Leprosy, caused by Mycobacterium leprae ,has been
considered incurable since ages and bears a social
stigma .
Due to the availability of effective antileprotic drugs
now it is entirely curable, but the deformities/defects
already incurred may not be reversed.
Use of antileprotic drugs can be dated back to centuries. Chaulmoogra oil ,with weak antileprotic property
was used in Indian medicine for centuries.
Sulfones- Dapsone
Phenazine derivatives-Clofazimine
Antitubercular drugs- Rifampicin, Ethionamide
Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline,
Clarithromycin
Sulfones-
Phenazine derivatives-Clofazimine
Antitubercular drugs- Rifampicin, Ethionamide
Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline
,Clarithromycin
Sulfones- Dapsone
Phenazine derivatives-
Antitubercular drugs- Rifampicin, Ethionamide
Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline
,Clarithromycin
Sulfones- Dapsone
Phenazine derivatives-Clofazimine
Antitubercular drugs- ,Ethionamide
Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline
,Clarithromycin
Diammino diphenyl sulfone,the oldest,cheapest,most active
member of its class.
Chemically related to sulfonamides and has the same mechanism
of action-inhibition of PABA incorporation into folic acid by folate
synthesis.
Specificity for M.leprae - due to the difference in affinity of its folate
synthase.
But Dapsone resistance among M.leprae, first noted in 1964,has
necessitated the use of multi drug therapy- MDT.
Dapsone resistant M.leprae have mutated folate synthase which
has lower affinity for dapsone. however the peak serum
concentration of dapsone after 100mg/day dose exceeds the MIC
for M.leprae by nearly 500 times ; it continues to be active against
low to moderately resistant bacilli.
The risk of relapse due to dapsone resistant bacilli is reported to be
2-3%.
Mild haemolytic aneamia
Gastric intolerance
Methaemoglobinaemia
Paresthesias
Cutaneous reactions
Sulfone syndrome – a reaction which develops 4-
6weeks after starting dapsone treatment ; consists of
fever , malaise , lymph node enlargement , desquammation of skin , jaundice & anaemia
Mild haemolytic aneamia
Gastric intolerance
Methaemoglobinaemia
Paresthesias
Cutaneous reactions
Sulfone syndrome – a reaction which develops 4-
6weeks after starting dapsone treatment ; consists of
fever , malaise , lymph node enlargement , desquammation of skin , jaundice & anaemia
Mild haemolytic aneamia
Gastric intolerance
Methaemoglobinaemia
Paresthesias
Cutaneous reactions
Sulfone syndrome – a reaction which develops 4-
6weeks after starting dapsone treatment ; consists of
fever , malaise , lymph node enlargement , desquammation of skin , jaundice & anaemia
Shouldnot be prescribed to patients with
- severe anaemia (Hb <7g/dL)
- G6PD deficiency
- hypersensitivity reactions
A dye with leprostatic and anti-inflammatory properties
The putative mechanisms of leprostatic action of Clofazimine are :-
a. interference with the template function of DNA in M.leprae.
b. alteration of membrane structure and its transport function.
c. disruption of mitochondrial electron transport chain.
When used alone, the clinical response to Clofazimine is slower than that to Dapsone and resistance develops in 1-3 years.
Dapsone –resistant M.leprae respond to Clofazimine, but apparently after a lag period of about 2 months.
Reddish black discolouration of exposed parts
Discolouration of hair and body secretions
Dryness of skin and itching
Acneform eruptions
Phototoxicity
Conjunctival pigmentation
Nausea, Anorexia
Abdominal pain
Weight loss
Enteritis with intermittent loose stools
This important tuberculocidal drug is also the most
potent cidal drug for M.leprae : rapidly renders leprosy
patients noncontagious.
Up to 99.9% M.leprae are killed in 3-7 days by
600mg/day dose.
Clinical effects of Rifampicin are rapid.
However the nerve damage already incurred is little
benefited.
It is not satisfactory ,if used alone- persisters are found
even after prolonged treatment and resistance
develops.
Hepatitis
Cutaneous syndrome-flushing, pruritus,rash
Flu syndrome- with chills,fever, headache,malaise and watering of eyes
Abdominal syndrome- nausea ,vomting,abdominalcrampswith/without diarrhoea.
Hepatitis
Cutaneous syndrome-flushing, pruritus,rash
Flu syndrome- with chills,fever, headache,malaise and watering of eyes
Abdominal syndrome- nausea ,vomting,abdominalcrampswith/without diarrhoea.
Urine and secretions may become orange-red but this is harmless.
However ,it should not be given to patients with hepatic or renal dysfunction , as well as during Erythema nodosum leprosum and Reversal reactions in leprosy patients , because it can release large quantities of mycobacterial antigens by inducing rapid bacillary killing.
To deal with dapsone resistant strains of M.leprae and to
shorten the duration of treatment,multidrug therapy
with Rifampicin,Clofazimine and Dapsone was
introduced by the WHO in 1981.
Following the initiative under WHO Action Programme
for Elimination of Leprosy, India introduced MDT for
Leprosy through NLEP-National Leprosy Eradication
Programme in 1982
Conventionally,all forms of leprosy had been treated
with dapsone alone-monotherapy.(100-200mg,daily-5
days a week.duration od treatment depening upon
type: TT- 4to 5 years,LL-8 to 12 years or lifelong.
The MDT is the regimen of choice for all cases of leprosy.
Initially under standard MDT,the PBL cases were treated with Dapsone +Rifampicin for 6 months, while MBL cases were treated with Dapsone+Rifampicin+ Clofazimine for a minimum of 2 years or till disease inactivity/skin smear negativity was achieved.
Due to operational reasons ,NLEP in India experimented with ‘fixed duration therapy of 24 month’(FDT-24) for MBL cases found that the relapse rates were similar to that in standard protocol.
Later,FDT-24 was recommended by WHO in 1994 for all MBL cases whether disease inactivity/skin smear negativity was achieved or not.
The 6 months FDT continues for PBL cases.
MDT leprosy
Reduced risk of
develpmntof resistance
Shortens duration of treatment
Quick relief & safe even
during pregnancy
Renders MBL cases
noninfectious
Many alternative regimens incorporating newer antileprotic drugs have been investigated. However, these are used only in case of Rifampicin - resistance or when it is impossible/inadvisable to employ the standard MDT regimen
Intermittent ROM-rifampicin 600mg+ ofloxacin400mg+ minocycline 100mg are given once a month for PBL and 12-24 month for MBL cases.
Single dose ROM-a single dose of rifampicin + ofloxacin+ minocycline was given for single lesion PBL.
Four drug regimen of rifampicin 600mg+sparfloxacin 200mg+clarithromycin 500mg+minocycline 100mg daily for 12 weeks.