Download MBBS Ophthalmology PPT 35 Ocular Pharmacology I Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Ophthalmology PPT 35 Ocular Pharmacology I Lecture Notes


Ocular Pharmacology-I

Learning Objectives

At the end of this class students shall have a

basic understanding of :

?pharmacokinetics and pharmacodynamics of

ocular drugs

?Ocular routes of drug administration

?Topical antibiotic and cycloplegic agents

2


Overview

Overview of ocular anatomy & physiology
Pharmacodynamics and Pharmacokinetics of ocular therapeutic agents
Ocular Routes of Drug Administration
Therapeutic & Diagnostic applications of Drugs in Ophthalmology
Ophthalmic Effects of Selected Vitamin Deficiencies & Zinc Deficiency
Systemic Agents with Ocular Side Effects
Conclusion

3

Anatomy of Eye

4


Tear Film

5

6
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

agonist or antagonist

?If the drug is working at the enzyme level, it can be

activator or inhibitor

7

Pharmacokinetics

?It is the 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

? IV

8
Pharmacokinetics of Ocular Drugs

? Classical pharmacokinetic theory based on
systemically administered drugs does not fully
apply to all ophthalmic drugs

?Topical route ? most commonly used

9

Absorption

Rate & extent of absorption of topically instilled drugs depends upon ?
"Drug penetration into the eye is approximately linearly related to its

concentration in the tear film."

1. Time the drug remains in the cul-de-sac &

precorneal tear film

2. Elimination by nasolacrimal drainage

3. Drug binding to tear proteins

4. Drug metabolism by tear & tissue proteins

5. Diffusion across cornea & conjunctiva

10
Distribution

Transcorneal absorption


Accumulation in aqueous humor




Distribution to intraocular structures

Trabecular meshwork pathway

Distribution to systemic circulation

11



Distribution

?Melanin binding of certain drugs ?
- Eg:
1. Mydriatic effect of alpha adrenergic agonists
slower in onset - darkly pigmented irides compared to
those with lightly pigmented irides

2. Atropine's mydriatic effect ? long lasting in non-albino
rabbits than in albino rabbits

3. Accumulation of chloroquine in retinal pigment
epithelium ? Bull's eye maculopathy

12


Metabolism

?Enzymatic biotransformation of ocular drugs

- significant

?Esterases ? particular interest

Eg: Development of prodrugs for enhanced

ocular permeability

1. Dipivefrin hydrochloride

2. Latanoprost

13

14
Drug Delivery in Eyes

Topical

Periocular Intraocular

Systemic

drop

Subconjunctival

Intracameral

Oral

ointment

Subtenon

Intravitreal

intravenous

gel

Peribulbar

Intramuscular

Soft contact lens

Retrobulbar

Ocular Routes of Drug Administration

Sr.N Route

Special Utility

Limitations &

o

Precautions

1.

Topical

--Convenient

--Compliance

-- Economical

--Corneal & conjunctival

--Relatively safe

toxicity

--Nasal mucosal toxicity

--Systemic side effects from

nasolacrimal absorption

2.

Subconjunctival, -Anterior segment

-Local Toxicity

sub-Tenon's &

infections

-Globe perforation

Retrobulbar

-Posterior uveitis

-Optic nerve trauma

injections

-Cystoid Macular

-Central retinal artery or

Edema (CME)

vein occlusion

3.

Intraocular

Anterior segment

-Corneal toxicity

Injections

surgery or infections

-Relatively short duration of

action

4.

Intravitreal

Immediate local effect Retinal toxicity

Injection

16
Factors influencing local drug penetration into ocular tissue

?Drug concentration and solubility:

higher concentration -- better penetration

e.g pilocarpine 1-4% but limited by reflex tearing

?Viscosity: addition of methylcellulose and polyvinyl

alcohol increases drug penetration by increasing

contact time with cornea and altering corneal

epithelium

?Lipid solubility: higher lipid solubility- more

penetration



17

Factors influencing local drug penetration into ocular tissue

? Surfactants: preservatives alter cell membrane in cornea

and increase drug permeability e.g. benzylkonium and

thiomersal

? pH: the normal tear pH is 7.4

If 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

18


TOPICAL

Drop (Gutta)- simplest and most 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



pul it forward slightly

INSTILL 1 drop

? measures to increase drop absorption:

-wait 5-10 minutes between drops

-compress lacrimal sac

-keep lids closed for 5 minutes after instil ation

19

Ointments

?Increase the contact time of ocular medication to ocular

surface, thus better effect

?It has the disadvantage of

blurring vision

?The drug has to be highly lipid soluble with some water

solubility to have maximum effect as ointment

20
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 steroids and local

anesthetics can be

applied this way

21

Periocular
Subconjunctival - To achieve higher concentration

Drugs which cannot penetrate cornea due to large

size

Penetrate via sclera

Subtenon--Ant. Subtenon? diseases anterior to the lens

Post. Subtenon? disease posterior to the lens

Retrobulbar- Optic neuritis

Papil itis

Posterior uveitis

Anesthesia

Peribulbar-- anesthesia

22


Intraocular injections

? Intracameral or intravitreal
? E.g.

? Intracameral acetylcholine

(miochol) during cataract

surgery

? Intravitreal antibiotics in

cases of endophthalmitis

? Intravitreal steroids in

macular edema

? Intravitreal Anti-VEGF for

DR

23

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

24


Systemic drugs

?Oral or IV

?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

?Ocular inflammation: more penetration

with ocular inflammation

25

Therapeutic applications of

Drugs in Ophthalmology

26
Common ocular drugs

?Antibacterials (antibiotics)

?Antivirals

?Antifungals

?Mydriatics and cycloplegics

?Antiglaucoma medications

?Anti-inflammatory agents

Corticosteroids

?Ocular Lubricants

NSAID's

?Local anesthetics

?Ocular diagnostic drugs

?Ocular Toxicology

27

Topical Antibacterial Agents

Commercially Available for Ophthalmic

Use

Azithromycin

1% solution

H

Conjunctivitis

Ciprofloxacin

0.3% solution;

H

-Conjunctivitis

hydrochloride

0.3% ointment

D-RCD -Keratitis

-Keratoconjunctivitis

-Corneal Ulcers

-Blepharitis

-Dacryocystitis

Erythromycin

0.5% ointment

H

-Superficial Ocular Infections

involving cornea or conjunctiva

Gatifloxacin

0.3% solution

H

Conjunctivitis

H- Hypersensitivity ; D-RCD ? Drug Related Corneal Deposits

28
Topical Antibacterial Agents Commercially

Available for Ophthalmic Use.....

Gentamicin

0.3%

H

Conjunctivitis, Keratitis

sulfate

solution

Levofloxacin

0.5%

H

Conjunctivitis

Levofloxacin

1.5%

H

Corneal Ulcers

Moxifloxacin

0.5%

H

Conjunctivitis

solution

Ofloxacin

0.3%

H

Conjunctivitis

solution

Corneal Ulcers

Tobramycin

0.3%

H

External infections of the eye

sulfate

solution

0.3%

ointment

29

Antibacterials( antibiotics)

? Penicillins
? Cephalosporins
? Sulfonamides
? Tetracyclines
? Chloramphenicol
? Aminoglycosides
? Fluoroquinolones
? Vancomycin
? Macrolides

30
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

clavulanate, cefaclor

? Used intravenously for the

treatment of orbital cellulitis

e.g. gentamicin, cephalosporin,

vancomycin,

? Can be injected intravitrally for

the treatment of

endophthalmitis

31

? Specific antibiotic for almost each organisms
? Sulfonamides- Chlamydial infections like TRACHOMA
INCLUSION CONJUNCTIVITIS
TOXOPLAMOSIS
Bacterial cell wall synthesis inhibitors-
Penicil in
Cephalosporins
I) First generation- Gram + cocci eg cephazoline
i ) Second generation --Gram ? ve and antistaphylococcal--
cefuroxime
i i) Third generation? Gram ?ve bacilli --ceftriaxones


32
? Side effects- allergic reaction
neutropenia
thrombocytopenia

Amino glycosides
Mainly against gram negative bacilli
Bacterial protein synthesis inhibitors
Gentamycin- 0.3% eye drops
Tobramycin- 0.3% eye drop
Neomycin-- 0.3-0.5% eye drops
Amikacin ----- 1% eye drops


33

Tetracycline

Inhibit protein synthesis

active against both gram+ and gram -ve, some

fungi and Chlamydia



Chloramphenicol

Broad spectrum ,bacteriostatic,

gram+/gram-ve, Chlamydia

0.5% Eye drops, ointment



34
Fluoroqinolones

?Most frequently used topical broad spectrum

antibiotics

?Ciprofloxacin ? 0.3% eye drops

?Ofloxacin - 0.3% eye drops

?Moxifloxacin - 0.5 % eye drops

?Levofloxacin and Besifloxacin eye drops

35

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

cephalosporins,

aminoglycosides,

vancomycin, or

fluoroquinolones.

? Bacterial conjunctivitis is

usually self limited but topical

erythromycin,

aminoglycosides,

fluoroquinolones, or

chloramphenicol can be used

36


Dacryocystitis - Infection of the lacrimal

sac

37

Hordeolum/ Stye ? Infection of the meibomian, Zeis

or Moll gland

38


Conjunctivitis ? Inflammatory process of

the conjunctiva

39

Blepharitis ? Bilateral inflammatory process of the

eyelids

40
Antiviral Agents for Ophthalmic Use

GENERIC NAME

ROUTE OF

OCULAR

INDICATIONS FOR USE

ADMINISTRATION

TOXICITY

Trifluridine

Topical (1% solution) PK, H

-Herpes simplex keratitis

- Keratoconjuctivitis

Acyclovir

Oral (200 mg

-Herpes zoster

capsules, 800 mg

ophthalmicus

tablets)

- Herpes simplex

Intravenous

iridocyclitis

Valacyclovir

Oral (500- & 1000

-Herpes simplex keratitis

mg)

-Herpes zoster

ophthalmicus

Famciclovir

Oral (125-,250 mg

-Herpes simplex keratitis

tablets)

-Herpes zoster

ophthalmicus

41

PK ? Punctate Keratopathy ; H - Hypersensitivity

Antiviral Agents for Ophthalmic Use...

GENERIC NAME

ROUTE OF

OCULAR

INDICATIONS FOR

ADMINISTRATION

TOXICITY

USE

Foscarnet

Intravenous

-----

Cytomegalovirus

Intravitreal

Retinitis

Ganciclovir

Intravenous, Oral

-----

Cytomegalovirus

Intravitreal implant

Retinitis

Valganciclovir

Oral

-------

Cytomegalovirus

Retinitis

Cidofovir

Intravenous

------

Cytomegalovirus

Retinitis

42
Antivirals

?Acyclovir- Most commonly used anti-viral

3% ointment 5 times-10-14 days
800mg oral 5 times 10-14 days
Intravenous for Herpes zoster retinitis
Others
Idoxuridine

INDICATIONS

Vidarabine

HZ keratitis

Cytarabine

Viral uveitis

Triflurothymidine
Gancyclovir

43

VIRAL DENTRITIC ULCER

44
CMV Retinitis

45

Antifungal Agents for Ophthalmic Use

Drug

Method of Administration

Indications for Use

Amphotericin B

0.1-0.5% solution

Yeast & fungal keratitis &

endophthalmitis

0.8-1 mg Subconjunctival

- Yeast & fungal endophthalmitis

5 microgram intravitreal

- Yeast & fungal endophthalmitis

injection

- Yeast & fungal endophthalmitis

Natamycin

5% topical suspension

-Yeast & fungal blepharitis

-Conjunctivitis ; keratitis

Fluconazole

Topical, Oral & Intravenous

Yeast keratitis & endophthalmitis

Itraconazole

Topical ,Oral

Yeast & fungal keratitis &

endophthalmitis

Ketoconazole

Oral

Yeast keratitis & endophthalmitis

Miconazole

1% topical solution

Yeast & fungal keratitis

46
ANTIFUNGAL

INDICATIONS

Fungal corneal ulcer

Fungal retinitis/ Endophthalmitis

Commonly used drugs are

? Polyenes

? damage cel membrane of susceptible fungi

? e.g. amphotericin B, natamycin, nystatin

? side ef ect: nephrotoxicity

? Imidazoles

? increase fungal cel membrane permeability

? e.g. miconazole, ketoconazole,fluconazole

? Flucytocine

? act by inhibiting DNA synthesis

47



48


Mydriatics and cycloplegics

? Dilate the pupil, ciliary muscle paralysis
? CLASSIFICATION

Short acting- Tropicamide (4-6 hours)
Intermediate- homatropine ( 24 hours)
Long acting- atropine (2 weeks)

Indications

corneal ulcer
uveitis
cycloplegic refraction

49

SR. DRUG

FORMULATIO INDICATIONS FOR USE OCULAR SIDE

NO.

N

EFFECTS

1

Atropine

0.5%, 1% & 2% -Cycloplegia

-Photosensitivity

solution; 1%

-Mydriasis

-Blurred vision

ointment

-Cycloplegic retinoscopy

-Dilated fundoscopic

Exam

2

Scopolamine 0.25% solution Cycloplegia

Photosensitivity

-Mydriasis

-Blurred vision

3

Homatropine 2% & 5%

Cycloplegia

Photosensitivity

solution

-Mydriasis

-Blurred vision

4

Cyclopentolat 0.5% 1%

Cycloplegia

Photosensitivity

e

solution

-Mydriasis

-Blurred vision

5

Tropicamide

0.5% & 1%

Cycloplegia

Photosensitivity

solution

-Mydriasis

-Blurred vision

50
Thank you

51

This post was last modified on 07 April 2022