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ANTILEPROTIC ANTILEPROTIC DRUGSDRUGSDr S.P. Dhanya
Assistant ProfessorPharmacology
Types
Paucibacillary Leprosy - Indeterminate TT
BT Multibacillary Leprosy – BB BL LL
Paucibacillary Leprosy
• <5 Hypoanesthetic skin lesions
• Normal/partially deficient CMI
• Bacilli rarely found• Lepromin test +ve • Prolonged remissions with
periodic exacerbations
Multibacillary Leprosy• >5 Hypoanesthetic skin lesions• mucus membrane involvement• CMI deficient• Bacilli numerous• Lepromin test -ve
ANTILEPROTIC DRUGS • Sulfones-Dapsone( DDS)
•Phenazine derivative -Clofazimine•ATT drugs - Rifampicin,
Ethionamide
Newer drugs• Fluroquinolones-
Pefloxacin,Ofloxacin,Sparfloxacin• Minocycline• Roxithromycin,Clarithromycin, Telithromycin• Rifapentine• Bromidoprim• Deoxyfructose serotonin
DAPSONEDAPSONE
• Oldest and cheapest• Related to Sulfonamide• 4-4diamino diphenyl sulfone MOA Inhibits incorporation of PABA
Bacteriostatic Dose-100mg/day
KINETICSKINETICS Complete oral absorption Undergoes enterohepatic circulation Wide distribution in body Poor CNS penetration Concentrated in skin,muscle,kidney,liver Metabolised by acetylation--
ACEDAPSONE
Adverse drug reaction• Mild hemolytic anemia-dose related• G-6PD deficient patients—Severe
hemolytic anemia• Gastric- intolerance, nausea, gastritis • CNS-wooly headedness-Headache,
mental symptoms-psychosis
• Peripheral neuropathy• Methhemoglobinemia,agranulocytosis-
rare• Hepatotoxicity• Nephrotoxicity• Cutaneous-
rash,photosensitivity,SJS,TEN
Dapsone syndrome• Maculopapular skin rash• Exfoliative dermatitis• Generalised lymphadenopathy• Fever• Jaundice• Occurs within 6 weeks of starting therapy
• Stop dapsone
Uses1. Leprosy2. Dermatitis herpetiformis3. Pneumocystitis carni pneumonia4. Rhinosporidiosis5. Pustular psoariasis6. Nodulocystic acne7. Brown recluse spider bite
Rifampicin
• Source-Str. mediterranei• Spectrum-bactericidal• MOA-Inhibit DNA dependent RNA
polymerase• Rapidly renders non infectious• MIC-0.3µg/ml• Component of multi drug treatment• DOSE -600mg/month
Uses1. TB2. Leprosy3. MAIC infection4. Meningococcal and H. influenza meningitis5. MRSA6. Diphtheria, Legionella7. Brucellosis8. Leishmaniasis
CLOFAZIMINE
• Phenazine dye• Antileprotic,• Antiinflammatory--high dose• Bacteriostatic • MOA Binds preferentially to mycobacterial DNAinterferes with template function• DOSE-100mg/day orally
Repository drug-
–Accumulated in fat and reticuloenothelial system– Poor CSF penetration– T1/2=70 days
ADR • Reversible discolouration (Reddish brown) of
skin ,hair ,conjunctiva ,cornea, secretions• Dreaded-Enteritis Abd pain with loose stools Deposition of clofazimine crystals in intestinal mucosa• Icthyosis, Acne like lesions• Photo toxicity Contraindicated in Pregnancy Hepatic ,renal impairment
Other drugs
OFLOXACIN Rifampicin resistance Dose 400mg/day PEFLOXACIN 400mg/day SPARFLOXACIN 400mg/day
• MINOCYCLINE 100mg/day CLARITHROMYCIN 500 mg/day
Treatment of Leprosy
Treatment of PBL
Dapsone -- 100mg/day selfRifampicin – 600mg/month-
supervised Duration --- 6 months
Treatment of MBL
Dapsone - 100mg daily - self administeredRifampicin – 600mg once a month-supervisedClofazimine- 50mg daily self 300mg once a month-supervised Duration of treatment - 12 months
Alternative regimens of MBL
Clofazimine 50mg/day+ Ofloxacin 400mg/day+ Minocycline 100mg/day OR Dapsone 100mg/day+ Ofloxacin 400mg/day+ Rifampicin 600mg/month
PBL with single lesion
• Earlier used• ROM regimen
R RIFAMPICIN 600mg+ O OFLOXACIN 400mg+ M MINOCYCLINE 100mg
LEPRA REACTIONS
• Immunologically mediated• Episodes of acute /subacute
inflammation • Occurs during the course of leprosy• Precipitated by malaise,
anxiety,acute infection
Type I Type II
• Erythema Nodosum Leprosum-Relapse
• In lepromatous• Type III HSR• Slow and insiduous• New crops of nodulesGlomerulonephritis,Hepatitis,ConjunctivitisKeratitis,fever• No tenderness
• Reversal/Upgrading or Downgrading
• In tuberculoid• Type IV HSR• Abrupt and sudden • Existing lesion-
Edema,erythema
• Tenderness
• Ulceration+• Multiple nerve• Precipitated by drug
• Main treatment-steroids
• Ulceration-• Single nerve• Due to high bacterial
load• Main Steroids
Type I Type II
Type 1
Mild analgesicsModerate to severe-Steroids
60 mg/day-PrednisoloneTaper off in 6-12 months
ClofazimineAzathioprineCyclosporine
Type II
• Steroids-1 mg/kg/day-taper off in 12 weeks• Clofazimine-300mg/day• Thalidomide-300-400mg/day• Colchicine• Pentoxyfylline• Zinc• Antimony compound• Chloroquine
Thalidomide• Immunomodulatory• MOA----Inhibit TNF α,Modulate
IL,lysosomal membrane stabilisation• Controls-Neuritis, Relieve pain Improve renal function
USES
1. ENL2. Aphthous stomatitis in HIV patient3. Behcet’s disease4. TB,Sarcoidosis5. GVHD6. IBD7. Sjogren’s syndrome,DLE/SLE8. Multiple myeloma
Adverse effects• Teratogenicity-Phocomelia
ADR• Painful peripheral neuropathy• Eosinophilia• Drowsiness• Allergic drug reactions
• Dose-100 mg---3 to 4 times daily
