

BB with the least effect on bronchoconstriction

Back 66

betaxolol

Front 67

To put the ciliary body to partial rest during periods of inflammation

To measure the refractive status of hyperopic children

To treat amblyopia in children

 To aid mydriasis during routine examination.

Back 67

anticholinergic/cycloplegics

Front 68

................ causes the least patient discomfort due to the mildest accommodative paralysis.

Back 68

Tropicamide

Front 69

.............. is the fastest and shortest acting medication while ............ is the slowest and longest acting.

Back 69

Tropicamide short

Atropine long

Front 70

Weaker than atropine stonger than homatropine.

Back 70

cyclopentolate

Front 71

Treatment of most forms of glaucoma via an increase in aqueous humor outflow TM.

Back 71

Use of muscarinic agonists

Front 72

What is the age cut off for cholinergics?

Back 72

< 40 y.o.

Front 73

Miosis – small pupil creates inability to function in low light conditions

Ciliary spasm – creates an inability to focus on desired objects, over-accommodate

Headaches – lasts about 2 weeks, then subsides.

Back 73

side effects of Cholinergics

Front 74

Clinical use: primary: glaucoma, miosis

Prototypical ophthalmic cholinergic

Oldest glaucoma medication, used in ancient Greece

MOA: Cholinergic stimulation of ciliary muscle opens trabecular meshwork facilitating aqueous outflow

Dark irises need higher concentrations

Can’t be used in people under 40 (Accom. Spasm)

Used for angle closure glaucoma

Back 74

Pilocarpine

Front 75

Clinical use: primary: glaucoma, miosis

Better IOP lowering effect than pilocarpine

Higher rate of side effects than pilocarpine (headaches)

Second drug of choice after pilocarpine has lost it’s effectivity

Back 75

Carbachol

Front 76

Organophosphorous compound

Inhibits acetylcholinesterase

Used for glaucoma

IOP reduced by enhanced aqueous outflow at CM – enhanced trabecular meshwork outflow

Potent and prolonged
Miosis begins within 10-30 minutes

May last from 1-4 weeks

IOP reduction maximal at 24 hours and lasts from days to weeks

Back 76

Echothiophate

Front 77

Accelerated cataract formation

Increased risk of retinal detachment

Iris cysts

Potential for systemic absorption and associated toxic responses of intense GI symptoms – diarrhea, nausea, and vomiting

Should be stopped if undergoing treatment with succinylcholine due to potentiation effects and potential prolonged postoperative respiratory paralysis.

Farmers exposed to organophosphate insecticides must be cautioned

Punctal occlusion is mandatory with this medicine.

Back 77

Side effects of Echothiophate

Front 78

(Prostagandin analogue), increases uveoscleral outflow

Back 78

Latanoprost

Front 79

Dorzolamide, brinzolamide

Back 79

Topical CAIs

Front 80

Oral CAI?

Back 80

Acetazolamide