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9/2/2012




                                      By- Jitendra Bhangale
                                    Assistant Professor & Head,
                                   Department of Pharmacology,
                                Smt N. M. Padalia Pharmacy College,
                                            Ahmedabad
                                                                                     1
                               © 2010 Delmar, Cengage Learning




It is a chronic infectious disease caused by M.leprae, an

acid fast, rod shaped bacillus.

It mainly affects the skin, peripheral nerves, and mucosa of

the respiratory tract etc.,

It has left behind a terrifying image in history and human

memory of mutilation, rejection and exclusion from society.
                                                                                     2
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 1
9/2/2012




Caused by a germ similar to that
which causes tuberculosis.

It attacks the nerves of the
hands, feet and face.

If left untreated can take away
the ability to move fingers, toes
and eyelids.

It can also destroy the ability to
feel pain so those affected are
prone to injuries and burns.

The longer the disease is left
undetected, the more likely it is
that the deformities, so often
associated with leprosy, will occur.
                                                                                     3
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




Lepromatous: damages respiration, eyes, and skin


Tuberculoid: affects nerves in fingers and toes, and


         surrounding skin


Borderline: has effects of both types


                                                                                     4
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 2
9/2/2012




    Examine skin


    Check for patches


    Test for sensation


    Count the number of patches

    Look for damage to nerves

                                                                                     5
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




    Test for sensation

Take a pointed soft object (feather, cotton wick)

Lightly touch alternately the patch & normal skin

Ask the person to point where they were touched

Ask them to close their eyes and repeat the procedure

In case of loss of sensation the person will be able to

point to where they were touched on the normal skin but

not on the patch                 © 2010 Delmar, Cengage Learning
                                                                                     6
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 3
9/2/2012




The diagnosis is made based on finding definite loss of

         sensation in one or more patches.

When you have examined the whole body, count the number

         of patches.

1-5 patches is paucibacillary (PB), more than 5 patches is

         multibacillary (MB) leprosy
                                                                                     7
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




PB Adult
 (6 blister packs)
    Rifampicin 600 mg once a month
    Dapsone 100 mg every day


MB Adult
 (12 blister packs)
    Rifampicin 600 mg once a month
    Clofazimine 300 mg once a month
    Clofazimine 50 mg and dapsone 100 mg every day                                   8
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 4
9/2/2012




                                                                                     9
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                    10
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 5
9/2/2012




Sulfones

     Dapsone
                                              Other
Phenazine derivative
                                                   Ofloxacin
     Clofazimine
                                                   Minocycline
Anti TB agents
                                                   Clarithromycin
     Rifampin

     Ethionamide
                                                                                    11
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




The      sulfones     are    derivatives     of    4,4-diaminodiphenylsulfone

(dapsone).

Dapsone is bacteriostatic, but not bactericidal.

Mechanism of action:-

They are competitive inhibitors of dihydropteroate synthase and

prevent the normal bacterial utilization of para-amino-benzoic acid.

Both possess approximately the same range of antibacterial activity

and both are antagonized by para-aminobenzoic acid.
                                                                                    12
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 6
9/2/2012




Untoward Effects

Methemoglobinemia,                Anorexia,       nausea,        and     vomiting,

headache,           nervousness,           insomnia,          blurred         vision,

paresthesias, reversible peripheral neuropathy




                                                                                    13
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




The rifamycins (rifampin, rifabutin, rifapentine) are a group of

structurally similar, complex macrocyclic antibiotics produced by

Streptomyces mediterranei .

Antibacterial Activity:- Rifampin inhibits the growth of most

gram-positive        bacteria      as     well     as     many       gram-negative

microorganisms such as Escherichia coli, Pseudomonas, indole-

positive and indole-negative Proteus, and Klebsiella. Rifampin is very

active    against     Staphylococcus        aureus      and    coagulase-negative

staphylococci.
                                                                                    14
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 7
9/2/2012




Mechanism of Action:-

Rifampin inhibits DNA-dependent RNA polymerase of mycobacteria

and other microorganisms by forming a stable drug-enzyme

complex, leading to suppression of initiation of chain formation in

RNA synthesis.

More specifically, the β subunit of this complex enzyme is the site

of action of the drug, although rifampin binds only to the

holoenzyme.
                                                                                    15
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




Nuclear RNA polymerases from a variety of eukaryotic cells do not

bind rifampin, and RNA synthesis is correspondingly unaffected in

eukaryotic cells.

High concentrations of rifamycin antibiotics can inhibit RNA

synthesis in mammalian mitochondria, viral DNA-dependent RNA

polymerases, and reverse transcriptases.

Rifampin is bactericidal for both intracellular and extracellular

microorganisms.
                                                                                    16
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 8
9/2/2012




Adverse effect:-

         Hepatitis and deaths

         Chronic liver disease

         Alcoholism

         Respiratory syndrome

         Cutaneous syndrome

         Flu syndrome

         Abdominal syndrome
                                                                                    17
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




Clofazimine         appears       to    preferentially      bind      to    GC-rich

         mycobacterial        DNA       and    also     increase      mycobacterial

         phospholipase A2 activity and inhibit microbial K+ transport.

It is weakly bactericidal against M. intracellulare.

The drug also exerts an antiinflammatory effect and prevents the

         development of erythema nodosum leprosum.

The compound also is useful for treatment of chronic skin ulcers

         produced by Mycobacterium ulcerans.
                                                                                    18
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                                                                                 9
9/2/2012




Thalidomide has been shown effective for the treatment of

erythema nodosum leprosum.

It has immunomodulatory actions and inhibits tumor necrosis

factor-a.




                                                                                       19
                                 © 2010 Delmar, Cengage Learning
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad




                                  By Jitendra Bhangale
                                                                                        20
   Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
                               © 2010 Smt N. M. Padalia




                                                                                                  10

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Leprosy by JITENDRA BHANGALE

  • 1. 9/2/2012 By- Jitendra Bhangale Assistant Professor & Head, Department of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad 1 © 2010 Delmar, Cengage Learning It is a chronic infectious disease caused by M.leprae, an acid fast, rod shaped bacillus. It mainly affects the skin, peripheral nerves, and mucosa of the respiratory tract etc., It has left behind a terrifying image in history and human memory of mutilation, rejection and exclusion from society. 2 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 1
  • 2. 9/2/2012 Caused by a germ similar to that which causes tuberculosis. It attacks the nerves of the hands, feet and face. If left untreated can take away the ability to move fingers, toes and eyelids. It can also destroy the ability to feel pain so those affected are prone to injuries and burns. The longer the disease is left undetected, the more likely it is that the deformities, so often associated with leprosy, will occur. 3 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad Lepromatous: damages respiration, eyes, and skin Tuberculoid: affects nerves in fingers and toes, and surrounding skin Borderline: has effects of both types 4 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 2
  • 3. 9/2/2012 Examine skin Check for patches Test for sensation Count the number of patches Look for damage to nerves 5 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad Test for sensation Take a pointed soft object (feather, cotton wick) Lightly touch alternately the patch & normal skin Ask the person to point where they were touched Ask them to close their eyes and repeat the procedure In case of loss of sensation the person will be able to point to where they were touched on the normal skin but not on the patch © 2010 Delmar, Cengage Learning 6 By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 3
  • 4. 9/2/2012 The diagnosis is made based on finding definite loss of sensation in one or more patches. When you have examined the whole body, count the number of patches. 1-5 patches is paucibacillary (PB), more than 5 patches is multibacillary (MB) leprosy 7 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad PB Adult (6 blister packs) Rifampicin 600 mg once a month Dapsone 100 mg every day MB Adult (12 blister packs) Rifampicin 600 mg once a month Clofazimine 300 mg once a month Clofazimine 50 mg and dapsone 100 mg every day 8 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 4
  • 5. 9/2/2012 9 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 10 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 5
  • 6. 9/2/2012 Sulfones Dapsone Other Phenazine derivative Ofloxacin Clofazimine Minocycline Anti TB agents Clarithromycin Rifampin Ethionamide 11 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad The sulfones are derivatives of 4,4-diaminodiphenylsulfone (dapsone). Dapsone is bacteriostatic, but not bactericidal. Mechanism of action:- They are competitive inhibitors of dihydropteroate synthase and prevent the normal bacterial utilization of para-amino-benzoic acid. Both possess approximately the same range of antibacterial activity and both are antagonized by para-aminobenzoic acid. 12 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 6
  • 7. 9/2/2012 Untoward Effects Methemoglobinemia, Anorexia, nausea, and vomiting, headache, nervousness, insomnia, blurred vision, paresthesias, reversible peripheral neuropathy 13 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad The rifamycins (rifampin, rifabutin, rifapentine) are a group of structurally similar, complex macrocyclic antibiotics produced by Streptomyces mediterranei . Antibacterial Activity:- Rifampin inhibits the growth of most gram-positive bacteria as well as many gram-negative microorganisms such as Escherichia coli, Pseudomonas, indole- positive and indole-negative Proteus, and Klebsiella. Rifampin is very active against Staphylococcus aureus and coagulase-negative staphylococci. 14 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 7
  • 8. 9/2/2012 Mechanism of Action:- Rifampin inhibits DNA-dependent RNA polymerase of mycobacteria and other microorganisms by forming a stable drug-enzyme complex, leading to suppression of initiation of chain formation in RNA synthesis. More specifically, the β subunit of this complex enzyme is the site of action of the drug, although rifampin binds only to the holoenzyme. 15 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad Nuclear RNA polymerases from a variety of eukaryotic cells do not bind rifampin, and RNA synthesis is correspondingly unaffected in eukaryotic cells. High concentrations of rifamycin antibiotics can inhibit RNA synthesis in mammalian mitochondria, viral DNA-dependent RNA polymerases, and reverse transcriptases. Rifampin is bactericidal for both intracellular and extracellular microorganisms. 16 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 8
  • 9. 9/2/2012 Adverse effect:- Hepatitis and deaths Chronic liver disease Alcoholism Respiratory syndrome Cutaneous syndrome Flu syndrome Abdominal syndrome 17 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad Clofazimine appears to preferentially bind to GC-rich mycobacterial DNA and also increase mycobacterial phospholipase A2 activity and inhibit microbial K+ transport. It is weakly bactericidal against M. intracellulare. The drug also exerts an antiinflammatory effect and prevents the development of erythema nodosum leprosum. The compound also is useful for treatment of chronic skin ulcers produced by Mycobacterium ulcerans. 18 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 9
  • 10. 9/2/2012 Thalidomide has been shown effective for the treatment of erythema nodosum leprosum. It has immunomodulatory actions and inhibits tumor necrosis factor-a. 19 © 2010 Delmar, Cengage Learning By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad By Jitendra Bhangale 20 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 10