病毒感染性疾病的藥物治療

Drugtreatment

ofviralinfectiousdiseasesBingDuGanRanXingJiBingDeYaoWuZhi

LiaoLecturer/Teacher

XXKnowledgeobjective:Tomasterthecommontreatmentdrugsanddrugtreatmentprinciplesforviralhepatitis,acquiredimmunodeficiency,herpeszosterandhand-foot-and-mouth

disease.Abilityobjective:toguidepatientstousedrugsrationally.Curriculumideologicalandpoliticalobjective:

thecurrentstateofthe

virus→Fearnatureandremain

modestLearning

objectivesAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisTreatmentof

COVID-19AcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisViral

hepatitisHerpes

zosterAcquiredimmunodeficiency

syndromeHand-foot-and-mouth

diseaseAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisDisease

overviewConcept:Viralhepatitisisatypeofinfectiousdiseasecausedbyhepatitisvirusinfection,divided HepatitisA(causedbyHAV

infection)into:HepatitisB(causedbyHBVinfection):epidemicin

ChinaHepatitisC(causedbyHCVinfection):epidemicinwestern

countriesHepatitisD(causedbyHDV

infection)HepatitisE(causedbyHEV

infection)AcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisDisease

overviewClinical

manifestations:AnorexiaGreasyaversionNauseaEpigastricdiscomfortFatigueHepatalgiaAbnormalliverfunctionJaundice

andfever(some

patients)AcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisCommontherapeutic

drugsAntiviral

drugsMechanismof

action:Doseandtreatment

course:①Produce

antiviral

protein

to

inhibit

virus

replication;

②Regulate

immunity,

enhance

andpromotetheactivityofnaturalkillercells,cytotoxicTcellsand

macrophages.OrdinaryIFN-α,3～5MU,3times/weekor1timeeveryotherday,subcutaneousorintramuscularinjection,withtreatmentcourseof1yearor

longer.PEG-IFNα2a,180μg,orPEG-IFNα2b,1.5μg/kg,subcutaneous

injection,

1

time

a

week,

with

treatment

courseof1yearor

longer.AcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisCommontherapeutic

drugsAntiviral

drugsα

interferon(IFN-α)Adverse

reactions:ThyroiddysfunctionCardiovascularcomplicationsretinopathyAutoimmunediseasesandrarekidneydamageMental

disorderMyelosuppressionFlu-likesyndromeHearing

lossAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisCommonlyuseddrugs:Lamivudine,Adefovir,Entecavir,TelbivudineandTenofovir.Mechanismofaction:inhibitviralpolymeraseorreverse

transcriptaseDoseand

courseDrug

nameDosageandmethodof

administrationLamivudineOral administration, 100mg/time, 1time/dayAdefovirOral administration, 10mg/time, 1time/dayEntecavirOral administration, 0.5mg/time, 1time/dayTelbivudineOral administration, 600mg/day, 1time/dayTenofovirOral administration, 300mg/day, 1time/dayCommontherapeutic

drugsAntiviral

drugsNucleotide

analoguesAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisCommontherapeutic

drugsAntiviral

drugsAnti-inflammatoryandhepatoprotective

drugsCommonlyused

drugs:PolyenoicacidphosphatidylcholinecapsuleB

vitaminsSilymarinpreparationsGlycyrrhizic

acidpreparationsGlucurolactoneGlutathioneAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisApplicationprinciplesoftherapeutic

drugsIndicationsforantiviraltherapyofhepatitis

BHBV-DNA≥105copies(104copies/mlfor

HBeAg-negative)ALT≥2timestheupperlimitof

normalLiverhistologyshowedKnodellHAI≥4,or≥G2inflammatory

necrosisPatients

with

①

and②

or

③

shouldreceiveantiviraltherapyAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisApplicationprinciplesoftherapeutic

drugsIndicationsforantiviraltherapyofhepatitisC:AllpatientswithpositiveHCV-RNAtestshouldbetreatedwithantiviral

therapy.Treatment

course:HBeAg-positive chronic hepatitis B: The treatment course of nucleotide analogues isrecommendedtobeatleast1yearaftereantigen

seroconversionHBeAg-negativechronichepatitisB:Thetreatmentcourseofnucleotideanaloguesisatleast

2yearsAcquiredimmunodeficiencysyndromeHerpeszosterhand-foot-and-mouth

diseaseViral

hepatitisPrecautionsfor

medicationInterferonandribavirincancauseteratogenicorembryoniclethaleffects.Therefore,duringtreatmentandwithin6monthsoftreatment,allwomenandmenofchildbearingagemusttakecontraceptive

measuresInterferonandribavirincancauseteratogenicorembryoniclethaleffects.Therefore,duringtreatmentandwithin6monthsoftreatment,allwomenandmenofchildbearingagemusttakecontraceptive

measuresDNA

levelsHepatitisCtreatmentrequiresregularmonitoringofliverfunction,HCV-RNAlevels,TSHandbloodlipid

levelsViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseViral

hepatitisHerpes

zosterAcquiredimmunodeficiency

syndromeHand-foot-and-mouth

diseaseViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCase

analysisCase:

Patient,

male,

45

years

old.

4

years

ago,

due

to

family

poverty,

he

went

out

to

workandsoldbloodmanytimesduringtheperiod.Afterearningmoney,hereturnedtohishometown,gotmarriedandhadchildren.Withlowfeveraccompaniedbyfatigue,anorexia

and

weight

loss,

he

was

admitted

to

the

hospital

for

more

than

months.

Physicalexamination:Perilabialpallor,oralmucosacoveredwithwhitemembranes,largejointdeformitiesofextremities.Laboratoryexamination:WBC2.5×109/L，HGB75g/L。Diagnosedas

AIDS.Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCase

analysisDiscussion:1.StatetheinfectionrouteofAIDSacquiredbythepatientinthecase.

Isitpossibleforhisfamilymemberstobeinfected?

Why?2.WhatarethedrugsforAIDS

treatment?Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseDisease

overviewConcept:Acquiredimmunodeficiencysyndrome(AIDS),orAIDS,isaninfectiousdiseasecausedbyhumanimmunodeficiencyvirus(HIV)

infection.Infection

processAdsorptionandpenetrationCircularizationandintegrationTranscriptionand

translationAssembly,maturation

and

buddingViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseDisease

overviewClinicalmanifestationsAcute

stage2～4weeksaftertheinitialHIV

infection.Clinicalmanifestationsincludefever,skinrash,lymphadenopathy,nausea,vomitingandneurologicalsymptoms,etc.,whichwillberelievedafter1～3

weeksHIVantigenandHIVRNAcanbefound,andHIVantibodyispositiveforabout2～6

weeksViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseDisease

overviewClinicalmanifestationsAsymptomatic

stage???Lastsfor6～8yearsorlonger,andthelengthoftimeisrelatedtothenumberandtypeofvirusinfection,theimmunestatusofthebody,therouteofinfection,nutritionalconditionsandother

factorsCD4+Tlymphocytecountdecreased

graduallyContagiousViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseDisease

overviewClinicalmanifestationsAIDS

stageFinalstageafterbeinginfectedwith

HIVAvarietyoffatalopportunisticinfectionsandmalignanttumors

appearMainmanifestations:fever,diarrhea,nightsweats,significantweightloss,systemiclymphadenopathylastingmorethan1

month,etc.Somepatientsshowedneuropsychiatric

symptoms.CD4+lymphocytecountin

patients＜200/μl.Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommontherapeuticdrugs(antiviral

drugs)Nucleosidereversetranscriptaseinhibitors(NRTIs)Commonlyuseddrugs:Lamivudine,Tenofovir,Abacavir,Zidovudine,Emtricitabine,

etc.Mechanismofaction:ThesedrugsarephosphorylatedtoformtriphosphatecompoundswithcompetitiveinhibitionofHIVreversetranscriptase

activity,blockHIVreversetranscription,andinhibitthesynthesisofviraldouble-stranded

DNAViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommontherapeuticdrugs(antiviral

drugs)Non-nucleosidereversetranscriptaseinhibitors

(NNRTIs)Commonlyuseddrugs:Nevirapine,Efavirenz,Etravirin,Ripavirin,

etc.Mechanismofaction:bindtothehydrophobicregionneartheactivesiteofHIVreversetranscriptaseandinterfereswiththeactivityofthe

enzymeViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommontherapeuticdrugs(antiviral

drugs)Proteaseinhibitors

(PIs)Commonlyuseddrugs:Ritonavir,Tiranavir,Atazanavir,Darunavir,Lopinavir,

etc.Mechanismofaction:inhibittheactivityofprotease,sothatthenewlyproducedHIVcannot

matureViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommontherapeuticdrugs(antiviral

drugs)Fusioninhibitors

(FIs)Commonlyuseddrugs:

EnfuvirtideMechanismofaction:actontheoutsideofCD4+TcellstopreventHIVfrominvadingcells.WhenHIVbindstotheCD4+cellreceptor,theviralmembraneandCD4+cellmembraneapproachandfuse,andviralparticlesenterthecell.FIsinterferewiththisinvasionprocessbyinhibitingthefusionofHIVviruswithhost

cells.Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommontherapeuticdrugs(antiviral

drugs)Proteaseinhibitors

(PIs)Commonlyuseddrugs:Ritonavir,Tiranavir,Atazanavir,Darunavir,Lopinavir,

etc.Mechanismofaction:inhibittheactivityofprotease,sothatthenewlyproducedHIVcannotmatureViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommontherapeuticdrugs(antiviral

drugs)Fusioninhibitors

(FIs)Commonlyuseddrugs:

EnfuvirtideMechanismofaction:actontheoutsideofCD4+TTcellstopreventHIVfrominvadingcells.WhenHIVbindstotheCD4+cellreceptor,theviralmembraneandCD4+cellmembraneapproachandfuse,andviralparticlesenterthecell.FIsinterferewiththisinvasionprocessbyinhibitingthefusionofHIVviruswithhost

cells.

Others:IntegraseinhibitorLategravir,CCR5antagonist,

etc.Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseApplicationprinciplesoftherapeutic

drugsClarifythetherapeutictargetof

antiviralReducetheincidenceandmortalityofHIV-relateddiseases,andreduce

theincidenceandmortalityofnon-AIDS-relateddiseases,sothatpatientscangetnormallifeexpectancy

andimprovethequalityoflifeRebuildormaintainimmune

functionInhibitviralreplicationtoreduceviralloadtothelowerlimitofdetectionandreducevirus

mutationReduceabnormalimmune

activationReduceHIVtransmissionandpreventmothertochild

transmissionViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseApplicationprinciplesoftherapeutic

drugsComprehensive

therapyPsychotherapyPrevention

andtreatmentofopportunisticinfectionAnti-HIV

therapy(key)SupportivetreatmentViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseApplicationprinciplesoftherapeutic

drugsTimingofinitiationofantiviraltherapyinadultsand

adolescentsAcute

stageThepatienthasclinical

symptomsAsymptomaticstageCD4+Tlymphocyte＜500/μL，

orCD4+Tlymphocyte＞500/μLbutwithadecreaseofCD4+T-lymphocytes100/μLperyear,viral

load>105copies/mL,combinedHBV/HCVinfection,pregnancy,HIV-relatednephropathy,andhighriskofcardiovascular

diseaseRecommendedschemefornewpatient:2NRTIs+1

NNRTIsViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseApplicationprinciplesoftherapeutic

drugsPrinciplesofapplicationoftherapeuticdrugsEvaluationofefficacyofantiviral

therapyVirologic

indicators:Immunologicalindexes:Clinical

symptoms:Plasmaviralloaddecreasesbymorethan1Lgwithin4weeksandreachesundetectablelevelsafter3to6months—themostimportantindicatorforefficacy

evaluation100

/μL

increase

in

CD4+

T

lymphocytes

1

year

after

treatment

or

30%

increase

in

CD4+T-lymphocytecount3monthsaftertreatmentcomparedto

pre-treatmentWeight

gain

is

the

most

sensitive

indicator

for

evaluating

the

efficacy

of

antiviral

therapy,andchildrencanbe

evaluatedcomprehensively in combination with nutritional, height and developmentalViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseAderversedrug

reactionsGastrointestinalsymptomsAllergic

reactionsPeripheralneuropathy(morecommoninnucleosidedrugs

)Liver

toxicityLacticacidtoxicityreactionOthers:Efavirenzcancauseabnormaldreams,daydreamsandpersonalitychanges;Zidovudineispronetocausefatigue,headache,andanemia;PatientstakingIndinavircanhavedryskin,crackedlips,thinninghair,

etc.Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseViral

hepatitisHerpes

zosterAcquiredimmunodeficiency

syndromeHand-foot-and-mouth

diseaseViral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseDisease

overviewConcept:herpeszosterischickenpoxthatlurksintheneuronsoftheposteriorrootganglionofthehumanspinal

cord-Skindiseasescausedbyherpeszostervirus(VZV).Mostofthemarefoundinthe

middle-agedandoldmen

overtheageof

50Predilectionsite:Innervationareaofintercostal,cervical,trigeminaland

lumbosacralnerves,arrangedinabandalongaperipheralnerve,andmostofthemarefoundononesideofthebody,generallynotexceedingthemedian

line.Localskinburning,sensitizationorpain(withgeneralmalaiseorfever)→irregular

erythemaoflocalskin→clustersofmiliarypapules

→blistersCourseofdisease:2～3

weeksPrognosis:Temporarypaleerythemaorpigmentation,neuralgia(nerve

paralysis)Viral

hepatitisAcquiredimmunodeficiency

syndromeHerpes

zosterhand-foot-and-mouthdiseaseCommonlyusedtreatment

drugsDrug

nameDosageandmethodof

administrationAcyclovirOral administration, 0.4g, 5 times/day; Creatinine clearancerateof10~25ml/min,3times/day;Creatinineclearance<

10ml/min,2

times/dayValacyclovirOraladministration,1g,3times/dayAcetaminophenOraladministration.300~600mg/timesforadults.Onceevery4~6hours.Nomorethan2g/dayforthe

elderly.IbuprofenOraladministration.200~400mg/timesfora