Leprosy by JITENDRA BHANGALE

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Antileprotic agent

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Leprosy by JITENDRA BHANGALE

  1. 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, anacid fast, rod shaped bacillus.It mainly affects the skin, peripheral nerves, and mucosa ofthe respiratory tract etc.,It has left behind a terrifying image in history and humanmemory of mutilation, rejection and exclusion from society. 2 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 1
  2. 2. 9/2/2012Caused by a germ similar to thatwhich causes tuberculosis.It attacks the nerves of thehands, feet and face.If left untreated can take awaythe ability to move fingers, toesand eyelids.It can also destroy the ability tofeel pain so those affected areprone to injuries and burns.The longer the disease is leftundetected, the more likely it isthat the deformities, so oftenassociated with leprosy, will occur. 3 © 2010 Delmar, Cengage LearningBy 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 LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 2
  3. 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 LearningBy 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 topoint to where they were touched on the normal skin butnot on the patch © 2010 Delmar, Cengage Learning 6By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 3
  4. 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 LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badPB Adult (6 blister packs) Rifampicin 600 mg once a month Dapsone 100 mg every dayMB 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 LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 4
  5. 5. 9/2/2012 9 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 10 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 5
  6. 6. 9/2/2012Sulfones Dapsone OtherPhenazine derivative Ofloxacin Clofazimine MinocyclineAnti TB agents Clarithromycin Rifampin Ethionamide 11 © 2010 Delmar, Cengage LearningBy 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 andprevent the normal bacterial utilization of para-amino-benzoic acid.Both possess approximately the same range of antibacterial activityand both are antagonized by para-aminobenzoic acid. 12 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 6
  7. 7. 9/2/2012Untoward EffectsMethemoglobinemia, Anorexia, nausea, and vomiting,headache, nervousness, insomnia, blurred vision,paresthesias, reversible peripheral neuropathy 13 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’badThe rifamycins (rifampin, rifabutin, rifapentine) are a group ofstructurally similar, complex macrocyclic antibiotics produced byStreptomyces mediterranei .Antibacterial Activity:- Rifampin inhibits the growth of mostgram-positive bacteria as well as many gram-negativemicroorganisms such as Escherichia coli, Pseudomonas, indole-positive and indole-negative Proteus, and Klebsiella. Rifampin is veryactive against Staphylococcus aureus and coagulase-negativestaphylococci. 14 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 7
  8. 8. 9/2/2012Mechanism of Action:-Rifampin inhibits DNA-dependent RNA polymerase of mycobacteriaand other microorganisms by forming a stable drug-enzymecomplex, leading to suppression of initiation of chain formation inRNA synthesis.More specifically, the β subunit of this complex enzyme is the siteof action of the drug, although rifampin binds only to theholoenzyme. 15 © 2010 Delmar, Cengage LearningBy 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 notbind rifampin, and RNA synthesis is correspondingly unaffected ineukaryotic cells.High concentrations of rifamycin antibiotics can inhibit RNAsynthesis in mammalian mitochondria, viral DNA-dependent RNApolymerases, and reverse transcriptases.Rifampin is bactericidal for both intracellular and extracellularmicroorganisms. 16 © 2010 Delmar, Cengage LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 8
  9. 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 LearningBy 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 LearningBy J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad 9
  10. 10. 9/2/2012Thalidomide has been shown effective for the treatment oferythema nodosum leprosum.It has immunomodulatory actions and inhibits tumor necrosisfactor-a. 19 © 2010 Delmar, Cengage LearningBy 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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