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Summer Final: Glaucoma > Prostaglandin Analogs > Flashcards

Prostaglandin Analogs Flashcards

1
Q

First study about prostaglandin analogs

A
  • demonstrates a reduction in IOP after tropical application of prostaglandins in 1977
  • does is crucial
  • high doses topically or intracamerally raised IOP
  • disruption of blood aqueous barrier
  • two decades of research to develop an analog of prostaglandins
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2
Q

PGs overview and MOA

A
  • all PGs have similar structure
  • they are products of prostaglandin F2a
  • converted by corneal enzymes into its active form
  • activates the F2a prostaglandin receptors on ciliary body
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3
Q

Types of PGs

A
  • latanprost, travoprost, and unoprostone are ESTERS

- Bbimatoprost described as ptrostamide

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4
Q

MOA of prostaglandins

A
  • increased outflow though UV pathways
  • small percentage increase in conventional outflow
  • does not reduce aqueous production
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5
Q

Two theories of PG MOA

A
  1. Relaxation of ciliary muscle

2. Dilated spaces between ciliary muscle bundle

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6
Q

Relaxation of ciliary muscle: PG

A
  • supported by experiments with pilocarpine pretreatment experiments in monkeys. Human experiments no effect
  • increase in CB thickness when treated with latanprost
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7
Q

Dilated spaces between ciliary muscel bundle theory: PG

A

PG induced stimulation of collagenase and other matrix metalloprotenases

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8
Q

Indications of PGs

A

Lower IOPS

  • POAG
  • NTG
  • PDS
  • XF
  • chronic angle closure glaucoma
  • caution with uveitis glaucaom
  • less effective in pediatric glaucoma
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9
Q

Contraindications of PG

A
  • allergy
  • pregnant or nursing
  • pediatric-less effective
  • iunclear PGS and ocular inflamamtion
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10
Q

PGs and inflammation

A
  • not first choice
  • some reports: association of PGs (latanprost) and CME
  • caution: PGS CME, itisi, or HSVK, or immediate post op
  • dont use: cases with complicated surgery, CME or risk of CME, torn posterior capsules
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11
Q

Don’t use PGs when

A

Cases with complicated surgery, CME or risk fo CME, torn posterior capsules

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12
Q

Dosing of PGs

A
  • once daily evening
  • helps prevent morning spikes in pressure
  • reduced redness (as patient has had sleep and 12 hours once last application)
  • should not be utilized more than once a day (twice daily less effective than once a day)
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13
Q

Side effects of PGs

A
  • conjunctival hyperemia
  • iris color change
  • eyelash changes
  • skin pigmentation
  • deepening of upper eye lid sulcus (DUES)
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14
Q

Types of hyperemia with PGs

A

Mild to moderate

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15
Q

Iris color changes in PGs

A
  • well documented side effect
  • overall incidence up to 30-40%
  • only half the number of patients notice the change
  • increase in melanin content not total number of melanocytes
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16
Q

Eyelashes and adnexa changes

A
  • increase in length, number and thickness of eyelashes
  • increase pigmentation of eyelashes
  • eye lash bristle
  • cosmetic use Latisse-Bimatoprost
  • skin pigment around eye also increase-wipe off excess decreases the side effect
17
Q

Orbital fat and PGs

A

Decreased orbital fat, sunken eye, and extra wrinkle on lid

18
Q

Uveitis and PGs

A
  • anecdotal and retrospective studies show possible association between the two
  • in clear causal relationship
  • inflamamtion similar to Tim I’ll in multicenter studies
  • 10 pateitns of 198, few cels were observed. Two of these had cells at baseline
  • risk overall low
19
Q

PGs and CME

A
  • anecdotasl reports
  • almost al the cases had other known risk factors to CME such as open posterior capsules, recent intraocualr surgeries, iritis, complicated surgery with vitreous loss
  • topical PGs dont affect retinal vasculature
20
Q

What protocol to follow if glaucaom patietns needs cataract surgery

A
  • stop PGs one month prior to surgery
  • put patient on other IOP lowering meds
  • have surgery
  • one month after surgery when out come successful restart PG analog
21
Q

Other local side effects of PGs

A
  • reactivation of herpes simplex keratitis or dermatitis

- controlled clinical trials-no reactivation of herpes

22
Q

PGS and systemic side effects

A
  • none
  • PGs reaches systemic circulation
  • metabolized by liver
  • elimation by kidneys
  • half life of 17m
  • in contrast to timolol no effect on blood pressure
23
Q

Drug interaction and PGs

A
  • eye drops containing thimerosol (preservative) will form a precipitate when mixed with latanaproist
  • use 5m apart
24
Q

PGs IOP reduction

A
  • latanaprost reduces mean diurnal IOP 7.9mmHg (about 32%)

- timolol 1.6mmHg less than latanaprost

25
Q

Comparison of PGs

A
  • all are similar
  • effective in all ethnic groups
  • PGs better than timolol in AA
  • no loss of effect over time
26
Q

Why are all drugs compared to timolol

A

BBlockers is considered the FDAs gold standard for glaucoma. Every drug that comes out has to prove noninferior to timolol.

27
Q

Additivity of PGs

A
  • PGs increase outflow

- so adding it with drugs that decrease production of aqueous makes sense

28
Q

BBlockers and PGs

A
  • BBlockers decrease aqueous production
  • several trials adding latanprost to timolol produced additional IOP decline
  • adding BBlockers to latanaprost gives additional 14% drop
29
Q

PGs work better for what kind of IOPs

A

Higher IOPs

-it will lower higher IOPs more than those in the teens

30
Q

CAI and PGs

A

Acetazolamide 250mg BID
Add PGs
Additional 15%

Latanaprost qd
Add dorzalamide TID
Additional 15% drop

Dorzolamide (trusopt) TID
Add PGs
Additional 24% drop

31
Q

Adrenergic agonsists

A
  • adding adrenergic agonists like brimonidine to latanaprost produces similar effect like adding dorxolamide
  • additional 15%
32
Q

Cholinergics agonists

A

Example pilocarpine

  • act by increasing TM outflow faciltiy
  • contraction of ciliary muscle
  • pulls on scleral spur
  • opens channel in TM
  • contraction of ciliary muscle should also contract spaces between muscel bundles

DONT COMBINE PILOCARPINE AND PGS
-cancel out each other

33
Q

Fixed combination of latanaprost

A

Xalacom avialable in some countries but not USA

34
Q

Advantages of fixed combination of PGs

A
  • more convenient
  • less expensive
  • improved compliance
  • for example
  • timolol BId and latanaprost qd
  • OR
  • xalacom qd (combination of latanaprost and timolol)
35
Q

So what’s the problem with combination PGs

A
  • FDA insists that combination of drug should produce additional 20% decrease in IOP
  • PGs give 32-33% already
  • additional of timolol or any other drug does not produce additional 20% decrease in IOP
36
Q

Unoprestone RESCULA

A
  • initally thought as PGs
  • now believe to improve TM
  • side effects similar to PGs
  • no heart/Lung issues
37
Q

Latanoprostene Bunod

A

NO donating prostanoid FP receptor agonist

38
Q

Best percentage of LBN

A

0.024%

Lowered it 9

39
Q

Summary of findings of LBN

A
  • statistically superior IOP lower vs latanaprost (>1mmHg) in phase II study
  • LBN statistically superior IOP lowering vs s timolol in 17/18 points in two phase II studies
  • LBN marked and sustained (24hrs) IOP lowering in healthy normotensive subjects
  • LBN no significant AES
  • LBN nocturnal IOP significantly lower than baseline and signicantly lower than timolol maleate

Summer Final: Glaucoma (15 decks)

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