prostaglandin analogs

what are prostaglandin analogs?

prodrugs of prostaglandin F2a converted by corneal enzymes into its active form; activates the F2a prostaglandin receptors on ciliary body

what is a produg

a drug that has a different structure outside the body and an active form inside

how prostaglandins enter anterior chamber?

PGA is oil soluble outside & is absorbed by epithelium

enzymes changes it to acidic form, soluble by water so it can pass though stroma & anterior chamber

latanoprost & travoprost are __ prodrugs

ester

bimatoprost is a __

prostamide (nitrogen attached to carbonyl group)

which PG has a trifluoride group?

travoprost

mechanism of action of prostaglandins

increases outflow through uveoscleral pathway

does not reduce aqueous production

two theories on how prostaglandins work

1. relaxation of ciliary muscle

2. dilated spaces between ciliary muscle bundles

evidence of relaxation of ciliary muscle theory

experiments with pilocarpine pretreatment in monkeys (but human experiments no effect)

increase in ciliary body thickness with latanoprost

evidence of dilated spaces between ciliary muscle bundles theory

PG induced stimulation of collagenase & other matrix metalloprotenases

what drug can nullify the effect of PGs by constricting the ciliary muscle?

pilocarpine

what converts latanoprost, travoprost & tafluprost into an acidic form?

esterase

what activates bimatoprost?

amidase

how prostaglandins change structure of ECM?

acidic form of prostaglandins recruits collagenase & matrix

indications for prostaglandins

POAG

NTG

pigment dispersion syndrome

exfoliation syndrome

chronic angle closure glaucoma

contraindications for prostaglandins

pregnancy or nursing

allergies to this drug

pediatric (less effective)

ocular inflammation

what ocular conditions should you avoid giving prostaglandins to

CME

iritis

uveitis

HSK

immediate post op

torn posterior capsules

What are the risk factors for development of cystoid macular edema after the use of prostaglandins?

Open posterior capsules

recent intraocular surgeries

iritis

complicated surgery with vitreous loss

how often should you give prostaglandins?

once daily evening (QHS)

why should you give PGs in evening?

helps prevent morning spike in pressure

prevents redness during the day

why should you not give PGs more than once a day?

twice daily is less effective bc causes inflammation & breaks down blood aqueous barrier

How are prostaglandins removed from systemic circulation?

Metabolized by liver, elimination by kidneys

side effects of PGs

conjunctival hyperemia

iris color change (increase melanin)

eyelash change

skin pigmentation

deepening of upper eye lid sulcus (decrease in fat)

list the PGs in order of which causes the most redness to the least

bimatoprost

travoprost

latanoprost

how do PGs change eyelashes?

increase length, number & thickness (bristle)

increase pigmentation eyelashes & lid

why don't PGs affect retinal vasculature?

the drug doesn't pass that far back

a study found CME with PGs but not when preservative free drug was used. what could have been the cause of the CME?

preservative BAK

what is the protocol to follow if glaucoma patient needs cataract surgery?

stop PGA 1 month prior to surgery

put pt on other IOP lowering med (timolol)

have surgery

1 month after surgery restart PGA

why do PGs have no systemic side effects?

short half life (17 mins)

what preservative does latanoprost interact with?

thimerasol (forms a precipitate)

how much does latanoprost reduce mean diurnal IOP

7.9 mm hg

how much does timolol reduce mean diurnal IOP

6.3 mm hg (1.6 less)

what drugs can be best combined with PGs?

beta blockers

carbonic anhydrase inhibitors

rhokinase inhibitors

alpha 2 agonists

what drugs should PG not be combined with?

cholinergic drugs (pilocarpine)

adding beta blockers to latanoprost gives additional __ % drop

14%

what percentage additional IOP drop do you get if you add acetazolamide 250 mg bid first & then PGs?

15% drop

what percentage additional IOP drop do you get if you add latanoprost qd and then dorzolamide tid?

15% drop

what percentage additional IOP drop do you get if you add dorzolamide tid and then PGs?

24% drop

adding an adrenergic agonist to latanoprost produces how much additional IOP drop?

15%

advantages of fixed combo PGs & beta blockers

more convenient

less expensiive

improved compliance

how much IOP reduction rate is considered PG non-responder?

how does latanoprostene bunod work?

releases nitric oxide and changes TM cells that are highly contractile in nature

how nitric oxide activates rhokinase

NO binds with soluble guanylate cyclase, which leads to increased conversion of cGTP to cGMP and this activates cGMP dependent protein kinase, which inhibits Rho A that activates Rhokinase

side effects of latanoprostene bunod

conjunctival hyperemia

growth of eyelashes

iris hyperpigmentation

blepharal pigmentation

foreign body sensation in eyes

Compared to latanoprost on average how much additional IOP lowering can be seen when using latanoprostene bunod ?

1 mm hg