Sandra

Manuel

FMMC,

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

To be avoided during

early pregnancy.

In patients with renal or hepatic damage.

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.