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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5200_Библиотеки_им_академика_М_И_Перельмана

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abuse.
AdverseEvents
Adverse effects includelipid elevations, abnormal liver function,alopecia, skin peeling, pruritus,dry skin,drymouth,epistaxis,paresthesia,paronychia,andpseudotumorcerebri.
Interactions
Drug interactions occur with methotrexate (MTX, Rheumatrex), alcohol, and progestin-only contraceptives.Womenmustnotingestalcoholduringtherapyorfor2monthsafterwardbecausealcohol prolongstheteratogenicpotentialofthedrug.
Methotrexate
MTXisusedtotreatgeneralizedpsoriasis.
MechanismofAction
MTXinhibitsfolicacidreductase,resultingintheinhibitionofcellularreplicationandselectionofthe mostrapidlydividingcells.
Dosage
Theinitialdoseis7.5mgaweekadministeredinthreedosesovera24-hourperiod.Itisthentitratedtoa doseof12.5to25mgaweek.Withimprovementinthedisease,thedoseisreducedandotheragentsare used.Folicacid,1mgdaily,shouldbetakenonnontreatmentdays.
Contraindications
MTXis contraindicatedinpregnancy andlactation,andthe drugis usedwithcautioninpatients with renal,hepaticdisordersandleukopenia.
AdverseEvents
Commonadverseeffectsincludeheadache,blurredvision,fatigue,malaise,gastrointestinal(GI)distress, gingivitis,hepatictoxicity,bonemarrowdepression,rashes,alopecia,andchillsandfever.
Interactions
There is an increased risk of toxicity if the patient is taking other medications, such as salicylates, phenytoin(Dilantin),andsulfonamides.UseofMTXalsodecreasestheserumlevelofdigoxin(Lanoxin).
Cyclosporine
MechanismofAction
Cyclosporinesuppressescell-mediatedimmunereactionsandhumoralimmunity.Itinhibitstheproduction ofIL-2,whichisresponsibleforproducingTcellproliferation.Cyclosporinepromotesrapidremission in severe psoriasis flares. It is usually used for short-term treatment (3–6 months) for severe exacerbationsduetotoxicity.
Dosage
Themaximumdoseforuseinpsoriasis is 2to5 mg/kg/d.Maintenancetherapyis atlower doses. Itis suppliedin100-mgtabletsanddosedtwicedaily.
Contraindications
Cyclosporineiscontraindicatedinpregnancyandlactationandmustbeusedwithcautioninpatientswith impairedrenalfunctionandmalabsorption.
AdverseEvents
Adverse effects include hypertension and nephrotoxicity, as well as tremor, gingival hyperplasia, GI upset,hirsutism,andacne.Lesionscanrecurwithindaystoweeksaftertreatmentends,andreboundswith worsesymptomsarenotuncommon.
Interactions
Cyclosporineuseincreasestheriskfornephrotoxicityifthepatientusesothernephrotoxicagents,andit also increases the risk for digoxin toxicity. Cyclosporine interacts with lovastatin, diltiazem, and ketoconazole,anditstherapeuticeffectisdecreasedwithconcomitanthydantoin(Dilantin),rifampin,and sulfonamideuse.Patientsmustavoidgrapefruitproducts.
PHOSPHODIESTERASE4INHIBITORS
Apremilast(Otezla)
MechanismofAction
Apremilast, an oral agent, is a small molecule specific to cyclic adenosine monophosphate. The underlyingmechanismisnotwellunderstood.Nopriorlabstudiesarerequiredpriortoinitiatingtherapy, unliketherequirementwithmostotheragents.
Dosage
Astarterpackisdesignedtoallowfortitrationtomaintenancedose30mgtwicedaily.
Contraindications
Patientswithaknownhypersensitivitytoapremilastanditsingredients.
AdverseEvents
ThemostcommonadverseeventisGIdistressanddiarrheawhichforsomemaybeself-limiting.Weight lossmayalsooccurasasideeffect.Cautionisneededwithuseinpatientswithahistoryofdepression, asthisdrugmayexacerbatesymptoms.
Interactions
Apremilast activity is decreased when coadministered with strong cytochrome P-450 inducers (i.e., rifampin),andmaydecreaseefficacy.
BIOLOGICS
ThebiologicsinteractwithspecifictargetsintheTcell–mediatedinflammatoryprocess. Theyhavean antiinflammatory effect through the inhibition of cytokine release, prevention of T cell activation, depletionofpathologicTcells,andblockingoftheinteractionsthatleadtoTcellactivationormigration intothetissue.TheyalsoalterthebalanceoftheTcelltypesandinhibitkeyinflammatorycytokines,such as TNF-alpha inhibitors (Enbrel and Humira), IL-17 blockage (Taltz Cosentyx and Siliq), IL-12/23 blockade(Stelara),andIL-23antagonists(Tremfya,Ilumya,Skyrizi).Testingfortuberculosis(TB)prior to drug initiation is recommended by placing purified protein derivative (PPD) intradermal or Quantiferon Gold via blood samples for all agents. For individuals who have received the Bacillus Calmette-Guerin (BCG) vaccine, a chest X-ray is recommended. If tested positive, a consult to the infectious diseasedepartmentis recommendedfortreatmentpriorto biologic use.Due tothe immune­suppressivenatureofthesedrugs,otherlaboratorystudiesrecommendedincludeCBC,CMP,lipidpanel, hepatitisB(musttreatpriortobiologicuse),andhepatitisC.
TNF-alphainhibitorswerethefirstbiologicsusedtotreatmoderatetosevereplaquepsoriasis. The followingarecurrentlyapproveddrugsinthisclass:
Etanercept(Enbrel) Infliximab(Remicade) Adalimumab(Humira) Certolizumabpegol(Cimzia)
MechanismofAction
BindsandinhibitsTNF,thecytokinethathelpsregulatethebody’simmuneresponsetoinflammation.Itis usedtotreatmoderatetoseverepsoriasis.
Dosage
Etanercept(Enbrel)inpsoriasis isdosedat50mgsubcutaneouslytwice aweekinitiallyfor3months.
Themaintenancedose is 50 mgsubcutaneouslyweekly, withamaximum of25mggivenatonesite.It requirestwoinjectionsinseparatesites.Infliximab(Remicade)isgivenbyintravenousinfusionoverat least 2 hours. The dose is 5 mg/kg at week 0, week 2, and week 6 and then once every 8 weeks. Adalimumab (Humira) is administered subcutaneously initially80 mgfollowed by 40 mgevery other weekstartingtheweekaftertheinitialdose.Certolizumab (Cimzia)isdosedat400mgsubcutaneously initiallyandtheneveryotherweek.
Contraindications
Contraindications include live vaccines, malignancy, and/or active infection. Caution is exercised in femalesofreproductiveage.Itisnotrecommendedforpatientsinpregnancyorthosewithimpairedrenal function,asthma,historyofblooddyscrasias,demyelinatingdisease,thatis,multiplesclerosis,historyof chronicrecurrentinfections,and/ormalignancy.Infliximabiscontraindicatedinpatientswithmoderateto severecongestiveheartfailure.
AdverseEvents
Adverse events include infection, injection site reaction, localized erythema, rash, upper respiratory infections,abdominalpain,andvomiting.
Interactions
There is an increased chance of infection with those individuals who are immunocompromised. Live vaccinesshouldbegivenpriortoinitiationoftherapyordosageshouldbewithheldfor2weeksbefore and then 1 month after administration of the vaccine to ensure adequate immune response. Similar discontinuationusedforvoluntarysurgicalprocedures.
Ustekinumab
MechanismofAction
Ustekinumab(Stelara)isahumanIL-12andIL-23antagonist.
Dosage
Administeredsubcutaneously,itisavailableintwoweight-baseddoses:Patientsweighinglessthan100 kg(220lbs)receivea45-mgdoseandthoseweighinggreaterthan100kg(220lbs)receive90mgfour timesayear.
Contraindications
Ustekinumabisnotrecommendedforpatientswithsensitivitytoanyoftheexcipients.
AdverseEvents
Mayincludenasopharyngitisandupperrespiratorytractinfections.Seriousinfectionsandmalignancies mayoccur.
Interactions
Livevaccinesshouldnotbegiventopatientstakinguste-kinumab.
Interleukin-17Inhibitors
MechanismofAction
Secukinumab (Cosentyx), Ixekizumab (Taltz), and Brodalumab (Siliq) are monoclonal antibodies that bindtoIL-17,blockingtheabilityofthecytokinetointeractwithitsreceptor.
Dosing
Thefollowingarethedosages: Secukinumab—300mgadministered subcutaneously(in divided doses of150 each) every weekfor 5
weeksandthenonceeverymonth Ixekizumab—80mgadministeredevery2weeksfor3monthsandthenonceevery4weeks Brodalumab—210mgadministeredatweeks0,1,and2andthenonceevery2weeks.
Contraindications
Similartoallotherbiologicagents.
AdverseEvents
Adverseeventsaresimilartothoseofallotherbiologicagents.
Contraindications
Nolivevaccines.
Interleukin-23inhibitors
MechanismofAction
Guzelkumab(Tremfya),Tildrakizumab(Ilumya),andrisankizumab(Skyrizi)blockIL-23.InhibitionofIL­23cytokinepreventsthecascadeofinflammatorycells.ByblockingtheIL23pathway,itactivatesand maintainstheThelper17pathway.
Dosing
Guselkumab 100 mg subcutaneously at weeks 0, 4, and then every 8 weeks. Tildrakizumab 100 mg subcutaneouslyatweeks0,4,andthenevery12weeks.
Contraindications
Similartoallotherbiologicagents.
AdverseEvents
Similartoallotherbiologicagents.
Contraindications
Nolivevaccines.
Biosimilarsarealsonowavailableforsomeoftheseagents.
SelectingtheMostAppropriateAgent
Selectionoftherapydependsonthepatient’sage,typeoflesion,involvement,andprevioustreatments. Mildtorelativelymoderatepsoriasis (lessthan10%BSA)canbetreatedbya primarycareprovider. Topicaltreatmentofpsoriasisisthefirststepandisusuallyeffectiveformilddisease.Patientswithmore generalizeddiseasearereferredtoadermatologistfortreatmentandphototherapy,andsystemicagents areused(Table14.2andFigure14.1).
Itappearsthatcombinationtherapywithsystemicagentsandothermodalitieshavesynergisticvalue.In combination therapy,the dose canoftenbe reduced, causingless toxicity fromhigher dose individual drugs. Systemic therapy with phototherapy is also effective, but time constraints of biweekly therapy hinderuse.
First-LineTherapy
First-linetherapyincludesmoisturizersandtopicalsteroids.For2weeks,ahigh-potencyorveryhigh– potencytopicalsteroidisappliedtwicedailyandcoveredbyanocclusivedressingofplasticwrap.A low-potency preparation is used on the face and intertriginous areas. An ointment is recommended becauseitprovidesthemostmoisture.Anemollientisalsousedtokeeptheskinhydrated.
Second-LineTherapy
Ifthepatient’sresponsetofirst-linetherapyisnotoptimal,severalsecond-linechoicesareavailable.If thepatientshowsagoodresponse,therapymayconsistofaweek’srestfromthetopicalcorticosteroids. Another option is the use of corticosteroids twice daily weekends and vitamin D analog twice daily weekdays.Limitingtheuseofhigh-potencytopicalcorticosteroidstoonceortwiceaweekandaddinga lower-strengthoravitaminDanalogtwicedailytotheregimenareotheroptions.Thisproducesabetter resultthaneitherdrugusedalone.Thetopicalcorticosteroidhelpscleartheplaquesandreducesirritation fromthevitaminDpreparation.
Third-LineTherapy
Iffirst-andsecond-linetreatmentsfail,apatientisreferredtoadermatologist,whomayuseultraviolet (UV)Blighttreatments,antimetabolites,biologicagents,orpsoralensplusUVA=PUVA.
TABLE14.2
RecommendedOrderofTreatmentforPsoriasis
Order Therapy Comments
First line
High-potencytopicalcorticosteroidsappliedtomoistskinanduse ofocclusivedressingtwicedailyfor2weeks.Useemollientsas adjuncttherapy
Usewhen<10%ofbodysurfacearea isaffected
Second line
Ifthepatientrespondedwelltofirst-linetherapy,providea1-week restfromthetopicalcorticosteroidsandinitiateanother2weeksof therapywiththesameagentfortwomoretimes
Ifthereisremission,applyingthe topicalsteroidsonceortwiceaweek
maymaintainremission OR Taperthehigh-potencytopicalcorticosteroidusetoonceortwicea
weekandaddavitaminDanalogtwicedaily
Third line
Refertodermatologistforsystemictherapy Forusewith>20%bodysurfacearea,
UVBisusedwithcoaltaroranthralin;
PUVAisusedwithpsoralens
PUVA,PsoralenandultravioletAtherapy;UVB,ultravioletBtreatments.
FIGURE14–1Treatmentalgorithmforpsoriasis.BSA,bodysurfacearea.
MONITORINGPATIENTRESPONSE
The goal of chronic topical corticosteroid therapy is to use the lowest effective potency to control symptoms.Initially,follow-upmayhavetobedonemonthlyandthenmayprogresstoevery2to3months.
PATIENTEDUCATION
DrugInformation
In patients with psoriasis, education regarding stress reduction and symptom control is important to preventprogressionofdiseaseandreachtherapygoals.Thepopulationshouldunderstandthatpsoriasis isnotcontagious.Inaddition,referralforcounselingmayhelpwithrelatedemotionalissues.
Psychosocial concerns should be addressed since this condition can affect self-esteem and social interactionswithothers.Patientsmayalsobenefitfrominformationandsupportfromgroupssuchasthe NationalPsoriasisFoundation(1-800-723-9166,www.psoriasis.org).
Demonstration for proper application of topical steroids is an important aspect of care. The medicationsaretobeusedtwicedailyandappliedlightlyonmoistskinformaximumbenefit.
LifestyleChanges
Symptomcontrol,ratherthancure,isthegoaloftherapy.Patientsmayhelpcontrolsymptomsbyexposing their skin to the sun. This should be accomplished by gradually increasing the length of exposure. Emphasisshouldbeplacedontheimportanceofusingsunscreenandavoidingsunburn.
Topreventinfection,patientsmusttakecaretonotcutthelesionswhenshaving(iftherearelesionsin thearea).Psoriasiscanbetriggeredbyinfections,stress,andchangesinclimatethatcandryskin.These shouldbeavoidedwhenpossible.
ComplementaryandAlternativeMedicine
Fishoilisthoughttoaltertheimmuneresponseandinsmallquantitiescanrelieveitchingandscaling.It hasaneffectonchronicplaquepsoriasisindosesof6to15gdaily.Analternativeistoeatfishthricea week.Aloeverawas showntobeeffectiveintreatmentofpsoriasis.Ina16-weekstudy,therewasan
82.8%clearingofpsoriaticplaquebyuseof0.5%hydrophilicaloeveracreamthricedaily.Glucosamine has been shown to relieve some of the pain of arthritis from psoriasis. Dietary changes to avoid inflammatorysubstancesareencouraged.
CASESTUDY1
P.B.isa58-year-oldwomanwithahistoryofhypertension.Sheseekstreatmentforscatteredplaques with a silvery-white scale on her elbows, forearms, and knees. The body surface area affected is approximately8%.Sheis veryself-consciousaboutthelesions:“Ijustwantthemtogoaway.” Her medicationsincludepropranolol40 mgthricedailyandfurosemide40mgdaily.Shehasapositive familyhistoryofpsoriasisandreportshighlevelsofstressinherjobandlife.Shesmokesapackof cigarettesperday.
Diagnosis:Psoriasis
1.ListspecificgoalsfortreatmentforP.B.
Answer: Will state relief from itch. Understands the possible side effects from topical steroid
therapy.
2.Whatdrugtherapywouldyouprescribe?Why?
Answer:Classonetopicalsteroid.Provideimprovementinscale,itch,andinflammation.
3.Whataretheparametersformonitoringthesuccessofthetherapy?
Answer:Thinningofscale,relieffromitch.
4.Discussspecificpatienteducationbasedontheprescribedtherapy.
Answer:Limituseofpotenttopicalsteroids.Theconditionwaxesandwanes.
5.Listoneortwoadversereactionsfortheselectedagentthatwouldcauseyoutochangetherapy.
Answer:Striae,skinthinning,hypopigmentation.
6.Whatwouldbethechoiceforsecond-linetherapy?
Answer:VitaminDanalog.
7.Whatover-the-counteroralternativemedicationswouldbeappropriateforP.B.?
Answer:Moisturizers.
8.WhatlifestylechangeswouldyourecommendtoP.B.?
Answer:Smokingcessation.Stressreductiontechniques.
9.Describeoneortwodrug–drugordrug–foodinteractionsfortheselectedagent.
Answer:Topicalagentsshouldbeusedatalternatingintervalsratherthandilutingtheeffect.
CASESTUDY2
J.D.is a 46-year-old male withnew onsetplaquepsoriasis.Familyhistoryis positive onmaternal side.Thelesionsareitchy,bleeding,andrubbingonclothing.Heisseekingaquickfixandwantstobe rid ofthisrash.Hehasnotbeeninforhisannualappointmentforthelastfewyears,sonobaseline laboratoryresultsexist.He denies jointpain,butlesionsareevidentonextensor surfacesincluding elbowsandkneesandondifficult-to-treatareassuchasscalp.Nootherhealthconcernsandcurrently takingnodailymedications.Headmitstoafamilyhistoryofirritablebowelsyndrome.
Diagnosis:Psoriasis
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