PRESENTATION BY DR.ASIF, HOUSE OFFICER IN EYE UNIT 2, MAYO HOSPITAL, LAHORE

1. Anti-Glaucoma Drugs
Dr. Muhammad Asif
Ismail
House Officer
EYE Unit-2
Mayo Hospital, Lahore

2. Presentation Layout
 What is Glaucoma?
 Anti-Glaucoma Drugs
Classification
Indications
Contraindications
 Summary

3. Glaucoma
 Glaucoma is a chronic, progressive optic
neuropathy caused by a group of ocular
conditions which leads to damage of optic nerve
with loss of visual function.
 The most common risk factor known is raised
intraocular pressure.
 Normal intraocular pressure = 10–20 mm Hg
 Suspicious case = 20–25 mm Hg
 Glaucoma = Above 25 mm Hg
 Hypotony = Below 10 mm Hg

4. Aqueous Production and its
Drainage
 Secreted by ciliary body ( posterior chamber )
 Drainage Route
 Primary (90%): Trabacular meshwork
 Uveoscleral outflow (10%)

5. Purpose of initiating Glaucoma
Therapy
The ultimate goal of glaucoma treatment is
 To preserve enough vision during patient’s lifetime
to meet their functional needs
 To delay glaucomatous process

6. Medical Aspects of Glaucoma
Therapy
When to treat?
 When glaucomatous damage is documented or
future damage is likely
What to prescribe?
 Start with one drug having least ocular and
systemic side effects
 Use least amount of medication
 In emergency, use two drugs

7. MOA of Anti-Glaucoma Drugs
Aim is to lower IOP to the target level
either by
 Reducing aqueous production from ciliary body
 Promoting aqueous humor outflow through
trabecular meshwork
 Promoting aqueous humor outflow via uveoscleral
pathway

8. Classification
Topical Drugs
 Beta Blockers
 Adrenergic agonists
 Prostaglandins
analogues
 Cholinergic agents
 Carbonic anhydrase
inhibitors
Systemic Drugs
 Carbonic Anhydrase
inhibitors
 Osmotic Agents

9. Beta Blockers
 First drug of choice for POAG
 Lowers IOP by reducing aqueous secretion by
acting on Beta-2 receptors
Non-Selective Selective
Timolol Betaxolol
Levobunolol Pindolol
Metipranolol Metaprolol
Carteolol

10. Mechanism of Action
Antagonize the effect of catecholamines
Reduction in Aqueous secretion
 Beta blockers reduce aqueous formation by 24-48
%

11. Beta Blockers
Timolol Maleate
0.25-0.5%
Eyedrops: BD
Eyegel: OD
Levobunolol
0.25-0.5%
Longer half-life
Betaxolol
0.25-0.5%
Fewer pulmonary
side effects
Increase perfusion
of optic nerve head
Carteolol
Less bradycardia
Least effect on
lipid profile

12. Beta Blockers
Additive to
 Miotics
 Adrenergic agonists
 CA inhibitors
 PG analogues
Good synergistic effect with miotics, used in POAG
unresponsive to single drug
Timolol and latanoprost combination results in an
additional IOP reduction of 13-37%
Betaxolol is the beta blocker of choice in patients at
risk for pulmonary disease

13. Side Effects and
Contraindications
• Stinging Local anaesthesia
• Dry eye Conjunctival hyperemia
Ocular
• Bronchospasm (less with betaxolol) Bradycardia
• Decreased Cardiac output Hypotension
• Depression Impotence
Systemic
• Bronchial asthma Emphysema
COPD Heart Blocks
CHF
Known Drug Allergies
Contraindications

14. Prostaglandin Analogues
(Mechanism of Action)
Stimulate prostanoids receptor in ciliary
muscles resulting in release of matrix
metalloproteinase
Degrade the extracellular matrix between
ciliary muscle bundles
Reduction of hydraulic resistance in
uveoscleral flow

15. Drugs
Latanoprost
• 0.005%
• Prodrug
• Activated during its
passage through cornea
• Lowers IOP by 25-30%
• Additive effect with
Timolol
Bimatoprost
• 0.01-0.03%
• Causes pigmentation of
skin
Others
• Travoprost 0.004%
• Tafluprost 0.0015%
• Unoprostone 0.12%

16. Side Effects
• Conjunctival hyperemia SPK
• CME Anterior Uveitis
• Blurred Vision Increased pigmentation of iris
• Trichiasis Hair growth around eye
Contraindications
• Ocular Infection
• Inflammation
Advantages
• Once daily dosing
• No cardiopulmonary side effects
• Additive to other antiglaucoma medications

17. Parasympathomimetics
(Cholinergics)
Mechanism
of
Action
Contractionof the iris sphincter: constricts the
pupil(miosis) mechanically moves the
iris away from trabecular meshwork
Contraction of longitudinal fibres of ciliary
muscle tension on the scleral spur
(opening the trabecular meshwork
facilitation in aqueous outflow

18. Parasympathomimetics
Direct Acting
e.g., Pilocarpine
Indirect Acting Or
Cholinestrase Inhibitors
Dual Action
e.g., Carbachol
Reversible
e.g., Physostigmine
Irreversible
e.g., Demecarium

19. Pilocarpine
• Long term treatment of elevated IOP in
patients having persistently occludable angle
despite laser iridotomy
• Prophylaxis of Angle closure glaucoma prior
iridectomy
Indications
• Uveitic glaucoma
Contraindications

20.  Blue eyes show maximal ocular
hypotensive response
 Darkely pigmented eyes demonstrate a relative
resistance to IOP reduction
 Miotics better tolerated in Aphakic eye
than in Phakic eyes

21. Available Preparations
Eyedrops
 Available in 1%, 2% and 4% strengths
 The onset of action - 20 minutes
 Peak in – 2 hours
 Duration of effect – 4 to 6 hours
 Prescribed every 6 or 8 hourly
Pilocarpine Gel (4%)
Causes 18 to
25% fall in IOP

22. Side Effects
Ocular
o Posterior synechiae
o Keratitis
o Myopia
o RD
o Blurred vision
o Cataract growth
o Miosis
o Color vision changes
Systemic
o Increased sweating
and salivation
o Urinary frequency
o Diarrhea
o bronchospasm

23. Carbachol
Indications
 Alternative to Pilocarpine in resistant or tolerant cases
Preparations
 0.75% and 3%
Duration of onset
 40 minutes
Duration of effect
 12 hours
Dosage
 2 to 3 times per day

24. Sympathomimetics (Adrenergic
Agonists)
Mode of Action
Decreasing Aqueous
Formation
By constricting the ciliary
blood vessels
Increasing Uveoscleral
Outflow
By an increase in PG

25. Classification
Sympathomimetics
Non-selective
(alpha-1,2 and beta-
1,2)
e.g., Epinephrine
Dipivefrine
Selective
(alpha-1, 2)
e.g., Apraclonidine
Selective
(alpha-2)
e.g., Brimonidine

26. Non-Selective
Epinephrine
 Preparations 0.5%, 1%, 2% eyedrops
 Dosage the action starts within 1 hour and lasts upto 12-24 hours
Dipivefrine
 Prodrug converted to epinephrine after its absorption into the eye
 More lipophilic than epinephrine (corneal penetration increased by
17 times)
 Preparations 0.1% eyedrops
 Dosage Twice daily
action and efficacy similar to 1% epinephrine

27. Clonidine
 Decreases Aqueous production
 Increases both trabecular and uveoscleral outflow (lesser
extent)
 Preparations 0.06%, 0.125%
 Dosage 6 to 8 hourly
 Side effects
 Conjunctively blanching
 Sedation
 Dry mouth
 hypotension

28. Apraclonidine
 Decreases aqueous production
 Decreases episcleral venous pressure
 Improves trabecular outflow
Peak action 2 hours
Duration of action 12 hours
Preparations 0.50 and 1%
Dosage 8 hourly
Uses
 Post-laser trabeculoplasty
 Post-lase iridotomy
 Post-posterior capsulotomy
 Post-cataract extraction
Side effects
 Allergic reactions
 Tachyphylaxis
 Conjunctival blanching
 Follicular conjunctivitis

29. Brimonidine
 More selective alpha-2 action
 Less ocular allergic reactions, Less tachyphylaxis
 Peak IOP reduction 26% (2 hours post-dose)
Conta-indications
 Infants
 Yonug children
(due to risk of respiratory depression, somnolence,
hypotension and seizures)

30. CA Inhibitors
 Potent and most commonly used systemic anti-glaucoma
drugs
Mechanism of Action
IOP
decreases
Reduction in
aqueous
humor
production
Inhibit CA
in ciliary
processes
>90% of ciliary
enzyme activity
must be abolished
to decrease
aqueous
production and
IOP

31. Drugs
Systemic
Actazolamide Methazolamide Dichlorphenamide Ethoxzolamide
Topical
Dorzolamide Brinzolamide Lodoxamide

32. Acetazolamide
 Reduces aqueous production by 30 to 40%
Uses
 control of very high IOP in acute angle closure
 Refusal of surgery
Dosage
 Oral 125 mg and 250 mg tablets 6 hourly
 500 mg Sustained release capsules B.D
 IV Preparations 500 mg (lowers IOP
within 20 minutes)
Side effects (Dose
related)
 Altered taste
 Loss of appetite
 Paesthesia of hands,
feet
 Sulfa allergy
 Hypokalemia
 Metabolic acidosis
 Renal stones
 Blood dyscariasis
Acetazolamide
Not metabolized,
Excreted in urine. Safe in
hepatic failure
Methazolamide
Metabolized by liver,
Decrease risk of systemic
adverse effects

33. CA Inhibitors
Dorzolamide
 Topical agent
Preparation 2%
 Fall in IOP 13 to 24%
Side effects
 Punctate keratitis
 bitter taste
 Allergic reactions
 transient burning due to
decrease in pH
Brinzolamide
Preparation 1%
 Suspension causes white
deposits in tera film

34. Hyperosmotics
 IV : Mannitol
 Oral : Glycerol
Mechanism of Action
Increase blood
osmolality
Osmotic gradient
created between
blood and vitreous
Drawing water
from vitreous
cavity
Decrease IOP

35. Mannitol
Concentration 20%
Dose 0.5 – 2.0 g/kg body weight
Side effects
 IOP rebound
 Increased aqueous flare
 Headache
 Mental confusion
 Backache
 CHF, MI
 Subdural, Subarachnoid
haemorrhage
Glycerol
Concentration 50%
Dose 1 – 1.5 g/kg
Side effects
 It precipitates hyperglycaemia
 Ketoacidosis in Diabetics

36. Hyperosmotics are contraindicated in patients with
renal failure or on dialysis
Rarely administered for longer duration, cause
effects are transient, result of rapid reequilibration
or osmotic gradient. Less effective overtime,
rebound increase in IOP may occur
Larger the dose, more rapid the administration,
greater decrease in IOP

37. COMPOUNDS CONCENTRATION DOSING
TIMOLOL/BRINZOLAMIDE 0.5% / 1% BD
TIMOLOL/DORZOLAMIDE 0.5% / 2% BD
TIMOLOL/LATANOPROST 0.5% / 0.005% OD, AT NIGHT TIME
TIMOLOL/TRAVOPROST 0.5% / 0.004% OD, AT NIGHT TIME
TIMOLOL/BIMATOPROST 0.5% / 0.03% OD, AT NIGHT TIME
TIMOLOL/BRIMONIDINE
TARTARATE
0.5% / 0.2% BD

38. Primary Open Angle Glaucoma
A. Single Drug Therapy
 Topical beta blockers : DOC, 1st line
Timolol maleate, Betaxolol, Levobunolol, Carteolol
 Latanoprost: 1st line
 Dorzolamide: 2nd line
 Pilocarpine: 2nd line
 Adrenergic Drugs: Dipivefrine hydrochloride (combined with beta-blockers
in patients where other drugs are contraindicated)
B. Combination Topical Therapy
 If one drug is not effective, then a combination of two drugs – one drug
which decreases aqueous production (timolol or other beta-blocker, or
brimonidine or dorzolamide) and other drug which increases aqueous
outflow (latanoprost or brimonidine or pilocarpine) may be used

39. Acute Primary Angle-Closure
Glaucoma
 Medical therapy is instituted as an emergency and temporary measure
before the eye is ready for operation;
 Systemic hyperosmotic agent intravenous mannitol (1gm/kg body weight)
 Acetazolamide 500 mg intravenous injection followed by 250 mg tablet
should be given 3 times a day
 Analgesics and anti-emetics
 Pilocarpine eyedrops 2 % pilocarpine should be administered every 30
minutes for 1-2 hours and then 6 hourly
 Beta blocker eyedrops like 0.5% Timolol maleate or 0.5% Betaxolol
should also be administered twice a day to reduce the IOP
 Corticosteroid eyedrops like Dexamethasone or Betamethasone should
be administered 3-4 times a day to reduce the inflammation

40. THANK YOU