Ocular Pharmacology and Toxicology 2

8/8/2019 Ocular Pharmacology and Toxicology 2

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Ocular pharmacologyOcular pharmacology

and toxicologyand toxicologyHatem Kalantan, MDHatem Kalantan, MDAssistant ProfessorAssistant Professor

Ophthalmology Dept.Ophthalmology Dept.College of MedicineCollege of MedicineKing Saud UniversityKing Saud University


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General pharmacologicalGeneral pharmacologicalprinciplesprinciples


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PharmacodynamicsPharmacodynamics

It is the biological and therapeutic effect ofIt is the biological and therapeutic effect ofthe drugthe drug (mechanism of action)(mechanism of action)

Most drugs act by binding to regulatoryMost drugs act by binding to regulatorymacromolecules, usually neurotransmittersmacromolecules, usually neurotransmittersor hormone receptors or enzymesor hormone receptors or enzymes

If the drug is working at the receptor level,If the drug is working at the receptor level,

it can beit can be agonist or antagonistagonist or antagonist If the drug is working at the enzyme level, itIf the drug is working at the enzyme level, it

can becan be activator or inhibitoractivator or inhibitor


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PharmacokineticsPharmacokinetics

It is the absorption, distribution,It is the absorption, distribution,metabolism, and excretion of the drugmetabolism, and excretion of the drug

A drug can be delivered to ocular tissue as:A drug can be delivered to ocular tissue as: Locally:Locally:

Eye dropEye drop

OintmentOintment

Periocular injectionPeriocular injection Intraocular injectionIntraocular injection

Systemically:Systemically:

OrallyOrally

IVIV


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Factors influencing localFactors influencing localdrug penetration into oculardrug penetration into oculartissuetissue Drug concentration and solubility:Drug concentration and solubility: the higher thethe higher the

concentration the better the penetration e.gconcentration the better the penetration e.gpilocarpinepilocarpine 11--44% but% but limited bylimited by reflex tearingreflex tearing

Viscosity:Viscosity: addition of methylcellulose and polyvinyladdition of methylcellulose and polyvinylalcohol increases drug penetration byalcohol increases drug penetration by increasingincreasingthe contact timethe contact time with the cornea andwith the cornea and alteringalteringcorneal epitheliumcorneal epithelium

Lipid solubility:Lipid solubility: because of the lipid richbecause of the lipid richenvironment of the epithelial cell membranes,environment of the epithelial cell membranes, thethehigher lipid solubility the more the penetrationhigher lipid solubility the more the penetration


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Factors influencing localFactors influencing localdrug penetration into oculardrug penetration into oculartissuetissue

Surfactants:Surfactants: the preservatives used in ocularthe preservatives used in ocularpreparationspreparations alter cell membrane in the corneaalter cell membrane in the cornea andandincrease drug permeability e.g. benzylkonium andincrease drug permeability e.g. benzylkonium andthiomersalthiomersal

pH:pH: the normal tear pH isthe normal tear pH is 77..44 and if the drug pH isand if the drug pH ismuch different, this will cause reflex tearingmuch different, this will cause reflex tearing

Drug tonicity:Drug tonicity: when an alkaloid drug is put inwhen an alkaloid drug is put inrelatively alkaloid medium, the proportion of therelatively alkaloid medium, the proportion of theuncharged form will increase, thus moreuncharged form will increase, thus morepenetrationpenetration


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Eye dropsEye drops

Eye dropsEye drops-- most commonmost common

one drop = 50 lone drop = 50 l

volume of conjunctival culvolume of conjunctival cul--dede--sac 7sac 7--10 l10 l

measures to increase drop absorption:measures to increase drop absorption:

--wait 5wait 5--10 minutes between drops10 minutes between drops

--compress lacrimal saccompress lacrimal sac--keep lids closed for 5 minutes afterkeep lids closed for 5 minutes after

instillationinstillation


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OintmentsOintments

Increase the contact timeIncrease the contact time of ocularof ocularmedication to ocular surface thusmedication to ocular surface thus

better effectbetter effect

It has the disadvantage ofIt has the disadvantage of visionvisionblurringblurring

The drug has to be high lipid solubleThe drug has to be high lipid solublewith some water solubility to have thewith some water solubility to have themaximum effect as ointmentmaximum effect as ointment


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PeriPeri--ocular injectionsocular injections

TheyThey reach behind irisreach behind iris--lenslensdiaphragmdiaphragm better thanbetter thantopical applicationtopical application

E.g. subconjunctival,E.g. subconjunctival,subtenon, peribulbar, orsubtenon, peribulbar, orretrobulbarretrobulbar

This route bypass theThis route bypass theconjunctival and cornealconjunctival and cornealepithelium which isepithelium which is goodgoodfor drugs with low lipidfor drugs with low lipid

solubilitysolubility (e.g. penicillins)(e.g. penicillins) Also steroid and localAlso steroid and local

anesthetics can be appliedanesthetics can be appliedthis waythis way


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Intraocular injectionsIntraocular injections

Intracameral orIntracameral orintravitrealintravitreal

E.g.E.g. IntracameralIntracameral

acetylcholine (miochol)acetylcholine (miochol)during cataract surgeryduring cataract surgery

Intravitreal antibiotics inIntravitreal antibiotics incases of endophthalmitiscases of endophthalmitis

Intravitreal steroid inIntravitreal steroid inmacular edemamacular edema

Intravitreal AntiIntravitreal Anti--VEGFVEGFfor DRfor DR


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SustainedSustained--release devicesrelease devices

These are devices thatThese are devices thatdeliver an adequatedeliver an adequatesupply of medication atsupply of medication at

a steadya steady--state levelstate level E.g.E.g.

Ocusert deliveringOcusert deliveringpilocarpinepilocarpine

Timoptic XE deliveringTimoptic XE deliveringtimololtimolol

Ganciclovir sustainedGanciclovir sustained--release intraocularrelease intraoculardevicedevice

Collagen shieldsCollagen shields


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Systemic drugsSystemic drugs

Oral or IVOral or IV

Factor influencing systemic drugFactor influencing systemic drug

penetration into ocular tissue:penetration into ocular tissue: lipid solubility of the drug:lipid solubility of the drug: moremore

penetration with high lipid solubilitypenetration with high lipid solubility

Protein binding:Protein binding: more effect with lowmore effect with lowprotein bindingprotein binding

Eye inflammation:Eye inflammation: more penetration withmore penetration withocular inflammationocular inflammation


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OcularOcularpharmacotherapeuticspharmacotherapeutics


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Cholinergic agonistsCholinergic agonists

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

(miostat)(miostat)

Uses:Uses: miosis, glaucomamiosis, glaucoma Mechanisms:Mechanisms: Miosis by contraction of the iris sphincter muscleMiosis by contraction of the iris sphincter muscle increases aqueous outflow through the trabecular meshworkincreases aqueous outflow through the trabecular meshwork

by longitudinal ciliary muscle contractionby 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, miotic, cataract, miotic

cysts, and rarely retinal detachmentcysts, and rarely retinal detachment systemic side effects: lacrimation, salivation, perspiration,systemic side effects: lacrimation, salivation, perspiration,

bronchial spasm, urinary urgency, nausea, vomiting, andbronchial spasm, urinary urgency, nausea, vomiting, anddiarrheadiarrhea


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

More potent with longer duration ofMore potent with longer duration ofactionaction

Reversible inhibitorsReversible inhibitors

e.g. physostigminee.g. physostigmine used in glaucoma and lice infestation ofused in glaucoma and lice infestation of

lasheslashes

can cause CNS side effectscan cause CNS side effects


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Indirectly actingIndirectly acting(anticholinesterases):(anticholinesterases): Irreversible:Irreversible:

e.g. phospholine iodidee.g. phospholine iodide Uses:Uses: inin

accommodativeaccommodativeesotropiaesotropia

side effects:side effects: iris cystiris cystand anteriorand anteriorsubcapsular cataractsubcapsular cataract

C/IC/I in angle closurein angle closureglaucoma, asthma,glaucoma, asthma,ParkinsonismParkinsonism

causes apnea if usedcauses apnea if usedwith succinylcholine orwith succinylcholine orprocaineprocaine


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Cholinergic antagonistsCholinergic antagonists

E.g. tropicamide, cyclopentolate, homatropine, scopolamine,E.g. tropicamide, cyclopentolate, homatropine, scopolamine,atropineatropine

CauseCause mydriasis (by paralyzing the sphincter muscle) withmydriasis (by paralyzing the sphincter muscle) withcycloplegia (by paralyzing the ciliary muscle)cycloplegia (by paralyzing the ciliary muscle)

Uses:Uses: fundoscopy, cycloplegic refraction, anterior uveitisfundoscopy, cycloplegic refraction, anterior uveitis 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 speciallyspecially in childrenin children they might cause flushing, fever,they might cause flushing, fever,

tachycardia, or deleriumtachycardia, or delerium Treatment by DC or physostigmineTreatment by DC or physostigmine


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Adrenergic agonistsAdrenergic agonists

NonNon--selective agonists (selective agonists (11,,22,, 11,, 22))

E.g. epinephrine, depevefrinE.g. epinephrine, depevefrin(pro(pro--drug of epinephrine)drug of epinephrine)

Uses:Uses: glaucomaglaucoma

Side effects:Side effects: headache,headache,arrhythmia, increased bloodarrhythmia, increased blood

pressure,pressure, conjunctivalconjunctivaladrenochromeadrenochrome, cystoid macular, cystoid macularedema in aphakic eyesedema in aphakic eyes

C/I in closed angle glaucomaC/I in closed angle glaucoma


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AlphaAlpha--1 agonists1 agonists E.g. phenylepherineE.g. phenylepherine

Uses:Uses: mydriasis (mydriasis (withoutwithout cycloplegia),cycloplegia),decongestantdecongestant Adverse effect:Adverse effect:

Can cause significantCan cause significant increase in blood pressureincrease in blood pressurespecially in infant and susceptible adultsspecially in infant and susceptible adults

Rebound congestionRebound congestion precipitation of acute angleprecipitation of acute angle--closure glaucoma inclosure glaucoma in

patients with narrow anglespatients with narrow angles


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AlphaAlpha--22 agonistsagonists E.g. brimonidine, apraclonidineE.g. brimonidine, apraclonidine Uses:Uses: glaucoma treatment, prophylaxis againstglaucoma treatment, prophylaxis againstIOP spiking after glaucoma laser proceduresIOP spiking after glaucoma laser procedures

Mechanism:Mechanism: decrease aqueous production, anddecrease aqueous production, andincrease uveoscleral outflowincrease 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, drowsiness,systemic: oral dryness, headache, fatigue, drowsiness,

orthostatic hypotension, vasovagal attacksorthostatic hypotension, vasovagal attacks

Contraindications:Contraindications: infants, MAO inhibitors usersinfants, MAO inhibitors users


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Alpha adrenergicAlpha adrenergic

antagonistsantagonists E.g. thymoxamine, dapiprazoleE.g. thymoxamine, dapiprazole

Uses:Uses: to reverse pupil dilationto reverse pupil dilationproduced by phenylepherineproduced by phenylepherine

Not widely usedNot widely used


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BetaBeta--adrenergic blockersadrenergic blockers

E.g.E.g. nonnon--selective: timolol,selective: timolol,

levobunolol, metipranolol,levobunolol, metipranolol,

carteololcarteolol selective: betaxolol (beta 1selective: betaxolol (beta 1

cardioselective)cardioselective)

Uses:Uses: glaucomaglaucoma

Mechanism:Mechanism: reduce thereduce the

formation of aqueousformation of aqueoushumor by the ciliary bodyhumor by the ciliary body

Side effects:Side effects:bronchospasmbronchospasm (less with(less withbetaxolol), cardiacbetaxolol), cardiac

impairmentimpairment


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Carbonic anhydraseCarbonic 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 suppressionaqueous suppression

Side effects:Side effects: myopia,myopia, parasthesiaparasthesia, anorexia, GI, anorexia, GIupset, headache, altered taste and smell, Na and Kupset, headache, altered taste and smell, Na and K

depletion, metabolic acidosis, renal stone, bonedepletion, metabolic acidosis, renal stone, bonemarrow suppression aplastic anemiamarrow suppression aplastic anemia

Contraindication:Contraindication: sulpha allergy, digitalis users,sulpha allergy, digitalis users,pregnancypregnancy


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Osmotic agentsOsmotic agents

Dehydrate vitreous bodyDehydrate vitreous body which reducewhich reduceIOP significantlyIOP significantly

E.G.E.G.

glycerol 50% syrup (cause nausea,glycerol 50% syrup (cause nausea,hyperglycemia)hyperglycemia)

Mannitol 20% IV (cause fluid overloadMannitol 20% IV (cause fluid overloadand not used in heart failure)and not used in heart failure)


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Prostaglandin analoguesProstaglandin analogues

E.g. latanoprost, bimatoprost, travoprost,E.g. latanoprost, bimatoprost, travoprost,unoprostoneunoprostone

Uses:Uses: glaucomaglaucoma Mechanism:Mechanism: increase uveoscleral aqueousincrease uveoscleral aqueous

outflowoutflow

Side effects:Side effects: darkening of the irisdarkening of the iris((heterochromia iridisheterochromia iridis), lengthening and), lengthening andthickening of eyelashes, intraocularthickening of eyelashes, intraocularinflammation, macular edemainflammation, macular edema


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Anti-inflammatory

corticosteroid NSAID


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CorticosteroidsCorticosteroids

TopicalTopical E.g. fluorometholone, remixolone, prednisolone,E.g. fluorometholone, remixolone, prednisolone,

dexamethasone, hydrocortisonedexamethasone, hydrocortisone

Mechanism:Mechanism: inhibition of arachidonic acid releaseinhibition of arachidonic acid releasefrom phospholipids by inhibiting phosphlipase Afrom phospholipids by inhibiting phosphlipase A22

Uses:Uses: postoperatively, anterior uveitis, severepostoperatively, anterior uveitis, severeallergic conjunctivitis, vernal keratoconjunctivitis,allergic conjunctivitis, vernal keratoconjunctivitis,prevention and suppression of corneal graftprevention and suppression of corneal graft

rejection, episcleritis, scleritisrejection, episcleritis, scleritis Side effects:Side effects: susceptibility to infectionssusceptibility to infections,,

glaucomaglaucoma,, cataractcataract, ptosis, mydriasis, scleral, ptosis, mydriasis, scleralmelting, skin atrophymelting, skin atrophy


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CorticosteroidsCorticosteroids

Systemic:Systemic:

E.g. prednisolone, cortisoneE.g. prednisolone, cortisone

Uses:Uses: posterior uveitis, optic neuritis, temporalposterior uveitis, optic neuritis, temporalarteritis with anterior ischemic optic neuropathyarteritis with anterior ischemic optic neuropathy

Side effects:Side effects:

Local:Local: posterior subcapsular cataractposterior subcapsular cataract, glaucoma,, glaucoma,central serous retinopathycentral serous retinopathy

Systemic: suppression of pituitarySystemic: suppression of pituitary--adrenal axis,adrenal axis,hyperglycemia, osteoporosis, peptic ulcer, psychosishyperglycemia, osteoporosis, peptic ulcer, psychosis


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NSAIDNSAID

E.g. ketorolac, diclofenac, flurbiprofenE.g. ketorolac, diclofenac, flurbiprofen

Mechanism:Mechanism: inactivation of cycloinactivation of cyclo--

oxygenaseoxygenase Uses:Uses: postoperatively, mild allergicpostoperatively, mild allergic

conjunctivitis, episcleritis, mild uveitis,conjunctivitis, episcleritis, mild uveitis,

cystoid macular edema, preoperativelycystoid macular edema, preoperativelyto prevent miosis during surgeryto prevent miosis during surgery

Side effects:Side effects: stingingstinging


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AntiAnti--allergicsallergics

Avoidance of allergens, cold compress, lubricationsAvoidance of allergens, cold compress, lubrications

AntihistaminesAntihistamines (e.g.pheniramine, levocabastine)(e.g.pheniramine, levocabastine)

DecongestantsDecongestants (e.g. naphazoline, phenylepherine,(e.g. naphazoline, phenylepherine,

tetrahydrozaline)tetrahydrozaline) Mast cell stabilizersMast cell stabilizers (e.g. cromolyn, lodoxamide, pemirolast,(e.g. cromolyn, lodoxamide, pemirolast,

nedocromil, olopatadine)nedocromil, olopatadine)

NSAIDNSAID (e.g. ketorolac)(e.g. ketorolac)

SteroidsSteroids (e.g. fluorometholone, remixolone, prednisolone)(e.g. fluorometholone, remixolone, prednisolone)

Drug combinationsDrug combinations


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AntibioticsAntibiotics

PenicillinsPenicillins

CephalosporinsCephalosporins

SulfonamidesSulfonamides TetracyclinesTetracyclines

ChloramphenicolChloramphenicol

AminoglycosidesAminoglycosides

FluoroquinolonesFluoroquinolones

VancomycinVancomycin

macrolidesmacrolides


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UsedUsed topicallytopically in prophylaxisin prophylaxis(pre and postoperatively) and(pre and postoperatively) andtreatment of ocular bacterialtreatment of ocular bacterialinfections.infections.

UsedUsed orallyorally for the treatmentfor the treatmentof preseptal cellulitisof preseptal cellulitise.g. amoxycillin withe.g. amoxycillin withclavulonate, cefaclorclavulonate, cefaclor

UsedUsed intravenouslyintravenously for thefor thetreatment of orbital cellulitistreatment of orbital cellulitise.g. gentamicin, cephalosporin,e.g. gentamicin, cephalosporin,

vancomycin, flagylvancomycin, flagyl Can be injectedCan be injected intravitrallyintravitrally forfor

the treatment ofthe treatment ofendophthalmitisendophthalmitis


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TrachomaTrachoma can be treated bycan be treated bytopical and systemictopical and systemictetracycline or erythromycin, ortetracycline or erythromycin, orsystemic azithromycin.systemic azithromycin.

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

Bacterial conjunctivitisBacterial conjunctivitis isisusually self limited but topicalusually self limited but topical

erythromycin, aminoglycosides,erythromycin, aminoglycosides,fluoroquinolones, orfluoroquinolones, orchloramphenicol can be usedchloramphenicol can be used


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AntifungalsAntifungals

Uses:Uses: fungal keratitis, fungal endophthalmitisfungal 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


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AntiviralsAntivirals

AcyclovirAcyclovir

interact with viral thymidineinteract with viral thymidinekinase (selective)kinase (selective)

used in herpetic keratitisused in herpetic keratitis TrifluridineTrifluridine

more corneal penetrationmore corneal penetration

can treat herpetic iritiscan treat herpetic iritis

GanciclovirGanciclovir

used intravenously for CMVused intravenously for CMVretinitisretinitis


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Ocular diagnostic drugsOcular diagnostic drugs

Fluorescein dyeFluorescein dye

Available as drops orAvailable as drops orstripsstrips

Uses:Uses: stain cornealstain cornealabrasions, applanationabrasions, applanationtonometry, detectingtonometry, detectingwound leak, NLDwound leak, NLDobstruction, fluoresceinobstruction, fluorescein

angiographyangiography Caution:Caution:

stains soft contact lensstains soft contact lens

Fluorescein drops canFluorescein drops canbe contaminated bybe contaminated byPseudomonas sp.Pseudomonas sp.


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Ocular diagnostic drugsOcular diagnostic drugs

Rose bengal stainRose bengal stain

Stains devitalized epitheliumStains devitalized epithelium

Uses:Uses: severe dry eye, herpetic keratitissevere dry eye, herpetic keratitis


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Local anestheticsLocal anesthetics

topicaltopical E.g. propacaine, tetracaineE.g. propacaine, tetracaine

Uses:Uses: applanation tonometry, goniscopy,applanation tonometry, goniscopy,removal of corneal foreign bodies,removal of corneal foreign bodies,removal of sutures, examination ofremoval of sutures, examination ofpatients who cannot open eyes becausepatients who cannot open eyes because

of painof pain Adverse effects:Adverse effects: toxic to cornealtoxic to corneal

epithelium, allergic reaction rarelyepithelium, allergic reaction rarely


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Local anestheticsLocal anesthetics

Orbital infiltrationOrbital infiltration

peribulbar or retrobulbarperibulbar or retrobulbar

causecause anesthesiaanesthesia andand akinesiaakinesia forforintraocular surgeryintraocular surgery

e.g. lidocaine, bupivacainee.g. lidocaine, bupivacaine


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Other ocular preparationsOther ocular preparations

LubricantsLubricants

drops or ointmentsdrops or ointments

Polyvinyl alcohol,Polyvinyl alcohol,cellulose,cellulose,methylcellulosemethylcellulose

Preserved orPreserved or

preservative freepreservative free


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Ocular toxicologyOcular toxicology


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Complications of topicalComplications of topical

administrationadministration Mechanical injuryMechanical injury from thefrom the

bottle e.g. corneal abrasionbottle e.g. corneal abrasion

Pigmentation:Pigmentation: epinephrineepinephrine--

adrenochromeadrenochrome Ocular damage:Ocular damage: e.g. topicale.g. topical

anesthetics, benzylkoniumanesthetics, benzylkonium

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

Systemic effect:Systemic effect: topicaltopicalphenylephrine can increasephenylephrine can increaseBPBP


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DigitalisDigitalis

A cardiac failure drugA cardiac failure drug

CausesCauses chromatopsiachromatopsia (objects appear(objects appearyellow) with overdoseyellow) with overdose


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ChloroquinesChloroquines

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

Used in malaria, rheumatoidUsed in malaria, rheumatoid

arthritis, SLEarthritis, SLE Cause vortex keratopathyCause vortex keratopathy

(corneal verticillata) which(corneal verticillata) whichis usually asymptomatic butis usually asymptomatic butcan present with glare andcan present with glare and

photophobiaphotophobia Also causeAlso cause retinopathyretinopathy

(bulls eye maculopathy)(bulls eye maculopathy)


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ChorpromazineChorpromazine

A psychiatric drugA psychiatric drug

CausesCauses corneal punctatecorneal punctate epithelialepithelialopacitiesopacities,, lens surface opacitieslens surface opacities

Rarely symptomaticRarely symptomatic

Reversible with drug discontinuationReversible with drug discontinuation


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ThioridazineThioridazine

A psychiatric drugA psychiatric drug

Causes aCauses a pigmentary retinopathypigmentary retinopathy afterafterhigh dosagehigh dosage


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DiphenylhydantoinDiphenylhydantoin

An epilepsy drugAn epilepsy drug

Causes dosageCauses dosage--related cerebellarrelated cerebellar--vestibular effects:vestibular effects:

HorizontalHorizontal nystagmusnystagmus in lateral gazein lateral gaze

DiplopiaDiplopia,, ophthalmoplegiaophthalmoplegia

Vertigo, ataxiaVertigo, ataxia

Reversible with the discontinuation ofReversible with the discontinuation ofthe drugthe drug


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TopiramateTopiramate

A drug for epilepsyA drug for epilepsy

CausesCauses acute angleacute angle--closure glaucomaclosure glaucoma(acute eye pain, redness, blurred(acute eye pain, redness, blurredvision, haloes).vision, haloes).

Treatment of this type of acute angleTreatment of this type of acute angle--

closure glaucoma is byclosure glaucoma is by cycloplegia andcycloplegia andtopical steroidstopical steroids (rather than(rather thaniridectomy) with the discontinuation ofiridectomy) with the discontinuation of

the drugthe drug


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EthambutolEthambutol

An antiAn anti--TB drugTB drug

Causes a doseCauses a dose--relatedrelated opticopticneuropathyneuropathy

Usually reversible but occasionallyUsually reversible but occasionallypermanent visual damage might occurpermanent visual damage might occur


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Agents that Can CauseAgents that Can Cause

Toxic Optic NeuropathyToxic Optic Neuropathy MethanolMethanol Ethylene glycol (antifreeze)Ethylene glycol (antifreeze) ChloramphenicolChloramphenicol IsoniazidIsoniazid EthambutolEthambutol DigitalisDigitalis ChloroquineChloroquine StreptomycinStreptomycin AmiodaroneAmiodarone QuinineQuinine

Vincristine and methotrexateVincristine and methotrexate(chemotherapy medicines)(chemotherapy medicines) SulfonamidesSulfonamides Melatonin with ZoloftMelatonin with Zoloft

(sertraline, Pfizer) in a(sertraline, Pfizer) in a

highhigh--protein dietprotein diet Carbon monoxideCarbon monoxide LeadLead MercuryMercury Thallium (alopecia, skin rash,Thallium (alopecia, skin rash,

severe vision loss)severe vision loss) Malnutrition with vitamin BMalnutrition with vitamin B--11

deficiencydeficiency Pernicious anemia (vitamin BPernicious anemia (vitamin B--

12 malabsorption12 malabsorption phenomenon)phenomenon) Radiation (unshieldedRadiation (unshielded

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


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HMGHMG--CoA reductaseCoA 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 causeCan cause cataractcataractin high dosages speciallyin high dosages specially

if used with erythromycinif used with erythromycin


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Ocular Pharmacology and Toxicology 2