Wk 14 - Prostaglandin Analogues Flashcards
Prostaglandin Analog MOA
• Recall that prostaglandins are endogenous pro-inflammatory molecules
• Prostaglandins and their analogs bind FP receptors on the ciliary muscle
o Activation of these receptors increases matrix metalloproteinases (MMPs)
o MMPs break down collagen fragments to create more space in the muscle
o More space means that more aqueous is able to flow out through the ciliary muscle and uveoscleral pathway
• So, the main mechanism for IOP lowering by prostaglandins is increasing uveoscleral outflow
o They may also increase trabecular meshwork outflow, but this is not well understood and not as big a component
o No inhibition of aqueous production
All prostaglandin analogs decrease IOP by about 30%!
- No tachyphylaxis
Analog Chemical Drug Categories
Prostaglandin analogs are produced as lipophilic prodrugs that can penetrate the cornea more easily
1) Ester-based drugs
are quickly hydrolyzed to their active form by tissue esterases
o Latanaprost, tafluprost, travaprost
2) Amide-based drugs are hydrolyzed less, so the concentration of drug must be higher for good penetration
o Bimatoprost
If patient’s IOP is not responding well to a PG, first try switching from ester to amide or vice versa
o Still not lowered enough—switch drug classes
Latanoprost (Xalatan)
• First PG analog available
Ester-based
Dosing: 1 gt qhs (every night)
o Works well at night, unlike beta blockers which only work well while awake
o Max dose effect in 12 hours
o Full drug effect may take up to two weeks
Compliance
o Qday dosing increases compliance 12% vs BID dosing
o Taking the drug at the same time every day is more important than taking it at night
• If patient will be more compliant using a PG every morning, that’s okay
o Xal-ease device helps patients self-administer drops
Storage
o Refrigerated for long term storage, but patient can keep it at room temperature
o Avoid direct sun and heat
Generically available
o Some inconsistency among manufacturers
• Inactive ingredients/vehicle
• Number of drops/bottle
o If IOP is fluctuating while using generic latanoprost, consider switching to a brand name
o Coupons and insurance may make brand name as affordable as a generic – always check!
Tafluprost (Zioptan)
Ester-based
Dosing: 1 gt qhs
o Max effect in 12 hours, with reduction starting at 4-6 hours
Preservative free
o Available in unit dose
o Refrigerate unopened drops
o Good for patients with dry eye or ocular surface disease
Travoprost (Travatan Z)
Ester-based
Dosing: 1 gt qhs
May be more effective in African American patients than other PGs
o Good, since they’re they highest risk patients
o Will probably lower IOP by 1 more mmHg, so it’s not imperative that you use travoprost instead of another PG in an AA patient
Formulations
o Generic travoprost – BAK preserved
o Travatan Z – preserved with Sofziatim
- Gentler to the ocular surface
Endurance of effect
o 44 hours after discontinuing dose, 85% of treatment persists
Bimatoprost (Lumigan)
Amide-based
o May lower IOP better in some patients who don’t respond well to ester-based PGs
o Originally called a “prostanoid,” but it’s really pretty much the same as all the PGs
Dosing: 1 gt qhs
• Formulation
o Initially 0.3% with lots of red eye complaints
o Now 0.1%, but BAK concentration is increased for better penetration
Unoprostone (Rescula)
• Prostaglandin-like drug
MOA: Enhances aqueous outflow through trabecular meshwork»_space;> uveoscleral
o Acts on Big Postassium (BK) channels to relax meshwork
o Little to no affinity for FP receptor
Dosing: bid
Role o Secondary or add-on med o 3-4 mmHg IOP reduction • ~70% as affective as a beta-blocker • Very safe with no real side effects
Prostaglandin Analog Side Effects
A. Conjunctival hyperemia
• Most common PG side effect
• Tell your patients!
o May think something is wrong, like an allergic reaction
o May affect compliance
• Seems to stabilize and decrease slightly over a few weeks
B. Burning and stinging
• Possible associated SPK/SPEE
• * Less with ester-based than amide-based
D. Intraocular inflammation
• Iritis in ~2% of patients
• Cystoid macular edema in 3-4%
o Cautions especially in aphakic patients and pseudophakic patients with torn posterior lens capsules
E. Reactivation of HSV
• Consider HSV history before starting a PG
• “May start and watch” – Dr. I. Ben Gaddie
o Benefits of PG therapy may be worth the risk of reactivation
o HSV keratitis is simple and easy to treat
o Monitor patient closely after starting PG therapy to catch flare-up early
F. Prostaglandin-associated periorbitopathy
• Can cause atrophy of orbital fat
• Resulting ptosis, enophthalmos, and deepened superior sulcus
• May be partially reversible over months after d/c
• Consider especially if initiating monocular therapy
G. Pigmentation and lash changes
a ) May increase melanin production by melanocytes of iris stroma
o Especially in patients with hazel or multicolored eyes
o Less in patients with blue or brown eyes
o May darken nevi
b ) May cause darkening of lids
o Reduce by wiping excess drop off of skin
c ) Hypertrichosis
o Alters growth cycle of lashes to make them thicker and longer
• Latisse (0.03% bimatoprost)
o Just old lumigan repackaged with a brush
o Spread on lash line to increase length, thickness, and pigmentation
H. Systemic side effects
• None!
Prostaglandin Analog Contraindications
A. History of irits, CME, or HSV
B. Following lens extraction
• Aphakia
• Pseudophakia with anterior chamber IOL
• Pseudophakia with posterior chamber IOL with YAG capsulotomy (torn posterior capsule)
C. Contact lens wear
• Chronic use of BAK preserved drugs can cause corneal damage
• CL wearers are at higher risk of keratitis
D. Hypersensitivity to BAK
E. Pregnancy
• Most drugs are category C
Melton and Thomas on Glaucoma Treatments
First-line treatments
• Prostaglandin analogs
o Safe, effective, qday dosing
o Shown to be very effective when dosed 3 times a week
• Possible consideration for the right patients
OR
• Beta-blockers
o Effective qday dosing and very inexpensive
Additive and secondary therapies
• Beta-blockers o Can be added to PG therapy • Alpha-agonists • CAIs • Rescula • Combination drops o First test effectiveness of the included drugs separately to determine value
