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Role of Prostaglandin Analogs in The Treatment of Glaucoma. Mahmood J Showail MD. Glaucoma. One of the most common cause of blindness in the world. . Glaucoma. Glaucoma is characterized by three factors: Elevated Intra Ocular Pressure (IOP) Optic nerve damage (cupping of the disc)

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  • One of the most common cause of blindness in the world.
  • Glaucoma is characterized by three factors:
    • Elevated Intra Ocular Pressure (IOP)
    • Optic nerve damage

(cupping of the disc)

    • Progressive loss of

visual field



Visual Field Loss

Optic Nerve Damage

Intraocular Pressure

glaucoma mechanisms of aqueous humor
GlaucomaMechanisms of aqueous humor
  • Aqueous is produced by the ciliary processes
  • It flows into the posterior chamber
  • Bathes the lens
  • Fills the anterior chamber
glaucoma aqueous flow dynamics
GlaucomaAqueous Flow Dynamics
  • Inflow should be equal to the outflow
  • Normal IOP is between 10 – 20 mmHg
  • Normally the IOP is highest in the morning and lowest in the evening
    • Diurnal curve
open angle glaucoma12
Open Angle Glaucoma
  • Most common form of glaucoma
  • Caused by blockage in the TM leading to decreased drainage of aqueous into the Schlemm’s canal
acg angle closure glaucoma
ACGAngle closure Glaucoma
  • Anatomically the angle is narrow
  • Risk of angle closure occurs when the pupil is dilated
glaucoma decrease the iop in glaucoma
GlaucomaDecrease the IOP in Glaucoma
  • Decrease the inflow
    • Blocking the mechanism of production
  • Increase the outflow
    • Through the trabecular meshwork
    • Through the uveoscleral channels
oag medical treatment
OAGMedical Treatment

Drugs to decrease the aqueous production:

  • Betablockers
    • Timolol (Cusimol)
    • Nyolol gel
    • Betoptic, Betagan

Side effects :

    • Decreased in heart rate
    • Respiratory difficulty.

Not for asthmatic patients.

oag topical medications cont
OAGTopical medications (cont.)
  • Epinephrine drugs
    • Dipivefrin (Propine)
  • Alpha adrenergic agonists
    • Apraclonidine (Iopidine)
    • Brimonidine (Alphagan)

Lower IOP by decreasing

the aqueous production

oag medications cont
OAGmedications (cont.)
  • Carbonic Anhydrase Inhibitors (CAI)
    • Trusopt 2%, Azopt (solution)
    • Diamox tablet/capsules
  • Combination CAI and Betablockers
    • Cosopt, Xolamol

Topical CAI is preferred as they have less side effects

oag glaucoma medications cont
OAGGlaucoma medications(cont.)
  • Prostaglandins
    • Latanaprost (Xalathan)
    • Travatan
      • Increase the outflow through the uveo-scleral channels.

Side effects:

Iris pigmentation and irritation/redness

glaucoma drugs prostaglandin analogs

Reduce IOP by increasing the outflow through uveoscleral channels

Lowers IOP in 3- 4 hrs after instillation



(0.005% Sol.)


Once daily at bedtime



Glaucoma DrugsProstaglandin Analogs

Contraindicated in asthmatic patients


Glaucoma DrugsProstaglandin Analogs

  • Action:
    • Reduce IOP by increasing the outflow through uveoscleral channels
    • Lowers IOP in 2 - 3 hrs after instillation
  • Generics
    • Travoprost
    • (0.004% Sol.)
  • Usage:
    • Once daily at bedtime
  • Brands
    • Travatan

Glaucoma DrugsProstaglandin Analogs

  • Action:
    • Reduce IOP by increasing the outflow through uveoscleral channels
  • Generics
    • Bimatoprost
    • (0.03% Sol.)
  • Usage:
    • Once daily at bedtime
    • Should NOT be used under 18 yrs of age.
  • Brands
    • Lumigan
glaucoma drugs side effects prostaglandin analogs

Change in iris color



Decreased VA

Sensitivity to light






Glaucoma Drugs – Side Effects Prostaglandin Analogs

Glaucoma DrugsCombination Drugs

  • Prostaglandin + Betablockers
    • Decrease production of aqueous humor
  • (double effectiveness)
  • Generics
    • Latanoprost +
    • Timolol
  • (0.005% with 0.5% solution)
  • Usage:
    • Once daily in the morning
  • Brands
    • Xalacom
  • Careful medical history is important
  • Notify the doctor if the patient suffers from:
    • Asthma
    • Heart disease
    • Diabetes
    • Hypoglycemia
    • Overactive thyroid gland
    • Hypotension
    • Vascular disorders
Latanoprost is a prostaglandin F2α analogue. Its chemical name is isopropyl - (Z) -7 [(1R,2R,3R,5S) 3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl] cyclopentyl] -5-heptenoate.
  • Its molecular formula is C26 H40 O5 and its chemical structure is:
Latanoprost is a colorless to slightly yellow oil & Benzalkonium chloride, 0.02% is added as a preservative.
Mechanism of Action
  • Latanoprost is a prostanoid selective F2-alpha prostaglandin receptor agonist which is believed to reduce the intraocular pressure by increasing the outflow of aqueous humor.
  • Studies in animals and man suggest that the main mechanism of action is increased uveoscleral outflow.
This drug decreasesIOP by increasing aqueous outflow through the uveoscleral outflowsystem.23 Compounds related to prostaglandins called prostamidesare also used to reduce IOP.4 These drugs, which have structuressimilar to those of prostaglandins, are thought to enhance outflowthrough both the uveoscleral outflow pathway and the traditionaloutflow system, but the actual mechanisms of their action arestill unknown. Trabecular meshwork and ciliary muscle are twomajor tissues of the outflow systems, but little is known aboutthe biological changes in these two tissues during long-termuse of prostaglandin analogues
Outflow of aqueous humor may be increased bythe prostaglandin analogues by alterations in the extracellularmatrix. Other changes may influence cellular metabolism, suchas the increases in IGF1, tumor necrosis factor superfamily-10and promelanosome-concentrating hormone
The recommended dosage is one drop (1.5 µg) in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal.
  • The dosage of XALATAN Sterile Ophthalmic Solution should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including XALATAN Sterile Ophthalmic Solution is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure lowering effect or cause paradoxical elevations in IOP.
Reduction of the intraocular pressure starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours.
  • XALATAN may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Absorption: Latanoprost is absorbed through the cornea where the isopropyl ester prodrug
  • is hydrolyzed to the acid form to become biologically active. Studies in man indicate
  • that the peak concentration in the aqueous humor is reached about two hours after
  • topical administration.
  • Patients with mean baseline intraocular pressure of 24 – 25 mmHg who were treated for
  • 6 months in multicenter, randomized, controlled trials demonstrated 6–8 mmHg reductions
  • in intraocular pressure. This IOP reduction with XALATAN Sterile Ophthalmic Solution
  • 0.005% dosed once daily was equivalent to the effect of timolol 0.5% dosed twice daily.
PHARMACODYNAMICS / KINETICS Onset of action: 3-4 hours  Peak effect: Maximum: 8-12 hours
  • Absorption: Through the cornea where the isopropyl ester prodrug is hydrolyzed by esterases to the biologically active acid. Peak concentration is reached in 2 hours after topical administration in the aqueous humor.
  • XALATAN has been reported to cause changes to pigmented tissues. The most
  • frequently reported changes have been increased pigmentation of the iris and
  • periorbital tissue (eyelid) and increased pigmentation and growth of eyelashes.
  • These changes may be permanent.
warnings precautions

Concerns related to adverse effects:

  • Bacterial keratitis: Inadvertent contamination of multiple-dose ophthalmic solutions, has caused bacterial keratitis.
  • Ocular effects: May permanently change/increase brown pigmentation of the iris, the eyelid skin, and eyelashes. In addition, may increase the length and/or number of eyelashes (may vary between eyes); changes occur slowly and may not be noticeable for months or years. Long-term consequences and potential injury to eye are not known.
adverse reactions significant
  • >10%: Ocular: Blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, and punctate epithelial keratopathy
1% to 10%:  Cardiovascular: Chest pain, angina pectoris  Dermatologic: Rash, allergic skin reaction  Neuromuscular & skeletal: Myalgia, arthralgia, back pain  Ocular: Dry eye, excessive tearing, eye pain, lid crusting, lid edema, lid erythema, lid discomfort/pain, photophobia  Respiratory: Upper respiratory tract infection, cold, flu
Special populations:
  • Contact lens wearers: Contains benzalkonium chloride which may be adsorbed by contact lenses; remove contacts prior to administration and wait 15 minutes before reinserting.
DRUG INTERACTIONS Bimatoprost: The concomitant use of Latanoprost and Bimatoprost may result in increased intraocular pressure. Risk D: Consider therapy modification
mechanism of action of bimatoprost latanoprost and travoprost in healthy subjects a crossover study
Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects: A Crossover Study

American Academy of Ophthalmology

K. Sheng Lim, MD12, Cherie B. Nau, BS1, Megan M. O'Byrne, MS3, David O. Hodge, MS3, Carol B. Toris, PhD4, Jay W. McLaren, PhD1, Douglas H. Johnson, MD1

  • To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility
  • Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover).
  • Participants
  • Thirty healthy adult subjects
  • Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation.
  • Bimatoprost, latanoprost, and travoprost have similar mechanisms of action. All 3 drugs reduce IOP without significantly affecting the aqueous production rate. All drugs increase aqueous humor outflow, either by enhancing the pressure-sensitive (presumed trabecular) outflow pathway or by increasing the pressure-insensitive (uveoscleral) outflow, but the assessment of the amount of flow through each pathway depends upon the measurement technique.