Final - Prostaglandin Analogs Flashcards
PGs basics
All PGs have similar structure
Prodrugs of Prostaglandin F2alpha
Converted by corneal enzymes into its active form
Activates receptors on ciliary body
PGs
- ester prodrugs
- prostamide
Latanoprost, Travoprost, Unoprost
Bimatoprost (nitrogen attached to carbonyl group)
MOA
-aqueous
Incr uveoscleral outflow (and small incr in conventional)
Does not reduce production
MOA
-theories
Relaxation of ciliary muscle
-incr in ciliary body thickness when tx w/ latanoprost
Dilated spaces b/w ciliary muscle bundles
-induced stimulation of collagenase/other matrix metalloprotenases
Indications
POAG NTG PDS XF Chronic angle closure
Caution w/ uveitic glaucoma
Less effective in pediatric glaucoma
Contraindications
Allergic
Pregnant/nursing (caution)
Pediatric (less effective)
Unclear assoc with ocular inflamm
PGs and inflammation
Not first choice
Some reports assoc latanoprost & CME
Caution with CME, iritis, herpes simplex keratitis, or immediately post-op
Don’t use: complicated sx, CME, torn post capsules
Treatment
QD
Helps prevent morning pressure spike
Reduced redness
BID less effective than QD
SE
Conj hyperemia Iris color change Eyelash changes Skin pigmentation Deepening of upper eyelid sulcus (DUES)
SE: iris color change
30-40% incidence
Only half notice the change
Incr in melanin content NOT total number of melanocytes
SE: eyelash & adnexa changes
Incr in legnth, number, thickness of lashes
Incr pigmentation of lashes
Eye lash bristle
Cosmetic use (Latisse = Bimatoprost)
Skin pigmentation around eye incr - wipe off excess to decr SE
Incr in orbital fat content
Uveitis an PGs
Possible association
No clear causal relationship
Inflamm similar to Timolol in multicenter studies
Overall risk low
PGs and CME
Almost all cases had other known factors (open post capsules, recent IO sx, iritis, etc.)
Topical PGs don’t affect retinal vasculature
Protocol if glaucoma pt needs ct sx
Stop PG one month prior to sx
Put on other IOP-lowering meds
Have surgery
Restart PG one month after
SE: herpes
Reactivation of herpes simplex keratitis or dermatitis
PGs and systemic SE
None
-vs timolol & BP effects
Metabolized by liver, eliminated by kidneys
Half-life of 17 min in human plasma
Drug interactions
Gtts containing thirmerasol (preservative) will form a precipitate when mixed when latanoprost
Use 5 min apart
PGs IOP reduction
Latanoprost reduces mean diurnal IOP 7.9mmHg (32%)
Timolol 1.6mmHg less than that (less effective than PGs)
Comparison of PGs
All are similar
Effective in all ethnic groups
PGs better than Timolol in AA
No loss of effect over time
Additivity
PGs incr outflow - adding it with drugs that decr production of aqueous makes sense
Beta blockers and PGs
BB decr production
Adding BB to Lataonprost gives add’l 14% drop
CAIs and PGs
Acetazolamide 250mg BID + PGs = add’l 15% decr
Latanoprost QD + Dorzolamide* TID = add’l 15% decr
Dorzolamide TID + PGs = add’l 24% decr
*Dorzolamide aka Trusopt
Standard drug that all must be non-inferior to/compared to
Timolol
Adrenergic agonists and PGs
E.g. Brimonidine
Similar effect to adding Dorzolamide: add’l 15% decr
Cholinergic agonists
E.g. pilocarpine
Incr trabecular outflow facility
- contraction of ciliary musc, pulls on SS, opens channels in TM
- contraction of CM should also contract spaces b/w muscle bundles
DON’T COMBINE pilocarpine and PGs (cancel each other out)
Fixed combination gtts
-examples
Xalacom available in some countries, not USA
Xalacom = Latanoprost + Timolol
Ganfort = Bimatoprost + Timolol
DuoTrav aka Extravan = Travoprost + Timolol
Fixed combination gtts
-advantages
Convenient
Less expensive
Improved compliance
Fixed combination gtts
-problems
FDA insists combos should produce add’l 20% decr in IOP
-PGs already give ~33% & add’n of Timolol/other does not prod that much add’l decr
Unoprostone RESCULA
Initially thought as a PG - reclassified as not
-now believed to improve TM outflow
SE similar to PG
No heart/lung issues
Latanoprostene Bunod
-what it is
Nitric oxide-donating prostanoid FP receptor agonist
From Bausch & Lomb
Latanoprostene Bunod
-MOA
Same as regular PGs (prodrug acting on ECM) PLUS changes TM cells architecture, that are highly contractile in nature (via NO)
Latanoprostene Bunod
-concentration used for trials
0.024%
Latanoprostene Bunod
-summary of findings
Statistically superior IOP lowering vs latanoprost in one study
Statistically superior IOP lowering vs Timolol in 17/18 in two studies
Marked/sustained 24 IOP lowering in healthy normotensive pts
No significant adverse events (avg 5-7% hypermia rates)
Nocturnal IOP significantly lower than baseline & Timolol maleate
