Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Pharmacotherapy of glaucoma

Pharmacotherapy of glaucoma

Related Books

Free with a 30 day trial from Scribd

See all

Related Audiobooks

Free with a 30 day trial from Scribd

See all
  • Be the first to comment

Pharmacotherapy of glaucoma

  1. 1. Pharmacotherapy of . Glaucoma Dr Manjuprasad Moderator: Dr Vijayalaxmi M.K
  2. 2. Overview • Introduction • Anatomy • Aqueous humour dynamics • pathophysiology • Drugs used in the treatment • Recent advances • Conclusion 2
  3. 3. Introduction • Glaucoma – ancient greek meaning clouded or blue- green hue • In Hippocratic aphorisms Glaucoma – blindness coming from advancing years • Second leading cause of blindness 3
  4. 4. • Glaucoma is not a single disease process but a group of disorders characterized by a progressive optic neuropathy resulting in a characteristic appearance of optic disc & specific pattern of irreversible visual field defects that are associated frequently but not invariably with ↑IOP 4
  5. 5. Anatomy of the eye 5
  6. 6. Aqueous humor • Derived from the plasma • 2.3µl/min Production: • Ultrafiltration • Secretion • Diffusion 6
  7. 7. Aqueous humor dynamics 7
  8. 8. Classification • Congenital glaucoma - Primary congenital glaucoma - Developmental glaucoma • Primary adult glaucoma - Primary open angle glaucoma - Primary angle closure glaucoma - Primary mixed mechanism glaucoma • Secondary glaucoma 8
  9. 9. Pathogenesis • All types of glaucoma – progressive optic neuropathy due to the death of retinal ganglion cells(RGCs) • RGCs death is initiated – block in transport of neurotrophins from brain to RGCs damaging cascade activation Apoptosis of RGCs • RGCs death – loss of retinal fibers – optic neuropathy & visual field defects 9
  10. 10. • Mechanical theory : ↑IOP – mechanical stretch of lamina cribrosa – axonal deformation & altered capillary blood flow -- ↓neurotrophins to reach RGC`s • Pressure independent factors - Failure of autoregulation - Vasospasm - Systemic hypotension - Blood / fluid loss • Excitotoxicity theory: glutamate , oxygen free radicals, nitric oxide 10
  11. 11. Congenital glaucoma • Seen in 1 in 10,000 births • Pathology- mal development of trabeculum • True congenital glaucoma • Infantile glaucoma • Juvenile glaucoma • Diagnosis – corneal diameter measurement - ophthalmoscopic evaluation of disc - gonioscopic examination 11
  12. 12. Primary open angle glaucoma • No obvious cause • Polygenic inheritence • ↑incidence in smokers • Blacks > whites • Pathology: - Age related thickening & sclerosis of trabeculae - Absence of giant vacuoles in cell lining canal of schlemm 12
  13. 13. Primary angle closure glaucoma • Increase in IOP – due to closure of angle of anterior chamber. Acute & chronic • Chronic PACG:- progress slowly with / without symptoms • Acute PACG:- -Is an emergency -Severe eye pain -Nausea, vomiting, prostration -Redness, photophobia, lacrimation -Rapid, progressive impairment of vision 13
  14. 14. Risk factors: • Hypermetropic eye • Small eye • 5th decade • Female > male • > in rainy season and dim light 14
  15. 15. Secondary glaucomas • Lens induced glaucoma • Pigmentary glaucoma • Neovascular glaucoma • Glaucoma associated with intravascular tumor • Traumatic glaucoma • Steroid induced glaucoma 15
  16. 16. 16
  17. 17. Drugs used in the treatment DRUGS THAT REDUCE AQUEOUS HUMOUR PRODUCTION I. Beta-Blockers : levobunolol, timolol, carteolol, betaxolol II. Alpha-2 Adrenergic Agonists : apraclonidine, brimonidine III. Carbonic Anhydrase Inhibitors :acetazolamide, dorzolamide 17
  18. 18. DRUGS THAT INCREASE AQUEOUS OUTFLOW I. Nonspecific Adrenergic Agonists :epinephrine, dipivefrin II. Parasympathomimetics : pilocarpine, carbachol, echothiophate III. Prostaglandin Analogues : latanoprost 18
  19. 19. Cholinergic agonists • Most commonly used – Pilocarpine • Derived from shrub – pilocarpus jaborandi MOA:- • Acts on M3 receptors – contraction of sphincter pupillae • Causes contraction of longitudinal ciliary muscle → trabecular outflow 19
  20. 20. • Onset of action – rapid peak effect – 30min lasts for 4 – 6hrs • S/E:- • LOCAL:- Superficial punctate keratitis , brow ache, induced myopia, increased risk of retinal detachment & iritis • SYSTEMIC – rare • Available as 0.5 to 10 % eye drops 20
  21. 21. • Pilocarpine gel (pilocarpine HCl 4%) HS • Membrane controlled delivery system:- -Insert placed in cul-de-sac that gradually release drug at rate of 20mcg/hr -Effective for 7 days • Pilocarpine soaked contact lens • Liposomal pilocarpine 21
  22. 22. ADRENERGIC AGONISTS Includes: • Non selective – epinephrine & dipivefrin • Selective alpha2 agonists- Apraclonidine, Brimonidine 22
  23. 23. • EPINEPHRINE:- • Directly acting sympathomimetic • MOA: • Reduced aqueous production due to alpha action • trabecular outflow via Beta receptor stimulation • Due to its CVS s/e , allergic reaction – no longer used • DIPIVEFRIN:- • Is a prodrug • Formed by di-esterification of epinephrine – lipophilicity– increased penetration to anterior chamber . 23
  24. 24. • Onset of action-30min, peak effect – 1hr • Used as an adjuvant therapy • Available as 0.1% solution , dosage BD A/E : • Less compared to epinephrine • Follicular conjunctivitis, blurring of vision, stinging 24
  25. 25. ALPHA2 AGONISTS MOA:- • Decrease aqueous humour production by alpha2 action on ciliary epithelium. APRACLONIDINE: • Also known as para amino clonidine • Available as 0.5 – 1 % , dosage BD • Short term use – Post op rise in IOP & adjuvant in POAG 25
  26. 26. BRIMONIDINE:- • 30 times more selective α2 agonist than apraclonidine • Additional neuroprotective effect • Available as 0.2 - 0.5% , applied BD • Uses:- in patients with contraindications to beta blockers, -short term use in post op raise in IOP 26
  27. 27. BETA BLOCKERS • Introduced in 1979 • Considered to be 1st line therapy for all types of glaucoma • Good efficacy • Minimal S/E MOA: • Decreases aqueous humour production by blocking beta2 receptors on ciliary epithelium. 27
  28. 28. TIMOLOL: • Introduced 1978 as 1st approved beta blocker for glaucoma • Most widely used ocular hypotensive agent • Due to its non selective beta action – cautious in COPD, asthma & heart failure • Available as 0.5 % solution & gel • S/E:- • Systemic • Local:- superficial punctate keratitis, corneal anesthesia CARTEOLOL: • Available as 1% solution 28
  29. 29. • LEVOBUNOLOL • Available as 0.5 – 1% solution, applied BD /OD • Metabolized to di- hydrolevobunolol • BETAXOLOL • Introduced in 1980s as 1st topical β1 blocker used in glaucoma • Clinical trials – lesser efficacy in reducing IOP compared to timolol • Additional neuroprotective effect. 29
  30. 30. CARBONIC ANHYDRASE INHIBITORS 2 types:- • Systemic CA inhibitors:- • Acetazolamide, Methazolamide • Topical CA inhibitors:- • Dorzolamide, Brinzolamide MOA:- • Blocks CA enzyme reversibly in ciliary body – reduces aqueous humour production 30
  31. 31. SYSTEMIC CARBONIC ANHYDRASE INHIBITORS DOSAGE:- • Acetazolamide 125mg, 250mg p.o TID or QID • Methazolamide 25mg, 50mg p.o BD or TID SIDE EFFECTS:- • High risk of systemic S/Es. • Paraesthesias, Kidney stones, aplastic anaemia, depression 31
  32. 32. TOPICAL CARBONIC ANHYDRASE INHIBITOR • DORZOLAMIDE:- • 1st topical CA inhibitor launched in market • Advantage – not absorbed systemically • Available as 2 % solution- applied TID • S/E:- systemic is minimal - local S/E includes corneal edema, allergic reaction, burning & stinging sensation • BRINZOLAMIDE • Available as 1% solution • Better tolerated than dorzolamide – its pH is 7.4 32
  33. 33. PROSTAGLANDIN ANALOGUES • Includes latanoprost, unoprostone, bimatoprost, travoprost. • MOA:- • Decreases IOP by increasing uveoscleral outflow 33
  34. 34. LATANOPROST:- • Introduced in 1996 • An ester prodrug analogue of PGF2α • Available as 0.0005% solution, OD (evening) • Requires refrigeration & protection from sunlight • S/E – conjunctival hyperemia ( initially), Iris pigmentation, cystoid macular odema 34
  35. 35. UNOPROSTONE:- • Available as 0.15% solution, BD • Additional neuroprotective effect – increasing microcirculation in optic nerve head. BIMATOPROST: • A synthetic prostamide analogue • Available as 0.03% solution , OD • Does not require refrigeration 35
  36. 36. TRAVAPROST • Synthetic PGF2α analogue • Available as 0.004% solution, OD at evening • Does not require refrigeration/ protection from sunlight 36
  37. 37. Surgical procedures 37 • Trabeculoplasty • Iridotomy • Iridectomy • Filtering procedures • Canaloplasty • Goniotomy • Goniocurettage • Cyclodialysis • Ciliarotomy
  38. 38. Other treatment modalities ALPHA LIPOIC ACID:- • Powerful antioxidant • Useful in glaucoma by decrease in nerve cell damage due to oxidative stress VITAMIN C :- • Said to increase aqueous outflow by reducing viscosity of hyaluronic acid in trabecular meshwork SALVIA MILTIORRHIZA:- • Chinese herb, given i.v said to improve microcirculation of RGCs 38
  39. 39. CANNABINOIDS • Believed to improve uveoscleral outflow • Not yet available for this purpose 39
  40. 40. Herbal products • Boerhavia Diffusa • Emblica Officinalis • Terminalia Chebulia • Commiphora Mukul • Curcuma Longa 40
  41. 41. FUTURE GLAUCOMA THERAPY • NMDA receptor antagonist:- • Provides neuroprotection by blocking glutamate mediated death of RGCs • Includes memantine & eliprodil • Riluzole:- • Is a presynaptic glutamate release inhibitor • Neuroprotective nature • Neuroprotective vaccines:- R16 41
  42. 42. Erythropoetin:- • Neuroprotective by inhibiting RGCs apoptosis • In animal studies – intravitreal injection enhances RGC survival Caspase inhibitors:- • Inhibits apoptosis of RGCs • Promising approach in terms of Rx of glaucoma iNOS inhibitors:- • Increased level of NO – neuronal damage via apoptosis 42
  43. 43. DRUG ELUTING MICRO STENTS • Microstents were coated with a polymer-drug compound and is implanted in the angle of iris and cornea • Diffusion controlled release of paclitaxel or mitomycin is used to avoid blocking of stent 43
  44. 44. Acute angle closure glaucoma • IOP – 40-70 mmHg • Systemic hyperosmotic agent- IV mannitol 1mg/kg • Actazolamide 500mg IV followed by 250mg TID • Analgesics and Antiemetics • Corticosteroids e/d like dexamethasone 3-4/day to reduce inflammation • Sx- periferal iridotomy filteration surgery 44
  45. 45. BIBLIOGRAPHY • Pharmacological aspects of therapeutics – Goodman and Gilman – 12th edition • Principles of pharmacology Sharma and sharma 2nd edition • Textbook of medical pharmacology – Dr.PadmajaUdaykumar – third edition • Essentials of medical pharmacology – K.D.Tripathi • A. K. Khurana - comprehensive ophthalmology • Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–7 • Killer HE, Miller NR, Flammer J, Meyer P, Weinreb RN, Remonda L, Jaggi GP. Cerebrospinal fluid exchange in the optic nerve in normal-tension glaucoma. Br J Ophthalmol. 2012;96:544–8. • Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126:498–505 • . Bergeå B, Bodin L, Svedbergh B. Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology. 1999;106:997–1004 • Rao HL, Addepalli UK, Jonnadula GB, Kumbar T, Senthil S, Garudadri CS. Relationship between intraocular pressure and rate of visual field progression in treated glaucoma. J Glaucoma. 2012 In press. 45
  46. 46. 46

    Be the first to comment

    Login to see the comments

  • VascoJrSamwel

    Nov. 5, 2019
  • meerashabnamsheik

    Dec. 28, 2019
  • PhanchitaPhuwasinsawat

    Jan. 23, 2020
  • alishanaik8

    Feb. 7, 2020
  • RapuluchukwuOgbue

    Apr. 15, 2020
  • KeerthiRaju5

    Sep. 3, 2020
  • KeerthiRaju5

    Sep. 3, 2020
  • KeerthiRaju5

    Sep. 3, 2020
  • SuneetKour1

    Sep. 9, 2020
  • AreenaNikhat

    Sep. 17, 2020
  • GraceNRaju

    Sep. 25, 2020
  • HimaBindu138

    Dec. 1, 2020
  • laksmidas

    Jan. 20, 2021
  • NaseemNoor

    Feb. 11, 2021
  • AbderrahimElhakioui

    Apr. 25, 2021
  • swetha1324

    Apr. 26, 2021
  • ChandanKumar1905

    May. 5, 2021
  • HridayDas4

    Jun. 5, 2021
  • KevinKiprotich6

    Jun. 10, 2021
  • VishwasKumar36

    Jun. 27, 2021

Pharmacotherapy of glaucoma

Views

Total views

20,648

On Slideshare

0

From embeds

0

Number of embeds

2,366

Actions

Downloads

1,686

Shares

0

Comments

0

Likes

97

×