1. OCULAR THERAPEUTICS
 Shashi Sharma
 Ajay Kumar Singh
• Department of Ophthalmology
• King George‘s Medical University, Lucknow (INDIA)

2. GENERAL
PHARMACOLOGICAL
PRINCIPLES

3. PHARMACODYNAMICS
 it is the biological activity and clinical effect of the drug*
 if the drug is working at the receptor level, it can be agonist or
antagonist
 if the drug is working at the enzyme level, it can be activator or
inhibitor
*American Academy of Ophthalmology Section 2;2010-11

4. PHARMACOKINETICS
 it is the absorption, distribution, metabolism, and excretion of
the drug
 drug can be delivered to ocular tissue as:
 locally:
 eye drop
 ointment
 periocular injection
 intraocular injection
 systemically:
 oral
 intravenous

5. EYE AND TOPICAL MEDICATIONS
Tear Film
 under normal circumstances the volume of tear fluid is 5-7 µl with
normal rate of secretion about 1-2 µl /min
 drop added cause an increasing in blinking, squeezing which propels
tears towards the sac.
 the drugs passes on lacrimal sac nasolacrimal system
bypass the liver
iris & ciliary body systemic circulation

6. Cornea
 it is a lipid - water - lipid layer
 the lipid content of the epithelium and the endothelium is 100 times
more than that of stroma.
 and therefore allow lipophilic than to hydrophilic substance.
 because of the dual nature of the corneal barriers, drugs possessing
both lipid and water solubility penetrate the cornea more readily.

7. FACTORS INFLUENCING LOCAL DRUG PENETRATION INTO
OCULAR TISSUE
 Drug concentration and solubility: the higher the concentration
the better the penetration e.g. pilocarpine 1-4% but limited by reflex
tearing
 Viscosity: addition of methylcellulose and polyvinyl alcohol
increases drug penetration by increasing the contact time with the
cornea and aiding drug penetration
 Lipid solubility: the higher lipid solubility the more the penetration

8.  Surfactants: the preservatives used in ocular preparations alter cell
membrane in the cornea and increase drug permeability e.g.
benzylkonium and thiomersal
 pH: the normal tear pH is 7.4 and if the drug pH is much different, this
will cause reflex tearing
 Drug tonicity: when an alkaloid drug is put in relatively alkaloid
medium, the proportion of the uncharged form will increase, thus more
penetration

10. EYE DROPS
 one drop = 50 µl
 one ml contains approx 20 drops
 volume of conjunctival cul-de-sac after drug instillation is 7-10 µl,
hence only 20% of the drug is retained
 topical medications are be used as
• solutions/suspensions
• ointments

11. OINTMENTS
 increase the contact time of ocular medication to ocular
surface thus better effect
 it has the disadvantage of vision blurring, hence night dosage
 the drug has to be high lipid soluble with some water solubility
to have the maximum effect as ointment

12. PERIOCULAR INJECTIONS
 bypass the conjunctival and corneal epithelial barrier
 subconjunctival, subtenon, retrobulbar injections allow medications
behind lens and diaphragm
 useful for
 drugs with low lipid solubility
 delivering medications closure to local site of action e.g. posterior
subtenon
 retrobulbar and peribulbar anesthesia techniques

13. INTRAOCULAR
 Intracameral and Intravitreal
 Intracameral is used during surgery : antibiotics,
mydriasis/miosis
 Intravitreal in diabetic macular edema, CRVO, retinal surgeries
 Intraocular implants : Gancicyclovir for CMV retinitis
 Retisert (Fluocinolone) for posterior uveitis

14. SYSTEMIC DRUGS
 Oral or Intravenous
 Factor influencing systemic drug penetration into ocular
tissue:
 lipid solubility of the drug: more penetration with high lipid
solubility
 protein binding: more effect with low protein binding
 better penetration in the inflamed eye

16.  New ocular drugs are designed aimed at improving penetration,
minimizing side effects and improving efficacy
 Prodrugs
 Activated by enzymatic system in the eye
 Lanatoprost prostagladin F2α
 Sustained release devices and gels
 Collagen corneal shields
 New technology in drug delivery
 Liposomes*
 Iontophoresis
*Mishra G, Mahuya B. Recent Applications of Liposomes in Ophthalmic Drug DeliveryJournal of Drug
Delivery;Volume 2011,Article ID 863734
Corneal esterases

17. ANTI INFLAMMATORY
LUBRICANTS
ANTI GLAUCOMA
MYDRIATICS & CYCLOPLEGICS

18. ANTI INFLAMMATORY THERAPY
CORTICOSTEROID NSAIDs IMMUNOSUPPRESSIVE
MAST CELL STABILIZERS

19. CORTICOSTEROIDS
 useful in control of inflammatory and immunological diseases of eye
 routes of administration
Topical Periocular Intravitreal Oral Intravenous
 their antiinflammatory and immunosuppressive action
 inhibition of lymphocytes proliferation, with a decrease of the cell-
mediated immunity
 inhibition of the degranulation of neutrophil granulocytes,
macrophages, mastcells and basophil granulocytes.
 decrease of vascular permeability
 decrease of prostaglandin production

20. Phospholipids from damaged cell membranes
Arachidonic acid
Leucotrienes PG-G2,
Thromboxane PG-D2, E2, F2
Phospholipase A2 Glucocorticoids
Lipo-oxygenase
Cyclo-oxygenase I & II
NSAIDS

21.  Indications
 post surgical inflammation
 allergic conjunctivitis and blepharitis
 vernal conjunctivitis, phylectunular keratoconjunctivitis
 disciform and interstitial keratitis
 corneal graft rejection
 scleritis and episcleritis, anterior and posterior uveitis
 traumatic inflammation of the eye
 papillitis and retrobulbar neuritis
 sympathetic ophthalmia
 herpes zoster ophthalmicus
 orbital pseudotumor
 VKH syndrome

22.  contraindications
TOPICAL SYSTEMIC
• acute viral infections
•fungal diseases
• ocular TB
• acute conjunctivitis
• caution in pregnancy and lactation
S- psychosis, headaches, pseudotumour
cerebri.
T- thrombosis (venous)
E- endocrinal- suppressed hypothalamic
pituitaryadrenal axis, retarded growth,
cushingoid state.
R- retention of fluid & sodium but loss of
potassium & systemic alkalosis.
O- osteoporosis & myopathies.
I- immunosuppression with secondary
infections esp. TB & fungal,
D- diabetes & hypertension, duodenal &
gastric (peptic)ulcers.

23.  Side effects
TOPICAL SYSTEMIC
• glaucoma
• cataract (PSC)
• dry eye
• reduced resistance to bacterial, fungal
and viral infections and secondary
infections
• scleral melting
• delayed wound healing
• eyelid skin atrophy
• ocular
•suppresion of hypothalamic pitutiary
adrenal axis
• hyperglycemia
• peptic ulcer
• osteoporosis
• psychiatric disturbances
• cushing’s habitus
• fetal abnormalities
• susceptibility to infections

24. TOPICAL CORTICOSTEROIDS
 available as solution, suspension and ointment
 Hydrocortisone 0.5-1.5%
 Prednisolone 0.12, 0.25, 1 %
 Dexamethasone 0.1%
 Betamethasone 0.1 %
 Triamcinolone 0.1%
 Fluromethalone 0.1%
 Loteprednol 0.2%,0.5%
 Difluprednate 0.005%
 anti-inflammatory action * prednisolone
acetate > fluorometholone acetate > dexamethasone acetate >
betamethasone
*Samudre S, Lattanzio F, Williams P, Sheppard J. Comparison of topical steroids .J Ocul
PharmacolThe. 2011;20:533-47.

25.  rise in IOP- maximum rise due to dexamethasone (0.1%) and
fluorometholone 0.1% is least
 Loteprednol 0.2%- ―soft‖ steroid-
 minimal effect on IOP & systemic side effects,
 approved for allergic conjunctivitis and combined with tobramycin 0.3%
for superficial bacterial infection with inflammation
 Triamcinolone acetonide (40mg/ml) (Kenacort) was approved by FDA
in 2007 for intraocular use in visualization during vitrectomy, chronic
non infectious uveitis, diabetic macular edema
 Retisert( flucinolone actetonide) used as intraocular implantation for
chronic uveitis

26. RECENT ADVANCES….
 DIFLUPREDNATE 0.05%( Diflucor, Diflupred)
 prednisolone derivative, in emulsion form exhibits enhanced , strong
efficacy and low side effects
 indicated in post operative inflammation and uveitis
 only qid dosing is required
 OZURDEX® (Allergan)
(dexamethasone intravitreal implant 0.7mg),
indicated in
 macular edema following retinal vein occlusion
 noninfectious posterior uveitis

27. ORAL CORTICOSTEROIDS
Short acting
Hydrocortisone 20mg/day  rapid acting
mineralocorticoid
activity
Cortisone 20-100mg/day
Intermediate
Prednisolone 1-2mg/kg/day 4 times more potent
than hydrocortisone
Methyprednisolone 4-32mg/day Selective than
prednisolone
Triamcinolone 4-32mg/day Only glucocorticoid
action
Long acting
Dexamethasone 0.5- 5mg/day
Highly selective
glucocorticoid
Marked pitutiary axis
suppressionBetamethasone 0.5- 5 mg/day

28.  Oral prednisolone in a dose of 1-2 mg/kg/day (or alternate days) is
used to treat orbital inflammations, panuveitis, postoperative
inflammation and systemic diseases causing ocular problems
alternate day therapy reduces the suppression of adrenal functions
 High dose of methylprednisolone i/v are given in pulses to treat optic
neuropathies
 DEFLAZACORT(Defcort)
 Recent glucocorticoid, derivative of prednisolone with less
complications
 6mg of deflazacort is equivalent to 5 mg of prednisolone

29. NON STEROIDAL ANTIINFLAMMATORY DRUGS
 Has 3 types of effects
 Anti-inflammatory
 Analgesic
 Antipyretic (COX-2)
 Inhibits the cyclooxygenase pathway

30. ORAL NSAIDS
Non selective
COX inhibitor
Propionic acid
derivative
Ibuprofen 400mg/day potent analgesic
Aryl acetic
derivative
Diclofenac
Aceclofenac
50mg tds analgesic,
antipyretic,
antiinflammatory
COX 2 inhibitor Nimesulide 100mg bd analgesic,
antipyretic
Poor anti
inflammatory
Paraaminophenol Paracetamol 300-600mg antipyretic

31. OCULAR INDICATIONS FOR USE OF NSAIDs
 prevention of intraoperative miosis
 reduction of postoperative inflammation
 prevention and treatment of cystoid macular edema
 non infectious uveitis
 scleritis and episcleritis
 allergic and giant papillary conjunctivitis
 after refractive surgery

32. FLURBIPROFEN KETOROLAC DICLOFENAC
Salient features 0.03% solution 0.5% solution
analgesic and anti-
inflammatory
0.1% solution
potent NSAID with
analgesia
Indication
inhibition of
intraoperative miosis
ocular itching due to
seasonal allergic
conjunctivitis
Foreign body sensation
and photophobia
iatrogenic
inflammation, post
cataract surgery pain
Dosage
1 drop every 30
minutes, 2 hrs
preoperatively (total of
four drops)
TDS QID
Side effects
• transient burning and
stinging
• may cause increased
bleeding tendency of
ocular tissues during
surgery
• transient burning and stinging
• decrease in corneal sensitivity

33. NEWER DRUGS
 Nepafenac 0.1% and Bromfenac 0.09%are topical, nonsteroidal
anti-inflammatory, recently introduced
 Nepafenac is a prodrug, converted by ocular tissue hydrolases to
amfenac, which inhibits the action of prostaglandin H
synthase(cyclooxygenase)
 patients treated with these drugs were less likely to have ocular pain
and measurable signs of inflammation (cells and flare) in the early
postoperative period as compared to ketorolac*
 indicated for the treatment of post operative pain and inflammation,
cystoid macular edema
*Ke TL, et al. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular
inflammation.. Inflammation. 2000;24(4):371-84

34. MAST CELL STABILIZERS AND ANTIHISTAMINES
 Human eye has about 50 million mast cells, which contains
preformed chemical mediators
Allergic conjunctivitis
IgE mediated hypersensitivity reaction
Mast cells and basophils
Histamine Leucotrines Chemotactic factors
capillary dilatation stimulates nerve endings
increased permeability
pain and itching
conjunctival injection and swelling

35. Class Generic
name
Mechanism Dosage Side effects
Mast cell
inhibitor
Cromolyn
sodium
inhibit neutrophil,
eosinophil,
monocyte
0.01% BD does not provide
immediate relief
H1 antagonist
+ mast cell
inhibitor
Azelastine HCL
provides
immediate relief
and prevent
further
degranulation
rapid onset
0.05% BD ocular burning,
stinging, dry eye
Epinastine HCL
Ketotifen
fumarate
Nedocromil
sodium
Olopatadine 0.05%, 0.01%
BD/OD
H1 antagonist
+
decongestant
Naphazoline
HCL/phenaramin
e maleate
short term relief
for mild allergy 0.05%/0.01% BD

36. IMMUNOSUPPRESSIVE
 not used as primary therapy
 cases non responding to steroids or steroids responders or started
having steroid complications
 avoided in children and pregnant women
 effect may take 1-4 weeks to develop, hence initial therapy with
corticosteroids is needed
 Azathioprine, Cyclosporin, Methotrexate are commonly being used

37. Drug Formulation Dosage Adverse
effects
Special
points
Methotrexate 2.5, 5, 7.5 mg Weekly GI symptoms,
hepatotoxic
( LFT)
Less cost,
Well tolerated
Azathioprine 25, 50 mg 1mg/kg Myelosuppressio
n
Onset take 4-5
weeks
Cyclosporine 25, 50 mg
0.05%,0.1%
emulsion
5mg/kg/day Nephrotoxic
(urea, creatinine)
Fast onset of
action
More efficacious
Dry eye
Mycophenolate
mofetil
250, 500 mg 1gm BD Myelosuppressio
n
High cost
Leflunomide 10, 20 mg 100mg/day GI upset,
hepatotoxic
Still under trial

38. MYDRIATICS AND CYCLOPLEGICS
 Mydriatics are the drugs which dilate the pupil and
cycloplegics are agents which causes paralysis of ciliary
muscles
Mydriatics
Adrenergic agonist Cholinergic antagonists
Adrenaline Phenylephrine Tropicamide

39. PHENYLEPHRINE (2.5%)
 most common sympathomimetic agent used
 acts on alpha 1 receptors of the dilator pupillae
 indication
 pupil dilation
 refraction
 before intraocular surgeries
 contraindication
 hypersensitive
 narrow angle glaucoma
 cardiac patients
 elderly patients

40.  Side effects
 initial stinging and burning
 systemic side effects include palpitation, tachycardia, headache,
arrythmias
 reflex bradycardia, pulmonary embolism, myocardial infaction

41. ADRENALINE
 acts on dilator fibres and directly produces dilation after
instillation of four drops of 1:1000 solution
 may be combined with procaine and atropine to achieve
mydriasis in severe iritis

42. CYCLOPLEGIC MYDRIATICS
 parasympatholytic agents are commonly used
 blocks the action of cholinergic stimulation causing paralysis of
accomodation and pupillary dilation
 indication
 refraction
 inflamation of uvea
 malignant glaucoma
 adverse reaction
 transient stinging and burning, increase in IOP, allergic lid reaction,
hyperemia
 flushing and dryness of skin, blurred vision, dryness of mouth and
nose, anhidrosis, fever, bladder distention and CNS disturbances

43.  precautions
 permanent mydriasis may occur in patients of keratoconus
 longer acting agents may cause posterior synechiae formation when
treating anterior segment inflammation
 avoid driving or any other task requiring alertness
 overdosage
 Administer parenteral physostigmine
 commonly used agents are atropine sulfate, homatropine,
cyclopentolate, tropicamide

44. ATROPINE
(1%)
HOMATROPIN
E (2%)
TROPICAMIDE
(0.5,1%)
CYCLOPENTOLA
TE (0.5,1)
Instillation regime rice grain size thrice
a day for 3 days
6-8 drops 10
min apart
2 drops 5 min
apart
2 drops 5 min
apart
Onset 18 hr after last
instillation
40 min after 2nd
drop
20 min after 2nd
drop
30 min after 2nd
drop
Recovery 10-14 days 3 days 4 hours 2 days
Indications refraction children
<7 yrs, strongest
cycloplegic
acts more
quickly and
shorter action,
early recovery
diagnostic
procedures
refraction, fundus
examination
short acting
Other Uses drug of choice in
anterior segment
inflammation,
penalisation in
amblyopia
low grade
Uveitis
pre and post
operatively,
provocative test
for glaucoma
most commonly
used post cataract
surgery
Side effects dose related side
effects
Similar as discussed before

45.  Atropine is the most effective cycloplegic followed by Cyclopentolate
(1%) & then Homatropine (2%) & Tropicamide
(0.5-1%).
 Cyclopentolate should not be prescribed in uveitis as it has
chemotactic effect on leucocytes.
 mydriasis is quickest with Tropicamide among all
parasympathomimetics (in 20 minutes) and is also shortest lasting
 2.5% Phenylephrine (selective Alpha-1 agonist) along with
anticholinergics like tropicamide 0.8 % induces
maximum mydriasis

46. TOPICAL HYPEROSMOTIC AGENTS
 these agents are helpful in treating corneal edema of diverse
etiology
 epithelial edema is more responsive as compared to stromal edema
 osmotic gradient is created between epithelium and tear film by
these agents
 water is then drawn towards the more osmotic compartment and is
thus eliminated from the epithelium and stroma

47.  commercially available are
 Topical NaCl solution (2% & 5%)
 Topical NaCl ointment (6% gel)
 dosage is 5 to 6 times a day for drops and 2-3 times a day for gels
till the desired response is achieved
 gel form is more superior in terms of efficacy and tolerability

48. OCULAR LUBRICANTS
 available as drops, gels and ointments
 indication
 protection and lubrication
 exposure keratitis, decreased corneal sensitivity, recurrent corneal
erosions
Hydrogels are the viscosity
enhancing active ingredients
of artificial tears
Reduce the risk of bacterial
contamination in
multidose containers,
and to prolong shelf life. E.g.
benzalkonium
Chloride, oxychloro complex

49.  adverse effects of tear substitute
 redness
 stinging and temporary blurring of vision
 hypersensitivity reactions
 various tear substitutes available can be categorized as
Cellulose derivatives Polyvinyl polymers
Carboxymethyl cellulose (CMC)
Hydroxyethyl cellulose (HEC)
Hydroxypropyl cellulose (HPC)
Hydroxypropylmethyl cellulose (HPMC)
Polyvinyl alcohol
Polyvinyl pyrrolidone
Polyethylene glycol

50. CELLULOSE DERIVATIVES POLYVINYL ALCOHOL BASED
polysaccharides synthetic polymer
mix well with other ophthalmic
products
does not mix well with other
ophthalmic products
only benefit in aqueous defeciency beneficial in lipid, aqueous and mucin
layer defeciencies
hypromellose can cause crusting of
lids mimicking blepharitis
short retention time on ocular surface
available as 0.5%, 1% soultion 1%, 1.4% solution
blurring of vision is common water soluble, does not blur vision

51. OINTMENTS
 major advantage is that ointment is retained longer than solution
 available as petrolatum, lanolin, mineral oil topical ointment
 dosage
 bed time is preferred
 Solution should be instilled prior to application of ointment
 recent advances
 Carbopal 980(polyacrylic acid) containing gel is developed minimises
blurring and less dose is required

52. ANTI GLAUCOMA DRUGS

53. Beta blockers Alpha
Agonists
(sympathomi
metics)
Prostaglandi
n analogues
Carbonic
anhydrase
inhibitors
Cholinergi
c
(parasymp
athomimeti
c)Non
selective
Selective
Timolol Betoxolol Brimonidine
0.2%
Latanoprost
0.005%
Dorzolamide2% Pilocarpine
Levobunolol Apraclonidine
0.5-1%
Bimatoprost -
0.03%
Brinzolamide
1%
Carbachol
Metipranolol Dipivefrin
0.1%
Travoprost –
0.004%
Carteolol Epinephrine
1-2%
Unoprostone
0.15%

54. CHOLINERGIC AGENTS
 Cholinergic drugs either act directly by stimulating cholinergic
receptors or indirectly by inhibiting the enzyme cholinesterase
 Topically applied cholinergic agents causes contraction
1] iris sphincter miosis
2] circular muscles of ciliary body relaxing zonular tension & forward lens
movement accommodation
3] longitudinal muscle of ciliary body Tension on scleral spur
Opening of trabecular meshwork
aqueous outflow

55. SIDE EFFECTS OF CHOLINERGIC AGENTS
 Lids
 orbicularis muscle spasm and lid twitching,
 Conjunctiva
 irritation,conjunctival hyperemia, allergic conjunctivitis
 Cornea
 epithelial staining and vascularisation, atypical band keratopathy.
 Iris
 hyperemia, pigment epithelial cyst formation, post operative iritis and
synechiae formation.

56.  Lens
 cataract, increase lens thickness – myopia
 Systemic
 sweating, salivation and lacrimation, nausea, vomiting and
abdominal cramps, night mare, bronchial spasm, asthma and
pulmonary edema.

57. PILOCARPINE
 oldest and most widely used cholinergic agent,
derived from the plant pilocarpus microphylus.
 Topical solution is available in two salts:
 Pilocarpine hydrochloride in the strengths of 0.25, 0.50, 1, 2, 3, 4%.
 Pilocarpine nitrate in the strengths of 1, 2 & 4%.
 produces a reduction in IOP that starts after one hour and lasts for 4 -
8 hours.
 IOP decrease is 15-20%

58. In open angle glaucoma
In angle closure glaucoma

59. INDICATIONS FOR PILOCARPINE
 First line for acute and chronic angle closure glaucoma, primary
open angle glaucoma
 Less certain indications in neovascular glaucoma,uveitis
related glaucoma
 Also used in laser trabeculoplasty, accommodative esotropia
 Diagnostically in Adie tonic pupil

60. CARBACHOL
 It is a synthetic derivative of choline.
 longer acting than pilocarpine.
 indications
 intracameral use 0.1% during anterior segment surgery
 can be used in patients who are allergic to pilocarpine

61. Β– BLOCKERS
 usually first line agent for treating most types of glaucoma
 excellent IOP lowering efficacy
 long duration of action
 few ocular side effects
 first commercially available β blocker
 for systemic use , was propanolol
 for topical use was timolol
 reduce IOP 20-30% with little or no effect on pupil size or
accomodation
 blurred vision associated with miotics is not seen here

62. MECHANISM OF ACTION
 decrease aqueous humour production by inhibition of catecholamine
stimulated synthesis of c-AMP
 effective in glaucomatous and normotensive eyes, indicated in
 primary and secondary open angle glaucoma
 secondary angle closure glaucoma after penetrating keratoplasty
 aphakic and pseudophakic glaucoma
 acute and chronic primary angle closure glaucoma
 developmental glaucoma

63. SYSTEMIC SIDE EFFECTS AND CONTRAINDICATIONS OF B
BLOCKERS
Side effects
 burning sensation
 hyperemia.
 superficial punctate Keratitis.
 corneal anesthesia.
 allergic blepharoconjunctivitis
 dry eye
 bronchospasm
 masking of hypoglycemia in
diabetes
 heart failure in pulmonary edema
 A-V dissociation and cardiac arrest
in patients with pre-existing partial
heart block
Contraindications
 bronchial asthma
 COPD
 sinus bradycardia
 2nd or 3rd degree A-V block
 sexual dysfunction

64. β blockers
NON
SELECTIVE
β1 β2
TIMOLOL LEVOBUNOL
OL CARTEOLOL
SELECTIVE
β1
BETAXOLOL

65. TIMOLOL
 first β-blocker to be commercially used in
ophthalmics in 1978
 it is non selective. inhibits both β1 and β2 receptors
 peak level of drug within 1-2 hours
 clinical effect may last upto 2 weeks after last use
 available in 0.25% and 0.5%
 administered in B.D. dose

66.  also available in gel solution : hence can be administered once daily
 Short term escape due to receptor alteration
 Long term drift due to tachyphylaxis
 contraindicated in asthmatic, heart failure patients

67. BETAXOLOL CARTEOLOL LEVOBUNOLOL
• Cardioselective B1
blocker
•Non Selective (Beta 1 and
Beta 2) blocker
• Non selective β1, β2
blocker
• safely used in asthmatic
and cardiac patients
•It has fewer side effects,
better for cardiovascular
patients
The long term drift is less
than timolol.
• 0.25%, 0.5% in BD dosage •1, 2% BD • 0.25% and 0.5%
•IOP lowering effect 26%
•response may require few
weeks to stabilise
•IOP lowering effect is 32%. •IOP lowering effect is 30%
•used in OD dosing as
longer half – life
• OPTIPRESS (0.5%) • OCUPRESS (1%) • BETAGAN (0.5 %)

68. ALPHA ADRENERGIC AGONIST
 Directly acting sympathomimetics
 Epinephrine
 Dipivefrin
 Alpha2 adrenergic agonists
 Apraclonidine
 Brimonidine
 Indicated in
 open angle glaucoma
 to control IOP spikes after laser procedures
 ocular hypertension

69. BRIMONIDINE
 recently introduced 2nd generation α-adrenergic receptor agonist,
with high degree selective to α2 receptors.
 dual action.
 it decreases aqueous humor production like β-blockers and also
increases the uveo scleral out flow like prostagladins.
 has binding sites in the iris epithelium, ciliary epithelium, ciliary
muscle, retina and retinal epithelium and choroid
 IOP reduction is 26% (2 hrs post dose) and has an additive
neuroprotective action

70.  available in 0.2% (0.15%, 0.1% )solution (5, 10, 15ml Packs). Instil
one drop 2-3 times daily.
 side effects include ocular allergy, follicular conjunctivitis, lid edema,
dry mouth, headache
 contraindicated in patients receiving MAO inhibitor therapy, tricyclic
antidepressant, produces cardiovascular instability in infants and is
therefore contraindicated in the first 5 years of life.
 Brimonidine’s effectiveness may be reduced by concomitant
administration of NSAIDs *
*Sponsel WE, et al: Latanoprost and brimonidine therapeutic and physiologic assessment before and
after oral nonsteroidal anti-inflammatory therapy,Am J Ophthalmol 133:11, 2002

71. CARBONIC ANHYDRASE INHIBITORS
 inhibits enzyme carbonic anhydrase present in pigmented and non
pigmented epithelium of ciliary body
 prevents the bicarbonate and sodium influx and decreases aqueous
formation
 useful in short term treatment of acute glaucoma
 onset of action within 1 hour and maximum effect in 4 hours

72. DORZOLAMIDE BRINZOLAMIDE
• local inhibition of CA in ciliary body minimizing side effects
• adverse effects include burning, stinging, blurred vision ,lsystemic side effect is
rare
• caution must be exercised in patients with compromised epithelium
2% solution, TDS 1% solution, TDS
has better penetration safe and well tolerated
DORZOX, TRUSOPT AZOPT
TOPICAL CARBONIC ANHYDRASE INHIBITORS

73. PROSTAGLADINS
 The PGs derivates primarily lower IOP by enhancing the uveo-
scleral outflow of the eye.
 two possible mechanism exists that have been studied are relaxation
of the ciliary muscle and remodeling the extra cellular matrix of the
ciliary muscle.
 first line for open angle glaucoma, ocular hypertension, exfoliation
and pigmentary glaucoma
 less certain indications in angle closure,neovascular glaucoma
 contraindicated in allergic patient, pregnancy, uveitic glaucoma

74. LATANOPROST TRAVOPROST BIMATOPROST
•Increases uveoscleral outflow Decreases resistance to
outflow
•Duration of action 12-24 hrs
•Wash out period 3-4 weeks
•burning stinging, conjunctival hyperemia, iris pigmentation, anterior uveitis,
hypertrichosis of eyelashes
0.005% OD 0.004% OD 0.03%, OD
Safest and most efficacious Best in maintenance on
diurnal variation of IOP
Controls diurnal variation
better than latanoprost
contraindicated with
pilocarpine
stable, safe and well
tolerable
highest incidence red eye
rate
XALANTAN, 9PM TRAVATAN LUMIGAN, CAREPROST

75. FIXED COMBINATIONS
 Advantages-
 Convenience
 Compliance
 Effectiveness
 Cost effectiveness
 Safety and tolerability
 Disadvantage
 Not always as additive as expected
 Best scientific combination
 one drug from group that reduce aqueous formation
 one that increases aqueous outflow

76. Few combinations available are
 Timolol 0.5% and Dorzolamide 2%
 Brimonidine 0.2% and Timolol 0.5%
 Latanoprost 0.005% and Timolol 0.5%
 Travaprost 0.004% and Timolol 0.5%
 Bimatoprost 0.03% and Timolol 0.5
.

77. SYSTEMIC ANTI GLAUCOMA
 Oral
 Acetazolamide
 Glycerine
 Intravenous
 Mannitol
 Neuroprotective agents
 Calcium channel blockers
 Nitric oxide synthase inhibitors
 Vasodialators
 Antioxidants

78. ACETAZOLAMIDE
 oral carbonic anhydrase inhibitor
a) Tablet 125mg/250mg, TDS/BD
 onset of action within 1 hr
 Peak at 4 hrs
 Duration of action 8-12 hrs
b) Slow release capsule
 Given OD/BD
 Duration of action upto 24 hrs
c) Intravenous
 500mg vials
 Immediate onset , peak action at 30 minutes
 useful in acute glaucoma, cystoid macular edema, altitude sickness,
epilepsy, respiratory stimulant

79. ADVERSE EFFECTS OF ORAL CAIS
 intolerance due to their adverse effects
 common in elderly people
 neurological/psychiatric
 Paresthesia, fatigue, malaise,
 Depression, headache, decreased libido
 gastrointestinal—
 metallic taste and discomfort,
 Nausea, abdominal cramps diarrhea

80.  renal/metabolic
 Increased micturation frequency
 Renal stones,hypokalemia(metabolic acidosis)
 May cause exacerbation of gout
 hematological
 Bone marrow depression,aplastic anemia
 teratogenic effect rarely: contraindicated in first trimester

81. HYPEROSMOTIC AGENTS
Increase the osmolarity of plasma
Leads to absorption of water from ocular tissues( mainly vitreous)
 indication
 acute glaucoma
 secondary glaucoma, preparation of patients before OT
 malignant glaucoma
 adverse effects
 headache, nausea, vomitting
 systemic hypertension
 congestive heart failure and pulmonary edema
 urinary retention and hyperglycemia

82.  Oral Glycerol
 50% solution in dose of 1.5 to 3 ml/kg body weight
 poorly penetrates into the eye
 diabetics may have problem due to caloric value, osmotic diuresis
and dehydration
 Mannitol
 20% concentration
 1-2gm/kg body weight or 5-10ml/kg body weight
 peak action-within 30 mins
 duration of action-upto 6hours
 choice for intravenous therapy

83. NEUROPROTECTIVE AGENTS
 To protect the optic nerve damage by-
 Block the endogenous substances which may have damaging effect on
ganglion cells
 Prevent neuronal degeneration and promoting regeneration
 Endogenous substances released during glaucoma are
 Excitotoxins-glutamate and aspartate
 Elevated intracellular Ca++
 Nitric oxide
 Free radicals
 Agents that promote regeneration
 Calcium channel blockers
 Nitric oxide synthase inhibitors
 Antioxidants
 Vasodilators

84.  Prostagladins analogs, beta blockers, alpha2 agonist are resonable
choices for first line therapy
 However, prostagladins with once daily dose are most effective
agents for IOP lowering and provide good 24 hr IOP control

85. THANK YOU