1. ANTILEPROTIC DRUGS
Dr. D. K. Brahma
Associate Professor
Department of Pharmacology
NEIGRIHMS, Shillong
2. INTRODUCTION
⢠Leprosy is caused by a slow-growing type of bacteria called Mycobacterium
leprae (M. leprae)
⢠Also known as Hansen's disease, after the scientist who discovered M. leprae
in 1873 - Dr. Gerhard Henrik Armauer Hansen of Norway
⢠Bears social stigma
⢠It primarily affects the skin, mucous membrane and the peripheral nerves
⢠Long Incubation period (3 â 5 years)
⢠Curable now â deformities/defects â may not reverse
4. DAPSONE (DDS)
⢠The simplest, oldest, cheapest, most active and most commonly used
⢠Diamino diphenyl sulfone (DDS)
⢠MOA:
⢠Leprostatic even at low concentration â higher conc. Arrests growth of may other bacteria
⢠Chemically related to Sulfonamides â same mechanism â inhibition of incorporation of PABA
into folic acid (folic acid synthase)
⢠Specificity to M leprae â affinity for folate synthase
⢠Doses for acute infection â too toxic
⢠Activity:
⢠Used alone â resistance â MDT needed
⢠Resistance â Primary and Secondary (mutation of folate synthase â lower affinity)
⢠2.5% to 40% Vs 20% Resistance
⢠However, 100 mg/day â high MIC -500 times and continued to be effective to low and
moderately resistant Bacilli (low % of resistant patient)
⢠Persisters. Also has antiprotozoal action (Falciparum and T. gondii)
5. DAPSONE (DDS)
⢠Pharmacokinetics:
⢠Complete oral absorption and high distribution (less CNS penetration)
⢠70% bound to plasma protein â concentrated in Skin, liver, muscle and kidney
⢠Acetylated and glucoronidae and sulfate conjugated â enterohepatic
circulation
⢠Half life 24-36 Hrs, but cumulative (1 â 2 weeks)
⢠ADRs: Generally Well tolerated drug (100 mg /day)
⢠Haemolytic anaemia (oxidizing property) - G-6-PD are more susceptible
⢠Gastric - intolerance, nausea, gastritis
⢠Methaemoglobinaemia, paresthesia, headache, mental symptoms and drug
fever
⢠Allergic rashes, FDE, phototoxicity, exfoliative dermatitis and hepatotoxicity etc.
6. SULFONE SYNDROME
⢠Sulfone syndrome: Starts after 4- 6 weeks of therapy, more common with
MDT
⢠Symptoms: Fever, malaise, lymph node enlargement, desquamation of skin,
jaundice and anemia â malnourished patients
⢠Management: stopping of Dapsone in severe cases, corticosteroid therapy
⢠Corticosteroids (prednisolone 40 â 60 mg/day) â severe cases â till reaction
controlled â tapered over 8-12 weeks
⢠Dapsone contraindications: Severe anaemia and G-6-PD deficiency and
hypersensitivity
7. CLOFAZIMINE
⢠A dye - Leprostatic and anti-inflammatory
⢠MOA: Interferes with template function of DNA in M. leparae
⢠Activity: Used alone resistance (1 -3 years) â but Dapsone resistance cases
responds in 2 months (lag period)
⢠Kinetics: orally effective â accumulates in fat in crystalline form â entry to CSF
poor â half life 70 days
⢠Used as component of MDT
⢠ADRs: - well tolerated
⢠Reddish-black discolouration of skin â exposed parts
⢠Discolouration of hair and body secretions, dryness of skin and itching, acneform
eruptions and phototoxicity â conjunctival pigmentation
⢠GI symptoms: Enteritis with intermittent loose stool, abdominal pain, anorexia and
weight loss â early and late symptoms
⢠Should be avoided in pregnancy and liver & kidney disease
8. OTHER DRUGS
⢠Rifampicin: Cidal. 99.99% killed in 3-7 days, skin symptoms regress within 2
months
⢠Not satisfactory if used alone â persisters even prolonged treatment
⢠Included in MDT to shorten the duration of treatment and also to prevent
resistance
⢠Not toxic and no induction of hepatic enzyme - dose as single dose only
⢠Should not be used in ENL and Reversal phenomenon
⢠Ofloxacin: all fluoroquinolones except ciprofloxacin are active. Used as
alternative to Rifampicin â 22 daily doses
⢠Minocycline: Lipophillic - enters M leprae. Less marked effect than
Rifampicin
9. TYPES OF LEPROSY
⢠Granulomatous infection â skin,, mucous membrane and nerves
⢠Systems of Classification:
⢠1st
(Based on immune system of the patient): Mainly two types: lepromatous
(sore on skin, nerves, and other organs) and tuberculoid (sore on skin)
⢠2nd
(Ridley-Jopling system â based on symptoms): Borderline tuberculoid leprosy
(BL), Borderline lepromatous (BL), Borderline leprosy (BB) and Intermediate
leprosy (I)
⢠For operational purposes: WHO
⢠Paucibacillary (>5 lesions): few bacilli and noninfectious â TT and BT and I
⢠Multibacillary (<5 lesions): large bacilli load and infectious â LL, BL and BB types
⢠Single lesion Paucibacillary: single lesion
10. NLEP 2009 CLASSIFICATION
Paucibacillary (PB) - TT and BT and I Multibacillary (MB) - LL, BL and BB
⢠1- 5 skin lesions
⢠No nerve/only one nerve involvement
+/- 1-5 skin lesions
⢠Skin smear negative at all sites
⢠6 or more skin lesions
⢠More than one nerve involved irrespective
of skin lesions
⢠Skin smear positive at any one of the sites
11. MDT LEPROSY â CONTD.
⢠Initially (1982) â PBL Dapsone + Rifampicin for 6 Months and MBL â Dapsone +
Rifampicin + Clofazimine â 2 years or till disease inactivity/smear negative â
with added 5 years surveillance for MBL cases
⢠However, 12 years study (in 1994) â fixed duration for 6 months and 2 years
was recommended â 12 million to 2.7 million and no resistance
⢠In 1999 â 6 months and 1 year recommended
12. WHO (1997) GUIDELINE â MDT
(FDT-12) â 1999 INDIA
Drug Paucibacillary (PB) Multibacillary (MB)
Rifampicin 600 mg once a month
Supervised
600 mg once a month Supervised
Dapsone 100 mg daily self administered 100 mg daily self administered
Clofazimine - 300 mg once a month Supervised
50 mg daily self administered
Duration 6 Months 12 Months
13. LEPROSY PATIENTS IN MEGHALAYA
Photo Courtesy: Dr. Anju R. Marak, SM&HO cum
DLO and DMO-MCH, Ri-Bhoi District, Meghalaya
14. REACTIONS ?
1. Lepra Reaction : Occurs in LL type (Type â III HSR) â coincides with institution of
chemotherapy or intercurrent infection
⢠Arthus type of reaction â release of antigens from killed bacilli - may be mild,
moderate and severe (ENL)
⢠Symptoms: enlarged lesions, become red (inflamed nodules and papules) and
painful, new lesions â fever and other constitutional symptoms
⢠Treatment:
⢠Mild analgesics
⢠Mild: Clofazimine - 200 mg daily
⢠Moderate to severe-Steroids: 60 mg/day-Prednisolone - taper off in 2-3 months
1. Reversal reaction Occurs in TT and BL cases (Type II HSR) â delayed
hypersensitivity to M. leprae antigens
⢠Symptoms: Cutaneous ulceration, multiple nerve involvement with swollen and
tender nerves â occurs suddenly even after completion of therapy âŚâŚ Treatment:
same as above
17. âThe biggest disease today is not leprosy or
tuberculosis, but rather the feeling of being unwanted,
uncared for, and deserted by everybody.â â Mother
Teresa
Thank you