ANTI-LEPROTIC DRUGS

1. GRACE COLLEGE OF PHARMACY,PALAKKAD
APPROVED BY PCI,GOVERNMENT OF KERALA AFFLIATED TO KERALA UNIVERSITY OF HEALTH SCIENCES
ANTI-LEPROTIC DRUGS
Prepared by:
Mr. GOKUL J SIDDHARTH
RESEARCH SCHOLAR
gokulsiddu@gmail.com

2. ANTI-LEPROTIC DRUGS
•Leprosy caused by Mycobacterium leprae.
•Considered as an incurable disease
•Chaulmoogra oil is used as anti-leprotic

3. Antileprotic Drugs:
Sulfones
• Dapsone(DDS)
Phenazine
derivatives
• Clofazimine
Anti-tubercular
drugs
• Rifampin
• Ethionamide
Other antibiotic
• Ofoloxacin
• Moxifloxacin
• Minocycline
• Clarithromycin

4. DAPSONE (DDS)
• Diamino diphenyl Sulfone(DDS)
• Simplest, oldest, cheapest, most active,mostcommonly used drugs.
Mode of action:
Chemically related to sulfonamides.

5. ADME
• Oral absorption.
• Widely distributed in the body.
• CSF penetration is poor.
• 70% plasma protein binding, more concentrated in skin, muscle, liver,
kidney.
• Metabolized by glucoronide conjugation and sulfates conjugation.
• Excreted in bile and reabsorbed from intestine.
• Final exretion by urine
Adverse effects
• Mild heamolytic anemia
• Dose related toxicity
• Patient with G-6-PD deficiency are more susceptible
• Gastric intolerance-nausea, anorexia
• Methaemoglobinaemia, headache, paresthesia, mental symptoms and
drug fever.

6. • Allergic rashes, phototoxicity,rarely exfoliative dermatitis
• Hepatitis agranulocytosis are rare.
• Leprae reaction,sulfone syndrome
Contraindications:
• Dapsone should not be used in patients with severe anemia with
(Hb˂7g/dl) and G-6-PD deficiency
Uses:
• Leprosy
• Dapsone + pyrimethamine combination used for chloroquine-resistant
malaria.
CLOFAZIMINE:
• It is a dye with leprostatic and anti-inflammatory properties.
Mode of action:
• Interfere template function of DNA in M.leprae

7. Resistance:
• Resistance produced in 1-3yrs when it is used alone
ADME
• Orally active/absorbed
• Accumulates in many tissues
• Entry into CSF is poor
• t½ -70days
Adverse effects:
Skin: Reddish black discoloration, discoloration hair other body
secretion, itching, phototoxicity, dry skin, conjunctival pigmentation
and cosmetic problems
GI: Enteritis,losesstool,nausea, abdominal pain, anorexia,weight loss
Contraindications:
Clofazimine contraindication with liver and kidney damage patients

8. Anti-TB Drugs
• Rifampin and Ethionamide
(Refer anti TB chapter)
OtherAntibiotic
OFLOXACIN:
• Active against M.leprae
Mode of action
• Ofloxacin inhibit topoisomerase IV and DNA gyrase
No DNAReplication
Inhibit cell division
• Component of Multi-drug Therapy (MDT)

9. Adverse effects:
• Abdominal pain cramp, Dry mouth, Fatigue,GI intolerance, Visual
Disturbance
MINOCYCLINE
• Tetracycline derivatives active against M.leprae
• Dose:100mg/day
• Used as alternative MDT regimen
Mode of action:
Minocycline bind and inhibit protein synthesis by binding to 30S
ribosomal subunit
Interfere the binding and attachment of aminoacyl tRNA
ribosomal complex
Bacteriostatic effect

10. Adverse effects:
• Numbness
• Hair loss
• Dizziness
• Muscle/joint pain
• Rashes, itching
• Loss of appetite
CLARITHROMYCIN
• Macrolide antibiotic having significant activity against M.leprae.
• Less bactericidal than Rifampin.
• Used as alternative MDT regimens.

11. Mode of action:
Clarithromycin
binding with 50S ribosomal subunit &Inhibit bacterial protein synthesis
Interfere protein translocation
Interfere protein synthesis
Bactericidal effects
Adverse effect :
• GI disturbance
• Nausea,vomoting
• Diarrhea
• Rashes, abdominal pain
• Elevated blood urea nitrogen

12. • Chemotherapy of leprosy:
• The WHO recommends the use of MDT for all leprosy cases.
• Leprosy has been classified into two types multibacillary and
paucibacillary leprosy.
• The objective 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 drugs resistant bacilli.
3.To prevent relapse by destroying the document bacilli (persisters)
4.To shorten the duration of effective therapy.
TREATMENT SCHEDULES OFTHERAPY
All drugs are administrated orally .
1.For multibacillary leprosy(LL,BL and BB)
• Rifampacin600mg.once monthly
• Clofazimine 300mg,once monthly
• Dapsone 100mg,daily
• Clofazimine 500mg
Supervised
Unsupervised (self-administrated)

13. • Duration of treatment is 2yrs,and later the patient should be followed
up for period of 5yrs.
• If clofazimine is unacceptable, the alternative drugs used is
ethionamide 250mg daily.
2. For paucibacillary leprosy (TT,BT,AND I)
• Rifampicin 600mg once monthly: supervised.
• Dapsone 100mg daily: unsupervised
Duration of treatment is 6 months, later the patient should be followed up
for a period of minimum 2years.
3.Alternative regimens
• Clofazimine 50mg+ any two newer
drugs(ofloxacin,minocycline,clarithromycin,etc..) daily for 6 months
followed by clofazimine 50mg + any one newer drugs daily for
another 18months.
• For single-lesion paucibacillary leprosy :(ROM regimens).

14. Rifampicin 600mg
Ofloxacin 400mg
Minocycline 100mg
LEPRAREACTIONS
•
• These are immunologically mediated reaction that occur during the
course of the disease.
• The exact cause of such reaction Is not clear and is usually precipitated
by infection trauma, mental stress,etc.
• There are two types of reaction:
1. Type 1 lepra reaction(reversed reaction):
It is a delayed type of hypersensitivity and is seen in borderline
categories of leprosy.
• Characterized by neuropathy with painful tender nerves lesions.
• There are also cutaneous ulceration; when they occur after the
initiation of therapy, they are known as reversal reaction.
• Type 1 lepra reaction is treated with oral prednisolone.
As a single dose

15. 2. Type 2 lepra reaction (erythema modosum leprosum):
• It is a type 2 hypersensitivity reaction and is commonly seen in
lepromatous leprosy.
• It is more severe than type 1 lepra reaction.
• It is characterized by tender,inflammed subcutaneous nodule with
fever,lymphadenopathy,arthritis, indocyclitis,nerve pain,orhitis etc.
• The type 2 reaction maybe be due to release of antigen from the dying
lepra bacilli.
• Severe from type 2 reaction is treated with thalidomide, but
pregnancy is the absolute contraindication..
• The other drugs used are aspirin,clofazimine, chloroquine and
prednisolone.

16. REFERANCE
KD Tripathi Essential of Medical Pharmacology
7th Edition Page no:765-779
©2013,KD Tripathi