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8/9/2019 Leprosy Class 2010
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Pharmacotherapy: Leprosy
Dr.U.P.RathnakarMD.DIH.PGDHM
www.pharmacologyfordummies.blogspot.com
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Gerhard ArmauerHansen (1841-1912)
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Leprosy is a diseaseNonfatal, chronic infectious diseaseMycobacterium LepraeEnters the human body through Upper
respiratory tractPathology is determined by theimmune response
Damages peripheral nervesDisability and deformity
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Mycobacterium leprae
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Leprosy - Case Definition
Cardinal Signs of LeprosyDefinite loss of sensation ina skin lesionSkin smears positive forAFBThickening of peripheralnerves
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Leprosy Classifications[Histology- Lab., research]
R idley-Jopling CMILepromatousLepromatous ( LL)(LL)
BorderlineBorderline lepromatouslepromatous (B L)(BL)BorderlineBorderline (BB )(BB)BorderlineBorderline TuberculoidTuberculoid (BT )(BT)
TuberculoidTuberculoid (TT )(TT)Indeterminate ( I )Indeterminate ( I )
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Leprosy Classifications[No. of skin leisions, Clinical assumption-Operational]
W.H.O Skin leisionsPaucibacillary (2-5 skin lesions -PBL )
[TT, BT & I]TT, BT & I]
M ultibacillary (>6 lesions -M BL )[LL, BL & BB]LL, BL & BB]
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T uberculoid
Lepramatous
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Classification of Antileprosy Drugs:Classification of Antileprosy Drugs:SulfoneSulfone::
D apsoneD apsone ( DDS )( DDS )
PhenazinePhenazine derivative:derivative:ClofazimineClofazimine
AntitubercularAntitubercular drugs:drugs:R ifampicinR ifampicin && EthionamideEthionamide
Other antibiotics:Other antibiotics:O
floxacinO
floxacin,,M
inocyclineM
inocycline,,C
larithromycinC
larithromycin
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Dapsone ( DDS, diaminodiphenyl sulfone )Dapsone ( DDS, diaminodiphenyl sulfone )Related to Sulfonamides.Related to Sulfonamides.
BacteriostaticBacteriostatic
InhibitsInhibits folatefolate synthasesynthase
DapsoneDapsone is cumulative andis cumulative and metabolisedmetabolised in liver.in liver.
It undergoesIt undergoes enterohepaticenterohepatic circulation.circulation.
t1/2: > 24 hours.t1/2: > 24 hours.
DDS
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Adverse effects: Adverse effects:
Allergic rashesAllergic rashesStevensStevens--Johnson syndromeJohnson syndrome
HaemolysisHaemolysis--common in G6common in G6--PDPDdeficiencydeficiencyMethemoglobinemiaMethemoglobinemiaHepatitisHepatitisAgranulocytosisAgranulocytosisGastric intoleranceGastric intolerance
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G6PD
G lucoseG
lucose -6-Phospate 6- Phoshogluconate
Hexokinase
NAD P NAD PH
GSS G GS H
Deficiency
GSH DEF.
Hemolysis
No protectionFor RBC·sAgainstOxidativesubstances
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Contraindications forContraindications for DapsoneDapsone: :
SevereSevere anaemiaanaemiaGG--66--PD deficiencyPD deficiency
Hypersensitivity reactionsHypersensitivity reactions
O ther uses ofO ther uses of DapsoneDapsone: :
DermatitisDermatitis herpetiformisherpetiformisMalaria ( combined withMalaria ( combined withpyrimethaminepyrimethamine ))
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ClofazimineClofazimine: :
Red purpleRed purple phenazinephenazine dye.dye.IncreasesIncreases mycobacterialmycobacterial phospholipasephospholipase A2A2activity, and inhibits microbial K+activity, and inhibits microbial K+transporttransportLeprostaticLeprostatic && antiinflammatoryantiinflammatory [E NL][ENL]Concentrated by macrophages.Concentrated by macrophages.
Absorbed orally t ½Absorbed orally t ½ - - 70 days.70 days.
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ClofazimineClofazimine :Adverse effects::Adverse effects:
ReddishReddish--black discoloration ofblack discoloration ofskin,hairskin,hair & body secretions.& body secretions.AcneAcnePhototoxicityPhototoxicityConjunctivalConjunctival pigmentationpigmentation
GIT symptomsGIT symptoms--Early & LateEarly & LateUses:Uses:
Leprosy andLeprosy and LepraLepra reactionreaction
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R ifampicinR ifampicin: :Bactericidal and makes leprosy patientsBactericidal and makes leprosy patientsnonnon--contagious.contagious.R ifampinR ifampin forms a stable complex with DNAforms a stable complex with DNAdependent R NA polymerase.dependent R NA polymerase.
It is given once a month under supervisionIt is given once a month under supervision
Drugs used in alternative MDT regimens:Drugs used in alternative MDT regimens:
Ethionamide,Ofloxacin,MinocyclineEthionamide,Ofloxacin,Minocycline&&ClarithromycinClarithromycin..
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WHO Multidrug therapyWHO Multidrug therapy
(MDT)(FDT)(MDT)(FDT)WHOWHO --MDTMDT --combination ofcombination of R ifampicinR ifampicin, ,ClofazimineClofazimine andand DapsoneDapsoneR ifampicinR ifampicin - -most importantmost important antileprosyantileprosy drugdrug - -included in the treatment of both types ofincluded in the treatment of both types ofleprosyleprosyTreatment of leprosy with only oneTreatment of leprosy with only one antileprosyantileprosydrug will always result in development of drugdrug will always result in development of drugresistance to that drugresistance to that drugMonotherapyMonotherapy should be considered as unethicalshould be considered as unethicalpracticepractice
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W hat are the basic principles in usingW hat are the basic principles in using MDTMDT for thefor thetreatment of leprosy?treatment of leprosy?
1.1. R ifampicinR ifampicin should be one ofshould be one ofthe components of MDTthe components of MDT - - atatleast once a monthleast once a month
2.2. In addition toIn addition to R ifampicinR ifampicin- -O ne more drug used in PBO ne more drug used in PB3.3. In addition toIn addition to R ifampicinR ifampicin- -Two more drugs used in MBTwo more drugs used in MB
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PaucibacillaryPaucibacillary Leprosy: [ W .H .O]Leprosy: [ W .H .O]S upervisedS upervised- - once a monthonce a month
R ifampicinR ifampicin 600mg600mgDapsoneDapsone 100mg100mg
S elf administeredS elf administered - -dailydailyDapsoneDapsone 100mg100mg
DurationDuration
6 months6 months
Rifampicin
Dapsone
Dapsone
Rifampicin
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Management of Leprosy:Management of Leprosy:(WHO recommended )(WHO recommended )
MultibacillaryMultibacillary Leprosy:Leprosy:S upervisedS upervised- - once a monthonce a monthR ifampicinR ifampicin 600mg600mg
ClofazimineClofazimine 300mg300mgDapsoneDapsone 100mg100mgS elf administeredS elf administered dailydaily
DapsoneDapsone 100mg100mgClofazimineClofazimine - -50mg50mg
DurationDuration
12 months12 months
Dapsone Rifampicin
Clofazimine
Clofazamine
Dapsone
Rifampicin
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RifampicinDapsone
Dapsone
Dapsone Rifampicin
Clofazimine
Clofazimine
Dapsone
Rifampicin
Rifampicin
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W hy isW hy is rifampicinrifampicin given only once agiven only once amonth?month?
R ifampicinR ifampicin is a very potent bactericidal agent is a very potent bactericidal agent Single dose of 600 mg is capable of killingSingle dose of 600 mg is capable of killing99.9% of organisms.99.9% of organisms.
R ate of killing is not enhanced by subsequent R ate of killing is not enhanced by subsequent doses.doses.R ifampicinR ifampicin exerts a delayed antibiotic effect forexerts a delayed antibiotic effect for
several days, during which the organism isseveral days, during which the organism isincapable of multiplying.incapable of multiplying.Once a month regimenOnce a month regimen - -feasible and cost feasible and cost- -effective for leprosy control programmes.effective for leprosy control programmes.
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W hy isW hy is clofazimineclofazimine given once a monthgiven once a monthin addition to the daily dose?in addition to the daily dose?
ClofazimineClofazimine is a repository drug,is a repository drug,Given as a loading dose of 300 mgGiven as a loading dose of 300 mgonce a monthonce a monthEnsures that the optimal amount of Ensures that the optimal amount of
clofazimineclofazimine is maintained, even if theis maintained, even if thepatient occasionally misses his or herpatient occasionally misses his or herdaily dose.daily dose.
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Community Vs Institutional careCommunity Vs Institutional care
CommunityCommunity carecare Pt Pt non contagiousnon contagiousInstitutionInstitution Individual cure Individual cureFDT may be extended if disease activityFDT may be extended if disease activity
persists.persists.
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Alternative regimens Alternative regimensS ingle lesionS ingle lesion- -S ingle doseS ingle dose
RR ifampicinifampicin ²² 600mg600mgOO floxacinfloxacin ²² 400mg400mgMM inocyclineinocycline ²² 100mg100mg
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LepraLepra reactionsreactions["T ype 1" and "T ype 2´]["T ype 1" and "T ype 2´]
Hypersensitivity reactionsHypersensitivity reactionsDying bacilliDying bacilli--release toxinsrelease toxins
JarishJarish--HerxheimerHerxheimer reactionreactionMild or severe [EN L]Mild or severe [EN L]Type IType I--EarlyEarly tt tt, Localized, nerve involvement , Localized, nerve involvement
Type IIType II --Late stages, Generalized, SevereLate stages, Generalized, SevereDrugsDrugs -- ClofazimineClofazimine ChloroquineChloroquine,,Thalidomide & Corticosteroids.Thalidomide & Corticosteroids.
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Leprosy prophylaxis:Leprosy prophylaxis:
BCG vaccine offers some protection.BCG vaccine offers some protection.Dapsone at half the therapeutic dose.Dapsone at half the therapeutic dose.
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G handhiji Prem Navas Leprosy Center in Kolka t a
Why s itua ted next to tr a cks?Only pla ce leper s were allo wed t o l ive .
Why fr on t d oor is so close t o th e t ra cks?Lepers no t allo wed t o use ma in roads
Social sti ma
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Last Sunday of January