basics in ocular pharmacology

1. OCULAR PHARMACOLOGY

2. Pharmacodynamics
• It is the biological and therapeutic effect of the drug
(mechanism of action)
• Most drugs act by binding to regulatory
macromolecules, usually neurotransmitters or
hormone receptors or enzymes
• If the drug is working at the receptor level, it can be
either
agonist antagonist

3. • If the drug is working at the enzyme level, it
can be
activator inhibitor

4. Pharmacokinetics
• It is the: ADEM
Absorption,
Distribution,
Metabolism, and
Excretion of the drug
• A drug can be delivered to ocular tissue as:
• Locally: Eye drop
Ointment
Periocular injection
Intraocular injection
• Systemically: Orally
Intravenous(I.V.)

5. Drug Delivery in Eyes
TOPICAL PERIOCULAR INTRAOCULAR SYSTEMIC
DROPS SUBCONJUNCTIVAL INTRACAMERAL ORAL
OINTMENT SUNTENON INTRAVITREAL INTRAVENOUS
GEL
PERIBULBAR/RETR
OBULBAR
INTRAMUSCULAR

6. 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
altering corneal epithelium
Lipid solubility :
Because of the lipid rich environment of the epithelial cell
membranes, the higher lipid solubility the more the penetration
Amphipathic- epithelium/endothelium----lipophilic
stroma---hydrophilic

7. Factors influencing local drug
penetration into ocular tissue
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
Molecular weight and size:

8. TOPICAL
Drop - simplest and more convenient
mainly for day time use
• 1 drop=50 microlitre
• Conjuctival sac capacity=7-13 micro liter so, even 1 drop is more than
enough
Method
-hold the skin below the lower eye lid
- pull it forward slightly
-INSTALL 1 drop
measures to increase drop absorption :
-wait 5-10 minutes between drops
-compress lacrimal sac -keep lids closed for 5 minutes after instillation

10. Ointments
 Increase the contact time of ocular
medication to ocular surface thus better effect
 It has the disadvantage of vision blurring
The drug has to be high lipid soluble with
some water solubility to have the maximum
effect as ointment

12. Peri-ocular injections
• They reach behind iris-lens diaphragm better than topical
application
E.g.
subconjunctival,
subtenon,
peribulbar, or
retrobulbar
• This route bypass the conjunctival and corneal epithelium
which is good for drugs with low lipid solubility (e.g.
penicillins)
• Also steroid and local anesthetics can be applied this way

13. Periocular
• Subconjunctival - To achieve higher concentration
-Drugs which can’t penetrate cornea due to
large size
-Penetrate via sclera
• Subtenon —
ant. Subtenon– disease ant to the Lens
Post Subtenon– disease posterior to the lens
Retrobulbar - Optic neuritis
Papillitis
Posterior uveitis
Anesthesia
• Peribulbar -- anesthesia

15. Intraocular injection
Intracameral or
intravitreal
E.g.
• Intracameral acetylcholine (miochol) during
cataract surgery
• Intravitreal antibiotics in cases of endophthalmitis
• Intravitreal steroid in macular edema
• Intravitreal Anti-VEGF for DR

17. Sustained-release devices
• These are devices that deliver an adequate
supply of medication at a steady-state level
E.g.
-Ocusert delivering pilocarpine
-Timoptic XE delivering timolol
-Ganciclovir sustained-release intraocular
device
-Collagen shields

19. Common ocular drugs
• Antibacterials (antibiotics)
• Antivirals
• Antifungal
• Mydriatics and cycloplegics
• Antiglaucoma
Corticosteroids
• Anti-inflammatory agents
NSAIDS
• Ocular Lubricants
• Ocular diagnostic drugs
• Local anesthetics
• Ocular Toxicology

20. Antibacterials( antibiotics)
• Penicillins
• Cephalosporins
• Sulfonamides
• Tetracyclines
• Chloramphenicol
• Aminoglycosides
• Fluoroquinolone
• Vancomycin
• macrolides

21. Antibiotics
• Used topically in prophylaxis (pre and postoperatively) and
treatment of ocular bacterial infections.
• Used orally for the treatment of preseptal cellulitis
e.g. amoxycillin with clavulonate, cefaclor
• Used intravenously for the treatment of orbital cellulitis
e.g. gentamicin, cephalosporin, vancomycin, flagyl
• Can be injected intravitrally for the treatment of
endophthalmitis

23. Specific antibiotic for almost each organisms
• Sulfonamiodes –

24. USES:
Chlamydial infections like TRACHOMA
INCLUSION CONJUNCTIVITIS
TOXOPLAMOSIS

25. Cephalosporins

26. • first generation- gm + cocci eg cephazolone
• second generation —Gm – ve and
antistaphylococcal— cefuroxime
• Third generation – Gm –ve bacilli –
ceftriaxones

27. • Side effects-
allergic reaction
Neutropenia
thrombocytopenia

28. Amino glycosides
• Mechanism of Action: Bacterial protein
synthesis inhibitors
• mainly against gm negative bacilli
• Gentamycin- 0.3% eye drop
• Tobramycin- Pseudomonas 1% eye drop
• Neomycin- 0.3-0.5% eye drop

29. Tetracycline
• Inhibit protein synthesis
• active against both gm+ and gm -, some fungi and
Chlamydia
Chloromphenicol
• Inhibit protein synthesis
• Broad spectrum ,bacteriostatic, gm+/gm-,
Chlamydia
• 0.5% Eye drop, ointment

30. Antibiotics
• Trachoma can be treated by topical and systemic
tetracycline or erythromycin, or systemic
azithromycin.
• Bacterial keratitis (bacterial corneal ulcers) can be
treated by topical fortified penicillins,
cephalosporins, aminoglycosides, vancomycin, or
fluoroquinolones.
• Bacterial conjunctivitis is usually self limited but
topical erythromycin, aminoglycosides,
fluoroquinolones, or chloramphenicol can be
used

31. Antivirals
Acyclovir
3% oinment 5 times-10-14 days
800mg oral 5 times 10-14 days
intravenous for Herpes zoster retinitis
Others INDICATIONS
Idoxuridine HZ keratitis
Vidarabine Viral uveitis
Cytarabine
Triflurothymidine
Gancyclovir

32. Cytomegalovirus Retinitis

33. Dendritic Ulcer

34. ANTIFUNGAL
INDICATIONS
• Fungal corneal ulcer
• Fungal retinitis/ Endophthalmitis
• Commonly used drugs are
Polyenes
-damage cell membrane of susceptible fungi
-e.g. amphotericin B, natamycin, nystatin
-side effect: nephrotoxicity
Imidazoles
increase fungal cell membrane permeability
• e.g. miconazole, ketoconazole,fluconazile
Flucytocine
act by inhibiting DNA synthesis

35. Fungal Ulcer

36. MYDRIATICS AND CYCLOPLEGIC
• MYDRIATICS- Dilate the pupil, by constriction of radial
muscles(sympathetic supply) e.g.Phenylepherine
• Cycloplegic – causes ciliary muscle paralysis(parasympathetic)
CLASSIFICATION
• Short acting- Tropicamide (4-6 hours)
• Intermediate- homatropine ( 24 hours)
• Long acting- atropine (2 weeks)
Indications
• corneal ulcer
• uveitis
• cycloplegic refraction

37. Antiglaucoma drugs
Beta blockers-
Selective – betaxolol
Non selective- timolol
Mechanism of Action:
reduces aqueous humour production
Reduces IOP
Side effect:
systemic ocular
Bradycardia Irritation
Sweating Frontal Headache
Anxiety Iris cyst
Follicular Conjunctivitis

38. Carbonic anhydrase inhibitors
Systemic Topical
• acetazoamide Dorzolamide
Brinzolamide
Mechanism of action-- reduce aqueous humour
formation
Side effect
Paresthesiae
Frequent urination
GI disturbances
Hypokalamia

39. • Hyperosmotic agent-
iv mannitol when IOP is very high 60-70
In adults the dose is 0.2 g/kg body weight.
In pediatric patients the dose is 0.2 g/kg body weight or 6 g/m² body surface area.
The infusion is given as a 15% to 25% solution over a period of 3 to 5 minutes to
produce a urine flow of at least 30 to 50 mL/hour.
• Prostaglandins
• Latanoprost (0.005% eye drop)
• increased aqueous out flow
• Reduced IOP
• Side effect– conjunctival redness,
iris and periocular pigmentation
hypertrichosis,
darkening of iris

40. ANTI INFLAMMATORY

41. • ANTI – INFLAMMATORY
Corticosteroids Non- steroidal
anti-inflammatory
drugs(NSAIDS)

42. CORTICOSTEROIDS

43. Corticosteroids
CLASSIFICATION
• Short acting
hydrocortisone,
cortisone,
prednisolone
• Intermediate acting :Trimcinolone,
Fluprednisolone
• Long acting
Dexamethasone ,betamethasone

45. Indications
• Topical
• allergic conjunctivitis,
• scleritis,
• uveitis,
• Allergic keratitis
• after intraocular and extra ocular surgeries
• Systemic (pathology behind the LENS)
• Posterior uveitis
• Optic neuritis
• corneal graft rejection
NEVER GIVE STEROID IF YOU ARE SUSPECTING ACTIVE INFECTION

46. Allergic Conjunctivitis

47. Episcleritis

48. Anterior Uveitis

49. Contraindications
Ocular
• Fungal Infections
• Glaucoma
• Corneal Epithelial defect
• Herpetic Epithelial Keratitis
Systemic
• Osteoporosis
• Diabetes Mellitus
• Congestive Heart Failure(CHF)
• Renal Filure
• Peptic Ulcer

50. Side effects
• Ocular
Glaucoma
Cataract
Activation of infection
Delayed wound healing

53. Pre-requisite
• BP
• Blood sugar
• Mantoux
• TC,DC,ESR
• CXR

54. NSAIDS
Topical use
• flurbiprofen
• indomethacine
• Ketorolac
Indications
• episcleritis and scleritis
• uveitis
• CME
• PRE operatively to maintain dilation of the pupil
Preservative used is Benzalkonium Chloride(BAK)

57. Ocular Lubricants
Indication
• ocular irritations in various diseases
• Dry eyes
Commonly available commercial tear substitutes
REFRESH TEARS
• TEAR PLUS
• MOISOL
• OCCUWET
• Genteal gel eye drops
Preservative used is Stabilized Oxycholrocomplex

58. Ocular diagnostic drugs
Fluorescein dye
Available as drops or strips
Dose: 2% Sodium Salt
Uses :
stain corneal abrasions,
applanation tonometry,
detecting wound leak,
NLD obstruction,
fluorescein angiography
Caution:
stains soft contact lens
Fluorescein drops can be contaminated by Pseudomonas sp.

60. Ocular diagnostic drugs
Rose bengal stain
Stains devitalized epithelium
Dose : 1%
Uses: severe dry eye, herpetic keratitis

61. Local anesthetics
Local anesthetics
• topical
E.g. Proparacaine—0.5%
tetracaine
Uses :
applanation tonometry,
goniscopy,
removal of corneal foreign bodies,
removal of sutures,
examination of patients who cannot open eyes because of pain
Adverse effects :
toxic to corneal epithelium,
allergic reaction rarely

62. Local anesthetics
• Orbital infiltration
-peribulbar or retrobulbar
-cause anesthesia and akinesia for intraocular
surgery
-e.g. Lidocaine—2%,
bupivacaine:0.5%

63. Orbital Infiltration

64. Ocular toxicology

65. Complications of topical administration
Mechanical injury from the bottle
e.g. corneal abrasion
Pigmentation: epinephrine
Ocular damage : e.g. topical anesthetics, benzylkonium
Hypersensitivity : e.g. atropine, neomycin, gentamicin
Systemic effect : topical phenylephrine can increase BP

66. Amiodarone
• A cardiac arrhythmia drug
• Causes optic neuropathy (mild decreased vision,
visual field defects, bilateral optic disc swelling)
• Also causes corneal vortex keratopathy (corneal
verticillata) which is whorl-shaped pigmented
deposits in the corneal epithelium

68. Digitalis
• A cardiac failure drug
• Causes chromatopsia (objects appear yellow)
with overdose

70. Chloroquines
• E.g. chloroquine, hydroxychloroquine
• Used in malaria, rheumatoid arthritis, SLE
• Cause vortex keratopathy (corneal
verticillata) which is usually asymptomatic but
can present with glare and photophobia
• Also cause retinopathy (bull’s eye
maculopathy)

72. Chorpromazine
• A psychiatric drug
• Causes corneal punctate epithelial opacities,
lens surface opacities
• Rarely symptomatic
• Reversible with drug discontinuation

73. Thioridazine
• A psychiatric drug
• Causes a pigmentary retinopathy after high
dosage

74. Ethambutol :
• An anti-TB drug
• Causes a dose-related optic neuropathy
• Usually reversible but occasionally permanent
visual damage might occur

76. • Thank u