OBAT-OBAT DALAM OBAT-OBAT DALAM ILMU PENYAKIT MATAILMU PENYAKIT MATA

Dr. IrvanDr. Irvan

Eye dropsEye drops

Eye drops- Eye drops- most commonmost common one drop = 50 µlone drop = 50 µl to increase drop absorption:to increase drop absorption:

-wait 5-10 minutes between drops-wait 5-10 minutes between drops

-compress lacrimal sac-compress lacrimal sac

-keep lids closed for 5 minutes -keep lids closed for 5 minutes after after instillationinstillation

Ointments Ointments

Increase the contact timeIncrease the contact time of ocular of ocular medication to ocular surface thus medication to ocular surface thus better effectbetter effect

It has the disadvantage of It has the disadvantage of vision vision blurringblurring

The drug The drug mustmust to be high lipid to be high lipid soluble with some water solubility to soluble with some water solubility to have the maximum effect as have the maximum effect as ointmentointment

Peri-ocular injectionsPeri-ocular injections

E.g. subconjunctival, E.g. subconjunctival, subtenon, peribulbar, or subtenon, peribulbar, or retrobulbarretrobulbar

This route bypass the This route bypass the conjunctival and corneal conjunctival and corneal epithelium which is epithelium which is good for drugs with low good for drugs with low lipid solubilitylipid solubility (e.g. (e.g. penicillins)penicillins)

Also steroid and local Also steroid and local anesthetics can be anesthetics can be applied this wayapplied this way

Intraocular injectionsIntraocular injections

Intracameral or Intracameral or intravitrealintravitreal

E.g.E.g.– Intracameral Intracameral

acetylcholine acetylcholine (miochol) during (miochol) during cataract surgerycataract surgery

– Intravitreal Intravitreal antibiotics in cases of antibiotics in cases of endophthalmitisendophthalmitis

– Intravitreal steroid in Intravitreal steroid in macular edemamacular edema

Systemic drugsSystemic drugs

Oral or IVOral or IV Factor influencing systemic drug Factor influencing systemic drug

penetration into ocular tissue:penetration into ocular tissue:– lipid solubility of the drug:lipid solubility of the drug: more more

penetration with high lipid solubilitypenetration with high lipid solubility– Protein binding:Protein binding: more effect with low more effect with low

protein bindingprotein binding– Eye inflammation:Eye inflammation: more penetration more penetration

with ocular inflammationwith ocular inflammation

Ocular Ocular pharmacotherapeuticspharmacotherapeutics

Cholinergic agonists Cholinergic agonists

Directly acting agonists:Directly acting agonists:– E.g. pilocarpine, acetylcholine (miochol), carbachol E.g. pilocarpine, acetylcholine (miochol), carbachol

(miostat)(miostat)– Uses:Uses: miosis, glaucoma miosis, glaucoma– Mechanisms:Mechanisms:

Miosis by contraction of the iris sphincter muscle Miosis by contraction of the iris sphincter muscle increases aqueous outflow through the trabecular increases aqueous outflow through the trabecular

meshwork by longitudinal ciliary muscle contractionmeshwork by longitudinal ciliary muscle contraction Accommodation by circular ciliary muscle contractionAccommodation by circular ciliary muscle contraction

– Side effects:Side effects: Local: diminished vision (Local: diminished vision (myopiamyopia), ), headacheheadache, ,

cataract, and rarely retinal detachmentcataract, and rarely retinal detachment systemic side effects: lacrimation, salivation, systemic side effects: lacrimation, salivation,

perspiration, bronchial spasm, urinary urgency, perspiration, bronchial spasm, urinary urgency, nausea, vomiting, and diarrheanausea, vomiting, and diarrhea

Cholinergic agonistsCholinergic agonists

Indirectly acting (anti-Indirectly acting (anti-cholinesterases) :cholinesterases) :

– More potent with longer duration of More potent with longer duration of actionaction

– Reversible inhibitorsReversible inhibitors e.g. physostigminee.g. physostigmine used in glaucoma used in glaucoma

Cholinergic Cholinergic antagonistsantagonists E.g. tropicamide, cyclopentolate, homatropine, E.g. tropicamide, cyclopentolate, homatropine,

scopolamine, atropinescopolamine, atropine CauseCause mydriasis (by paralyzing the sphincter muscle) mydriasis (by paralyzing the sphincter muscle)

with cycloplegia (by paralyzing the ciliary muscle)with cycloplegia (by paralyzing the ciliary muscle) Uses:Uses: fundoscopy, cycloplegic refraction, anterior fundoscopy, cycloplegic refraction, anterior

uveitisuveitis Side effects:Side effects:

– local: local: allergic reactionallergic reaction, blurred vision, blurred vision– Systemic: nausea, vomiting, pallor, vasomotor collapse, Systemic: nausea, vomiting, pallor, vasomotor collapse,

constipation, urinary retention, and confusionconstipation, urinary retention, and confusion– specially specially in childrenin children they might cause flushing, fever, they might cause flushing, fever,

tachycardia, or deltachycardia, or deliirium rium – Treatment by physostigmineTreatment by physostigmine

Adrenergic agonistsAdrenergic agonists

Non-selective agonists (Non-selective agonists (αα11, , αα22, , ββ11, , ββ22))– E.g. epinephrine, depevefrin E.g. epinephrine, depevefrin

(pro-drug of epinephrine)(pro-drug of epinephrine)– Uses:Uses: glaucoma glaucoma– Side effects:Side effects: headache, headache,

arrhythmia, increased blood arrhythmia, increased blood pressure, pressure, conjunctival conjunctival adrenochromeadrenochrome, cystoid , cystoid macular edema in aphakic macular edema in aphakic eyeseyes

Adrenergic agonistsAdrenergic agonists

Alpha-1 agonistsAlpha-1 agonists E.g. phenylepherineE.g. phenylepherine Uses:Uses: mydriasis ( mydriasis (withoutwithout cycloplegia), cycloplegia),

decongestantdecongestant Adverse effect:Adverse effect:

– Can cause significant Can cause significant increase in blood increase in blood pressurepressure specially in infant and susceptible specially in infant and susceptible adultsadults

– Rebound congestionRebound congestion– precipitation of acute angle-closure precipitation of acute angle-closure

glaucoma in patients with narrow anglesglaucoma in patients with narrow angles

Adrenergic agonistsAdrenergic agonists

Alpha-2 agonistsAlpha-2 agonists– E.g. brimonidine, apraclonidineE.g. brimonidine, apraclonidine– Uses:Uses: glaucoma treatment, prophylaxis glaucoma treatment, prophylaxis

against IOP spiking after glaucoma laser against IOP spiking after glaucoma laser proceduresprocedures

– Mechanism:Mechanism: decrease aqueous production, decrease aqueous production, and increase uveoscleral outflowand increase uveoscleral outflow

– Side effects:Side effects: local: allergic reaction, mydriasis, lid retraction, local: allergic reaction, mydriasis, lid retraction,

conjunctival blanchingconjunctival blanching systemic: oral dryness, headache, fatigue, systemic: oral dryness, headache, fatigue,

drowsiness, orthostatic hypotension, vasovagal drowsiness, orthostatic hypotension, vasovagal attacksattacks

– Contraindications:Contraindications: infants infants

Alpha adrenergic Alpha adrenergic antagonistsantagonists E.g. thymoxamine, dapiprazoleE.g. thymoxamine, dapiprazole Uses:Uses: to reverse pupil dilation to reverse pupil dilation

produced by phenylepherine produced by phenylepherine Not widely usedNot widely used

Beta-adrenergic Beta-adrenergic blockersblockers E.g. E.g.

– non-selective: timolol, non-selective: timolol, levobunolol, metipranolol, levobunolol, metipranolol, carteololcarteolol

– selective: betaxolol (beta 1 selective: betaxolol (beta 1 “cardioselective”)“cardioselective”)

Uses:Uses: glaucoma glaucoma Mechanism:Mechanism: reduce the reduce the

formation of aqueous formation of aqueous humor by the ciliary bodyhumor by the ciliary body

Side effects:Side effects: bronchospasmbronchospasm (less with (less with betaxolol), cardiac betaxolol), cardiac impairmentimpairment

Carbonic anhydrase Carbonic anhydrase inhibitorsinhibitors E.g. acetazolamide, methazolamide, E.g. acetazolamide, methazolamide,

dichlorphenamide, dorzolamide, brinzolamide.dichlorphenamide, dorzolamide, brinzolamide. Uses:Uses: glaucoma, cystoid macular edema, glaucoma, cystoid macular edema,

pseudotumour cerebripseudotumour cerebri Mechanism:Mechanism: aqueous suppression aqueous suppression Side effects:Side effects: myopia, myopia, parasthesiaparasthesia, anorexia, GI , anorexia, GI

upset, headache, altered taste and smell, Na upset, headache, altered taste and smell, Na and K depletion, metabolic acidosis, bone and K depletion, metabolic acidosis, bone marrow suppression “aplastic anemia”marrow suppression “aplastic anemia”

Contraindication:Contraindication: sulpha allergy, digitalis sulpha allergy, digitalis users, pregnancyusers, pregnancy

Osmotic agentsOsmotic agents

Dehydrate vitreous bodyDehydrate vitreous body which which reduce IOP significantlyreduce IOP significantly

E.G. E.G. – glycerol 50% syrup (cause nausea, glycerol 50% syrup (cause nausea,

hyperglycemia)hyperglycemia)– Mannitol 20% IV (cause fluid Mannitol 20% IV (cause fluid

overload and not used in heart overload and not used in heart failure)failure)

Prostaglandin Prostaglandin analoguesanalogues E.g. latanoprost, bimatoprost, travoprost, unoprostoneE.g. latanoprost, bimatoprost, travoprost, unoprostone Uses:Uses: glaucoma glaucoma Mechanism:Mechanism: increase uveoscleral aqueous outflow increase uveoscleral aqueous outflow Side effects:Side effects: darkening of the iris ( darkening of the iris (heterochromia iridisheterochromia iridis), ),

lengthening and thickening of eyelashes, intraocular lengthening and thickening of eyelashes, intraocular inflammation, macular edemainflammation, macular edema

Anti-inflammatory

corticosteroid NSAID

CorticosteroidsCorticosteroids

TopicalTopical– E.g. fluorometholone, remixolone, E.g. fluorometholone, remixolone,

prednisolone, dexamethasone, hydrocortisoneprednisolone, dexamethasone, hydrocortisone– Mechanism:Mechanism: inhibition of arachidonic acid inhibition of arachidonic acid

release from phospholipids by inhibiting release from phospholipids by inhibiting phosphlipase A2phosphlipase A2

– Uses:Uses: postoperatively, anterior uveitis, severe postoperatively, anterior uveitis, severe allergic conjunctivitis, vernal allergic conjunctivitis, vernal keratoconjunctivitis, prevention and keratoconjunctivitis, prevention and suppression of corneal graft rejection, suppression of corneal graft rejection, episcleritis, scleritisepiscleritis, scleritis

– Side effects:Side effects: susceptibility to infectionssusceptibility to infections, , glaucomaglaucoma, , cataractcataract, ptosis, mydriasis, skin , ptosis, mydriasis, skin atrophyatrophy

CorticosteroidsCorticosteroids

Systemic:Systemic:– E.g. prednisolone, cortisoneE.g. prednisolone, cortisone– Uses:Uses: posterior uveitis, optic neuritis, posterior uveitis, optic neuritis,

temporal arteritis with anterior ischemic temporal arteritis with anterior ischemic optic neuropathyoptic neuropathy

– Side effects:Side effects: Local: Local: posterior subcapsular cataractposterior subcapsular cataract, glaucoma, , glaucoma,

central serous retinopathycentral serous retinopathy Systemic: suppression of pituitary-adrenal axis, Systemic: suppression of pituitary-adrenal axis,

hyperglycemia, osteoporosis, peptic ulcer, hyperglycemia, osteoporosis, peptic ulcer, psychosispsychosis

NSAIDNSAID

E.g. ketorolac, diclofenac, E.g. ketorolac, diclofenac, flurbiprofenflurbiprofen

Mechanism:Mechanism: inactivation of cyclo- inactivation of cyclo-oxygenase oxygenase

Uses:Uses: postoperatively, mild postoperatively, mild allergic conjunctivitis, episcleritis, allergic conjunctivitis, episcleritis, mild uveitis, cystoid macular mild uveitis, cystoid macular edema, preoperatively to prevent edema, preoperatively to prevent miosis during surgerymiosis during surgery

Anti-allergics Anti-allergics

Avoidance of allergens, cold compressAvoidance of allergens, cold compress AntihistaminesAntihistamines (e.g.pheniramine, levocabastine) (e.g.pheniramine, levocabastine) DecongestantsDecongestants (e.g. naphazoline, phenylepherine, tetrahydroz (e.g. naphazoline, phenylepherine, tetrahydrozooline)line) Mast cell stabilizersMast cell stabilizers (e.g. cromolyn, lodoxamide, pemirolast, nedocromil, (e.g. cromolyn, lodoxamide, pemirolast, nedocromil,

olopatadine)olopatadine) NSAIDNSAID (e.g. ketorolac) (e.g. ketorolac) SteroidsSteroids (e.g. fluorometholone, remixolone, prednisolone) (e.g. fluorometholone, remixolone, prednisolone) Drug combinationsDrug combinations

Antibiotics Antibiotics

PenicillinsPenicillins CephalosporinsCephalosporins SulfonamidesSulfonamides TetracyclinesTetracyclines ChloramphenicolChloramphenicol AminoglycosidesAminoglycosides FluoroquinolonesFluoroquinolones VancomycinVancomycin macrolidesmacrolides

Antibiotics Antibiotics

Used Used topicallytopically in prophylaxis in prophylaxis (pre and postoperatively) (pre and postoperatively) and treatment of ocular and treatment of ocular bacterial infections.bacterial infections.

Used Used orallyorally for the treatment for the treatment of preseptal cellulitisof preseptal cellulitise.g. amoxycillin with e.g. amoxycillin with clavulonate, cefaclorclavulonate, cefaclor

Used Used intravenouslyintravenously for the for the treatment of orbital cellulitistreatment of orbital cellulitise.g. gentamicin, e.g. gentamicin, cephalosporin, vancomycin, cephalosporin, vancomycin, metronidazole (metronidazole (flagylflagyl) )

Can be injected Can be injected intravitrallyintravitrally for the treatment of for the treatment of endophthalmitisendophthalmitis

AntibioticsAntibiotics

TrachomaTrachoma can be treated by can be treated by topical and systemic topical and systemic tetracycline or tetracycline or erythromycin, or systemic erythromycin, or systemic azithromycin.azithromycin.

Bacterial keratitisBacterial keratitis (bacterial (bacterial corneal ulcers) can be corneal ulcers) can be treated by topical fortified treated by topical fortified penicillins, cephalosporins, penicillins, cephalosporins, aminoglycosides, aminoglycosides, vancomycin, or vancomycin, or fluoroquinolones.fluoroquinolones.

Bacterial conjunctivitisBacterial conjunctivitis is is usually self limited but usually self limited but topical erythromycin, topical erythromycin, aminoglycosides, aminoglycosides, fluoroquinolones, or fluoroquinolones, or chloramphenicol can be chloramphenicol can be usedused

Antifungals Antifungals

Uses:Uses: fungal keratitis, fungal endophthalmitis fungal keratitis, fungal endophthalmitis PolyenesPolyenes

– damage cell membrane of susceptible fungidamage cell membrane of susceptible fungi– e.g. amphotericin B, natamycine.g. amphotericin B, natamycin– side effect: nephrotoxicityside effect: nephrotoxicity

ImidazolesImidazoles– increase fungal cell membrane permeabilityincrease fungal cell membrane permeability– e.g. miconazole, ketoconazolee.g. miconazole, ketoconazole

FlucytocineFlucytocine– act by inhibiting DNA synthesisact by inhibiting DNA synthesis

Antivirals Antivirals

AcyclovirAcyclovirinteract with viral interact with viral thymidine kinase thymidine kinase (selective)(selective)used in herpetic keratitisused in herpetic keratitis

TrifluridineTrifluridinemore corneal more corneal penetrationpenetrationcan treat herpetic iritiscan treat herpetic iritis

GanciclovirGanciclovirused intravenously for used intravenously for CMV retinitis CMV retinitis

Ocular diagnostic Ocular diagnostic drugsdrugs Fluorescein dyeFluorescein dye

– Available as drops or Available as drops or strips strips

– Uses:Uses: stain corneal stain corneal abrasions, applanation abrasions, applanation tonometry, detecting tonometry, detecting wound leak, fluorescein wound leak, fluorescein angiographyangiography

– Caution:Caution: stains soft contact lensstains soft contact lens Fluorescein drops can Fluorescein drops can

be contaminated by be contaminated by Pseudomonas sp.Pseudomonas sp.

Ocular diagnostic Ocular diagnostic drugsdrugs Rose bengal stainRose bengal stain

– Stains devitalized epitheliumStains devitalized epithelium– Uses:Uses: severe dry eye, herpetic keratitis severe dry eye, herpetic keratitis

Local anestheticsLocal anesthetics

topicaltopical– E.g. propacaine, tetracaineE.g. propacaine, tetracaine– Uses:Uses: applanation tonometry, applanation tonometry,

goniscopy, removal of corneal goniscopy, removal of corneal foreign bodies, removal of sutures, foreign bodies, removal of sutures, examination of patients who cannot examination of patients who cannot open eyes because of painopen eyes because of pain

– Adverse effects:Adverse effects: toxic to corneal toxic to corneal epithelium, allergic reaction rarelyepithelium, allergic reaction rarely

Local anestheticsLocal anesthetics

Orbital infiltrationOrbital infiltration– peribulbar or retrobulbarperibulbar or retrobulbar– cause cause anesthesiaanesthesia and and akinesiaakinesia

for intraocular surgeryfor intraocular surgery– e.g. lidocaine, bupivacainee.g. lidocaine, bupivacaine

Other ocular Other ocular preparationspreparations LubricantsLubricants

– drops or drops or ointmentsointments

– Polyvinyl alcohol, Polyvinyl alcohol, cellulose, cellulose, methylcellulosemethylcellulose

– Preserved or Preserved or preservative freepreservative free

Ocular toxicologyOcular toxicology

Complications of Complications of topical administrationtopical administration Mechanical injuryMechanical injury from from

the bottle e.g. corneal the bottle e.g. corneal abrasionabrasion

Pigmentation:Pigmentation: epinephrine-epinephrine-adrenochromeadrenochrome

Ocular damage:Ocular damage: e.g. e.g. topical anesthetics, topical anesthetics, benzylkoniumbenzylkonium

Hypersensitivity:Hypersensitivity: e.g. e.g. atropine, neomycin, atropine, neomycin, gentamicingentamicin

Systemic effect:Systemic effect: topical topical phenylephrine can phenylephrine can increase BPincrease BP

Amiodarone Amiodarone

A cardiac arrhythmia drugA cardiac arrhythmia drug Causes Causes optic neuropathyoptic neuropathy (mild decreased vision, visual (mild decreased vision, visual

field defects, bilateral optic disc swelling)field defects, bilateral optic disc swelling) Also causes corneal vortex keratopathy (corneal Also causes corneal vortex keratopathy (corneal

verticillata) which is whorl-shaped pigmented deposits verticillata) which is whorl-shaped pigmented deposits in the corneal epitheliumin the corneal epithelium

Digitalis Digitalis

A cardiac failure drugA cardiac failure drug Causes Causes chromatopsiachromatopsia (objects (objects

appear yellow) with overdose appear yellow) with overdose

Chloroquines Chloroquines

E.g. chloroquine, E.g. chloroquine, hydroxychloroquinehydroxychloroquine

Used in malaria, Used in malaria, rheumatoid arthritis, rheumatoid arthritis, SLESLE

Cause vortex Cause vortex keratopathy (corneal keratopathy (corneal verticillata) which is verticillata) which is usually asymptomatic usually asymptomatic but can present with but can present with glare and photophobiaglare and photophobia

Also cause Also cause retinopathyretinopathy (bull’s eye maculopathy)(bull’s eye maculopathy)

Chorpromazine Chorpromazine

A psychiatric drugA psychiatric drug Causes Causes corneal punctatecorneal punctate

epithelial opacitiesepithelial opacities, , lens surface lens surface opacitiesopacities

Rarely symptomaticRarely symptomatic Reversible with drug Reversible with drug

discontinuationdiscontinuation

Thioridazine Thioridazine

A psychiatric drugA psychiatric drug Causes a Causes a pigmentary retinopathypigmentary retinopathy

after high dosageafter high dosage

Diphenylhydantoin Diphenylhydantoin

An epilepsy drugAn epilepsy drug Causes dosage-related cerebellar-Causes dosage-related cerebellar-

vestibular effects: vestibular effects: – Horizontal Horizontal nystagmusnystagmus in lateral gaze in lateral gaze– DiplopiaDiplopia, , ophthalmoplegiaophthalmoplegia– Vertigo, ataxia Vertigo, ataxia

Reversible with the Reversible with the discontinuation of the drugdiscontinuation of the drug

Topiramate Topiramate

A drug for epilepsyA drug for epilepsy Causes Causes acute angle-closure acute angle-closure

glaucomaglaucoma (acute eye pain, redness, (acute eye pain, redness, blurred vision, haloes).blurred vision, haloes).

Treatment of this type of acute Treatment of this type of acute angle-closure glaucoma is by angle-closure glaucoma is by cycloplegia cycloplegia (rather than iridectomy) (rather than iridectomy) with the discontinuation of the drugwith the discontinuation of the drug

Ethambutol Ethambutol

An anti-TB drugAn anti-TB drug Causes a dose-related Causes a dose-related optic optic

neuropathyneuropathy Usually reversible but Usually reversible but

occasionally permanent visual occasionally permanent visual damage might occurdamage might occur

Agents that Can Cause Agents that Can Cause Toxic Optic Toxic Optic Neuropathy Neuropathy Methanol Methanol Ethylene glycol (antifreeze) Ethylene glycol (antifreeze) Chloramphenicol Chloramphenicol Isoniazid Isoniazid Ethambutol Ethambutol DigitalisDigitalis Chloroquine Chloroquine Streptomycin Streptomycin Amiodarone Amiodarone Quinine Quinine Vincristine and Vincristine and

methotrexate methotrexate (chemotherapy medicines) (chemotherapy medicines)

Sulfonamides Sulfonamides Melatonin with Zoloft Melatonin with Zoloft

(sertraline, Pfizer) (sertraline, Pfizer)

high-protein diet high-protein diet Carbon monoxide Carbon monoxide Lead Lead MercuryMercury Thallium (alopecia, skin Thallium (alopecia, skin

rash, severe vision loss) rash, severe vision loss) Malnutrition with vitamin Malnutrition with vitamin

B-1 deficiency B-1 deficiency Pernicious anemia (vitamin Pernicious anemia (vitamin

B-12 malabsorption B-12 malabsorption phenomenon) phenomenon) Radiation (unshielded Radiation (unshielded

exposure to >3,000 rads).exposure to >3,000 rads).

HMG-CoA reductase HMG-CoA reductase inhibitors (statins)inhibitors (statins) Cholesterol lowering agentsCholesterol lowering agents E.g. pravastatin, lovastatin, simvastatin, E.g. pravastatin, lovastatin, simvastatin,

fluvastatin, atorvastatin, rosuvastatinfluvastatin, atorvastatin, rosuvastatin Can cause Can cause cataractcataract in high dosages specially if in high dosages specially if

used with erythromycinused with erythromycin

Other agentsOther agents

methanolmethanol – optic atrophy and – optic atrophy and blindnessblindness

Contraceptive pillsContraceptive pills – pseudotumor – pseudotumor cerebri (papilledema), and dryness cerebri (papilledema), and dryness

ChloramphenicolChloramphenicol and and streptomycinstreptomycin – – optic atrophyoptic atrophy

Hypervitaminosis AHypervitaminosis A – yellow skin and – yellow skin and conjunctiva, pseudotumor cerebri conjunctiva, pseudotumor cerebri (papilledema), retinal hemorrhage.(papilledema), retinal hemorrhage.

Hypovitaminosis AHypovitaminosis A – night blindness – night blindness (nyctalopia), keratomalacia.(nyctalopia), keratomalacia.

Thank youThank you

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