leprosy class 2010

8/9/2019 Leprosy Class 2010

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Pharmacotherapy: Leprosy

Dr.U.P.RathnakarMD.DIH.PGDHM

www.pharmacologyfordummies.blogspot.com



Gerhard ArmauerHansen (1841-1912)



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



Mycobacterium leprae



Leprosy - Case Definition

Cardinal Signs of LeprosyDefinite loss of sensation ina skin lesionSkin smears positive forAFBThickening of peripheralnerves



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 )



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]



T uberculoid

Lepramatous



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



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



Adverse effects: Adverse effects:

Allergic rashesAllergic rashesStevensStevens--Johnson syndromeJohnson syndrome

HaemolysisHaemolysis--common in G6common in G6--PDPDdeficiencydeficiencyMethemoglobinemiaMethemoglobinemiaHepatitisHepatitisAgranulocytosisAgranulocytosisGastric intoleranceGastric intolerance



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



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 ))



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.



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



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..



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



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



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



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



RifampicinDapsone

Dapsone

Dapsone Rifampicin

Clofazimine

Clofazimine

Dapsone

Rifampicin

Rifampicin



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.



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.



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.



Alternative regimens Alternative regimensS ingle lesionS ingle lesion- -S ingle doseS ingle dose

RR ifampicinifampicin ²² 600mg600mgOO floxacinfloxacin ²² 400mg400mgMM inocyclineinocycline ²² 100mg100mg



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.



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.



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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leprosy class 2010

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