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Antileprotic drugs - drdhriti
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 – 5 years)
• Curable now – deformities/defects – 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 – higher conc. Arrests growth of may other bacteria
• Chemically related to Sulfonamides – same mechanism – inhibition of incorporation of PABA
into folic acid (folic acid synthase)
• Specificity to M leprae – affinity for folate synthase
• Doses for acute infection – too toxic
• Activity:
• Used alone – resistance – MDT needed
• Resistance – Primary and Secondary (mutation of folate synthase – lower affinity)
• 2.5% to 40% Vs 20% Resistance
• However, 100 mg/day – 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 – concentrated in Skin, liver, muscle and kidney
• Acetylated and glucoronidae and sulfate conjugated – enterohepatic
circulation
• Half life 24-36 Hrs, but cumulative (1 – 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 – malnourished patients
• Management: stopping of Dapsone in severe cases, corticosteroid therapy
• Corticosteroids (prednisolone 40 – 60 mg/day) – severe cases – till reaction
controlled – 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) – but Dapsone resistance cases
responds in 2 months (lag period)
• Kinetics: orally effective – accumulates in fat in crystalline form – entry to CSF
poor – half life 70 days
• Used as component of MDT
• ADRs: - well tolerated
• Reddish-black discolouration of skin – exposed parts
• Discolouration of hair and body secretions, dryness of skin and itching, acneform
eruptions and phototoxicity – conjunctival pigmentation
• GI symptoms: Enteritis with intermittent loose stool, abdominal pain, anorexia and
weight loss – 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 – 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 – 22 daily doses
• Minocycline: Lipophillic - enters M leprae. Less marked effect than
Rifampicin
9. TYPES OF LEPROSY
• Granulomatous infection – 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 – 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 – TT and BT and I
• Multibacillary (<5 lesions): large bacilli load and infectious – 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 – CONTD.
• Initially (1982) – PBL Dapsone + Rifampicin for 6 Months and MBL – Dapsone +
Rifampicin + Clofazimine – 2 years or till disease inactivity/smear negative –
with added 5 years surveillance for MBL cases
• However, 12 years study (in 1994) – fixed duration for 6 months and 2 years
was recommended – 12 million to 2.7 million and no resistance
• In 1999 – 6 months and 1 year recommended
12. WHO (1997) GUIDELINE – MDT
(FDT-12) – 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 – III HSR) – coincides with institution of
chemotherapy or intercurrent infection
• Arthus type of reaction – 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 – 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) – delayed
hypersensitivity to M. leprae antigens
• Symptoms: Cutaneous ulceration, multiple nerve involvement with swollen and
tender nerves – occurs suddenly even after completion of therapy …… Treatment:
same as above
17. “The biggest disease today is not leprosy or
tuberculosis, but rather the feeling of being unwanted,
uncared for, and deserted by everybody.” – Mother
Teresa
Thank you