2022_Unit_2(B)_Leprosy Notes_JPRaval_MSc_Pages_1_10
2022_Unit_2(B)_Leprosy Notes_JPRaval_MSc_Pages_1_10
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NOTE
Disclaimer
This study material is prepared by Dr. Jignesh P. Raval; The basic objective of this
material is to supplement teaching and discussion in the classroom in the subject.
Students are required to go for extra reading in the subject through library work.
Antimycobacterials: AntiLeprotic agents…………………………………………….Dr. Jignesh P.Raval
Introduction:
Antitubercular drugs- used to treat tuberculosis (TB), caused by Mycobacterium
tuberculosis.
Antileprotic drugs- used to treat leprosy, caused by Mycobacterium leprae.
Mycobacteria are intrinsically resistant to most antibiotics due to following characteristics:
1. They grow slowly compared with other bacteria; antibiotics that are most active against
growing cells are relatively ineffective.
2. Mycobacterial cells can also be dormant and thus completely resistant to many drugs or
killed only very slowly by the few drugs that are active.
3. Lipid-rich mycobacterial cell wall is impermeable to many agents.
4. Mycobacterial species are intracellular pathogens, and organisms residing within
macrophages are inaccessible to drugs that penetrate these cellspoorly.
5. Finally, mycobacteria are notorious for their ability to develop resistance.
Combinations of two or more drugs are required to overcome these obstacles and to prevent
emergence of resistance during the course of therapy. The response of mycobacterial infections
to chemotherapy is slow, and treatment must be administered for months to years, depending
on which drugs are used.
Leprosy
Alternative Name of Leprosy: Hansen's disease
Leprosy is an infectious disease derived from the French work "leper" and from the Greek
word "lepros" which means scaly, referring to the scales that form on the skin in some
cases of leprosy and that has been known since biblical times.
Leprosy is characterized by disfiguring skin sores, nerve damage, and progressive
debilitation.
Leprosy is caused by a bacterium which affects various parts of the body, including in
particular the skin and nerves.
Leprosy is a difficult disease to transmit and has a long incubation period.
Children are more susceptible than adults to contracting the disease.
Causes of Leprosy
Leprosy is caused by the organism : Mycobacterium leprae:
Mycobacterium leprae grow slowly and mainly affect the skin, nerves, and mucous
membranes. Children are more susceptible than adults to contracting the disease.
Person to Person: Most scientists believe that leprosy spreads from person to person
through infected respiratory droplets. While this is one mode of leprosy transmission.
Stages of leprosy:
1st stage: A bacterium enters through skin, the skin sensation become dull and small
patches develop. In this stage the bacteria multiply in the axoplasm of nerve fibers
causing tingling sensations.
2nd stage: skin becomes thick and wrinkled, ears become swollen, nodules are formed in
skin of nose and throat. These nodules discharge fluid which is highly infectious.
3rd stage: the bacteria burst out of the nerve cell and go to peripheral tissues and begin
to proliferarate. This results in deformities in hands, feet, face and toes etc.
Classification
Types of Leprosy
There are two main types of leprosy:
1. Tuberculoid (Paucibacillary leprosy)
2. Lepromatous ((Multibacillary Hansen’s disease))
Both types of leprosy produce lesions on the skin, but the latter form i.e. Lepromatous is most
severe which produces large disfiguring nodules.
This chronic infectious disease usually affects the skin and peripheral nerves but has a
wide range of possible clinical manifestations.
Patients are classified as having paucibacillary or multibacillary Hansen's disease.
Paucibacillary Hansen's disease is milder and characterized by one or more
hypopigmented skin macules.
Transmission:
Nasal droplet
Infected soil
Aerosolized M.Leprae
Sneeze
Direct dermal inoculation
Leprosy can also be hereditary
Routes of transmission are still being researched for leprosy
Treatments of Leprosy
1. Historically, there was no cure for leprosy. With early diagnosis and treatment of
leprosy the symptoms and complications can be minimized.
2. It is important to note that treatment of leprosy differs depending upon the form of the
disease. Treatment will generally continue for one year for tuberculoid leprosy and for
two years for lepromatous leprosy.
3. Treatment of leprosy typically involves medicines along with supportive care.
Supportive care is aimed at treating symptoms and associated complications. A number
of different antibiotics are used to kill the bacteria that cause the disease.
4. Aspirin, prednisone, or thalidomide are used to control inflammation.
5. Many times, medicine for treatment of leprosy can be provided at no cost to patients by
their family doctor or through the Hansen's Disease Clinic closest to them. A person
should see improvements after two to three months of beginning treatment.
6. Pre-modern treatment : Chaulmoogra oil
7. Modern treatment is use of : Dapsone;
Rifampicin
Clofazimine
Pharmacological Treatment:
Multiple Drug Treatment (MDT)
There are several effective chemotherapeutic agents:
Dapsone (diaphenylsulfone, DDS)
Rifampicin (RFP)
Clofazimine (CLF),
Ofloxacin (OFLX)
Minocycline (MINO) constitute the backbone of the multidrug therapy (MDT) regimen.
1. Chaulmoogra oil
A common pre-modern treatment of leprosy was chaulmoogra oil.
It contains glycerides of chaulmoogric acid and Hydnocarpic acid.
The oil has long been used in India as an Ayurvedic medicine for the treatment of
leprosy and various skin conditions. It has also been used in China and Burma.
A component of chaulmoogra oil found in seeds of the tree Hydnocarpus wightiana
(known as chaulmugra in Hindi and Persian), it has played a key role in the treatment of
leprosy since antiquity.
H 2N S NH2
O
DDS (Dapsone)
• Chemically – Sulfonamides i.e. sulfone
• Mode Of Action: It acts by inhibiting the folate synthesis
• Pharmacokinetic properties:
• Oral Tablets (Available in 25mg & 100 mg tablets);
• Half life (T ½) = 24-48 hrs
• It is metabolized in the liver and excreted through urine.
c. Synthesis:
• Dapsone, (4,4-diaminodiphenylsulfone) (34.2.3), is synthesized from either 4-
chloronitrobenzene or from the sodium salt of 4-acetamidobenzenesulfonic acid.
• Reacting 4-chloronitrobenzene with sodium sulfide gives 4,4-dinitrodiphenylthioester
(34.2.1), and oxidation of the sulfur atom in this compound using potassium dichromate
in sulfuric acid gives 4,4-dinitrodiphenylsulfone (34.2.2). Reduction of the nitro group in
the resulting compound using tin dichloride in hydrochloric acid makes the desired
dapsone.
Anorexia: is an eating disorder characterized by immoderate food restriction and irrational fear of gaining weight, as
well as a distorted body self-perception. It typically involves excessive weight loss and is usually found more in
females than in males.
Anemia: is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the
blood.
Hemolytic anemia: is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either
in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular).
Rifampicin
Mechanism of action:
• Rifampicin inhibits bacterial DNA-dependent
DNA dependent RNA synthesis by inhibiting bacterial
DNA-dependent RNA polymerase enzyme.
Pharmacokinetics:
Rifampicin is given orally and is widely distributed in the tissues and body fluids.
Rifampicin is easily absorbed from the gastrointestinal tract because its ester functional
group is quickly hydrolyzed in the bile. (i.e. Enterohepatic cycling)
Plasma half-life(T ½) is 1-5
5 hrs. ,
Though urinary elimination accounts for only about 30% of the drug excretion. About 60% to
65% is excreted through the feces.
Unwanted effects:
Orange colour of body fluids.
Hepatotoxicity- liver failure in severe cases
Respiratory problems- breathlessness
Cutaneous - flushing, , rash, redness and watering of eyes.
Abdominal - nausea, vomiting, abdominal cramps with or without diarrhoea.
Flu-like symptoms - fever, headache.
Clofazimine
Generic Name: Clofazimine
Clofazimine is a fat-soluble
soluble riminophenazine dye
Used in combination with rifampicin and dapsone as
multidrug therapy (MDT) for the treatment of leprosy.
It has been used investigationally in combination with other
antimycobacterial drugs to treat Mycobacterium – avium
infections in AIDS patients
It is dye having Anti-inflammatory
inflammatory activity
Mode Of Action:
Against Leprosy bacilli may involve action on DNA i.e. Clofazimine works by binding to
the guanine bases of bacterial DNA, thereby blocking the template function of the DNA
and inhibiting bacterial proliferation.
Pharmacokinetic properties:
Oral; 6-7 weeks; Plasma Half Life ((T ½) is 8 weeks
Clofazimine is given orally and is widely distributed in the tissues and body fluids.
But clofazimine has a very long half life of about 70 days.
It is metabolised in the liver and excreted through urine.
Uses:
• Clofazimine
imine exhibits a bactericidal effect between that of dapsone and rifampicin.
Adverse
dverse Drug Reactions(ADRs):
Reactions(ADRs)
Reddish urination
Blue – black discoloration of lesions