This document summarizes various classes of anti-glaucoma medications, including their mechanisms of action and examples of drugs. It focuses on prostaglandins, describing how latanoprost, bimatoprost, and travoprost work. It also discusses adrenergic medications, carbonic anhydrase inhibitors, cholinergic drugs, and hyperosmotic agents for treating glaucoma. Side effects are provided for each class.

1. Guide: Dr Shobha Pai
Dr Madhurima
Anti-Glaucoma Medications

2. Classification
Decreasin
g
production
• ADRENERGIC ANTAGONISTS
• ADRENERGIC AGONISTS
• CARBONIC ANHYDRASE INHIBITORS
Increasing
outflow
• MIOTICS
• PROSTAGLANDINS
Others
• HYPEROSMOTICS
• NEWER DRUGS

3. PROSTAGLANDINS
 Newer class of drugs
 Introduced in the 1990s
 Very potent in reducing IOP
 Eicosanoids

4. Mechanism of action
 Mixed pharmacological
responses
 4 types- EP, FP, IP and
TP
 Two mechanisms
 Relaxation of ciliary
muscle and increase in
uveoscleral outflow
 Remodelling of trabecular
meshwork extracellular
matrix

5. Latanoprost:
o Potent prostaglandin F2α agonist
o First to be approved for use
o 0.005% dose OD-bed time
o 25-30% reduction in IOP
o Efficacy >Timolol BD
>Timolol gel OD
>Brimonidine

6. Latanoprost
o No adverse systemic side effects
o Effects continue for 24 hours unlike Timolol which
does not act in the night
o Increase in retinal microcirculation and pulsatile
blood flow
o Storage: refrigeration when not opened, once
opened can be stored in room temperature for 6
weeks

7. Bimatoprost Travoprost
 0.03% solution
 Once daily
 Chemical structure
differs from other PGs
 Approved in 2001
 Efficacy is
comparable to
Latanoprost
 More local side effects
 0.004% solution
 Twice daily dose is
also effective
 Available as BAK free
 Duration of action can
be more than 40
hours from once daily
dose
 Superior to
Latanoprost and
Timolol, in IOP control
and visual field
progression

8. Isopropyl Unoprostone
 22-Carbon molecule
 Trabecular flow
 Prodrug derived from pulmonary metabolite
 Efficacy comparable to Timolol given twice daily
 0.12% solution BD
 Reduces IOP by 11-23%

9. Drug combinations
 All agents can be combined with Timolol with
evening dosing
 With topical Carbonic Anhydrase inhibitors
 With Brimonidine
 PG + Brimonidine> Timolol + Dorzolamide
 With cholinergics

10. Side effects
 Hyperpigmentation
 Lashes-increase in length and number
 Conjunctival hyperemia
 Iris pigmentation
 Dry eye, SPK
 Reactivation of Herpes
 Acute uveitis
 Cystoid macular edema
 Choridal effusion
Contraindicated in inflammtory
glaucoma

11. Adrenergic system
 Adrenergic agonists have been used as ocular
hypotensives since 1900, with sub conjunctival
injection of epinephrine
 In eye, stimulation of α1 receptors causes
mydriasis, vasoconstriction, raise in IOP and
eyelid retraction
 Stimulation of α 2 receptors decreases aqueous
formation and probably increases outflow
 Associated with prostaglandin action

12. Epinephrine and Dipivefrin
 Increases aqueous outflow by both conventional
and uveoscleral outflow
 Epinephrine has a low solubility and hence
decreased efficacy
 Dipivefrin is a prodrug with increased lipid
solubility and increased corneal penetration.
 As efficacious as betaxolol 0.5%

13. Side effects
Hypertension, cardiac disease,
thyrotoxicosis-C/I
Tearing, hyperemia,
blepharoconjunctivitis
Adrenochrome deposits- cul de sac,
upper tarsal conjunctiva, corneal
epithelium, nasolacrimal system
Macular edema- especially in
aphakics

14. α2 ADRENERGIC AGONISTS
 Clonidine, a potent α2 agonist was found to have
IOP reducing activity
 Clonidine has ability to penetrate blood brain
barrier
 Non selective adrenergic agonists are not
approved for use
 Mechanism of action:
They reduce IOP by decreasing aqueous
formation.

15. Apraclonidine
 Derivative of clonidine without systemic side
effects
 Prodrug
 Anterior segment vasoconstriction and thus
reduces aqueous production
 1% - acute rise in IOP
 0.5% - long term control
 Efficacy comparable to Timolol

16. Brimonidine
 Potent ocular hypotensive
 More selective to α 2 receptors
 0.15% solution BD/TID
 Neuroprotective properties
 Can cause cardiovascular instability in children <
5 years
 Sleepiness and lethargy- great caution in
children less than 15 years
 Not to be given with NSAIDs

17. Side effects
Ocular Systemic
 Follicular
conjunctivitis
 Apraclonidine has
higher rates of
tachyphylaxis and
allergy
 Hyperemia, itching
and photophobia
 Blurred vision
 Dry mouth
 Fatigue, drowsiness,
headache
 Hypotension
 Bradycardia and
hypothermia in
neonates

18. Adrenergic antagonists
 1967- Phillips and co workers reported IV
propranolol decreased IOP
 Until the advent of prostaglandins, adrenergic
antagonists were among the most useful drugs
 Act on β 2 receptors present on the ciliary
epithelium and decrease aqueous production

19. Timolol Maleate
 Non selective β antagonist
 Reduces IOP without change in refractive status,
pupil size
 0.25%, 0.5% twice daily formulation
 Action begins in 20-30 minutes and lasts till 24-48
hours
 Long term drift is seen
 Additive properties with pilocarpine, carbonic
anhydrase inhibitors and adrenergic agonists
 Timolol Hemihydrate

20. Betaxolol
 Selective β1 antagonist
 It is thought to decrease IOP by either acting on β
receptors or through a non adrenergic pathway
 0.5% used twice daily
 Neuroprotective effect
 Safe is asthmatics
 40% patients experience burning
 Microsuspension forms

21. Levobunolol:
Non selective β antagonist, available in 0.5% given
once daily
Carteolol:
Preferred for cardiac patients. 1% and 2% solution,
twice daily dosage
Metipranolol : Non selective β antagonist, 0.3%
solution for twice daily dosage

22. Side effects
Ocular Systemic
 Stinging, itching,
burning
 Keratoconjunctivitis
Sicca
 Corneal anaesthesia
 Systemic side effects
can be caused even
with low concentration
 CNS symptoms, CVS
symptoms
 Bronchoconstriction,
Increase in serum
tryglycerides
 Altered response to
hypoglycemia
 Fetal arrhythmias—
contraindicated in
pregnancy

23. CARBONIC ANHYDRASE
INHIBITORS
 Sulfonamides
 Only systemic group of drugs still approved for
long term use
 Acetazolamide was first introduced in 1954 as
an antiglaucoma drug
 Methazolamide, ethoxzolamide,
dichlorphenamide
 Dorzolamide, brinzolamide- Topical

24. Mechanism of action
 This enzyme is present in many tissues in the
body-renal cortex, gastric mucosa, RBC, lung,
pancreas, CNS
 Type II isoenzyme is present in the ciliary
epithelium, in the basolateral surface
 Decreases production of bicarbonate and
decreased formation of aqueous
 Also, intracellular pH that is needed for ion
transport is disturbed by CAIs.

25. Topical CAIs
• Acts on CAI II isoenzyme in
ciliary epithelium and also RBCs
• 2% solution, BD
• Response peaks 3 hours after
dosing
Dorzolamide
• 1% solution for TID application
• As efficacious as Dorzolamide
2% BD
• Lesser ocular side effects
• Effects are additive to Timolol
Brinzolamide

26. Acetazolamide
 Reduce the formation of aqueous by 40%
 Many other mechanisms proposed: buffer
system, vasoconstriction of anterior uveal tract
 Penetrates cornea poorly
 250mg every 6 hours given orally
 125mg, 250mg and 500 mg, sustained release
preparation
 “Emergency ampuoles”

27. Methazolamide
 It is a systemic CAI
 Lesser protein bound than acetazolamide
 25-50mg given twice daily
 Can cause urolithiasis
 Advantages over Acetazolamide:
 Not actively secreted by kidney, can be given in
patients with renal problems
 Diffuses more easily into eye
 Dosing is convenient

28. Side effects
 Ocular side effects:
 Irritation, myopic shift, SPK
 Systemic side effects:
 Paraesthesia around mouth and finger tips,
 Increased frequency urination, gastric irritation
 Electrolyte imbalance
 Metabolic acidosis
 Caution: liver disease, adrenal insufficiency, sickle
cell disorder, pregnancy
 Blood dyscrasias and Steven Johnson
Syndrome
Contraindicated in Fuchs endothelial
dystrophy

29. CHOLINERGIC DRUGS
 Oldest effective anti glaucoma medications
 Mechanism of action
 In angle closure: They constrict the pupil and pull
the peripheral iris away from the trabeculum.
 In open angle: They contract the ciliary body thus
opening the scleral spur and opening the trabecular
meshwork

30. Directly acting agents
 Acetyl choline:
 Prototype of this group
 Not used topically
 Pilocarpine:
 Most widely prescribed miotic
 Available in 0.25-10%, QID application
 1%- light irides
 2%- dark irides
 Various methods are devised to decrease the
number of applications

31. Soft contact lens
Ocusert
Pilocarpine gel
Pilocarpine polymer

32. METHACHOLINE:
•Used in the past
•Diagnosis of Adie’s pupil
•Synthetic derivative acetyl choline
CARBACHOL:
•More powerful miotic than pilocarpine
•More side effects
•Intracameral injection in post opperative patients
ACECLIDINE:
•Used in Europe
•Less effective than piolcarpine
•Less ciliary spasm and accomodation

33. Indirectly acting agents
 They inhibit the enzyme acetylcholinesterase and
potentiate the effect of endogenous acetylcholine
 More side effects than directly acting agents
1. Echothiophate: cataract and iris epithelial cyst
2. Demecarium Bromide: Long acting
3. Isoflurophate: Not in clinical use
4. Physostigmine and Neostigmine: Short acting
agents

34. Side effects
Ocular:
 Conjunctival injection
 Periocular pain
 Miosis and dim illumination
 Fluctuating myopic shift
 Anterior subcapsular opacity and iris epithelial
cysts
 Allergic blepharoconjunctivitis
 Retinal hole and detachment
 Vitreous abnormalities to be ruled out before
starting on miotics

35.  Pupil to be dilated twice a year to
 visualize the disc
 visualize peripheral retina
 prevent formation of posterior synichiae
 2.5% phenylephrine can be used without
decreasing outflow capacity
 Contraindicated in intraocular inflammation and
hypersensitivity
 Peptic ulcer, retinal abnormalities, chronic
obstructive pulmonary disease and high myopia-
relative contraindications

36. Systemic side effects
 Nausea, vomiting, abdominal cramping
 Salivation, sweating
 Bradycardia, hypotension and bronchospasm
 Multiple applications should be avoided, punctal
occlusion
 “Choline apnoea”
Cholinergic toxicitiy:
 2mg Atropine s.c or i.v
 Inj. Pralidoxime 25mg/kg infused over 2 hours

37. HYPEROSMOTIC AGENTS
 Useful in short term management of glaucoma
 Osmoreceptors present in hypothalamus send
efferent to the optic nerve
Increase the osmolality of plasma
Draw water from eye to intravascular compartment through
blood vessels of uvea and retina

38. Oral agents
 Slow onset of action and less efficacious
 Isosorbide: 45% solution, 1.5-4ml/kg
 It is not metabolized; no effect on blood sugar
levels
 Absolute alcohol: 1-1.8ml/kg, 40-50% solution
Glycerol: most common. 50% solution, 1-
3ml/kg
Penetrates eye poorly
Nausea and vomiting
Ketoacidosis

39. Intravenous agents
 Faster action with more efficacy
 Urea:
 20% solution, 2-7ml/kg
 Penetrates eye better, less efficacious
 Old solutions not to be used
Mannitol: agent of choice as intravenous
agent
2.5-7ml/kg of 20% solution
Action starts in 20-30 minutes, lasting for
6 hours
Cellular dehydration in CNS- dementia
and disorientation
Congestive heart failure

40. Side effects
 Nausea, vomiting, headache and diuresis
 Intense diuresis- acute retention
 Pulmonary edema and congestive cardiac failure
 Subdural hematoma due to shrinkage of vessels
 Cellular dehydration
 Extravasation of urea can lead to skin necrosis

41. Class of drug Mechanism of
action
Concentration % IOP
reduction
Important
side effect
Prostaglandin
s
•Latanoprost
•Bimatoprost
•Travoprost
Increase
uveoscleral
pathway
0.005%
0.03% HS
0.004%
25-32% Hypertrichosis
Increased
pigmentation
Hyperemia
β antagonists
•Timolol
•Levobunolol
•Betaxolol
Decrease
aqueous
production 0.5% BD
20-30%
15-20%
Bradycardia,
heart block,
bronchospas
m
Stinging
Adrenergic
agonists
•Apraclonidine
•Brimonidne
Decrease
aqueous
production
Increase
outflow
0.5-1% BD, TID 20-30%
Hypotension,
tachyphylaxis,
follicular
conjunctivitis

42. Class of drug Mechanism
of action
Concentratio
n
% IOP
reduction
Important
side effect
CAIs
•Acetazolamide
•Dorzolamide
•Brinzolamide
Decrease
aqueous
production
250mg QID
2% BD,TID
1% BD, TID
15-20% SJS, blood
dyscrasias
Miotics
•Pilocarpine
Increase
outflow
1% QID 15-25% Myopic shift,
Retinal
detachment
Hyperosmotics
•Glycerol
•Mannitol
Draw water
from eye to
intravascular
compartmen
t
50% solution 1.5-3ml/kg
20% solution 2,5-7ml/kg
Nausea,
ketoacidosis
Urine
retention, CCF

43. Prostaglandins
β blockers
αAgonists
Carbonic anhydrase
inhibitors
Miotics
Nonselective
adrenergic
agonists
Selective β
blockers

44. Drug combinations
Combination Trade name Concentration % IOP
reduction
Timolol/Dorzolamide Cosopt 0.5%/2% BD 25-30%
Timolol/ Latanoprost Xalcom 0.5%/0.005% HS Greater
than
monotherap
y
Timolol/Travoprost Duotrav 0.5%/0.004% HS Greater
than
monotherap
y
Timolol/ Bimatoprost Ganfort 0.5%/0.003% HS Greater
than
monotherap
y
Timolol/ Brimonidine Combigan 0.5%/0.2% BD Greater
than

45. Newer investigational drugs
Neuroprotective agents:
 Anecoratve: Not in clinical use
 Cannabinoids: Schedule I drug, many systemic
side effects
 Cellular skeletal modulators:
 Ethacrynic acid- corneal edema
 Latrunculin B – no corneal edema

46.  Memantine:
 NMDA antagonist
 Used for parkinconism
 Prevents calcium influx
 Completed stage III clinical trial with promising
results
 Other cellular signaling pathways
 Olmesartan
 Lomerizine
 Nilvadipine

47.  Nitrous oxide:
 Aminoguanidine-inhibitor of iNOS
 Rat model study
 NO generated by glial cells
 Prostanoid agents:
 Tafluprost
 Not efficacious, withdrawn
 Rho kinase inhibitors
 Increase aqeuous outflow
 In clinical trials

48. References
 Becker –Shaffer’s diagnosis and therapy of the
glaucomas, 8th edition
 Shields Textbook of Glaucoma, 6th edition
 AAO- Glaucoma, 2011-12
 Kanski and Bowling- Clinical Ophthalmology