Prostaglandin Analogs Flashcards
First study about prostaglandin analogs
- 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
PGs overview and MOA
- 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
Types of PGs
- latanprost, travoprost, and unoprostone are ESTERS
- Bbimatoprost described as ptrostamide
MOA of prostaglandins
- increased outflow though UV pathways
- small percentage increase in conventional outflow
- does not reduce aqueous production
Two theories of PG MOA
- Relaxation of ciliary muscle
2. Dilated spaces between ciliary muscle bundle
Relaxation of ciliary muscle: PG
- supported by experiments with pilocarpine pretreatment experiments in monkeys. Human experiments no effect
- increase in CB thickness when treated with latanprost
Dilated spaces between ciliary muscel bundle theory: PG
PG induced stimulation of collagenase and other matrix metalloprotenases
Indications of PGs
Lower IOPS
- POAG
- NTG
- PDS
- XF
- chronic angle closure glaucoma
- caution with uveitis glaucaom
- less effective in pediatric glaucoma
Contraindications of PG
- allergy
- pregnant or nursing
- pediatric-less effective
- iunclear PGS and ocular inflamamtion
PGs and inflammation
- 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
Don’t use PGs when
Cases with complicated surgery, CME or risk fo CME, torn posterior capsules
Dosing of PGs
- 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)
Side effects of PGs
- conjunctival hyperemia
- iris color change
- eyelash changes
- skin pigmentation
- deepening of upper eye lid sulcus (DUES)
Types of hyperemia with PGs
Mild to moderate
Iris color changes in PGs
- 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
Eyelashes and adnexa changes
- 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
Orbital fat and PGs
Decreased orbital fat, sunken eye, and extra wrinkle on lid
Uveitis and PGs
- 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
PGs and CME
- 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
What protocol to follow if glaucaom patietns needs cataract surgery
- 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
Other local side effects of PGs
- reactivation of herpes simplex keratitis or dermatitis
- controlled clinical trials-no reactivation of herpes
PGS and systemic side effects
- none
- PGs reaches systemic circulation
- metabolized by liver
- elimation by kidneys
- half life of 17m
- in contrast to timolol no effect on blood pressure
Drug interaction and PGs
- eye drops containing thimerosol (preservative) will form a precipitate when mixed with latanaproist
- use 5m apart
PGs IOP reduction
- latanaprost reduces mean diurnal IOP 7.9mmHg (about 32%)
- timolol 1.6mmHg less than latanaprost