Tuberculosis REMERGING as a plague globally Tuberculosis and Leprosy 2002 2010 1 billion persons newly colonzied lungs Pulmonary TB lymph nodes tuberculous adenitis or scrofula Brain and CNS Meningeal TB skin and the bones Mycobacterium tuberculosis Tuberculosis Chest X ray with TB cavity right upper lobe 1 Therapy Reasons Mycobacteria live dormantly Mycobac agile in developing resistance Patient compliance drug toxicity drug interactions HIV and TB Isoniazid INH Niconyl Hyzyd Rifampin Rifadim Rimactane Ethambutol Myambutol Pyrazinamide Streptomycin Moxifloxacin gatifloxacin Ethionamide Trecator sc Aminosalicylic acid PAS Panasol Cycloserine Amikacin Kanamycin Capreromycin Linezoid III Isoniazid INH First Line Second Line Resistance Bacteriostatic resting mycobac Bactericidal growing mycobact Mycolic acid inh kas katg Catalase peroxidase catalase peroxidase prodrug I Active drug Mechanism of action Inhibits synthesis of mycolic acids 2 Absorption Distribution and Excretion Well absorbed by GI tract Acetylation Scandanavians Jews North african caucasians Diffuses all body fluids including CSF CONHNH2 slow Al antacids interfere with absorption Eliminated via renal system 24 hrs Genetically determined Acetyltransferases fast Inuit japanese CONHNHCOCH3 Untoward Effects Hepatic Necrosis 20 yrs old INH Acetyl INH Hypersensitivity fever various skin eruptions etc Hematological reacns eosinophilia thrombocytopenia etc CONHNH2 CONHNHCOCH3 Arthritic symptoms pyridoxine deficiency competes with vit B6 O CH3 C N NH2 Acetyl hydrazone CYP 450 Hepatic Necrosis 3 Rifamycins RIF bactericidal Drug Interactions rifampin rifabutin rifapentine coadministration cycloserine Rifampin Disulfiram CNS side effects such as dizziness or drowsiness Anticonvulsants i e carbamazepine Hepatotoxicity I Mechanism of action Coordination difficulties and psychotic episodes DNA dependent RNA polymerase Increases their conc in serum by inhibiting hepatic metabolism II Resistance DNA RNA Untoward Effects rpoB polymerase Generally well tolerated Induces hepatitis in patients with chronic liver dis old age and alchohol Flulike symptoms By inducing CYPs decrease half life of HIV protease inhibitors digitoxin verapamil etc Rifapentine half life rifampin rifabutin rifabutin preferred in HIV infected patients 4 Ethambutol Myambutol I Untoward Effects Arabinosyltransferase D arabinose arbinogalactan Optic neuritis visual acuity red green reversible Synthesis of outer coating of cell wall Well absorbed Less toxic so replaced Aminosalicylic acid Effective when given with INH Streptomycin Pyrazinamide Important for short term TB treatment Very potent against mycobacteria Recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated OR Added in patients with serious forms of TB i e Disseminated meningitis Pyrazinamide deamidase Pyrazinoic acid Mycobacteria tuberculosis 5 Quinolones I Gatifloxacin Tequin Moxifloxacin Avelox Absorption Distribution and Excretion Well absorbed from GI Most active Diffuses all body fluids including CSF DNA syn Eliminated via glomerular filtration half life in older II Untoward Effects Liver injury inhibits urate excretion gout anorexia vomiting etc Ethionamide Trecator sc Linezoid NADPH specific FAD monooxygenase I Mechanism binds P site of 50S and inhibits protein synthesis II Untoward Effects Myelosuppression including anemia leukopenia thrombocytopenia Palpitation in patients on adreneric or serotonergic drugs Peripheral and optic neuropathy prodrug I Active drug Mechanism of action Inhibits synthesis of mycolic acids 6 II Absorption Distribution and Excretion Slowly absorbed Diffuses all body fluids including CSF Cycloserine Seromycin Aminosalicylic acid act in a manner like PABA Eliminated via hepatic sys Secondary agent when primary agents fails III Untoward Effects Anorexia nausea vomiting Postural hypotension depression dowsiness common Blurred vision headache VitB6 relieves neurological sym Immunomodulators Interferon Actimmune Activates macrophages to kill M tuberculosis Aerosolised delivery in lungs of multidrug resistant TB patients enhances local immune stimulation Summary TB caused by Mycobacterium tuberculosis affects lung kidney skin Bone Combinatorial treatment therapy plus Interferon 7 Leprosy Mycobacterium leprae chronic ID skin peripheral nerves and mucous membranes eyes respiratory tract also known as Hansen s disease as bacillus causing it was discovered by G A Hansen in 1873 Picture 3 Chronic insensate patch due to leprosy infection Ho Chi Minh City Vietnam Courtesy of D Scott Smith MD common in warm wet areas in the tropics subtropics Multidrug therapy Sulphones Rifampin Clofazimine Picture 7 Man with advanced deformities caused by unmanaged leprosy Keratitis loss of eyebrow thickened skin and typical hand impairments Ho Chi Minh City Vietnam Courtesy of D Scott Smith MD Sulfones Dapsone Alvosulfon bacteriocidal and bacteriostatic I Mechanism similar to Sulphonamides PABA Folic acid Bact growth III Untoward Effects Hemolysis hemolytic anemia Anorexia nausea vomiting Skin rashes Sulphone syndrome fever jaundice malaise exacerbation of lepromatos leprosy by inducing endotoxin formation 8 Drug Interactions Rifampin Rifadin Rimactane Dapsone clofazimine Probenecid anti inflammatory Increases effect dapsone toxicity Clofazimine Lamprene rifampin Decrease dapsone levels I Mechanism inhibits DNA dependent RNA polymerase II Absorption Distribution Excretion rapidly absorbed accumulates in tissue II Untoward effects Skin discoloration eosinophilic enteritis occasional GI intolerance Most prescribed drugs in 2005 lect 12 15 Other Drugs Thalidomide immunomodulatory inhibits TNF not known for leprosy Ethionamide can substitute Clofaziminen Name Class x1000 Amoxil amoxicillin mod Penicillin amoxicillin clavulanate mod Pen lactamse inhibitor azithromycin Macrolides Cephalexin Ist generation cephalosporins doxycycline hyclate Tetracycline derivative Natural penn 52 104 Augmentin Zithromax Keflex Vibra Tabs Penicillin VK Minocycline hydrochloride Tetracycline derivative Tetracycline CEFTIN IIIrd generation cephalosporins Cefzil IIIrd generation cephalosporins Tobramycin Macrolides 18 326 38 110 24 092 10 716 8 872 4 663 2 728 2 484 2 411 2 343 9
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