Antileprotic drugs - drdhriti

A Power point presentation on the Drugs used in Leprosy (Antileprotic Drugs) suitable for Undergraduate level Medical Students and also others

1. Dr. D. K. Brahma
Associate Professor
Department of Pharmacology
NEIGRIHMS, Shillong

2. 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. lepraein 1873
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

3. Chaulmoogra oil
Discovery of sulfonamides
1940 onwards
1.Sulfones–Dapsone( DDS)
2.Phenazinederivative -Clofazimine
3.Antituberculardrugs -Rifampicin, Ethionamide
4.Other Antibiotics: Ofloxacin, Moxifloxacin,
Minocyclineand Clarithromycin

4. The simplest, oldest, cheapest, most active and most commonly
used
Diaminodiphenylsulfone(DDS)
MOA:
◦Leprostaticeven 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 folatesynthase
◦Doses for acute infection –too toxic
Activity:
◦Used alone –resistance –MDT needed
◦Resistance –Primaryand Secondary (mutation of folatesynthase–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 antiprotozoalaction (Falciparumand T. gondii)

5. Pharmacokinetics:
◦Complete oral absorption and high distribution (less CNS
penetration)
◦70% bound to plasma protein –concentrated in Skin, liver,
muscle and kidney
◦Acetylated and glucoronidaeand sulfate conjugated –
enterohepatic circulation
◦Half life 24-36 Hrs, but cumulative (1 –2 weeks)
ADRs: Generally Well tolerated drug (100 mg /day)
◦Haemolyticanaemia(oxidizing property) -G-6-PD are
more susceptible
◦Gastric -intolerance, nausea, gastritis
◦Methaemoglobinaemia, paresthesia, headache, mental
symptoms and drug fever
◦Allergic rashes, FDE, phototoxicity, exfoliativedermatitis
and hepatotoxicityetc.

6. Sulfonesyndrome:Starts after 4-6 weeks of
therapy, more common with MDT
◦Symptoms: Fever, malaise, lymph node
enlargement, desquamation of skin, jaundiceand
anemia –malnourished patients
Management:stopping of Dapsonein severe
cases, corticosteroid therapy
◦Corticosteroids (prednisolone 40 –60 mg/day) –
severe cases –till reaction controlled –tapered over
8-12 weeks
Dapsonecontraindications: Severe anaemia
and G-6-PD deficiency and hypersensitivity

7. A dye -Leprostaticand 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 discolourationof skin –exposed parts
◦Discolourationof hair and body secretions, dryness of skin and
itching, acneformeruptions 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. Rifampicin: Cidal. 99.99% killed in 3-7 days, skin
symptoms regress within 2 months
◦Not satisfactory if used alone –persisterseven
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 ENLand Reversalphenomenon
Ofloxacin: all fluoroquinolonesexcept
ciprofloxacin are active. Used as alternative to
Rifampicin –22 daily doses
Minocycline:Lipophillic-enters M leprae. Less
marked effect than Rifampicin

9. Granulomatous infection –skin,, mucous membrane
and nerves
Systems of Classification:
◦1
st
(Based on immune system of the patient): Mainly two
types: lepromatous(sore on skin, nerves, and other organs)
and tuberculoid(sore on skin)
◦2
nd
(Ridley-Joplingsystem –based on symptoms):
Intermediate leprosy (I), Borderline leprosy (BB), Borderline
tuberculoidleprosy (BL), Borderline lepromatous(BL)
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. NLCP (1955) –NLEP (2005)
Monotherapy -1982 and since then MDT
Elimination achieved in India in 2005 (prevalence rate ?) -
“< 1 case per 10,000”
Leprosy classified as LL, BL, BB, BT and TT
For operational purposes:
◦Paucibacillary: few bacilli and non-infectious –TT and BT
◦Multibacillary: large bacilli load and infectious –LL, BL and BB
types
◦Single lesion Paucibacillary: single lesion
Historically: All were treated by Dapsonealone 100-200
mg daily: forTT 4 –5 years and for LL8 –12 years
Drawback: delayed Bacteriological cure and emergence of
resistance -Multidrug therapy introduced (MDT)

11. Paucibacillary(PB) -TT and BTMultibacillary(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 positiveat any one
of the sites

12. Photo Courtesy: Dr. AnjuR. Marak,
SM&HO cum DLO and DMO -MCH,
Ri-BhoiDistrict, Meghalaya

13. Drug Paucibacillary(PB) Multibacillary(MB)
Rifampici
n
600 mg once a month
Supervised
600 mg once a month
Supervised
Dapsone100 mg daily self
administered
100 mg daily self
administered
Clofazimi
ne
- 300 mg once a month
Supervised
50 mg daily self
administered
Duration 6 Months 12 Months
MBL: FDT-24 introduced in India in 1990, but not
continued
Alternative regimens: are used only in case of Rifampicin
resistance or when it is impossible to employ standard MDT.

14. 1.LepraReactionOccurs in LL or BL type (Type –III HSR) –
coincides with institution of chemotherapy or intercurrent
infection
◦Arthustype 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
2.Reversal reaction Occurs in TT and BL cases (Type II HSR)
–delayed hypersensitivity to M. lepraeantigens
•Symptoms: Cutaneous ulceration, multiple nerve involvement
with swollen and tender nerves –occurs suddenly even after
completion of therapy …… Treatment: same as above