Final - Prostaglandin Analogs

Question 1

PGs basics

Answer 1

All PGs have similar structure

Prodrugs of Prostaglandin F2alpha

Converted by corneal enzymes into its active form

Activates receptors on ciliary body

Question 2

PGs

• ester prodrugs
• prostamide

Answer 2

Latanoprost, Travoprost, Unoprost

Bimatoprost (nitrogen attached to carbonyl group)

Question 3

MOA

-aqueous

Answer 3

Incr uveoscleral outflow (and small incr in conventional)

Does not reduce production

Question 4

MOA

-theories

Answer 4

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

Question 5

Indications

Answer 5

POAG
NTG
PDS
XF
Chronic angle closure

Caution w/ uveitic glaucoma
Less effective in pediatric glaucoma

Question 6

Contraindications

Answer 6

Allergic
Pregnant/nursing (caution)
Pediatric (less effective)
Unclear assoc with ocular inflamm

Question 7

PGs and inflammation

Answer 7

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

Question 8

Treatment

Answer 8

QD

Helps prevent morning pressure spike

Reduced redness

BID less effective than QD

Question 9

SE

Answer 9

Conj hyperemia
Iris color change
Eyelash changes
Skin pigmentation
Deepening of upper eyelid sulcus (DUES)

Question 10

SE: iris color change

Answer 10

30-40% incidence
Only half notice the change
Incr in melanin content NOT total number of melanocytes

Question 11

SE: eyelash & adnexa changes

Answer 11

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

Question 12

Uveitis an PGs

Answer 12

Possible association
No clear causal relationship
Inflamm similar to Timolol in multicenter studies
Overall risk low

Question 13

PGs and CME

Answer 13

Almost all cases had other known factors (open post capsules, recent IO sx, iritis, etc.)

Topical PGs don’t affect retinal vasculature

Question 14

Protocol if glaucoma pt needs ct sx

Answer 14

Stop PG one month prior to sx
Put on other IOP-lowering meds
Have surgery
Restart PG one month after

Question 15

SE: herpes

Answer 15

Reactivation of herpes simplex keratitis or dermatitis

Question 16

PGs and systemic SE

Answer 16

None
-vs timolol & BP effects
Metabolized by liver, eliminated by kidneys
Half-life of 17 min in human plasma

Question 17

Drug interactions

Answer 17

Gtts containing thirmerasol (preservative) will form a precipitate when mixed when latanoprost

Use 5 min apart

Question 18

PGs IOP reduction

Answer 18

Latanoprost reduces mean diurnal IOP 7.9mmHg (32%)

Timolol 1.6mmHg less than that (less effective than PGs)

Question 19

Comparison of PGs

Answer 19

All are similar

Effective in all ethnic groups

PGs better than Timolol in AA

No loss of effect over time

Question 20

Additivity

Answer 20

PGs incr outflow - adding it with drugs that decr production of aqueous makes sense

Question 21

Beta blockers and PGs

Answer 21

BB decr production

Adding BB to Lataonprost gives add’l 14% drop

Question 22

CAIs and PGs

Answer 22

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

Question 23

Standard drug that all must be non-inferior to/compared to

Answer 23

Timolol

Question 24

Adrenergic agonists and PGs

Answer 24

E.g. Brimonidine

Similar effect to adding Dorzolamide: add’l 15% decr

Question 25

Cholinergic agonists

Answer 25

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)

Question 26

Fixed combination gtts

-examples

Answer 26

Xalacom available in some countries, not USA

Xalacom = Latanoprost + Timolol
Ganfort = Bimatoprost + Timolol
DuoTrav aka Extravan = Travoprost + Timolol

Question 27

Fixed combination gtts

-advantages

Answer 27

Convenient
Less expensive
Improved compliance

Question 28

Fixed combination gtts

-problems

Answer 28

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

Question 29

Unoprostone RESCULA

Answer 29

Initially thought as a PG - reclassified as not
-now believed to improve TM outflow

SE similar to PG

No heart/lung issues

Question 30

Latanoprostene Bunod

-what it is

Answer 30

Nitric oxide-donating prostanoid FP receptor agonist

From Bausch & Lomb

Question 31

Latanoprostene Bunod

-MOA

Answer 31

Same as regular PGs (prodrug acting on ECM) PLUS changes TM cells architecture, that are highly contractile in nature (via NO)

Question 32

Latanoprostene Bunod

-concentration used for trials

Answer 32

0.024%

Question 33

Latanoprostene Bunod

-summary of findings

Answer 33

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