Glaucoma C

Question 1

Prostaglandin, Prostamide & Prostone Analogs (PGAs): Mechanisms of Action

Answer 1

• increase uveoscleral outflow
  >minor contributing effect on conventional (TM) outflow
  >PGF2a (FP) receptors in uveal outflow pathway
• prostamide bonus
  >also decr. outflow resistance (tonography)
  >prostamide (EP2) receptons on enod cells of TM

Question 2

PGA options

Answer 2

All prodrugs (of PGF2/PGE2)
* latanoprost (oldest)
* travoprost
>similar profile to latanoprost
>SofZia as preservative in Travatan Z
* tafluprost
* bimatoprost
>prostamide (unmetabolized)
* omidenepag (newest)
>selective non-prostanoid ester (recent FDA approval)
>outperforms other drugs

Unoprostone - also now latanoprost+netarsudil & latanoprost+NO donor combos

Question 3

Clinical implications of uveoscleral remodeling

Answer 3

• very long duration
• 24 hr control
• mostly qd (daily) dosing
• AM/PM dosing?
• every other day dosing should suffice?

Question 4

Ocular side-effects of PGAs (latanoprost as prototype)

Answer 4

• conjunctival hyperemia (25 - 35%; reason for night time dosing?)
• irritation/SPK - minimal effect with omidenepag
• irrev. iris color change (5-20%; greater in green & hazel irides)
• thickening/lengthening lashes (hypertrichosis)
• darkening of periorbital dermis (least but more visible in Caucasians)*
• altered orbital fat production (DUES)#
• choroidal detachment
• (re)activation
• CME (pseudophakics/aphakics)
• uveitis?

Question 5

Why monocular PGA therapy may not be acceptable?

Answer 5

Clinical management of cosmetic side-effects
* avoid monocular therapy with PGAs?
* protect against periorbital melanosis with petroleum jelly cover of skin pre-instillation?

Question 6

Systemic Side-effects of PGAs

Answer 6

• essentially none (short systemic t1/2; 17 min for Xalatan)
• relatively rare & mild
• nasal congestion
• flu-like symptoms (including upper respiratory infections)
• nausea & vomiting
• little effect on BP at doses used
• All category C drugs (relevant to pregnant women)