Clinical Features of Leprosy and Pharmacology of Anti-leprosy drugs

1. Pharmacology
Anti-Leprotic Drugs
Nem Kumar Jain
MS (Pharm.) Pharmacology & Toxicology
Assistant Professor, School of Pharmacy
ITM University Gwalior

2. Leprosy
 Leprosy (Hansen’s disease) is a chronic, systemic infectious disease.
 Chronic granulomatous inflammation caused by Acid Fast Mycobacterium
leprae
 Which cannot be grown on culture media
 affecting primarily the peripheral nerves and secondarily the skin,
mucous membranes, the eyes, bones, lymph nodes and viscera.
 nine - banded armadillo is considered as its primary reservoir
 Replicate very slow (every 12 days once).
 Has an affinity for macrophages & Schwann cell.
 It grows best at 27-30 C, hence its predilection for cooler areas of the
body.
 Skin, peripheral nerves, anterior chamber of the eye, upper respiratory
tract & testes.

3. Leprosy
 Mode of Transmission: The disease is believed to be spread through droplets
from the nose or mouth of a patient to the skin and respiratory tract of another
person, require prolonged/ frequent contact
 The bacteria multiply very slowly and therefore leprosy is not highly infectious
 About 95% of people have natural immunity against leprosy
 Incubation period: This ranges from 9 months to 20 years.
 Epidemiology:
 Males are more prone to develop leprosy than female
 Children too are more susceptible
 According to WHO: India, Brazil, Indonesia, Myanmar and Nigeria are with most cases.
 Risk factors: Living in abovementioned endemic regions, low socioeconomic class

4. Leprosy
 Classification: based on clinical forms
 Tuberculoid type (TT)
 Lepromatous type (LL)
 Borderline (BB)
 Borderline lepromatous (BL)
 Borderline tuberculoid (BT)
 Indeterminate (I)
 WHO: Operational Classification
 Paucibacillary leprosy (PB) (Non-
infectious): This includes TT, BT, I
and polyneuritic.
 Multibacillary leprosy (MB)
(Infectious): This includes LL, BL
and BB.
 PB Case: A case of leprosy with 1 to 5
skin lesions and without demonstrated
presence of bacilli in a skin smear.
 MB Case: A case of leprosy with 6 or
more skin lesions; or with nerve
involvement; or with demonstrated
presence of bacilli in a slit skin smear
irrespective of the number of skin
lesions.

5. Leprosy
 At least one of the following CARDINAL SIGNS must be present to diagnose
leprosy:
 1. Hypo-pigmented or reddish skin lesion (s) with definite sensory deficit
 2. Involvement of the peripheral nerves, as demonstrated by definite
thickening with loss of sensation and/or weakness of muscles of the
corresponding nerve: lead to organ deformity
 3. Demonstration of Mycobacterium leprae (M leprae) in the lesions.
 The first two cardinal signs can be identified by clinical examination alone while the
third can be identified by microscopic examination of the slit skin smear.
PB
MB Nerve enlargement

6. Anti-Leprotic Drugs
 Classification:
1. Sulfone: Dapsone (DDS)
2. Phenazine derivative: Clofazimine
3. Anti-tubercular Drugs: Rifampin, Ethionamide
4. Other antibiotics: Ofloxacine, Moxifloxacine, Minocycline, Clarithromycin
 Dapsone:
 It is diamino diphenyl sulfone (DDS), the simplest, oldest, cheapest, most active
and most commonly used member of its class.
 Activity and mechanism : Dapsone is chemically related to sulfonamides and has
the same mechanism of action, i.e. inhibition of PABA incorporation into folic
acid; its antibacterial action is antagonized by PABA.
 It is leprostatic at low concentrations
 Specificity for M. leprae may be due to difference in the affinity of its folate
synthase

7. Anti-Leprotic Drugs
 Dapsone-resistance among M. leprae, first noted in 1964
 Primary-in untreated patients, i.e. they have acquired infection from a patient
harbouring resistant bacilli
 Secondary-which develops during therapy in an individual patient with a single
drug
 The incidence of primary dapsone resistance varied from 2.5% to 40%.
 Warrants use of Multi-Drug Therapy (MDT)
 Pharmacokinetics: completely absorbed after oral administration and is widely
distributed in the body, though penetration in CSF is poor
 penetration in CSF is poor. It is 70% plasma protein bound, but more importantly
concentrated in skin (especially lepromatous skin), muscle, liver and kidney
 Dapsone is acetylated as well as glucuronide and sulfate conjugated in liver
 Metabolites are excreted in bile and reabsorbed from intestine, so that ultimate
excretion occurs mostly in urine

8. Anti-Leprotic Drugs
 Adverse effects :
 Dapsone is generally well tolerated at doses 100 mg/ day or less
 Mild haemolytic anaemia is common
 Patients with G-6-PD deficiency are more susceptible
 Gastric intolerance-nausea and anorexia
 Other side effects are methaemoglobinaemia, headache, paresthesias, mental
symptoms and drug fever.
 Cutaneous reactions include allergic rashes, fixed drug eruption, hypermelanosis,
phototoxicity and rarely exfoliative dermatitis.
 Hepatitis and agranulocytosis are other rare complications.
 Lepra reaction and sulfone syndrome
 Contraindications: Dapsone should not be used in patients with severe anaemia
with Hb < 7g%, G-6-PD deficiency and in those showing hypersensitivity reactions.
 Other use In combination with pyrimethamine, dapsone can be used for
chloroquine-resistant malaria.

9. Anti-Leprotic Drugs
 Clofazimine: It is a dye with leprostatic and antiinflammatory properties; acts probably
by interfering with template function of DNA in M. leprae.
 When used alone, resistance to clofazimine develops in 1-3 years.
 Clofazimine is used as a component of multidrug therapy of leprosy. Because of its
antiinflammatory property, it is valuable in lepra reaction.
 Adverse effects:
 reddish-black discolouration of skin
 Enteritis with intermittent loose stool, nausea, abdominal pain, anorexia and weight loss can
occur
 Avoid during pregnancy and liver and kidney patients
 Rifampin:
 an important antitubercular drug; also bactericidal toM. leprae; rapidly renders leprosy patients
noncontagious
 Up to 99.99% M. leprae are killed in 3-7 days.
 The 600 mg monthly dose used in leprosy is ;-elatively nontoxic and does not induce
metabolism of other drugs. It should not be given to patients with hepatic or renal dysfunction
 Ethionamide: hepatotoxic, only when clofazimine cant be used or absolut
necessary

10. Multidrug therapy

11. Reactions in leprosy
 Lepra reaction : These occur in LL, usually with institution of chemotherapy and/
or intercurrent infection. It is a Jarish Herxheimer (Arthus) type of reaction due to
release of antigens from the killed bacilli.
 It may be mild, severe or life threatening (erythema nodosum leprosum).

12. Reactions in leprosy
 Sulfone syndrome It is the reaction which develops 4-6 weeks after dapsone
treatment: consists of fever, malaise, lymph node enlargement, desquamation of
skin, jaundice and anaemia. It is generally seen in malnourished patients.
 Reversal Reaction: This is seen in TT- is a manifestation of delayed
hypersensitivity to M leprae antigens. Cutaneous ulceration, multiple nerve
involvement with pain and tenderness occur suddenly even after completion of
therapy. It is treated with clofazimine or corticosteroids.