hanseníase

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