Medical Therapy in Glaucoma M. GHASSAMI MD Medical Therapy in Glaucoma The Ocular Hypertension...
41
Medical Therapy in Glaucoma M. GHASSAMI MD
Medical Therapy in Glaucoma M. GHASSAMI MD Medical Therapy in Glaucoma The Ocular Hypertension Treatment Study demonstrated that topical ocular hypotensive
Medical Therapy in Glaucoma The Ocular Hypertension Treatment
Study demonstrated that topical ocular hypotensive medications can
delay or prevent onset of glaucoma and progression of visual
defects in people with elevated IOP but who have no evidence of
glaucomatous damage.
Slide 4
3 targets for glaucoma management LOWER IOP SAFE AND EASY TO
USE NEUROPROTECTION/ VASOPROTECTION
Slide 5
Characteristics Effective(decrease in IOP) Patient compliance
Medical Economy Circadian control of IOP
Slide 6
Prostaglandin Analogs Cholinergic Agents Beta Blockers
Adrenergic Agents Carbonic anhydrase inhibitors Hyperosmotics Fixed
combination of topical IOP-lowering drugs. Medical Therapy in
Glaucoma
Slide 7
(HYPOTENSIVE LIPIDS) IN GLAUCOMA Prostaglandin Analogs
Slide 8
Prostaglandin Therapy A. Robin Johns Hopkins University
Baltimore, USA The most desirable traits for first-line therapy for
glaucoma are safety, efficacy and ease of use. On this basis, the
first-line medication of choice should be latanoprost.
Slide 9
Research & Development Center, Santen Pharmaceutical Co.
Ltd., Ikoma, Nara, Japan. [email protected] Cardiovascular drug
reviews 2006 PMID: 1 6939629 To date, three prostanoids
(latanoprost, travoprost and bimatoprost) have been launched in
many countries, Hence, prostanoids currently occupy center stage
among glaucoma medications.latanoprosttravoprost bimatoprost It
cannot be denied that in terms of efficacy, safety, patient
compliance, and medical economy prostanoids are currently the
first-line medicines among ocular antihypertensive drugs.
Slide 10
European journal of ophthalmology 2007 Jul-Aug changes in
medical and surgical treatments of glaucoma between 1997 and 2003
in France. CONCLUSIONS: Between 1997 and 2003, new glaucoma drugs,
primarily prostaglandins, improved intraocular pressure control and
delayed surgery, reducing glaucoma surgery by 22%.
Slide 11
Slide 12
Latanoprost reduces the need for surgery in glaucoma patients
Ref: 1) J of Glaucoma 2000; 9: 183-186 2) Drugs of future 1998;
23(8): 908-911
Slide 13
Four agents are in the category Latanoprost (approved in the
United States in 1996) Unoprostone (approved in 2000), Travoprost
(approved in 2001), Bimatoprost (approved in 2001) Prostaglandin
Analogs
Slide 14
History and Name Prostaglandins are metabolic products of
arachidonic acid, a 20-Carbon structurs. They are group of lipids
that are derived enzymatically from fatty acids.
Slide 15
History and name The name prostaglandin derives from the
prostate gland.prostate gland Many other tissues secrete
prostaglandins for various functions, and have important functions
in the body. In eye the nonconventional outflow (uveoscleral
outflow) is improved with resulting decrease in IOP.
Slide 16
Mechanism of action of bimatoprost, latanoprost, and travoprost
in healthy subjects. A crossover study.bimatoprostlatanoprost
travoprost CONCLUSIONS: 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.Bimatoprostlatanoprost travoprostIOPaqueous
humor Department of Ophthalmology, Mayo Clinic, Rochester,
Minnesota, USA. Ophthalmology 2008 May PMID: 18452763
Slide 17
Two major routes aqueous outflow. Prostaglandin analogs act by
increasing outflow, primarily through the uveoscleral pathway (blue
arrows), with some contribution through the conventional trabecular
outflow pathway (green arrows).
Slide 18
MECHANISM OF ACTION Studies of human autopsy eyes revealed high
levels of specific binding sites for PGs. in areas of the ciliary
muscles and iris sphincter muscle. PGs. decreased fibrillar
collagen and increased matrix metalloproteinase (MMP)-1, -2, and -3
in the ciliary muscle and sclera.
Slide 19
MECHANISM OF ACTION MMPs causes cytoskeletal alteration.
Collagen reduction in the sclera. Dilated spaces between ciliary
muscle bundles. Relaxation of the ciliary muscle. Increased trans
scleral permeability. And thereby facilitates uveoscleral
outflow.
Slide 20
FLUCTUATIONS IN IOP Medications with a long-term circadian
control of IOP are hypothesized to have better clinical
effectiveness. When we use PGs. at 9 pm.reduction in IOP occurs
within 3-4 hours, peaks within 8-12 hours. (and thats also the time
when IOP is at its peak) Therefore 2 peaks meet i.e. the IOP at its
peak and Latanoprost at its peak..and persists for up to 24 hours
or longer after topical application Ref: 1. Drugs and Aging 1999;
14(5): 387-398 2. Drugs and Aging 2003; 20(8): 597-630 3. AHFS
2000; 2596-2600 4. Can. J. Ophthalmol; 33(5); 1998; 255-266
Slide 21
FLUCTUATIONS IN IOP PG analogs potentially can reduce IOP below
episcleral venous pressure, (unlike medications that increase
outflow facility.) Reducing glaucomatous damage during sleep. (when
ocular perfusion pressure may be reduced secondary to decreased
systemic blood pressure.)
Slide 22
FLUCTUATIONS IN IOP PGs are as effective at night as during the
day. Latanoprost compared agents a fairly uniform circadian
reduction in IOP. Ref: Invest ophthalmol Vis Sci 2000; 41:
2566-2573 Not only controlling peak IOP is important but the drug
should also control fluctuations in IOP
Slide 23
Prostaglandin Analogs MECHANISM OF ACTION: uveoscleral outflow
Pharmacodynamic: control fluctuations in IOP
Slide 24
TREATMENT REGIMEN The recommended treatment regimen is one
drop. Maximum effect achieved with a concentration of 5mcg/ml
given. More frequent dosing of these agents resulted in decreased
efficacy of the drug (related to development of receptor
subsensitivity) Ref: 1. Drugs and Aging 1999; 14(5): 387-398 2.
Drugs and Aging 2003; 20(8): 597-6303.
Slide 25
one drop at 9 pm Prime time for instillation of
Latanoprost:
Slide 26
Administration Latanoprost (0.005%), Travoprost (0.004%), and
Bimatoprost (0.03%) are administered similarly as one drop daily to
the eye. In contrast, 0.15% Unoprostone is administered as one drop
two times daily to the eye.
Slide 27
INDICATIONS Clinical studies have also demonstrated that PGs
lower IOP in patients with: Ocular hypertention POAG NTG
Exfoliation syndrome, Pigment dispersion syndrome, Chronic
angle-closure glaucoma. Stroid induced glaucoma may be less
effective in pediatric patients.
Slide 28
LATANOPROST Latanoprost, was the first clinically practical
prostaglandin for the treatment of glaucoma, Latanoprost has
Undergone extensive clinical trials for efficacy, drug
interactions, and side effects. In a pooled analysis of 1,389
patients, who were of four ethnic origins, from eight countries,
after 3 to 6 months of treatment. Latanoprost resulted in an
average7.9 mm Hg Decrease in mean diurnal IOP. monotherapy with
latanoprost reduced IOP levels by 29-32% over 1-12 mounths.
Slide 29
Latanoprost Storage latanoprost exhibits thermal and
ultraviolet instability. Protect from light. Store unopened
bottle(s) under refrigeration and 2 o to 8 o C (36 o to 46 o F).
Once a bottle is opened for use, it may be stored at room
temperature up to 25 o C (77 o F) for 6 weeks. The other agents are
recommended to be stored at room temperature.
Slide 30
( Travoprost ( Travatan. Travoprost is a prodrug and has
little, if any, pharmacologic activity until hydrolyzed in vivo to
travoprost free acid. Travoprost 0.004% lowered IOP more than
timolol, The decrease from baseline was 30% to 33% for travoprost
compared with a 22% to 29% decrease for timolol.
Slide 31
( Lumigan ) Bimatoprost latanoprost and bimatoprost caused
similar IOP reductions (p