Prostaglandin analogs Flashcards
if someone complains about a headache, what does this mean?
side effect of the drug
is dose crucial in PG?
yes
high doses of PG can do what to iop?
increase
most commonly utilized drug for glaucoma as a stand alone single drug?
prostaglandin analog
which drug is the most utilized in terms of a compound?
beta blocker
what are the 4 various prostaglandin analogs?
latanoprost, travoprost, bimatoprost, tafluprost
how is bimatoprost different from other PGs?
includes amide group
what is a prodrug?
different structure outside of body than inside of body;
compound of structure in bottle changes when placed into eye –> able to pass through
esterase does what?
turns prodrug into active drug
what are prodrugs of prostaglandin F2alpha
Prostaglandin analogs
what is the mechanism of action for PG?
! Increases outflow through uveoscleral pathway.
! Small percentage increase in conventional outflow.
! Does not reduce aqueous production
! Mechanism not fully understood
! All PGs have similar structure
! They are prodrugs of Prostaglandin F2α
! Converted by corneal enzymes into its active form
! Activates the F2α prostaglandin receptors on ciliary body
prostaglandin analogs (PGs)
! All PGs have similar structure
! They are prodrugs of Prostaglandin F2α
! Converted by corneal enzymes into its active form
! Activates the F2α prostaglandin receptors on ciliary body
prostaglandin analogs (PGs)
two theories of moa of PG
! Two theories
- Relaxation of ciliary muscle
- Dilated spaces between cliliary muscle bundles
what drug constricts cil muscle?
pilocarpine
pilocarpine acts oppositely to PG (T/F)
true
Supported by experiments with pilocarpine pretreatment experiments in monkeys
Human experiments no effect
Increase in ciliary body thickness when treated with latanoprost
relaxation of cil muscle theory
! PG induced stimulation of collagenase and other matrix metalloprotenases
! Still being investigated.
dilated spaces b/w cil muscle bundles-theory 
what does collagenase do?
cleave collagen
what has upregulation of collagen?
myopia
PG is the first line therapy to lower iop in what types of glaucoma?
◦ Primary open angle glaucoma (POAG), ◦ Normal tension glaucoma (NTG), ◦ Pigment dispersion syndrome (PDS), ◦ Exfoliation syndrome (XF) and ◦ Chronic angle closure glaucoma ◦ Caution with uveitic glaucoma and ◦ Less effective in pediatric glaucoma
if anatomy of eye is normal, drugs work. therefore pg doesnt work as well in what type of glaucoma?
pediatric glaucoma
if anatomy of eye is normal, drugs work. therefore pg doesnt work as well in what type of glaucoma?
pediatric glaucoma
contraindications to PG
Pregnant or nursing caution
Pediatric – less effective
Unclear PGs and ocular inflammation
allergic to this drug
contraindications to PG
Pregnant or nursing caution
Pediatric – less effective
Unclear PGs and ocular inflammation
allergic to this drug
pt A needs cataract surgery, taking PG (causes problems postoperatively). so what do we do?
1 month before surgery, they need to stop PG. Put them on a different med that lowers IOP (beta blocker, brimonidine, apriclonidine, CAI). Do surgery. After surgery they can start back on PG.
! Not first choice
! Some reports : association of PGs
(latanoprost) and cystoid macular edema
! Caution: PGs CME, iritis or hepes simplex keratitis, or immediate post-op
! Don’t use- cases with complicated surgery, CME or risk of CME, torn posterior capsules.
PGs and inflammation
! Not first choice
! Some reports : association of PGs
(latanoprost) and cystoid macular edema
! Caution: PGs CME, iritis or hepes simplex keratitis, or immediate post-op
! Don’t use- cases with complicated surgery, CME or risk of CME, torn posterior capsules.
PGs and inflammation
treatment protocol for PG
! Once daily evening
! Helps prevent morning spike in pressure
! Should not be utilized more than once daily
◦ Twice daily less effective than once daily
why do we put PG in the evening?
because it causes redness.
PG should not be exposed to high temperature. Why?
molecule is unstable at high temps
why should we refrigerate PG?
if cold, we can definitely tell it has gone in the eye
what are all the side effects of PG?
Conjunctival hyperemia ! Iris color change ! Eyelash changes ! Skin pigmentation ! Deepening of upper eye lid sulcus (DUES)
name drugs with side effects for conj hyperemia (from greatest to lowest)
bimatoprost > travopost > latanoprost (least redness)
worst side effect of PG
iris color change
incidence of iris color change after PG?
30-40%
Well documented side effect
• Overall incidence up to 30-40 %
• Only half the number of patients notice the change
•I ncrease in melanin content not total number of melanocytes
iris color change
whats the max volume of conj sac?
30 ul
a drop is how much ul?
50 ul
how long should eyes be closed after putting a drop in?
1 minute
how long should eyes be closed after putting a drop in for anesthetics?
1 minute
how long should eyes be closed after putting a drop in for glaucoma/any therapy medication?
5 minutes
if i am prescribing drug a and drug b. if a is applied first, drug b could wash it out. how much time do we wait to apply second drop?
15 min
if i am prescribing AT with another drug. when do we put it in?
before for soothing, as long as theres a 15 min gap between the next drop
is skin pigmentation and eyelash lengthening reversible?
yes
DUES
extra wrinkle/fold; happens because eyeball sinks in (drugs have fat decreasing property)
Anecdotal and retrospective studies show possible association between the two.
! No clear causal relationship
! Inflammation similar to timolol in multicentre
studies
! 10 patients of 198, few cells were observed. Two of these had cells at baseline
! Risk overall low
uveitis and PGs
Anecdotal reports
! Almost all the cases had other known risk
factors to CME
“ Open posterior capsules, recent intraocular surgeries, iritis, complicated surgery with vitreous loss
! Topical PGs don’t affect retinal vasculature “ Monkey experiments with high dose
“ Human experiments with BID (twice daily)
PGs and CME
if lens is removed from eye, is there a chance that CME can develop?
yes! but maybe PG shouldnt be blamed, it is most likely due to drug preservative, which causes edema. PF drug did not find CME.
! Stop prostaglandin analog one (1) month prior to surgery
! Put patient on other IOP lowering medications
! Have surgery
! 1 month after surgery when out come successful restart prostaglandin analog
what protocol to follow if glaucoma pt needs cataract surgery?
! Stop prostaglandin analog one (1) month prior to surgery
! Put patient on other IOP lowering medications
! Have surgery
! 1 month after surgery when out come successful restart prostaglandin analog
what protocol to follow if glaucoma pt needs cataract surgery?
what drug does not have a systemic side effect?
PG
what eyedrop has thimerasol (preservative)?
CLs solution
Eye drops containing thimerasol (preservative) will form a precipitate when mixed with latanoprost
! Use 5 minutes apart
drug interactions with PG
Eye drops containing thimerasol (preservative) will form a precipitate when mixed with latanoprost
! Use 5 minutes apart
drug interactions with PG
PG IOP reduction of latanoprost ?
PG IOP reduction of timolol compared to latanoprost?
! Latanoprost reduces mean diurnal IOP
7.9 mmHg (about 32 %)
! Timolol 1. 6 mmHg less than latanoprost
second line of glaucoma therapy drug?
timolol
all PGs work better than timolol (T/F)?
true
comparing PGs to each other, are there any that are better?
no
whats different than black persons eye to white person?
pigment takes drug and absorbs it; therefore drug is not available to receptors
is there a loss of effect over time for PG?
no
are PGs effective in all ethnic groups?
yes
PGs increase outflow
! So adding it with drugs that decrease production of aqueous makes sense
additivity
PGs increase outflow
! So adding it with drugs that decrease production of aqueous makes sense
additivity
IOP=
production and removal
for additivity, which drugs can we use for glaucoma?
drug that decreases production
! Beta blockers decrease aqueous production
! Several trials adding latanoprost to timolol produced additional IOP decline (i.e., 24-37% decline)
! Adding beta blockers to latanoprost gives additional 14% drop.
beta blockers and PGS
ADDING ANY group to PG other than pilocarpine will reduce iop by what percent?
15%
brimonidine is what type of drug?
alpha 2 agonist
WHATS the efficacy of dorzolamide?
not as good as PG, lower achieving drop
what type of drug is pilocarpine?
cholinergic - increases TM outflow
In monkeys yes it does not work In humans it still works
Latanoprost qd
Add pilocarpine 2% qd Additional 7% drop in IOP
why do combo of pg and cholinergic agonist not work?
! More convenient ! Less expensive ! Improved compliance ! For example ! Timolol BID and latanoprost qd ! Or ! Xalacom qd (combination of latanoprost and timolol)
advantages of fixed combo drugs
! More convenient ! Less expensive ! Improved compliance ! For example ! Timolol BID and latanoprost qd ! Or ! Xalacom qd (combination of latanoprost and timolol)
advantages of fixed combo drugs
FDA insists that combination of drug should produce additional 20% decrease in IOP
PGs give 32-33% already
Addition of timolol or any other drug does not produce additional 20% decrease in IOP
whats the problem with the combo of PGs?
Initially thought as a prostaglandin ! Now believed to improving trabecular outflow -side effects similar to pg -no heart/lung issues
unoprostone (rescula)
Initially thought as a prostaglandin ! Now believed to improving trabecular outflow -side effects similar to pg -no heart/lung issues
unoprostone (rescula)
besides timolol, what can be used as a second line of drug for glaucoma?
unoprostone
