Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.

1

Leprosy is caused by a slow-growing type of bacteriacalled Mycobacterium leprae (M. leprae)Also known as Hansen's disease, after the scientist hodiscovered M. leprae in 1873It primarily affects the skin and the peripheral nervesLong Incubation period (3 – 5 years)

Sulfones – DAPSONE ( DDS)-DIAMINO DIPHENYLSULFONE

Phenazine Derivative - CLOFAZIMINEAntitubercular Drugs - RIFAMPICIN, ETHIONAMIDEAntibiotics: OFLOXACIN, MOXIFLOXACIN, MINOCYCLINEAND CLARITHROMYCIN

The simplest, oldest, cheapestMOA: Leprostatic even at low concentration

Chemically related to Sulfonamides – same mechanism –inhibition of incorporation of PABA into folic acid (folic acidsynthase)Specificity toM leprae – affinity for folate synthase

Activity: Used alone – resistance – MDT neededResistance – Primary and Secondary (mutation of folate synthase –lower affinity)However, 100 mg/day – high MIC -500 times and continued to beeffective to low and moderately resistant Bacilli (low % of resistantpatient) Persisters. Also has antiprotozoal action (Falciparumand T. gondii)

Pharmacokinetics: Complete oral absorption and high distribution(less CNS penetration) Half life 24-36 Hrs, but cumulative

70% bound to plasma protein – concentrated in Skin, liver, muscleand kidneyAcetylated and glucoronidated and sulfate conjugated –enterohepatic circulation

ADRs: Generally Well tolerated drugHaemolytic anaemia (oxidizing property) - G-6-PD are moresusceptibleGastric - intolerance, nausea, gastritisMethaemoglobinaemia, paresthesia, allergic rashes, FDE,phototoxicity, exfoliative dermatitis and hepatotoxicity etc.

Active against protozoaCombined with pyrimethamine alternative tosulfadoxine-pyrimethamine for P.falciparum andtoxoplasma gondii infectionActive against Pneumocystis jiroveciiAlso has anti-inflammatory property

Symptoms: Fever, malaise, lymph node enlargement,desquamation of skin, jaundice and anemiaStarts after 4- 6 weeks of therapy, more common withMDTManagement: stopping of Dapsone, corticosteroidtherapyDapsone contraindications: Severe anaemia and G-6-PD deficiency

Phenazine dye – antileprotic, anti-inflammatory andBacteriostaticMOA: Interference with template function of DNA

Alteration of membrane structure and transportDisruption of mitochondrial electron transport

Monotherapy causes resistance in 1 – 3 yearsDapsone resistants respond to ClofazimineKinetics: absorbed orally (70%) and gets deposited insubcutaneous tissues – as crystals

Half life – 70 days

ADRs: well toleratedSkin: Reddish-black discolouration of skin,discolouration of hair and body secretions

Dryness of skin and troublesome itching,phototoxicity, conjunctival pigmentation

GIT: Nausea, anorexia, abdominal pain and loosestool (early and late) – dreaded enteritis

Contraindication: Early pregnancy, liver and kidneydiseases

Rifampicin: Cidal. 99.99% killed in 3-7 days, skinsymptoms regress within 2 months

Included in MDT to shorten the duration oftreatment and also to prevent resistanceNo toxic dose as single dose onlyShould not be used in ENL and Reversalphenomenon

Ofloxacin: all fluoroquinolones except ciprofloxacin areactive. Used as alternative to RifampicinMinocycline: Lipophillic - enters M leprae. Less markedeffect than Rifampicin

Anti leprotic and anti tubercularIt is a fast acting drug than dapsoneBut it is more expensive and more toxicIt is orally effective and it is administered dailyPoorly tolerated –hepatotoxicity250mg/day

Only macrolide with activity against M. lepraeLess bactericidal than rifampinMonotherapy- 500mg daily/ 8wks- 99.9% killingSynergistic action with minocyclineUsed in alternative MDT regimenMINOCYCLINEHigh lipophilicity –penetrates into M.leprae100mg/dayAntileprotic activity rif>mino >Clari8 wks treatment

The acute exacerbation which occurs during the course ofleprosy is called as lepra reactionIt occursin LL type- after starting with chemotherapy andintercurrent infectionsJerish Hexheimer (Arthus) type reaction due to release ofantigens from killed bacilliMay be mild severe or life threatening ENL- erythemaNodosum LeprosumTreatment-clofazimine -200mgDapsone temporary withdrawalSevere reaction- prednisone-40-60 mg.. Tapered in 2-3monthsThalidomide –alternative to prednisolone in ENL

TT and BL casesManisfestation of delayed hypersensitivity to M.lepraeantigensCutaneous ulceration, multiple nerve involvement withtender nervesTreatment-Clofazimine/ corticosteroids

Lepromatous-LLBorderline –BLBorderline tubercular-BTTuberculoid TT

Conventional monotherapyMT-Dapsone 100-200m-/ 5/7 days in weekTT-4-5 yrsLT- 8-12 yrs or life long

TuberculoidAnaesthetic patch

CMI-cell mediatedimmunity is normalLepromin test is positiveBacilli rarely found inbiopsyProlonged remission withperiodic exacerbations

LepromatousDiffuse skin and mucousmembrane, nodulesCMI is absent

Lepromin test is negetiveSkin and mucous membrbiopsy +ve for bacilliPrognosis to anaesthesiaof distal parts, atropy

Monotherapy - 1982 and since then MDTElimination achieved in India in 2005 (prevalence rate ?)Leprosy classified as LL, BL, BB, BT and TTFor operational purposes:Paucibacillary: few bacilli and non-infectious – TT and BTMultibacillary: large bacilli load and infectious – LL, BL andBB types

Single lesion Paucibacillary: single lesion

MULTIBACILLARY

RIFAMPIN-600mg OD/once permonth

Dapsone -100mg daily

Clofazimine-300mg once/month50mg-OD

Duration -12 months

PAUCIBACILLARY

RIFAMPIN-600mg OD/onceper month

Dapsone -100mg daily

6 months

Alternativeregimens

Intermittent ROM Rifampin 600mg + Oflox 400mg + Minocycline 100

Once/month PBL 3-6months

MBL 12-24 months

Clofazimine 50mg +(any 2)6months

Ofoxacin 400mg Minocycline100mg

Clarithromycin500mg

RMMx regimenMoxiflox 400mg + minocycline 200mg Rifampin 600mg

PBL- 6dosesMBL-12 doses

Clofazimine 50mg(any 1)

4 drug regimenRifampin 600mgFor 12wks is similarto standard MDT for12 months

Ofloxacin 400mgMinocycline 100mg

Sparfloxacin 200mg

18 months

Clarithromycin500mg

Minocycline 100mg

THANK YOUDownload slides from

Authorstream-raghuprasadaSlideshare-raghuprasada

Youtube-raghuprasada