ANTILEPROTIC DRUGS

Dr.Ramya.R

© 2009 Chettinad Hospital & Research Institute

 LEPROMATOUS LEPROSY

• The cell-mediated immunity (CMI) is impaired

against lepra bacilli, hence the course of the
disease progresses very rapidly.

• This is characterized by extensive bilateral skin

lesions which contain numerous lepra bacilli.

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 TUBERCULOID LEPROSY
• The cell-mediated immunity is intact and is
characterized by the predominant peripheral
nerve involvement with a single or few skin
lesions.

• The bacilli are seen rarely.

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 TUBERCULOID LEPROSY (Contd..)
• Plenty of lepra bacilli are seen in the skin
lesions of borderline (BB), borderline lepro-
matous (BL) and lepromatous leprosy (LL),
hence these groups are called as multibacillary
leprosy (MBL).
• Borderline tuberculoid (BT), tuberculoid (TT)
and indeterminate (I) leprosy are referred to
as paucibacillary leprosy.

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 DRUGS USED IN LEPROSY
• Diaminodiphenylsulphone (DDS) or dapsone,
clofazimine, rifampicin, ethionamide,
ofloxacin, minocycline, clarithromycin.

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 DIAMINODIPHENYLSULPHONE (DDS) OR
DAPSONE
• Dapsone a sulphone, is the oldest, cheapest
and most widely used agent for the treatment
of leprosy even today.

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 DIAMINODIPHENYLSULPHONE (DDS) OR
DAPSONE
• Dapsone a sulphone, is the oldest, cheapest
and most widely used agent for the treatment
of leprosy even today.

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 MECHANISM OF ACTION
• Sulphones are chemically related to
sulphonamides and have the same
mechanism of action.

• Lepra bacilli utilize PABA for the synthesis of

folic acid, which in turn, is necessary for its
growth and multiplication.

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 MECHANISM OF ACTION (Contd..)
• Dapsone is structurally similar to PABA, hence
competitively inhibits folate synthetase
enzyme and prevents the formation of THFA
(tetrahydrofolic acid).

• Thus dapsone produces leprostatic effect.

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 PHARMACOKINETICS
• Dapsone is given orally and is almost
completely absorbed from the gut, bound to
plasma proteins, widely distributed in the
body, concentrated mainly in the infected
skin, muscle, liver, kidney, etc.
• It is partly secreted in bile and undergoes
enterohepatic cycling.
• Dapsone is metabolized by acetylation and
excreted in urine.
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 ADVERSE EFFECTS
• The common adverse effects are dose-related
haemolytic anaemia and methaemoglo-
binaemia, particularly in patients with G6PD
deficiency.
• Other side effects are anorexia, nausea,
vomiting, fever, headache, allergic dermatitis,
itching and peripheral neuropathy.

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 ADVERSE EFFECTS (Contd..)
• Dapsone may cause exacerbation of
lesions-'sulphone syndrome', which is
character-
ized by fever, dermatitis, pruritus,
lymphadenopathy, methaemoglobinaemia,
anaemia and hepatitis.

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 RIFAMPICIN
• It is the most effective and rapidly acting
bactericidal drug for lepra bacilli; hence WHO
recommends the use of rifampicin in all types
of multidrug regimens.
• It kills most of the bacilli.

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 CLOFAZIMINE
• It is a phenazine dye and has weak
bactericidal activity against lepra bacilli.
• It has anti-inflammatory effect, and hence is
also useful in the treatment of type-2 lepra
reaction.
• Clofazimine binds to mycobacterial DNA to
inhibit its template function.
• It also has good activity against dapsone
resistant organism.
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 CLOFAZIMINE (Contd..)
• It is given orally - the presence of food
increases its absorption.
• It is not metabolized in the body and is
excreted slowly in the faeces via bile.
• It tends to accumulate in tissues and produce
red-to-brown discolouration of the skin on
exposed parts.

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 CLOFAZIMINE (Contd..)
• It can cause pigmentation of the conjunctiva
and cornea, discolouration of the hair, tears,
sweat, urine, etc. Nausea, vomiting,
diarrhoea, and abdominal pain are its
other side effects.

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 ETHIONAMIDE
• It is a second-line antitubercular drug and is
also effective against lepra bacilli.
• Ethionamide can be used as an alternative
drug, when there is a contraindication for the
use of clofazimine or if it is unacceptable.
• It may cause hepatotoxicity.
• The newer agents that are found to be
effective against lepra bacilli are minocycline,
clarithromycin, pefloxacin and ofloxacin.
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 CLARITHROMYCIN
• It is a macrolide antibiotic and has bactericidal
activity against Mycobacterium leprae.

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 MINOCYCLINE
• It is the only tetracycline that has antileprotic
activity.

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 OFLOXACIN
• It has significant bactericidal activity against
lepra bacilli, but it is less effective than
rifampicin.

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 CHEMOTHERAPY OF LEPROSY
• The WHO recommends the use of MDT for all
leprosy cases. Clinically, leprosy has been
classified into two types, multibacillary and
paucibacillary leprosy. The objectives and
need for MDT are:
1.To make the patient non-contagious as early
as possible by killing the dividing bacilli.
2. To prevent the development of drug-
resistant bacilli.
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 TREATMENT SCHEDULES OF LEPROSY
All drugs are administered orally.
1.For multibacillary leprosy (LL, BL and BB)
• Rifampicin 600 mg, once monthly Supervised
• Clofazimine 300 mg, once monthly
• Dapsone 100 mg, daily Unsupervised (self-
• Clofazimine 50 mg, daily administered)

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TREATMENT SCHEDULES OF LEPROSY (Contd..)
• Duration of treatment is 2 years, and later the
patient should be followed up for a period of
minimum 5 years.

• If clofazimine is unacceptable, the alternative

drug used is ethionamide 250 mg daily,
unsupervised.

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TREATMENT SCHEDULES OF LEPROSY (Contd..)
2. For paucibacillary leprosy (TT, BT and I)
• Rifampicin 600 mg, once monthly: supervised.
• Dapsone 100 mg daily: unsupervised.
• The duration of treatment is 6 months, and
later the patient should be followed up for a
period of minimum 2 years.

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TREATMENT SCHEDULES OF LEPROSY (Contd..)
3. Alternative regimens
• Clofazimine 50 mg + any two newer drugs
(ofloxacin, minocycline, clarithromycin, etc.)
daily for 6 months followed by clofazimine 50
mg + any one newer drug daily for another 18
months.

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TREATMENT SCHEDULES OF LEPROSY (Contd..)
• For single-lesion paucibacillary leprosy: (ROM
regimen)
Rifampicin 600 mg
Ofloxacin 400 mg as a single dose
Minocycline 100 mg

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 LEPRA REACTIONS
• These are immunologically mediated reactions
that occur during the course of the disease.
• The exact cause of such reactions is not clear
and is usually precipitated by infection,
trauma, mental stress, etc. There are two
types of reactions:

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 LEPRA REACTIONS (Contd..)
1. Type-1 lepra reaction (reversal reaction): It is a
delayed type of hypersensitivity and is seen in
borderline categories of leprosy. It is
characterized by neuropathy with painful
tender nerve lesions. There are also cutaneous
ulcerations; when they occur after the
initiation of therapy, they are known as
reversal reactions. Type-1 lepra reaction is
treated with oral prednisolone.

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 LEPRA REACTIONS (Contd..)
2. Type-2 lepra reaction (erythema nodosum
leprosum): It is a type-III hypersensitivity
reaction and is commonly seen in lepromatous
leprosy. It is more severe than type-1 lepra
reaction. It is characterized by tender, inflamed
subcutaneous nodules with fever,
lymphadenopathy, arthritis, iridocyclitis, nerve
pain, orchitis, etc.

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 LEPRA REACTIONS (Contd..)
The type-2 reaction may be due to release of
antigen from the dying lepra bacilli. Severe form
of type-2 reaction is treated with thalidomide,
but pregnancy is the absolute
contraindication.The other drugs used are
aspirin, clofazimine, chloroquine and
prednisolone.

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 QUESTIONS
1.Mention the antileprotic drugs. Explain the
mechanism of action and adverse effects of
dapsone.
2. Mention two drugs used for the treatment of
erythema nodosum leprosum with their basis.
3. Mention the treatment schedule for
lepromatous leprosy.

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 QUESTIONS (Contd..)
4. Write briefly on:
(i) Dapsone
(ii) Lepra reaction
(iii) Clofazimine
(iv) Treatment of lepra reaction.

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Thank you!

© 2009 Chettinad Hospital & Research Institute