drugs acting on the eye (updated) - ksumsc – king saud ...ksumsc.com/download_center/2nd/1)...
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Pharmacology of drugs acting on the eye
Ø OutlinecommonroutesofadministrationofdrugstotheeyeØ DiscussthepharmacokineticsofdrugsappliedtopicallytotheeyeØ ClassifydrugsusedfortreatmentofdisordersoftheeyeØ Elaborateonautonomic,anti-inflammatorydrugs&drugsusedforglaucomaØ Hintonoculartoxicityofsomedrugs
extrainformationandfurtherexplanation
important
doctorsnotes
Drugsnames
Mnemonics
Objectives:
color index:
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MiosisMydriasis
Accommodationforlightintensity Anatomy
Accommodationfornear/farvision: Eyeaccommodation2:05min
Drugscanbedeliveredtooculartissueas
Locally(Topically)
Eyedrops Ointments Injections
Periocularinjection. Intraocularinjection.
Systemically
Orally IV
Locally:Advantages:• Convenient,Economic,Relativelysafe.Disadvantages:• Compliance,Corneal&conjunctivaltoxicity.
Overview
Eyedrops Ointments
Definition
• Eyedropsaresaline containingdrops“liquid”
• Mostcommonrouteofadministration.
• Onedrop=50μl /4hours(usually)
Ointmentisasmoothoilypreparation,Asaruleofthumb,anointmentbaseismoreocclusiveandwilldrivethemedicationintotheskinmorerapidlythanasolutionorcreambase.
AdvantagesConvenient,costsless,appliedfrequently.
Increasesthecontacttimeofocularmedicationtoocularsurfaceàprovidingbettereffect.
Disadvantages
Thecontacttimebetweenthedrugandtheeyeislow duetofastremovalbytears àThushastobeusedseveraltimes. Oneoftheproblemsofeyedropsis poorcompliantofthepatient.
Thedrughastobehighlylipidsolubletohavethemaximumeffectasointment.t’saGreasysubstancesothecontacttimebetweenthemedicationandthetissueislonger
Eyeinjections
Techniqu
es
intra-ocularin
jections
Fora
nteriorsegmen
tsurgery,
infections&re
tinitis
1- Intra-cameral:“insideanteriororposterior
chamberoftheeye”
E.g.•Intra-cameralacetylcholine or lidocaineduringcataractsurgery. ADRs
2- Intra-vitreal"insidetheeye"
E.g.• Intravitrealantibioticsincasesof
endophthalmitis (aninflammationoftheinternalcoatsoftheeye)
• Intravitrealsteroidinmacularedema(thebuild-upoffluidinthemacula,anareainthecenteroftheretina.)
-Retinaltoxicity.-Intraoculartoxicity.- Cornealtoxicity.
Peri-ocularinjections
1-SubconjunctivalSub=under
2- Retro-bulbar“behindtheeyeball”
Retro=behind
3- Peri-bulbar“aboveandbelowtheorbit”
Peri=around
4-subtenon
Advantages:• They reachbehindtheiris-lensdiaphragmbetterthantopicalapplications.• Drugspenetrationisgenerallyweakerforlowlipid-solubledrugs,howeverinjectionscan
bypasstheconjunctivalandcornealepitheliumwhichisgoodfordrugswithlowlipidsolubility(e.g.penicillins)
• Steroidandlocalanestheticscanbeappliedthisway.• Usedforinfectionofanteriorsegmentandinflammationofuvea.Disadvantages:• Localtoxicity,tissueinjury,globeperforation,opticnervedamage.
رابكلمة كامیتذكرنا للكامیراتالیكا وكانون شركة
(Leica=acetylcholine) (Canon=lidocaine)
TheAntibiotic andsteroidcansaveourvitality
vitalنربطھا بكلمة
Absorptio
nIsdeterm
inedby: Drugresidencetime→ thetimedrugremainsincul-de-sac,tear.Itcanbeprolongedbyplugging
tearductsorchanging the formulation.Metabolism →esterasesElimination → bynasolacrimaldrainageorbindingtotearprotein.Diffusion →acrosscornea&conjunctiva.
Distrib
ution Aftercornealabsorptionthedrugaccumulates
intheaqueoushumor,intraocularstructuresorsystemicallydistributed.*Melaninbindingprolongstheeffectofα-agonistsinpatientswithdarkpigmentediris.
Metab
olism
Significantbiotransformationtakesplaceintheeye.Esterases activatepro-drugs,e.g.:- Dipivefrin→(adrenaline)- Latanoprost →(PGF2α)
Pharmacokineticsoftopical(local)drugsOralorIV
- Factorsinfluencingsystemicdrugpenetrationintooculartissue:• lipidsolubilityofthedrug:Morepenetrationwithhighlipidsolubility• Proteinbinding: (bounddrug):Not Freetodistributealloverthebody,ItlocalizedinthebloodMoreeffectwithlowproteinbinding(inverseproportion)• Eyeinflammation:Morepenetrationwithocularinflammation.
(Dipivefrin=adrenaline)(dipivefrin=Adrenaline) أو ممكن نقول أبي أدرنالین
Eye ParasympatheticN.S. SympatheticN.S.
Iris
radialmuscle Noeffect Contraction(Mydriasis)(α1)
circularmuscle Contraction(miosis)(M3) Noeffect
Ciliarymuscle Contraction(M3)(accommodationfornearvision)
Relaxation(β2)
Lens Thick,moreconvex Thin,moreflat
Conjunctivalbloodvessels ConjunctivalVasodilatationandcongestionofbloodvessels
ConjunctivalVasoconstriction(α1)anddecongestionofbloodvessels
Accommodation nearvision farvision
Suspensoryligaments relaxation contraction
*Ciliarymuscleistheoppositeofthesuspensoryligament
اح ھذا بیتك الثاني ارت
Drugsa
ctingon
parasympatheticsystem
Cholinergicagonists
Directagonists
Indirectagonists(anticholinesterases)
Reversible
Irreversible
Cholinergic(muscarinic)antagonists
NaturalAlkaloids
Syntheticatropinesubstituses
sympatheticsystem
Adrenergicagonists
Non-selectiveagonists
Selectiveα1agonists
Selectiveα2agonists
Betablocker
Selectiveβ1Non-selective
Non-selective
Oculardrugs
Autonomicdrugs
Miotics
Mydriatics
Cycloplegics
AntiglaucomaDrugs
Anti-inflammatory
drugs
Steroids
NSAIDs
Chemotherapeutics
Antibacterial
Antifungal
Antiviral
Localanesthetics
Ocularlubricants
Cholinergicagonists
Drug
Directagonists Indirectagonists(anticholinesterases)
AcetycholineMreceptorMethacholineM+NreceptorCarbachol
PilocarpineMreceptor
ReversibleBindforshorttimewithAchesterasethenleaveit
Irreversible
PhysostigmineDemecarium
EchothiophateIsoflurophate
Indicatio
ns
Specificuses:
1-Inductionofmiosis insurgery2- Openangleglaucoma*Acetylcholinehasveryshortdurationofactionsonomedicalapplicationforit.
OpenangleglaucomaWhynotforclosedaswell?Closedangleglaucomaisanemergencycasewhichrequiredsurgery
Specificuses:1- Glaucoma2- Accommodative esotropia
Generaluses:1- Glaucoma(open&closedangle).2- Counteractactionofmydriatics.afterfunduscopicexamination3- Tobreakiris-lensadhesions.Sequencesofmydriatics drugsfollowedbymiotics drugs(Contractionfollowedbyrelaxation)4- Inaccommodativeesotropia (ecothiophate).الحول5- inliceinfestationoflashes(physostigmine)
0Mech.Ofa
ction 2contractions:
1- ConstrictionofthepupillaryCircularmuscle(sphinctermuscle)(miosis)drugscausesconstrictionarePreferredintreatmentofglaucoma2-Contractionoftheciliarymuscle(accommodationfornearvision)Decrease inintraocularpressure↓IOP.increases aqueousoutflowthroughthetrabecularmeshworkintocanalofSchlemm**IncreasedlacrimationConjunctivalVasodilatationmayLeadtocongestionineye
ADRs - Diminishedvision(myopia).
- Headache
صار (Carb)من كثرة الكرب(achol)شخص اكول
tropiaEso=thiophateEco
**Theaqueoushumorissecretedbytheepitheliumofciliarybody.Producedbyacombinationofactivetransportofionsandultrafiltrationofinterstitialfluid.Thefluidflowsoverthesurfaceofthelens,outthroughthepupilintotheanteriorchamber.FlowsthroughthetrabecularmeshworkintoSchlemm’s canalbyciliarymusclecontraction.andiscollectedinthescleralveins.Asaresultofmiosis oftheirismusclewhichpulledawayfromthecanalofSchliemannsotheangleoffiltrationwillincrease
Cholinergic(muscarinic)antagonists
Drug Naturalalkaloids Syntheticatropinesubstitutes
1- AtropineNotusedbecauseithasverylongdurationofaction2- Scopolamine(Hyoscine)
1- Homatropine2- Tropicamide3- Cyclopentolate
Duratio
n Longdurationofaction1- Atropine:7-10days2- Scopolamine(Hyoscine):3-7days
Shortdurationofaction1- Homatropine:1-3days2- Tropicamide:6hoursWidelyused
3- Cyclopentolate:24hours
Mech.of
actio
n
2 Relaxations:1- Passive*mydriasis→duetorelaxationofcircularmuscles.2- Cycloplegia (lossofnearaccommodation)→duetorelaxationofciliarymuscle.(ThiseffectisduetoblockingofparaS only!)- Increased IOP→glaucoma.(especiallyangleclosureglaucoma)- Decreased lacrimalsecretion→sandyeye.- Lossoflightreflex.
Indicatio
ns
1- Topreventadhesioninuveitis&iritis.(becausetheyaredoingmydriasis)2- Funduscopicexaminationoftheeye.3- Measurementofrefractiveerror.(problemwithfocusingoflightontheretinaduetotheshapeoftheeye)
Contra-
indicatio
ns Glaucoma(angleclosureglaucoma) →Becausethereisnomiosis →whichmakesthefiltrationC.Ieasier>IOPmayrisedangerously→ acuteattackofeyepain.
ngcomiaredropEye
totreattheglaucomatolateIt
أي مرض بالعین یسبب كربة وھم للشخص
*Active vs. passive mydriasis:• Atropine (anticholinergic): Blocking muscarinic receptorsà relaxing circular muscles à Passive Mydriasis• Sympathetic stimulation: activation of a receptors in radial muscles à contraction àActive mydriasis** in the sympathetic system, activation of a receptors leads to smooth muscle contraction, and activation of b2 receptors leads to smooth muscle relaxation
• Contractionofdilator(radial) Pupillae (Active mydriasis)→ α1• meantheirisgototheback.• Relaxation ofciliarymuscles(accommodationforfarvision)β2** =reducefiltrationangle.
• Increase inintraocularpressureIOP• Lacrimationα1• Vasoconstriction ofconjunctivalbloodvesselsα1 .(usedasdecongestiondrug)• α&βreceptorsinthebloodvesselsoftheciliaryprocesseshelpinregulationofaqueoushumour formation
Adrenergicagonists
Drug
Non-selectiveagonists(α1,α2,β1,β2)
Selectiveα1agonists Selectiveα2agonists
1- Epinephrine2- Dipivefrin(pro-drugofepinephrine)
Phenylephrine Apraclonidine(eyedrop)
Mecha
nism
of
actio
n
- Increaseuveoscleraloutflowofaqueoushumor.
- ActiveMydriasis(withoutcycloplegia).becausetheireffectisontheradialmuscle,nottheciliarymusclewhichisinnervatedbyparasympathetic*nolossofaccommodation
- Decrease productionofaqueoushumor.
- Increaseuveoscleraloutflowofaqueoushumor.
- Inhibitssympatheticworking.
Routeof
administration Usedlocallyaseye
drops.Eyedrops
Indicatio
ns Openangleglaucoma. 1- Funduscopicexaminationof
theeye.2- Topreventadhesioninuveitis&iritis.3- Decongestantinminorallergichyperemiaofeye.
1- Openangleglaucomatreatment2- ProphylaxisagainstIOPspikingafterglaucomalaserprocedures.
ADRs
1- Headache.2- Arrhythmia.3- Increasedbloodpressure.
1- Maycausesignificantincreaseinbloodpressure.2- Reboundcongestion.3- Precipitationofacuteangle-closureglaucomainpatientswithnarrowangles.
1- Headache.2- Bradycardia.3- Hypotension.
Contra-
indicatio
ns
Inpatientswithnarrowangles(lowdrainage)astheymayprecipitateclosedangleglaucoma.(α1effect)→becauseitisdoingmydriasis.
بمعجزة عیستذكرنا Epinephrine=Dipivefrin) إبراء األكمة(ى
Drug Non-selective Selectiveβ1Non-selective(cardio-selective)
1- Timolol2- Carteolol
Betaxolol
Mech.
Of
actio
n
• Actonciliarybodytodecrease productionofaqueoushumor.• Blockingofβ2 >blockingtherelaxationeffectontheciliarymuscle.
Rout
ofad
min.
Giventopicallyaseyedrops
Indicatio
ns - Canbeusedinpatientswithhypertension&ischemicheartdisease.
- Used intreatmentofopenangleglaucoma.- β-adrenergicblockertimolol,areeffectiveintreatingchronicglaucomabutare
notusedforemergencyloweringofintraocularIndicationspressure.
ADRs Ocularirritation.
Contra-
indicatio
ns 1- Inasthmapatients.(becausetheeffectofβ2> bronchospasm)2- PatientswithCVSdisorders.(becausetheeffectofβ1 ontheheart)
Notes
Β blockersarethemostpopular&effectivetreatmentofopenangleglaucomaAFTERprostaglandins.
!(blockers)طلع مقفل (beta)باب البیت(lol) لووول
العینجاء وقت قطرة
للعینالجزر مفید
عینبیتك من جمالھ كسر العدو
Timolol =longtime
Adrenergicagonists:Betablockers
OcularactionsParasympatheticN.S.
SympatheticN.S.
Cholinergicagonists Cholinergic(muscarinic)antagonists
*These 2areoppositetoeachother • Contraction ofdilator(radial)Pupillae (Active mydriasis)→ α1
• Relaxation ofciliarymuscles(accommodationforfarvision)→β2
2contractions:1- ConstrictionofthepupillaryCircularmuscle(sphinctermuscle)(miosis)drugscausesconstrictionarePreferredintreatmentofglaucoma2-Contractionoftheciliarymuscle(accommodationfornearvision).
2 relaxations:1- Passive *mydriasis →duetorelaxationofcircularmuscles.2- Cycloplegia (lossofnearaccommodation)→duetorelaxationofciliarymuscle.
Decrease inintraocularpressure↓IOP.
Increased IOP→ glaucoma.(especiallyangleclosureglaucoma)
Increase inintraocularpressureIOP
increasesaqueousoutflow α&βreceptorsinthebloodvesselsoftheciliaryprocesseshelpinregulationofaqueoushumour formation
Increasedlacrimation Decreased lacrimalsecretion→sandyeye.
Lacrimationα1
ConjunctivalVasodilatationmayLeadtocongestionineye
Lossoflightreflex. Vasoconstriction ofconjunctivalbloodvesselsα1 (used asdecongestiondrug)
Decreasing productionofaqueoushumor:
Betablockers.
Alpha-2agonists.
Carbonicanhydraseinhibitors.
Increasing outflowofaqueoushumor:
Prostaglandins.
Adrenergicagonists,nonspecific.
Parasympathomimetics.
ThemaingoalistodecreaseIOP by:
Prostaglandins andBetablockersarethemostpopular
Howglaucomaoccurs?1- open:angleoffiltrationisopen(canalofSchlemm )buttheproblemisincreasingintheproductionofaqueoushumor.2- closedangleglaucoma:heretheangleoffiltrationisnarrowbymydriatic drugsneedsurgerytotreatit.
Watchitfrom4:30
)برا )Prost(aglandinsإن فیھ دجاج بروست )nergic)Adreأدري sympathomimetics)Para عشان كذا تبي تصرفني بسرعةincrease(
ouflow) اني سیارةdraseinhibitors)anhybonicCar( ؟ قدام بیتكBeta(blockers) 1+1=2((فیھ ألف وحدة ووحدة(Alpha(
Carbonicanhydraseinhibitors&prostaglandinanaloguesDrug
CarbonicanhydraseinhibitorsE.g.acetazolamide(oral)
dorzolamide (topical)preferred
ProstaglandinanaloguesE.g.latanoprost,
travoprost
Mech.ofa
ction Decrease productionofaqueoushumorbyblocking
carbonicanhydraseenzymerequiredforproductionofbicarbonateions →(transportedtoposteriorchamber,carryingosmoticwaterflow).
Increaseuveoscleral aqueousoutflow.Latanoprost ispreferredduetolesseradverseeffects.TheyhavereplacedbetablockersTheyareusedtopicallyaseyedrops&onceaday.
Indi-
catio
n
openangleglaucoma
ADRs
• Myopia (Nearsightedness), malaise, anorexia, • GI upset, headache.• Metabolic acidosis, renal stone.
• Pigmentationoftheiris(heterochromiairidis)
• Intraocularinflammation.• Macularedema.
Contra-
indicatio
n • Sulfaallergy becausetheyaresulfaderivatives.• Pregnancy• Digitalisusers.
مرة (Prost)جربت دجاج البروست (dayaonce)وحدة بحیاتي
IriseupwithBigbroast=(iris)(Pigmentation)(Prostaglanin)
Ops!IcannotseeanyCars=(carbonicanhydrase)becauseIhaveMyopia
Developmentofangleclosureglaucomaanditsreversalbymiotics:
Mydriasisoccursinaneyewithnarrowiridocorneal angle,andtheirismakescontactwiththelensblockingpassageoftheaqueousfromtheposteriortotheanteriorchamber.
Possiblybuildsupbehindtheiriswhichbulgesforwardandclosestheiridocornealanglethusblockingaqueousoutflow.
Miotic makestheiristhinandpushesitawayfromthelensremovingthepupillaryblockandrestoringaqueousdrainage.
- Acute,painfulincreasesofintraocularpressureduetoocclusionoftheoutflowdrainagepathway.- TheonlywaytotreatitisSurgery,butbeforesurgerywegivehimtreatmenttodecreaseIOP.- Emergencysituationthatrequiretreatmentbeforesurgery(Iridectomy).
Treatmentofnarrowclosedangleglaucoma(acute):
Theuseofdrugsislimitedto:
Oral Acetazolamide
Topicalcholinomimetics e.g.:pilocarpine
Osmoticagents hypertonicsolutionsof(Mannitol,Glycerol).
Analgesics pethidineormorphine(forpain)
Mech.
ofaction 1. Canrapidly↓IOPby↓vitreousvolume.
2. Glycerol50%syrup,orally(causenausea,hyperglycemia).3. Mannitol20%IV(causefluidoverloadandnotusedinheartfailure).4. DehydratevitreousbodywhichreduceIOPpriortoanteriorsurgical
procedures5. IV infusion ofhypertonicsolution(mannitolol,Glycerol)
Indi-
catio
ns UsedonlyinacutesituationstotemporarilyreducehighIOPuntilmoredefinitive
treatmentscanberendered.(priortoanteriorsurgicalprocedure)
ADRs
- Diuresis,circulatoryoverload,pulmonaryedema- Heartfailure- Centralnervoussystemeffectssuchasseizure,andcerebralhemorrhage.
Drug
Corticosteroids NSAIDsTopical Systemic 1- Ketorolac
2- Diclofenac3- Flurbiprofen
1- Prednisolone2- Dexamethasone3- Hydrocortisone
1- Prednisolone2- Cortisone
Mech.
of
actio
n - InhibitionofarachidonicacidreleasefromMOAphospholipidsbyinhibitingphosphlipase A2
- COX(cyclo-oxygenase)inhibitors
Indicatio
ns
1- Anterioruveitis.2- Severeallergicconjunctivitis.3- Scleritis.4- Preventionandsuppressionofcornealgraftrejection.5-postoperatively
2- Posterioruveitis.1- Opticneuritis.
1- Ketorolac:Cystoidmacularedemaoccurringaftercataractsurgery.2- Diclofenac:Postoperativeinflammation,mildallergicconjunctivitis,milduveitis.3- Flurbiprofen:Preoperativelytopreventmiosis duringcataractsurgery.*Becausetheyinhibitprostaglandinswhichproducemiosiswithoutactionofcholinergic.
ADRs
- Glaucoma,cataract,mydriasis(especiallyifitis usedforalongtime)- Skinatrophy.- Secondaryinfection.- Delayedwoundhealing.(healingisslowbecauseitisanimmunesuppression)
- Stinging(irritation)- Sterilecornealmelt&perforation.
AmiodaroneChloroquine
1- Pigmenteddepositsofcornea.2- Opticneuropathy(milddecreasedvision+visualfielddefects)3- Retinopathy.
Digitalis 1- Oculardisturbances2- Chromatopsia (objectsappearyellow,overdosingcancauseoculardisturbances)(FACT:Van gogh usedtotakedigitalis)
Phenothizines 3- Brown pigmentarydepositsinthecornea,conjunctiva&eyelid.
Steroids 1- Cataractformation2- IncreaseIOP3- Glaucoma(longtermuse)
Ethambutol(TB Medication)
1- OpticneuropathyCharacterizedbygradualProgressivecentralscotomasandvisionloss.
Sildenafil 1- Causesabluish haze2- LightsensitivityItInhibitsPDE5inthecorpuscavernosum toachievepenileerectionItalsomildlyinhibitsPDE6whichcontrolsthelevelofcyclicGMPintheretina→seeingabluishhaze&causinglightsensitivity
ومصابة تاجتلبس أمي الملكةبالعمى
)بنيبعید عن موزیتي ) ذا زیتي لونھ كأنو( نقرأ اسم الدرق
لھا العمىإثم بتول سبب
ة الدكاتر بسالیدزتذكرنا أزرق دایم لونھا
:قادة فريق علم األدوية
عبدالرحمن ذكري &لي التميمي :الشكر موصول ألعضاء الفريق املتميزين
الشثريري
باراسيرنا جواهر اخليال
شذا الغيهب روان سعد القحطاني
الشيبيمال آ
References:1- 436doctorsslides2- Team4353-Pharmacology(Lippincotts IllustratedReviewsSeries),5thedition.
@pharma436
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