Mechanism of action, Uses, sideeffect, contraindications of Commonly used anti glaucoma drugs. 1.Prostaglandin analogue 2.Betablocker 3.Alpha agonists 4.Miotics 5.carbonic anhydrase inhibitor

1. ANTI-GLAUCOMA DRUGS
DR.ANKITA MAHAPATRA
1ST YR PG, DEPT OF
OPHTHALMOLOGY
VSSIMSAR,BURLA

2. AIM OF GLAUCOMA TREATMENT
MECHANISMS
Reducing aqueous
production in the
ciliary body
Promoting aqueous
humour outflow
through the
trabecular meshwork
Promoting aqueous
humour outflow via
the uveoscleral
pathway
IOP to levels that permit normal functioning of OPTIC NERVE and prevent further damage.
Medications directed towards preventing neural cell loss (under investigation): MEMANTIN ,
BRIMONIDINE

3. INREASE TRABECULAR
OUTFLOW:
1.MIOTICS(PILOCARPINE)
2.EPINEPHRINE,DIPIVEFRI
NE
3.BIMATOPROST
INCREASE UVEOSCLERAL
OUTFLOW:
1.PROSTAGLANDIN
(LATANOPROST)
2.ALPHA AGONISTS:
EPINEPHRINE, DIPIVEFRINE
BRIMONIDINE
APRACLONIDINE
DECREASE AQUEOUS
OUTFLOW:
1.CAI : ACETAZOLAMIDE,
DORZOLAMIDE
2.ALPHA AGONISTS: EPINEPHRINE,
DIPIVEFRINE,CLONIDINE,
BRIMONIDINE, APRACLONIDINE
3. BETA BLOCKERS: TIMOLOL,
BETAXOLOL,LEVOBUNOLOL
DRUGS:

4. PARASYMPATHOMIMETICS( CHOLINERGICS)
MECHANISMOFACTION
Contraction of the iris sphincter: Constricts the pupil(miosis)
Mechanically moves away the iris from trabecular meshwork
Contraction of the longitudinal fibers of the ciliary muscle
Tension on the scleral spur(Opening the TRABECULAR MESHWORK)
Facilitation aqueous outflow

5. PARASYMPATHOMIMETICS
DIRECT ACTING
Eg. PILOCARPINE
INDIRCT ACTING OR
CHOLINESTERASE
INHIBITORS
REVERSIBLE eg.
PHYSOSTIGMINE
IRRIVERSIBLE eg.
ECHOTHIPHATE IODIDE,
DEMECARIUM,
DIISOPROPYL-FLUORO-
PHOSPATE
DUAL ACTION
Eg.: CARBACHOL

7. PILOCARPINE :
 INDICATIONS :
I. Long-term t/t of elevated IOP in patients having persistently occludable
angle despite Laser iridotomy
II. Pplx of Angle closure Glaucoma prior to Iridectomy.
 CONTRAINDICATIONS:
Uveitic Glaucoma
Blue eyes show maximal ocular hypotensive responses
Darkly pigmented eyes demonstrate a relative resistance to IOP reduction
Miotics better tolerated in Aphakic eye than in Phakic eye.

8. AVAILABLE PREPARATIONS:
A. Eyedrops
 Available in 1%, 2% and 4% strengths.
 The onset of action:20 minutes
 Peaks in 2 hours
 Duration of effect :4-6 hours
 Prescribed every 6 or 8 hourly.
B. Ocuserts
 Pilo-20 & Pilo-40
 Changed once in a week.
 Pilo-20 used in patients controlled with 2 percent or less concentration of eyedrops
 pilo-40 in those requiring higher concentration of eyedrops.
C. Pilocarpine gel (4%)
Causes 18-25%
fall in IOP.

9. CARBACHOL :
INDICATIONS: alternative to pilocarpine in resistant or tolerant cases.
PREPARATIONS: 0.75% , 3%
DOSAGE: Duration of onset : 40 mins , Duration of effect : 12 hours
2-3 times/d
OCULAR :
Posterior synechiae, Keratitis
Myopia, Retinal detachment
Blurred vision, Cataract growth
Miosis, Colour vision changes
Brow ache , Epiphora
Accommodative spasm
SYSTEMIC:
Increased sweating &
salivation
Urinary frequency
Diarrhea
Bronchospasm
SIDE-EFFECTS:

10. SYMPATHOMIMETICS
NONSELECTIVE
( alpha-1,2, beta-1,2 )
Eg. Epinephrine
Dipivefrine
Selective
(alpha-1,2)
Eg. Apraclonidine
Selective
(alpha-2)
Eg. Brimonidine

12. 1.Epinephrine.
Preparations: 0.5% , 1 % , 2% eyedrops.
Dosage: The action starts within 1 hour and lasts up to 12-24 hrs
2. Dipivefrine (Propine or dipivalylepinephrine):
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 : Action and efficacy similar to 1% epinephrine.
Twice daily

13. CLONIDINE :
I. Decrease aqueous production
II. Increase both trabecular and uveoscleral
outflow (lesser extent)
 PREPARATIONS : 0.06% , 0.125 %
6-8 hrly
 SIDE EFFECTS : Conjunctival blanching
Sedation
Dry mouth
Hypotension

14. APRACLONIDINE :
I. Decrease aqueous production
II. Decrease episcleral venous pressure
III. Improves Trabecular outflow
peak action : 2 hrs
Duration of action : 12 hrs
PREPARATIONS: 0.50 , 1 %
8hrly
USES: Post- Laser trabeculoplasty
& YAG laser iridotomy
& posterior capsulotomy
& cataract extraction
SIDE EFFECTS : Allergic reaction
Tachyphlaxis
Conjunctival blanching
Follicular conjunctivitis
BRIMONIDINE :
I. More selective alpha-2 action
II. Less Tachyphylaxis ,Ocular allergic Reactions
III. Not to be used in infants and young children,
as risk of respi depression, Somnolence,
Hypotension, seizure
IV. Peak IOP reduction 26% ( 2 hours postdose)
Caution
recommended
when using
with MAOI,
TCA

15. ADRENERGIC ANTAGONISTS(BETA BLOCKERS)
NON-SELECTIVE
(BETA-1,2 )
Eg. TIMOLOL,
LEVOBUNOLOL, CARTELOL,
METIPRANOLOL
SELECTIVE
(BETA-1)
Eg. BETAXOLOL

16. BLOCKADE OF BETA RECEPTORS IN CILLIARY
PROCESS (INHIBIT cAMP PRODUCTION)
DECREASED RATE OF AQUEOUS
PRODUCTION(20-50%)
MECHANISM OF ACTION :
 Topical β-blockers reduce aqueous formation by 20% to 50% in
awake humans.
 β-blockers are less effective during sleep
 Systemic absorption, leads to IOP lowering in untreated contralateral eye also.

17. 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
SIDEEFFECTS
*INCREASE
PERFUSION OF OPTIC
NERVE HEAD
CARTELOL
*LESS EFFICACY
*INTRINSIC
SYMPATHOMIMETIC
ACTIVITY, LESS
BRADYCARDIA
DRUGS:
CARTELOL HAS
LEAST EFFECT
ON LIPID
PROFILE

18. Beta-blockers have very good synergistic effect when combined with
Miotics ; and are thus often used in combination in patients with
POAG, unresponsive to the single drug.
Dosing first thing in the morning preffered, to blunt an early morning pressure rise.
ADDITIVE TO: Miotics
Adrenergic agonists
Carbonic anhydrase inhibitors
PG Analogues
Timolol and Latanoprost combination causes an additional IOP
reduction of 13-37%
Betaxolol is the beta blocker of choice In patients at risk for
pulmonary diseases

19. CONTRAINDICATIONS:
Bronchial Asthma
Emphysema
COPD
Heart blocks,
Congestive Heart Failure
Cardiomyopathy.
known drug allergies.
OCULAR:
STINGING
LOCAL ANESTHESIA
DRY EYE
CONJUNCTIVAL HYPEREMIA
SPK
SYSTEMIC :
BRONCHOSPASM( LESS WITH BETAXOLOL)
BRADYCARDIA
DECREASED CARDIAC OUTPUT
HYPOTENSION
DEPRESSION
IMPOTENCE
ALTERED LIPID PROFILE
SIDE EFFECTS :
Reduced glucose tolerance,
masking of hypoglycemic signs and symptoms
Occurs in Diabetics.
Abrupt withdrawal of beta blockers can exacerbate
Symptoms of Hyperthyroidism.

20. PROSTAGLANDIN ANALOGUES:
STIMULATES PROSTANOID RECEPTOR IN CILIARY MUSCLE
RELEASE OF MATRIX METALLOPROTEINASE
DEGRADE THE EXTRACELLULAR MATRIX BETWEEN CILIARY MUSCLE BUNDLES
REDUCTION OF HYDRAULIC RESISTANCE TO UVEOSCLERAL FLOW
MECHANISM OF ACTION :

21. LATANOPROST
0.005%
PRODRUG
ACTIVATED DURING ITS PASSAGE
THROUGH CORNEA
LOWERS IOP BY 25-30%
ADDITIVE EFECT WITH TIMOLOL
BIMATOPROST
0.01%, 0.03%
CAUSES PIGMENTATION OF SKIN
OTHERS:
TRAVOPROST 0.004%
TAFLUPROST 0.0015% (FIRST
PRESERVATIVE FREE PG ANALOGUE)
UNOPROSTONE 0.12%
DRUGS:
UNOPROSTONE increases retinal blood flow

22. ADVANTAGES:
• Once daily dosing
• Lack of cardiopulmonary side effect
• Additive to other anti-glaucoma medications
SIDE EFFECTS:
Conjunctival hyperaemia
SPK
CME
Anterior uveitis
Blurred vision
CONTRAINDICATIONS:
Ocular infection
Inflammation
Increased pigmentation of iris, lashes
Hypertrichosis
Trichiasis
Districhiasis
Hair growth around eye

23. CARBONIC ANHYDRASE INHIBITOR
INHIBIT CARBONIC
ANHYDRASE IN
CILLIARY PROCESSES
REDUCTION IN
AQUEOUS HUMOR
PRODUCTION
IOP DECREASES
MECHANISM OF ACTION:
Potent and most commonly used Systemic Anti-Glaucoma drugs
>90% of ciliary
enzyme activity
must be abolished
to decrease
aqueous production
and IOP

24. SYSTEMIC
ACETAZOLAMIDE METHAZOLAMIDE DICHLORPHENAMIDE ETHOXZOLAMIDE
TOPICAL
DORZOLAMIDE BRINZOLAMIDE LODOXAMIDE
DRUGS:

25. ACETAZOLAMIDE:
Reduces aqueous production by 30-40%
USE: control of very high IOP in Acute angle closer
Refusal of surgery
DOSAGE: 250mg tabs 6hrly
SR 500mg BD
500mg IV lowers IOP within 20 minutes
SIDE EFFECTS (Dose related):
Altered taste
loss of appetite
Paraesthesia of hands, feet
Sulfa allergy
Hypokalaemia
Metabolic acidosis
Renal stones
Blood dyscrasias
ACETAZOLAMIDE
Not metabolized, excreted in
urine.
Can be given in hepatic failure.
METHAZOLAMIDE
Metabolized by liver.
Decrease risk of systemic
adverse effects

26. DORZOLAMIDE:
• Topical agent
• PREPARATION: 2%
• FALL IN IOP: 13-24%
• SIDE EFFECTS:
Punctate keratitis
Bitter taste
allergic reaction
Transient burning d/t decrease in ph
BRINZOLAMIDE:
1% preparations
Suspension causes white deposits in tear
film
Eyes with compromised endothelial function, are at risk of corneal decompensation.

27. HYPEROSMOTICS:
IV: Mannitol
ORAL: Glycerol
Increase blood osmolality
Osmotic gradient created between blood and vitreous
Drawing water from Vitreous cavity
Decrease IOP
MECHANISM OF ACTION :

28. MANNITOL:
20%
0.5- 2.0 g/kg Body weight
s/e: IOP rebound
Increased aqueous flare
headache
Mental confusion
Backache
CHF, MI
Subdural, Subarachnoid haemorrhage
Larger the dose, more rapid the administration, greater decrease in IOP.
Rarely administered for longer duration, cause effects are transient, result of rapid reequilibration
of Osmotic gradient. Less effective overtime, rebound increase in IOP may occur.
GLYCEROL:
• Concentration 50%
• 1-1.5 g/kg dosing
• It precipitates hyperglycaemia,
Ketoacidosis in DIABETICS
Hyperosmotics are contraindicated in
patients with renal failure or on dialysis

29. FIXED COMBINATIONS:
COMPOUNDS CONCENTRATION
TIMOLOL/BRINZOLAMIDE 0.5%/1%
TIMOLOL/DORZOLAMIDE 0.5%/2%
TIMOLOL/LATANOPROST 0.5%/ 0.005%
TIMOLOL/TROVAPROST 0.5%/ 0.004%
TIMOLOL/BIMATOPROST 0.5%/0.03%
TIMOLOL/BRIMONIDINE
TARTARATE
0.5%/ 0.2%
DOSING
BD
BD
OD, AT NIGHT TIME
OD, AT NIGHT TIME
OD, AT NIGHT TIME
BD

30. I] PRIMARY OPEN ANGLE GLAUCOMA
(A) SINGLE DRUG THERAPY
1. Topical beta-blockers: DoC, 1st line
Timolol maleate, Betaxolol, Levobunolol, Carteolol
2. Latanoprost: 1st line
3. Dorzolamide: 2nd line
4. Pilocarpine: 2nd line
5. 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 betablocker, or
brimonidine or dorzolamide) and other drug which increases aqueous outflow
(latanoprost or brimonidine or pilocarpine) may be used.

31. II] ACUTE PRIMARY ANGLE-CLOSURE GLAUCOMA
Medical therapy is instituted as an emergency and temporary measure before
the eye is ready for operation;
1. Systemic hyperosmotic agent intravenous mannitol (1 gm/kg body weight)
2. Acetazolamide 500 mg intravenous injection followed by 250 mg tablet
should be given 3 times a day.
3. Analgesics and anti-emetics
4. Pilocarpine eyedrops 2 percent pilocarpine should be administered every 30
minutes for 1-2 hours and then 6 hourly
5. Beta blocker eyedrops like 0.5 percent timolol maleate or 0.5 percent
betaxolol should also be administered twice a day to reduce the IOP.
6. Corticosteroid eyedrops like dexamethasone or betamethasone should be
administered 3-4 times a day to reduce the inflammation