Download OCULAR PHARMACOLOGY

OCULAR PHARMACOLOGY
Dr. Jamshed Ahmed
Assistant Professor
Ophthalmology Unit-II
Dow Medical college &
Civil Hospital Karachi
MEANS OF OCULAR DRUGS ADMINISTRATION
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EYE DROPS
ONITMENTS
PERIOCULAR INJECTIONS
INTRACAMERAL
INTRAVITREAL INJECTIONS
SUSTAINED RELEASE PREPARATIONS
SYSTEMIC THERAPY
INTRAVENOUS INJECTIONS
METHODS OF OCULAR DRUG DESIGN AND DELIVERY
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PRO - DRUGS
SUSTAINED RELEASE DEVICES AND GELS
COLLAGEN CORNEA SHIELDS
LOCAL ANESTHETIC DRUGS
Classification
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1) Esters

a) Esters of benzoic acid
 Cocaine (topical only)
 Butacain
 Benzocaine (topical only)
 Piperocaine
b) Esters of paba 2-Chloroprocaine (Nesacaine)
 Procaine (Novocain)
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c) Esters Of Meta Amino Benzoic Acid
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Propoxycaine (Ravocaine)
Butethamine
Tetracaine (Pontocaine)
Lidocaine (Xylocaine)
Bupivacaine
Mepivacaine (Carbocaine)
Dibucaine
2) Quinolones
 Centbundine
LOCAL ANESTHETICS
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Topical:
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Propacaine, Tetracaine.
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Uses :
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Applanation tonometry
 A goniscopy,
 Aremoval of corneal foreign bodies,
 Removal of sutures,
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Examination of patients who cannot
open eyes because of pain.
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Adverse effects :
 Toxic to corneal epithelium
 Allergic reaction rarely
Local Anesthetics
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Infiltration Anaesthesia
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Peribulbar.
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Retrobulbar.
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Sub tenon.
Cause anesthesia and akinesia for intraocular surgery e.g.
 Lidocaine.
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bupivacaine
Ocular Lubricants
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Ocular Lubricants Indication ocular irritations in various diseases Dry eyes
Commonly available commercial tear substitutes:
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Systane eye Drops
Lacri-Lube
Genteal eye drops
OCULAR PHARMACOTHERAPEUTICS
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AUTONOMIC NERVOUS SYSTEM
 PARASYMPATHETIC (CHOLINERGIC)
 SYMPATHETIC
(ADRENERGIC)
PARASYMPATHETIC (CHOLINERGIC) SYSTEM
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DRUGS AFFECTING THE PARASYMPATHETIC SYSTEM MAY BE:
 CHOLINERGIC STIMULATING (AGONIST)
 CHOLINERGIC BLOCKING
(ANTAGONIST)
ACETYLECHOLINE IS THE NEUROTRANSMITTER THAT STIMULATES TWO
MAJOR TYPES OF CHOLINERGIC RECEPTORS:
 NICOTINIC(LOCATED PREDOMINANTLY IN MOTOR ENDPLATES OF
SKELETAL MUSCLES
 MUSCARINIC(SMOOTH & CARDIAC MUSCLES)
CHOLINERGIC STIMULATING DRUGS (AGONIST)

DIRECT ACTING CHOLINERGIC DRUG
 PILOCARPINE
 CARBACHOL
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INDIRECTLY ACTING MUSCARINIC AGENTS
 CHOLINESTERASE INHIBITORS (SAME AS DIRECTLY ACTING

CHOLINERGIC AGENTS BUT HAVE LONGER DURATION OF ACTION)
TWO CLASSES:
•
•
REVERSIBLE INHIBITORS
e.g PHYSOSTIGMINE
IRREVERSIBLE INHIBITORS e.g ECOTHIOPHATE
DIRECTLY ACTING CHOLINERGIC DRUGS
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PILOCARPINE
ACTIONS:
 LIKE ACETYLECHOLINE ACTS DIRECTLY ON SMOOTH MUSCLES
 STIMULATES THE SPHINCTER PUPILLAE MUSCLE (MIOSIS)
 STIMULATES THE CIRCULAR CILIARY MUSCLE (ACCOMMODATION)
 STIMULATES THE LONGITUDINAL CILIARY MUSCLE (INCREASES
OUT FLOW OF AQUEOUS HUMOR THROUGH TRABECULAR
MESHWORK)
PILOCARPINE
CONT….
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PREPARATION & DOSAGE:
 1%, 2%, 3%, 4% USED q.I.d AS MONOTHERAPY OR IN COMBINATION
WITH BETA-BLOCKER b.d ADMINISTRATION
 PILOCARPINE GEL (PILOCARPINE ADSORBED ON TO A PLASTIC GEL).
ONCE DAILY AT BED TIME ( SO THAT INDUCED MYOPIA AND MIOSIS
LAST ONLY DURING SLEEP)
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INDICATIONS:
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PRIMARY OPEN ANGLE GLAUCOMA. DECREASE IOP BY INCREASING
OUT FLOW FACILITY
PRIMARY CLOSED ANGLE GLAUCOMA. RESULTANT MIOSIS PULLS
THE PERIPHERAL IRIS AWAY FROM THE TRABECULUM, THUS
OPENING THE ANGLE
ACCOMMODATIVE ESOTROPIA
PILOCARPINE
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CONT…..
OCULAR SIDE EFFECTS:
 MIOSIS
 CATARACTOGENESIS
 BROW ACHE
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MYOPIA SHIFT
EXACERBATION OF SYSPTOMS OF CATARACT
VISUAL PROBLEM IN DIM ILLUMINATION
INCREASE INCIDENCE OF RETINAL DETACHMENT
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SYSTEMIC SIDE EFFECTS:
CHOLINERGIC BLOCKING DRUGS (ANTAGONIST)
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THE MUSCARINIC ACTIONS OF CHOLINERGIC DRUGS ARE ANTAGONIZED BY
ATROPINE GROUP OF DRUGS. MEMBERS OF ATROPINE GROUP ARE:
 ATROPINE
 HOMATROPINE
 CYCLOPENTOLATE
 TROPICAMIDE
ATROPINE
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ACTIONS:
 DILATATION OF THE PUPIL
 CYCLOPLEGIA
 STABILIZES THE BLOOD AQUEOUS BARRIERS
DURATION OF ACTION
7-14 DAYS
INDICATIONS:
 CYCLOPLEGIC IN IRIDOCYCLITIS / KERATITIS
 REFRACTION IN CHILDREN
 CILIARY BLOCK & RUBEOTIC GLAUCOMA
SIDE EFFECTS:
 SYSTEMIC ABSORPTION ESPECIALLY IN CHILDREN MAY LEAD TO:
•
FLUSHING, FEVER, TACHYCARDIA & DELIRIUM.PRECIPITATION
OF ANGLE CLOSURE GLAUCOMA, MALIGNANT HYPERTHERMIA
ATROPINE GROUP OF DRUGS CONT.
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OTHER DRUGS:
 HOMATROPINE:
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• 2 - 5% , ONSET OF ACTION 30 - 60 MIN, DURATION
CYCLOPENTOLATE:
•
03 DAYS
0.5 - 1%, ONSET OF ACTION 20 - 40 MIN, DURATION 02 DAYS
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TROPICAMIDE:
•
0.5% - 1%, ONSET OF ACTION 20 - 40 MIN, DURATION
4 - 6 HRS
SYMPATHETIC (ADRENERGIC) SYSTEM
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ADRENERGIC NEURONS SECRETE NORADRENALINE AT SYMPATHETIC
POST-GANGLIONIC NERVE ENDINGS
FOUR MAIN TYPE OF ADRENERGIC RECEPTORS:
 ALPHA - 1
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ARTERIOLES, DILATOR PUPILLAE & MULLER MUSCLE
STIMULATION- HYPERTION, MYDRIASIS, LID RETRACTION
ALPHA - 2
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INHIBITORY RECEPTORS, ON CILIARY EPITHELIUM
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STIMULATION - DECREASE AQUEOUS SECRETION
UVEOSCLERAL OUT FLOW
BETA - 1
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PRESENT ON CARDIAC MUSCLES
BETA - 2
& INCREASE
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PRESENT ON BRONCHIAL & CILIARY EPITHELIUM
STIMULATION - BRONCHIAL DILATATION, INCREASE AQUEOUS
PRODUCTION
DIRECT ACTING ALPHA 1 ADRENERGIC AGENTS
PHENYLEPHRINE:
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PREPARATION
• 2.5%, 10% EYE DROPS
INDICATION
• PRIMARY CLINICAL USE IS STIMULATION OF IRIS
DILATOR MUSCLE TO PRODUCE MYDRIASIS
SIDE EFFECTS
• SYSTEMIC ABSORPTION MAY ELEVATE BLOOD
PRESSURE
ALPHA 2 ADRENERGIC AGONIST
BRIMONIDINE 2% b.d
 ACTION:
• DECREASE IOP BY BOTH DECREASING AQUEOUS
SECRETION AND ENHANCING UVEOSCLERAL
OUTFLOW
 INDICATION:
• OPEN ANGLE GLAUCOMA
 SIDE EFFECTS:
• OCULAR S/E IS ALLERGIC CONJUNCTIVITIS. SYSTEMIC
S/E INCLUDE XEROSTOMIA, DROWSINESS AND
FATIGUE.
APRACLONIDINE
 ACTION:
• SIMILAR TO BRIMONIDINE. NOT SUITABLE FOR
LONG-TERM USE B / C OF TACHYPHYLAXIS.
 INDICATION;
• AFTER LASER SURGERY ON THE ANTERIOR SEGMENT
TO OFFSET AN ACUTE RISE IN IOP.
BETA- ADRENERGIC ANTAGONISTS (BETA BLOCKERS)
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THESE AGENTS LOWER IOP BY REDUCING AQUEOUS
HUMOR PRODUCTION AS MUCH AS 50%.
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NONSELECTIVE BETA 1 & BETA 2 ANTAGONIST
– TIMOLOL MALEATE 0.25% - 0.5% b.d
• OCULAR S/E ALLERGY, CORNEAL
PUNCTATE EPITHELIAL EROSIONS AND
REDUCED AQUEOUS TEAR SECRETION.
• SYSTEMIC S/E BRADYCARDIA &
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–
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HYPOTENSION FROM BETA 1 BLOCKADE.
(CONTRINDICATED CONGESTIVE CARDIAC
FAILURE). BRONCHOSPASM MAY BE
INDUCED BY BETA 2 BLOCKADE.
LEVOBUNOLOL 0.5% ONCE DAILY
CARTEOLOL 1%-2% b.d
METIPRANOLOL YDROCHLORIDE 0.1%, 0.3% b.d.
CARDIOSELECTIVE BETA 1 ANTAGONIST
– BETOXOLOL 0.5%
• INDICATIONS:
– REDUCTION OF IOP IN ALL TYPES OF
GLAUCOMA.
CARBONIC ANHYDRASE INHIBITORS
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THESE AGENTS LOWER IOP BY INHIBITING CILIARY BODY
CARBONIC ANHYDRASE.
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TOPICAL AGENTS
 DORZOLAMIDE 2% t id
 BRINZOLAMIDE 1% t id
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OCULAR SIDE EFFECTS:
• ALLERGIC CONJUNCTIVITIS
CARBONIC ANHYDRASE INHIBITORS CONT.
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SYSTEMIC AGENTS (useful as short-term treatment)
 ORAL
• PREPARATIONS:
• ACETAZOLAMIDE TABLETS
• 250mg dose is 250-1000mg
• onset of action is within 1 hour, with a peak at 4 hours
and a duration up to 12 hours.
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PARENTAL
• I/V INJECTION 500mg ACETAZOLAMIDE
• onset of action with in 15-20 minutes.
SIDE EFFECTS:
• COMMON:
– PARAESTHESIAE
– MALAISE COMPLEX
• UNCOMMON:
– GASTROINTESTINAL COMPLEX
– RENAL STONE FORMATION
– STEVENS - JOHNSON SYNDROME
– BLOOD DYSCRASIAS
HYPEROSMOTIC AGENTS
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ACTION
 INCREASED SERUM OSMOLARITY REDUCES IOP AND
VITREOUS VOLUME BY DRAWING FLUID OUT OF THE EYE
ACROSS VASCULAR BARRIERS.
AGENTS
 INTRAVENOUS
• MANITOL 1g / kg body weight or 5ml / kg body weight.
Peak action is achieved in 30 minutes, with a duration of up
to 6 hours.
• UREA
 ORAL
• GLYCEROL + lemon juice 1g / kg body weight or 2ml / kg
body weight. Peak action with in 1 hour, with a duration up
to 3 hours.
• ISOSORBIDE (non-metabolized sugar)
USES (used with care in patients with compromised heart)
 SHORT-TERM MANAGEMENT OF ACUTE GLAUCOMAS
 REDUCING VITREOUS VOLUME PRIOR TO CATARACT
SURGERY
PROSTAGLANDIN ANALOGUES
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REDUCE IOP BY ENHANCING UVEOSCLERAL OUTFLOW.
AGENTS
 LATANOPROST 0.005% ONCE DAILY
• OCULAR SIDE EFFECTS:
– CONJUNCTIVAL HYPERAEMIA.
– EYELASH LENGTHENING &
HYPERPIGMENTATION OF IRIS, LASHES, AND
PERIORBITAL SKIN.
• SYSTEMIC SIDE EFFECTS:
– OCCASIONAL HEADACHE AND UPPER
REPIRATORY SYSPTOMS.
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TRAVOPROST .004% SIMILAR TO LATANOPROST
BIMATOPROST 0.3% UVOSCLERAL OUTFLOW +
TRABECULAR OUTFLOW.
UNOPROSTONE ISOPROPYL 0.15%, b.d.
GLUCOCORTICOIDS
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ACTION:
 INHIBITION OF ARACHIDONIC ACID RELEASE FROM
PHOSPHOLIPIDS
AGENTS
 DEXAMETHASONE 0.1%
 PREDNISOLONE ACETATE 0.1%
 FLUOROMETHALONE ACETATE 0.1%
TOPICAL
 TO PREVENT OR SUPRESS CORNEAL GRAFT REJECTION
 ANT: CHAMBER REACTION AFTER ANT: SEGMENT
SURGERY
 FILTERATION BLEB SCARING
 IMMUNE OR TRUMATIC IRITIS & UVITIS
GLUCOCORTICOIDS
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SUBCONJUNCTIVAL, ANT & POST SUBTENON INJECTION
(Triamcinolone acetonide or methylprednisolone acetate)
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SEVERE OCULAR INFLAMMATION
INTRAVITREAL INJECTION
(Triamcinolone acetonide 2mg in 0.05ml)
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ENDOPHTHALMITIS
GLUCOCORTICOIDS
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SAYSTEMIC THERAPY
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ORAL 1mg / kg per day
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GIANT CELL ARTERITIS
SEVERE OCULAR INFLAMMATIONS
INTRAVENOUS
•
OPTIC NEURITIS
GLUCOCORTICOIDS
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CONT….
ADVERSE EFFECTS
 OCULAR
• GLAUCOMA
• POSTERIOR SUBCAPSULAR CATARACTS
• EXACERBATION OF BACTERIAL & VIRAL INFECTIONS
• PTOSIS
• MYDRIASIS
• SCLERAL MELTING
• EYE SKIN ATROPHY
 SYSTEMIC
• SUPPRESSION OF THE PITUITARY-ADRENAL AXIS
• GLUCONEOGENESIS RESULTING FROM
•
•
•
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HYPERGLYCEMIA
ASEPTIC NECROSIS OF HIP
PEPTIC ULCER
DIABETES
INSOMNIA
REDISTRIBUTION OF FAT FROM THE PERIPHERY TO
THE TRUNK
ANTIBIOTICS
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ANTIBACTERIALS
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PENICILLINS AND CEPHALOSPORINS
 SULPHONAMIDES
 TETRACYCLINES
 CHLORAMPHENICOL
 AMINOGLYCOSIDES
 FLUOROQUINOLONES
 MISCELLANEOUS ANTIBIOTICS
• VANCOMYCIN
• ERYTHROMYCIN
• POLYMYXIN B
• BACITRACIN
ANTIFUNGAL AGENTS
 POLYENES
 IMIDAZOLES
 FLUCYTOSINE
ANTIVIRAL AGENTS
 TOPICAL ANTIVIRAL AGENTS
 SYSTEMIC ANTIVIRAL AGENTS
PENICILLINS AND CEPHALOSPORINS
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BETA-LACTUM CONTAINING ANTIBACTERIAL AGENTS
BACTERIAL SUSCEPTIBILITY PATTERNS AND RESISTANCE TO
BETA-LACTAMSES HAVE DETERMINED THE CLASSIFICATION OF
THE CEPHALOSPORINS AS:
 FIRST GENERATION(activity against gram+ & gram- organisms)
• CEPHALEXIN
• CEFAZOLINE (fortified topical drops 50mg/ml in bacterial
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keratitis)
SECOND- GENERATION
• CEFOXITIN
• CEFUROXIME
THIRD-GENERATION
• CEFOTAXIME
– SYSTEMIC (1g I/V b.d IN GONOCOCCAL
KERATOCONJUNCTIVITIS)
– TOPICAL ( 50 mg/ml for gram -ve coverage in keratitis
and endophthalmitis)
– INTRAVITREAL( 2mg in 0.1 ml in endophthalmitis)
SULPHONAMIDES
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SULPHONAMIDES ARE ONLY BACTERIOSTATIC AGENTS
SUSCEPTIBLE ORGANISMS INCLUDE STREPTOCOCCUS
PNEUMONIAE, CORYNEBACTERIUM DIPHTHERIAE, H
INFLUENZAE, ACTINOMYCES AND CHLAMYDIA TRACHOMATIS.
SULPHACETAMIDE OPHTHALMIC SOLUTION 10% -30%
USED IN BACTERIAL CONJUNCTIVITIS
COMMON SIDE EFFECTS
 LOCAL IRRITATION
 ITCHING
 PERIORBITAL EDEMA
 TRANSIENT STINGING
TETRACYCLINS
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BROAD-SPECTRUM BACTERIOSTATIC ANTIBIOTICS

SYSTEMIC THERAPY
 USED FOR CHLAMYDIAL INFECTIONS
 STAPHYLOCOCCAL INFECTIONS OF THE MEIBOMIAN
GLANDS

TOPICAL THERAPY
 IN THE FORM OF ONITMNT FOR LOCAL APPLICATION AT
THE LID MARGINS IN BLEPHRITIS

PRECAUTIONS

SHOULD NOT BE GIVEN TO CHILDREN AND PREGNANT
WOMENS, BECAUSE IT CAN BE DEPOSITED IN GROWING
TEETH, DISCOLOURING THEM.
CHLORAMPHENICOL

BROAD-SPECTRUM BACTERIOSTATIC AGENTS

TOPICAL THERAPY

DROPS 0.5%
 ONITMENTS

USES
 BACTERIAL CONJUNCTIVITIS
 POSTOPERATIVELY AFTER ANTERIOR SEGMENT SURGERY
AMINOGLYCOSIDES
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BACTERIOCIDAL AGENTS HAVE ACTIVITY AGAINST AEROBIC
GRAM NEGATIVE BACILLI INCLUDE:
 GENTAMICIN
• TOPICAL
(CONJUNCTIVITIS)
– DROPS 0.3%
– FORTIFIED DROPS 15mg / ml (1.5%)
– ONITMENT0.3%
• PERIOCULAR INJECTION (KERATITUS)
– 20 mg
 TOBRAMYCIN
• TOPICAL
– DROPS 0.3%
– FORTIFIED DROPS
– ONITMENT 0.3%
• USES
– CONJUNCTIVITIS/ KERATITIS/ ENDOPHTHALMITIS
 AMIKACIN
• TOPICAL
– FORTIFIED DROPS 10mg / ml (KERATITIS/
ENDOPHTHALMITIS)
• INTRAVITREAL INJECTION 0.4mg in 0.1ml
• USES:
– ENDOPHTHALMITIS
FLUOROQUINOLONES

HIGHLY EFFECTIVE BROAD-SPECTRUM ANTIMICROBIALS

AGENTS
 NORFLOXACIN
0.3% solution. (Conjunctivitis /
keratitis)
 OFLOXACIN
0.3% solution (Conjunctivitis / keratitis)
 CIPROFLOXACIN
0.3% solution (Conjunctivitis / keratitis )
 GATEFLOXACIN
 MOXI FLOXACIN
MISCELLANEOUS ANTIBIOTICS
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VACOMYCIN
 BACTERICIDAL FOR MOST GRAM-POSITIVE ORGANISMS
 PREPARATIONS
• DROPS 50mg/ ml infectious keratitis
• PERIOCULAR INJECTIONS 25 mg endophthalmitis
• INTRVITREAL INJECTIONS 1mg in 0.1 ml
endophthalmitis
POLYMYXIN (bactericidal)
BACITRACIN (inhibits bacterial cell wall synthesis)
FUSIDIC ACID (effective against gram +ve organisms)
ANTIFUNGAL AGENTS


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POLYENES ARE TOPICALLY ACTIVE AGAINST A VARIETY OF
FILAMENTOUS FUNGI, INCLUDING ASPERGILLUS, FUSARIUM.
AGENTS:
 NATAMYCIN 5% suspension
 AMPHOTERICIN B reconstituted at 0.25%-0.5% in sterile water
IMIDAZOLES
 MICONAZOLE 1% solution applied topically
 KETOKONAZOLE 200mg tab for oral therapy in fungal keratitis
FLUCYTOSINE oral therapy 50-150mg/kg daily in divided doses.
ANTIVIRAL AGENTS

TOPICAL ANTIVIRAL AGENTS


ACICLOVIR
• 3% ONITMENT USED 5 TIMES DAILY IN KERATITIS.
 GANCICLOVIR
• 0.15% GEL USED 5 TIMES DAILY
 TRIFLUOROTHYMIDINE
• 1% DROPS USED EVERY 2 HOURS
SYSTEMIC ANTIVIRAL AGENTS (ACUTE HERPES ZOSTER)
 ACYCLOVIR
• 600 mg 5 TIMES A DAY
 FAMCICLOVIR
• 500mg THREE TIMES A DAY
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