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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
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