ANTIBACTERIAL AntiLeprotic _12 Jan 2024.ppt

DRUGS FOR LEPROSY

1. CLASSIFICATION
•1.SULFONE-DAPSONE
•2.PHENAZINE DERIVATIVE-
CLOFAZAMINE
•3.ANTI TUBERCULOUS DRUGS
RIFAMPIN,ETHIONAMIDE
•4.OTHERS-
CLAIRTHROMYCIN,MINOCYCLINE,
•OFLOXACIN

2. DAPSONE
•MOA-inhibits bacterial folate synthetase
•Prevents folic acid synthesis,BACTERIOSTATIC
•Widely distributed after oral administration
•Poor CSF penetration
•Concentrated in skin,muscle,liver&kidney
•Acetylated in liver
•Entero hepatic circulation
•Elimination is 1-2 weeks

3. contd
•PTERIDINE+PABA
• ↓DIHYDROPTEROATE
• SYNTHETASE
•DIHYDROTEROIC ACID(precursur folic
• acid)
•Dapsone is a structural analogue&competetive
antagonist of PABA
•Also competetive inhibitor of the enzyme

4. ADVERSE DRUG REACTIONS
•MILD HEMOLYTIC ANEMIA
•GASTRIC INTOLERANCE
•OTHERS
•SULFONE SYNDROME(LL)
•REVERSAL REACTIONS(TUBERCULIOD)
•LEPRA REACTIONS(LL)
•C/I-Hb Below 7 gm%,G6pd
defiency,hypersensetivity

5. clofazamine
•Dye - leprostatic &anti inflammatory action
•Binds to mycobacterial DNA,increases
mycobacterial phospholipase A2.
•Dapsone resistant strains killed after 50
days
•Orally active poor, csf entry
•TI/2 is around 70 days

6. ADR-CLOFAZAMINE
•Adverse drug reactions-red brown discolour of
skin,dryness&itching,
•Discoluration of hair, body
secretions,eruptions ,photosensitivity
•Early symptoms-irritant effects
•Eosinophilic enteritis
•Late symptoms-clofazamine crystals-loose
stools,git symptoms
•c/i-pregnancy&liver&kidney disease

7. ETHIONAMIDE
•Alternative to clofazamine
•Causes hepatotoxicity

8. Other antimicrobial agents
•OFLOXACIN-COMPONENT OF MDT
• GOOD RESPONSE,USED INSTEAD
OF RIFAMPYCIN 400mg/day
•MINOCYCLINE-100mg/day
•Alternative MDT regimen
•CLAIRTHROMYCIN-500mg/day

9. RIFAMPIN
•Bactericidal to M.Lepra
•Patient becomes non contagious in 3-7 days
•Used in multi drug therapy
•Shortens duration of treatment
•450-600 mg per month
•c/i-liver &kidney disease
•RIFABUTIN-bactericidal

10. RIFAMPICIN-first line drug in TB
•Wide spectrum
•Inhibits DNA DEPENDENT RNA
POLYMERASE
•Bactericidal for intra cellular & extra
cellular organisms.
•Good distribution including csf
•Induces cytochrome enzymes

11. RIFAMPICIN
•CHEMOPROPHYLAXIS-MENINGIOCOCCAL
DISEASE& MENINGITIS
•IN STAPH.ENDOCARDITIS-WITH
VANCOMYCIN or β LACTUMs
•CHRONIC FURUNCULOSIS
•ERADICATION OF STAPH NASAL CARRIER
•BRUCELLOSIS –with DOXYCYCLINE
•LEGIONELLA infections

12. RIFAMPICIN-ADR
•HEPATITIS-OLD AGE,OTHER
DRUGS,LIVER DISEASE,ALCOHOL.
•FLU-LIKE SYNDROME
•ORANGE –RED COLOUR URINE
•ENZYME INDUCER-↓T1/2 OF
DIGIXON,KETOCONAZOLE,etc.
•GIT
DISTURBANCES,HYPERSENSITIVITY.

13. THALIDOMIDE
•Immunomodulator-inhibits tumour necrosis
factor α
•Used for treatment of erythema nodosum
leprosom
•100mg-300mg/day
•STEPS-SYSTEM FOR THALIDOMIDE
EDUCATION & PRESCRIBING SAFETY

14. RIFAMPICIN-ADR
•HEPATITIS-OLD AGE,OTHER
DRUGS,LIVER DISEASE,ALCOHOL.
•FLU-LIKE SYNDROME
•ORANGE –RED COLOUR URINE
•ENZYME INDUCER-↓T1/2 OF
DIGIXON,KETOCONAZOLE,etc.
•GIT
DISTURBANCES,HYPERSENSITIVITY.

15. ESSENTIALS OF DIAGNOSIS
•*Pale anesthetic macular or nodular and
erythematous skin lesions
•*Superficial nerve thickening with
associated anesthesia
•*History of residence in endemic area in
childhood
•*Presence of acid fast bacclli or
characteristic histological nerve changes

16. TYPES
•LEPROMATOUS- TUBERCULOID
•Defective CMI CMI intact
•Progressive &malignant benign ,less so
•Nodular macular lesions
•Slow symmetric nerve severe asymmetric
•Abundant bacilli few bacilli
•Negative lepromin positive lepromin

17. FIVE CLINICAL TYPES
•Tuberculoid leprosy-skin macules withclear
centers,no virchow cells ,CMI
normal,lepromen test +
•Lepromatous leprosy-infiltration of
skin,thick glossy,virchow cells +,large
nerve trunks involved,atrophy of
muscle&skin.
•BT,BL,BODERLINE DISEASE.

18. MANAGEMENT
•CONVENTIONAL SINGLE DOSE
THERAPY –NOT ADMINISTERED NOW
•MDT –Has advantages
•Prevents drug resistance to monotherapy
•Eliminates persisters
•Reduces duration of therapy
• Single dose Rifampicin kills 95% within 4
days

19. WHO RECOMMENDED
REGIMEN
•For Mutibacillery-Dapsone 100mg/day&
Clofazamine50mg/day&300mg once a month
& Rifampicin 600mg once a month
•Duration-12 months
•For Paucibacillery- Dapsone100mg/day for 6
months. & Rifampicin-600mg once a month
•For single skin lesion PB-Rifampicin-
600mg&Ofloxacin400mg&minocycline100mg.

20. ALTERNATIVE REGIMINS
Clofazamine 50mg+any two of
ofloxacin400mg/minocycline100mg/clairthromyci
n500mg daily for 6months foll by
Clofazamine50mg+any one of ofloxacin
400mg/minocycline100mg daily for
additional 18 months.
Instead of clofazamine,ofloxacin or minocycline
may be substituted.
Only one lesion-ROM REGIMEN

21. Reactions in leprosy
•SULFONE SYNDROME-5-6 WKS after treatment ,fever ,exfoilative
dermatitis,hepatic necrosis,anemia.(exacerbation of LL-Jarish
–herxheimer type)
•LEPRA REACTION-Immune injury from antigen antibody
complex deposition,erythema nodosum leprosm-arthus type
reaction.
•Treat with predisone60mg/day or thalidomide 300mg /day-
erythema nodosom leprosom
•Clofazamine is effective
• analgesics,antibiotics.
•Reversal reactions-in TT-delayed hyper sensitivity
•Treat with clofazamine or corticosteroids
•

22. •Environment: human, mice, nine-banded armadillo
Microorganism: Gram + rod
Spore former: NO
Motile: NO
Susceptibility: anyone
Communicability: infectious
Exposure: exposure to skin
Incubation: 2-20 years
Primary Treatment: antibiotics; multi-drug
treatment
Prognosis: antibiotics keep disfigurement to a
minimum
Quarantine recommended: occasionally
Use as a biological weapon: NO
 

23. Lepra bacilli

24. Boderline tuberculoid

25. Tuberculoid leprosy

26. Lepromatous leprosy

27. Lenonine facies

28. Macule in tuberculoid leprosy

30. DRIVE TO ERADICATE
LEPROSY