Topically administered ophthalmic drugs have complex pharmacokinetics due to factors affecting absorption such as precorneal tear film and drainage through nasolacrimal pathways. Distribution occurs across the cornea and into intraocular structures. Common routes of administration include eye drops, ointments, and periocular injections. Key drug classes include antibiotics, antivirals, antifungals, glaucoma medications, anti-inflammatories, and anesthetics. Adverse effects depend on drug class but can include blurred vision, allergic reactions, and increased intraocular pressure. Systemic absorption may also cause toxicity.

1. TABINDAH HESAM
JUNIOR RESIDENT 1
Deptt of PHARMACOLOGY
JNMC
Pharmacokinetics and Toxicology
of Ocular Therapy

2. Anatomy of the Eye

3. Contd....

4. Anatomy of lacrimal
apparatus

5. Tear Film

6. Pharmacokinetics of Ocular
Therapeutic Agents

7. Pharmacokinetics of Ocular
Drugs
Classical pharmacokinetic theory based on
systemically administered drugs does not
fully apply to all ophthalmic drugs.
Topical route (ointments, drops) is most
commonly used route.

8. Absorption

9. Factors affecting absorption of
drugs
Rate and extent of absorption of
topically instilled drug depends upon:
 The time the drug remains in the cul-de-
sac,
 Precorneal tear film,
 Elimination by nasolacrimal drainage,
 Drug binding to tear proteins,
 Drug metabolism by tear and tissue
proteins, and
 Diffusion across the cornea and

10. Other factors...
 Concentration gradient between tear film
and cornea/conjunctival epithelium
(linear relation)
 Size of molecule, chemical structure,
steric configuration
 Trilaminar structure of cornea
 Integrity of anatomical barrier

11. Distribution
Transcorneal absorption
Accumulation in aqueous humor
Distribution in intraocular structure
{Trabecular
meshwork}
Distribution to systemic circulation

12.  Melanin binding of certain drugs is an
important factor in some ocular
compartments.
 The mydriatic effect of adrenergic–receptor
agonists depends upon iris pigmentation.
 Atropine's mydriatic effect lasts longer in non-
albino rabbits than in albino rabbits.
 In the retinal pigment epithelium,
accumulation of chloroquine causes a toxic
retinal lesion known as a “Bull's-eye"
maculopathy, which is associated with a
decrease in visual acuity.

13. General principles of local eye
therapy
1. Non-pharmacological modalities: Eye rest,
bed rest, proper lighting, protection from
lighting and trauma, hot or cold compress,
eye exercises, nutritional management.
Maintenance of hygiene and aseptic
precaution in health care giver.
2. Pharmacological management: To rule out
any precipitating factors (bronchial asthma in
a patient of glaucoma), family history of
glaucoma before prescribing Corticosteroids.

14. Contd..
 No attempt should be made to dilute or otherwise
modify the ophthalmic preparation.
 The remnant should not be preserved for future
use once the patient gets well.
 Only one drop should be instilled at one time
because that is the capacity of cunjunctival sac.
Second medication, if needed to be instilled,
should be used after 5 minutes.
 Associated conditions like DM and HTN should be
treated.

15. DRUG DELIVERY STRATEGY

16. TOPICAL
EYE-DROPS:
 Simplest and most convenient for ambulatory and
working patients.
 Only one drop should be instilled at one time because
that is the capacity of cunjunctival sac.
Method: hold the skin below the lower eye-lid
Pull it forward slightly
Instill one drop
 Measures to increase absorption:
-Wait for 5 minutes if another medication needs to be
instilled

17.  OINTMENT:
- Acts as a reservoir of the drug.
- Slow release.
- Confers higher penetration.
- Prolongs action
Disadvantage:
Blurring of vision.

18. Peri-ocular Injections
 They reach behind iris-lens diaphragm better than
topical application.
eg; Subconjunctival, subtenon, peribulbar and
retrobulbar.
 This route bypasses the conjunctival and corneal
epithelium which is good for drugs with low
solubility. Example-Penicillin.
 Also steroids and local anesthetics can be
applied this way.

19. Contd...
 Subconjunctival-to achieve higher penetration,
drugs which can’t penetrate cornea, penetrate via
sclera.
 Subtenon Anterior subtenon:disease ant. to
the lens
Posterior subtenon:disease
posterior to the lens.
 Retrobulbar-Optic neuritis, Papillitis, Posterior
uveitis, Anesthesia.
 Peribulbar- Anesthesia.

20. Intraocular injections
 Intracameral or intraviteral.
Examples:
 Intraviteral acetylcholine
during cataract surgery.
 Intraviteral antibiotics in case of cataract surgery.

21. Contd...
Intraviteral steroid
injection
Intraviteral anti
VEGF in DR

22. •These are devices that
deliver drugs at a
constant rate (follow
zero order kinetics).
eg;
-Ocusert delivering
pilocarpine.
-Timoptic XE delivering
timolol.
Contd...

23. Contd...
 Ganciclovir sustained
release device.
 Collagen shield.

24. Common ocular drugs
 Antibacterials
 Antivirals
 Antifungals
 Mydriatics and cycloplegics
 Antiglaucoma
 Anti-inflammatory agents(NSAIDS and
Corticosteroids)
 Ocular lubricants
 Ocular diagnostic drugs
 Local anesthetics

26. Common ocular infections
Blepharitis Acute
cojunctivitisACUTE-Topical erythromycin or
sulfacetamide.
Recurrent- topical CS
CHRONIC- requires antiseborrhic
treatment.
Choice of drug depends
upon suspected infected
agent and its predicted
antibiotic sensitivity.

27. Hordeolum(stye) Dacryocystitis
Treatmnent comprises of hot compress
and antibiotics.

28. Antiviral agents

30. Contd...
 Viral keratitis:
Epithelial- topical
Stromal-oral treatment.
When treating viral keratitis topically, there is a very
narrow margin between the therapeutic topical antiviral
activity and the toxic effect on the cornea; hence, patients
must be followed very closely
 Herpes Zoster ophthalmicus needs topical acyclovir
plus systemic therapy.
 Viral retinitis requires prolonged treatment, by either
intravitreal or IV drugs.

31. Antifungal agents

33. Antiprotozoal infections
 Parasitic infections involving the eye usually
manifest themselves as a form of uveitis, an
inflammatory process of either the anterior or
posterior segments and, less commonly, as
conjunctivitis, keratitis, and retinitis.
 eg; Ocular toxoplasmosis, Acanthamoeba
keratitis.
 Toxoplasmosis may present as a posterior (e.g.,
focal retinochoroiditis, papillitis, vitritis, retinitis) or
occasionally as an anterior uveitis.
 Treatment is indicated when inflammatory lesions
encroach upon the macula and threaten central
visual acuity.

34. contd,..
 Several regimens have been recommended with
concurrent use of systemic steroids:
 pyrimethamine, sulfadiazine, and folinic acid
(leucovorin)
 pyrimethamine, sulfadiazine, clindamycin, and
folinic acid
 sulfadiazine and clindamycin
 clindamycin
 trimethoprim-sulfamethoxazole with or without
clindamycin

35. AUTONOMIC AGENTS IN EYE

38. Glaucoma
 Characterized by progressive optic nerve cupping
and visual field loss.
 Elevated IOP is a risk factor for glaucoma. A
reduction of IOP by 30% reduces disease
progression from ~35-10%, even for normal-
tension glaucoma patients.

39. Types of Glaucoma
 PRIMARY GLAUCOMA-Angle closure glaucoma
-Open angle glaucoma
 SECONDARY GLAUCOMA-Drug induced
-Traumatic
-Following cataract
surgery
 CONGENITAL GLAUCOMA

40.  Current pharmacotherapies are targeted at :
-decreasing the production of aqueous humor at the ciliary
body
-and increasing outflow through the trabecular meshwork
and uveoscleral pathways.
Few General consideratios:
 young patients usually are intolerant of miotic therapy
secondary to visual blurring from induced myopia.
 direct miotic agents are preferred over cholinesterase
inhibitors in "phakic" patients (i.e., those patients who have
their own crystalline lens) because the latter drugs can
promote cataract formation
 in patients who have an increased risk of retinal detachment,
miotics should be used with caution because they have been
implicated in promoting retinal tears in susceptible individuals
(such tears are thought to be due to altered forces at the
vitreous base produced by ciliary body contraction induced
by the drug).

41. The drugs which increases the outflow of aqueous
humor:
1. Cholinergic agonists(Miotics)
-Pilocarpine drops 0.25%
-Pilocarpine Ocusert.
2. Cholinesterase inhibitors( Miotics)
-Physostigmine0.25% ointment
3. Prostaglandin Analogues
-Latanoprost
-Bimatoprost
-Travoprost

42. Drugs which decrease the production
of aqueous humor
 Non selective beta blockers
-Timolol0.25-0.5%
 Selective beta blockers
-Betaxolol0.5%
-Cartelol 1%
-Levobunolol0.5%
-Metppranolol0.3%
 Non selective adrenergic agonists
- Dipivefrine0.1%; Epinephrine0.5-2%
 Selective alpha 2 adrenergic agonists
-Apraclonidine0.5-1%
-Brimonidine0.2%

43. Contd...
 Carbonic anhydrase inhibitiors
a) Topical: Brinzolamide 1% suspension
Dorzolamide 2%
b)Systemic:Acetazolamide(diamox) 250 mg qid
Methazolamide 25 mg qid

44. Side effects
 Physostigmine- Follicular conjunctivits
- Retinal detachment
-HS reaction
 Beta blockers-: Topical-Dryness of eyes,stinging,
redness, corneal hyposthesia, allergic
blepharoconjunctivitis,blurred vision.
 Dipivefrine- Ocular allergic reaction, redness of
eyes.
 PG analogues-Conjunctival redness, iris and
periocular pigmentation , hypertrichosis,darkening
of iris.

45. MYDRIATICS AND MIOTICS

46. Mydriatics
Required for:
1.Determination of
refractive error.
2.Fundoscopic
examination of eyes.
3.Treatment of
iridocyclitis.
4. Breaking the
adhesions between
the lens and ciliary body
by alternating with
miotics.
Side effects- Blurred

47. Mydriatics

48. MIOTICS
1.Cholinomimetics
- Pilocarpine0.5% drps, ocusert.
2.Cholinesterase inhibitors
-Physostigmine 1% drops
USE: Treatment of glaucoma.
SIDE EFFECTS:
Headache, brow-ache, vascular
congestion,blurring of vision,
burning sensation ,Prolonged use may cause viterous
hemorrhage
and myopia

49. Immunosuppressive and anti mitotic
agents
 Flurouracil and miotomicin-C
USES:
1. to limit scarring after surgical procedures
2.for life threatening ocular manifestations of certain
systemic diseases like wegner’s granulomatosis and
Behcet’s disease.
 Anti VEGF: Bevacizumab, Ranibizumab,Pegatinib.
 Verteporfin- inhibitor of choroidal NV.
 Afllibercept-fusion protein.
All these agents are given intavitreally and can cause pain,
conjunctival hemorrhage and endophthalmitis.
OCRIPLASMIN-a recombinant selective proteolytic enzyme
used for breaking age related viteromacular adhesions.

50. Local anesthetics
 These agents are used topically:
-to remove foreign body
-Prior to tonometry
-for preop preparation esp tetracaine and
proparcaine are used.
- in the manipulation of nasolacrimal system..
- during the use of excimer laser(tetarcaine).
-for infilteration and retrobulbar block
anesthesia.(lignocaine and bupivacaine) .

51. Routes of administration of
local anesthesia

52. NSAIDS and
Corticosteroids

53. CORTICOSTEROID
 Classification:
1. Short-acting- Hydrocortisone(1% S,O) cortisone,
prednisolone 1%S.
1. Intermediate acting-Triamcinolone, Fluprednisolone.
2. Long acting-Dexamethasone(0.1% S,O
betamethasone(0.1% S,O)
 Indications:
1. TOPICAL- allergic conjunctivitis, uveitis, allergic keratitis,
after intraocular and extraocular surgeries.
2. SYSTEMIC-Posterior uveitis,Optic neuritis, Corneal graft
rejection
3. INTRAVITERAL-ARMD,DR, CME.

54. Side effects
 Open angle glaucoma with topical treatment.
 Posterior subcapsular cataract(steroid cataract).
 Secondary infection.
 Delayed wound healing.
Undiagnosed red eye may be due to herpes
simplex infection and use of CS may aggravate
leading to corneal ulceration and loss of vision.
 Contraindications :Herpetic epithelial keratitis
due to active viral replication, fungal disease of
the eye, other viral diseases of cornea and
conjunctiva, oculer TB.

55. NSAIDS
 Flurbiprofen 0.03% eye drops
 Diclofenac 0.1%eye drops
 Ketorolac 0.055 eye drops
INDICATIONS: Episcleritis and scleritis
- Uveitis
-CME
-Preoperatively to maintain
dilatation of pupil.

56. Ocular Lubricants
 Used for ocular irritation.
 Dry Eyes
 Commonly available preparations:
REFRESH TEARS
TEAR PLUS
MOISOL
OCCUWET
DUDROP

57. Ocular diagnostic drugs
 Rose-bengal stains:
-Stains devitalised tissue of cornea and
conjunctiva.
 Fluoroscein:
-for detecting epithelial defect.
-to detect leakage of aqueous humor after trauma
or surgery.
-Patency of the nasolacrimal system.
 In the posterior segment of the eye, fluorescein
and indocyanin green are used for retinal
angiography.

58. OCULAR TOXICOLOGY

59. Some drugs causing ocular
toxicity
DRUGS
 Ethambutol
 Chloroquin
 Chlorpromazine
 Chloramphenicol
 Aminoglycosides
 Sildenafil
 Antimuscarinic
 Vigabatrin
 Tamoxifen
 Digoxin
 Alendronate
OCULAR TOXICITY
Optic neuritis
Retinopathy
Retinal pigmentation
Retinal pigmentation
Optic neuritis
Blue Vision
Glaucoma
Visual field constriction
Visual field constriction &
cataract
Scotoma
Conjunctivitis; iritis

60. Bull’s eye maculopathy
CHLOROQUIN

61. Angle closure glaucoma
TOPIRAMATE

62. Tamoxifen

63. VIGABATRIN
VISUAL FIELD
CONSTRICTION

64. NAION
TOPIRAMATE, SILDENAFIL

65. THANK YOU