Antimicrobials

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What are antimicrobials

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  • Trifluridine
  • Antimicrobials

    1. 1. ANTIMICROBIALS… Presented by… VINOD B.DARADE ASHISH A. UBALE ROHIT KAMBALE SWAPNIL RATHOD Guided by.. Mr. prashant PANDEY
    2. 2. What are Antimicrobials? An antimicrobial is a substance that either kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoan's. History The history of antimicrobials begins with the observations of Pasteur and Joubert, who discovered that one type of bacteria could prevent the growth of another.
    3. 3. Terminology… INFECTION- An infection is the invasion of body tissues by disease causing microorganisms. MICROBIOCIDAL- kills the microbes. MICROBIOSTATIC- inhibits the growth of microbes DISINFECTANT- used on non-living objects or outside the body. ANTISEPTIC- substances that are applied to living tissue/skin to reduce the possibility infection. CHEMOTHERAPY- Treatment of systemic infection with specific drug without affecting the host.
    4. 4. ClassificationON THE BASIS OF1. 2. 3. 4. 5. 6. CHEMICAL STRUCTURE MECHANISM OF ACTION TYPE OF ORGANISM SPECTRUM OF ACTIVITY TYPE OF ACTION ANTIBIOTICS OBTAINING FROM
    5. 5. 1.ON THE BASIS OF CHEMICAL STRUCTURE1.Sulphonamide and related drugs- Dapson(DDS), Paraaminosalisylic acid 2.Diaminopyridines- Trimethoprim, Pyrimethamin 3.Quinolones- nalidixic acid 4.B-lactum antibiotics- penicilines, cephalosporin 5.Tetracyclin- oxytetracyclin, doxytetracyclin 6.Nitrobenzene derivative- chloramphenicol 7.Amino glycosides- streptomycin, gentamicin 8.Macrolide antibiotics- erythromycin, clarithromycin 9.Lincosamide antibiotic- lincomycin, clindamycin 10.Glycopeptide antibiotics- vancomycin 11.Nitrofuran derivative- nitrofurantoin derivatives 12.Nitroimidazoles- metronidazoles 13.Polyene antibiotics- Nystatin, Amphoterecin-B 14.Azole derivatives- Ketoconazole, fluconazol
    6. 6. 2. ON THE BASIS OF MECHANISM OF ACTION1. 2. 3. 4. 5. 6. 7. 8. Inhibit cell wall synthesi penicillin, cephalosporin Cause leakage from cell membrane- Amphoterecin-b Nystatin Inhibit protein synthesis- tetracycline, chloramphenicol, erythromycin Cause misreading of m-RNA code and affect permeabilitystreptomycin, gentamycin Inhibit DNA gyrase- Fluroquinolones, ciprofloxacin Interfere with DNA function- Rifampin, metronidazole. Interfere with DNA synthesis- Acyclovir, Zidovudine Interfere with intermediary metabolism- Sulphonamides, sulphones, ethambutol
    7. 7. 3. ON THE BASIS OF TYPES OF ORGANISM AGAINST WHICH PRIMARILY ACTIVE1. Antibacterial- Penicillin's, amino glycosides 2. Antifungal- Griseofulvin, Amphoterecin-b, ketoconazol 3. Antiviral-Acyclovir, Amantidin, Zidovudin 4. Antiprotozoal- Chloroquine, Pyrimethamine 5. Anthelmentic- Mebendazole, pyrantel 4. ON THE BASIS OF SPECTRUM OF ACTIVITY1. Narrow Spectrum- Penicillin-G, Erythromycin 2. Broad Spectrum- tetracycline, Chloramphenicol 5. ON THE BASIS OF TYPE OF ACTION1. Primarily bacteriostatic- Sulphonamide, Erythromycin, ethambutol 2. Primarily bactericidal- Rifampin, isoniazide, penicillin
    8. 8. PROBLEMS THAT ARISE WITH THE USE OF AMAs 1.Toxicity 2.Hypersensitivity reactions 3.Drug resistance 4.Superinfection 5.Nutrirional Deficiencies 6. Masking an action
    9. 9. CHOICE OF AN ANTIMICROBIAL AGENTPATIENT RELATED FACTORS 1. Age 2. Renal & hepatic function 3. Drug allergy 4. Impaired host defense 5. Pregnancy 6. Genetic factors DRUG RELATED FACTORS 1. Spectrum of activity 2. Type of activity 3. Sensitivity of organism 4. Relative toxicity 5. Pharmacokinetic profile 6. Route of administration 7. Cost
    10. 10. COMBINED USE OF ANTIMICROBIALS1. 2. 3. 4. To achieve synergism To reduce adverse effects To prevent emergence of resistance To broaden the spectrum of antimicrobial action PROPHYLACTIC USE OF ANTIMICROBIALS1.Prophylaxis against Specific organismE.g.. Rheumatic fever, T.B , HIV infection, Cholera, Plague 2.Prevention of infection in high risk situationE.g.. Dental extraction, Catheterization, Chronic obstructive lung disease. 3.Prevention of infection in general – E.g. Neonates, Viral upper respiratory tract infection.
    11. 11. Problems that arise with the use of AMA’s 1. Toxicity-such as local irritancy, systemic toxicity 2. Hypersensitivity reactions 3. Drug resistance 4. Super infection 5. Nutritional deficiencies 6. Masking of an infection
    12. 12. Combined use of antimicrobialsTo achieve synergism To reduce adverse effect To prevent resistance To broaden the spectrum of antimicrobial action
    13. 13. SULFONAMIDESThey are the first antimicrobial agents  Because of rapid emergence of bacterial resistance and availability their current utility is limited  CLASSIFICATION1. Short acting- Sulphadiazine 2. Intermediate acting- Sulphamethoxazole 3. long acting- Sulphadoxine 4. Special purpose- Mafenide, Silver
    14. 14. Antibacterial Spectrum – It is primarily Bacteriostatic against Grampositive and Gramnegative bacteria. [Gram-positive: Gram-positive bacteria retain the color of the crystal violet stain in the Gram stain.] [Gram-negative: Gram-negative bacteria lose the crystal violet stain in Gram's method of staining ]
    15. 15. MECHANISM OF ACTIONCertain microbes require p-aminobenzoic acid (PABA) in order to synthesize dihydrofolic acid which is required to produce purines and ultimately nucleic acids.  Sulfonamides,chemical analogs of PABA, are competitive inhibitors of dihydropteroate synthetase.  Sulfonamides therefore are reversible inhibitors of folic acid synthesis and bacterostatic not bacteriocidal. 
    16. 16. p-Amino benzoic acid Di hydro folate sulphonamides synthatase [compete with PABA] Di hydropholic acid Trimethoprime Tetra hydro folic acid Di hydro folate reductase Purins
    17. 17. USESIn treating urinary tract infections  Combination of Trimethoprime and Sulphamethoxazole is used in many bacterial infections  Also used in treatment of Malaria and Toxoplasmosis 
    18. 18. Adverse effects Fever, rash  Photosensitivity  Nausea, vomiting,diarrhea  urinary tract problems  Stevens-Johnson syndrome  Hemopoietic disturbances  granulcytopenia
    19. 19. COTRIMOXAZOLE The fixed dose combination of Trimethorime and Sulphamethoxazole is called as COTRIMOXAZOLE Concentration ratio of Sulphamethoxazole and Trimethoprime is 20:1 Spectrum of action- Salmonella thypi, klebsilla, enterobacter, shigella
    20. 20. p-Amino benzoic acid Di hydro folate sulphonamides synthatase [compete with PABA] Di hydropholic acid Trimethoprime Tetra hydro folic acid Di hydro folate reductase Purins DNA
    21. 21. Uses Urinary tract infection  Respiratory tract infection  Typhoid  Dysentery Adverse effect Patients with renal disease may cause Uremia  bone marrow toxicity due to Cotrimoxazole  Thrombocytopenia  Megaloblastic anemia
    22. 22. QUINOLONESThese are synthetic antimicrobials having a Quinolone structure.  Active against Gram negative Bactria.  Classification1. Nalidixic Acid 2. Fluro- quinolonesa. First generation quinolonesNorfloxacin, ofloxacin, Ciprofloxacin b. Second generation quinoloneslevofloxacin, Moxifloxacin.
    23. 23. Mechanism of actionQuinolones and fluoroquinolones are chemotherapeutic bactericidal drugs, eradicating bacteria by interfering with DNA replication UsesIn treatment of serious bacterial infections  Hospital-acquired infections  Pneumonia  Genitourinary infections  Ciprofloxacin used in Typhoid  Respiratory infection  Tuberculosis 
    24. 24. Adverse effectcardiac arrhythmias Convulsions tendon rupture phototoxicity
    25. 25. ANTIBIOTICS  An antibiotic is a selective poison.  It has been chosen so that it will kill the desired bacteria, but not the cells in your body. Each different type of antibiotic affects different bacteria in different ways.  For example, an antibiotic might inhibit a bacteria's ability to turn glucose into energy, or the bacteria's ability to construct its cell wall. Therefore the bacteria dies instead of reproducing.
    26. 26. Beta-lactam Antibiotics  Antibiotics have a bactericidal effect.  Those antibiotics having a B-lactum ring in their structure are called as the Beta-lactam Antibiotics  Penicilline was the first antibiotic to be used clinically.  It was obtained from the fungus penicillium notatum.
    27. 27. Mechanism of action All b-lactam antibiotics interfere with the synthesis of bacterial cell wall  Rapid cell wall synhesis occurs when the organisms are actively multiplying; B-lactam antibiotics are more lethal in this phase.
    28. 28. PENICILLIN Mechanism of action All penicillin like antibiotics inhibit synthesis of peptidoglycan, an essential part of the cell wall.  They do not interfere with the synthesis of other intracellular components. The continuing buildup of materials inside the cell exerts ever greater pressure on the membrane, which is no longer properly supported by peptidoglycan.  The membrane gives way, the cell contents leak out, and the bacterium dies. These antibiotics do not affect human cells because human cells do not have cell walls
    29. 29. Classification 1.Natural penicillins  PenG, PenV, Benzathine Pen, Procaine Pen 2.Aminopenicillins  Ampicillin, Amoxicillin 3.Penicillinase resistant penicilline  Oxacillin, Dicloxacillin 4.Extended - Spectrum Penicillins Carbenicillin , Mezlocillin, Piperacillin, Ticarcillin,
    30. 30. Adverse effects Local irritancy and direct toxicity  Hyper sensitivity Uses Streptococcal infections  Meningococcal infections  syphilis  tetanus  gas gangrene.
    31. 31. CEPHALOSPORIN These are a group of Semi synthetic antibiotics derived from cephalosporin-c obtained from a fungus Cephalosporium.  Chemically related to penicillin ClassificationFirst generation - Cefazolin, cephalexin, Cephadroxil Second generation - Cefuroxime, cephaclor Third generation- cefixime, ceftibuten. Fourth generation- Cefepime
    32. 32. Mechanism of action All Cephalosporin are bactericidal  They have the same mechanism of action as penicillin. i.e. inhibition of bacterial cell wall synthesis.  They bind to different proteins than those which bind to penicillin.  Resistance is developed.
    33. 33. Adverse effects      Pain after i/m injection Hypersensitivity Nephrotoxicity Bleeding occurs Neutropenia and thrombocytopenia Disulfiram like interactions Uses     Alternative to penicillin-g Respiratory, urinary and soft tissue infections Meningitis Typhoid Infections in cancer
    34. 34. TETRACYCLINE These are the class of antibiotics having a nucleus of four cyclic rings. Mechanism of action The tetracycline's are primarily bacteriostatic.  They easily enters into microbes because of their high lipid solubility.  Inhibit protein synthesis by binding to 30s ribosomes in susceptible organism.  Tetracycline antibiotics are protein synthesis inhibitors, inhibiting the binding of aminoacyltRNA to the mRNA-ribosome complex.
    35. 35. Antimicrobial spectrumAll types of Gram-positive and negative cocci are sensitive  Most gram positive bacilli  Enterobacteria are now largley resistant.  Administration Oral capsules are mostley used  Capsule shuould be taken ½ hr before or the 2 hr before the meal.  I/m route is painful.
    36. 36. Adverse effects Irritative effects  Dose related toxicity like liver damage, kidney damage, photo toxicity  Increase intracranial pressure  Hypersensitivity  Super infection Precautions Tetracycline's should not be used during pregnancy, lactation  Should be used cautiously in renal or hepatic insufficiency
    37. 37. Uses used in the treatment of infections of the urinary tract and the intestines  especially in patients allergic to β-lactams and macrolides  current use is in the treatment of moderately severe acne  it is also used in veterinary medicine on pigs  They may have a role in reducing the duration and severity of cholera  for the treatment of certain inflammatory disorders.
    38. 38. Chloramphenicol It was initially obtained from the Streptomyces venezuelae.  excellent BBB penetration  It has antibacterial activity because of nitrobenzene substitution in their chemical structure. Mechanism of action Chloramphenicol is a bacteriostatic drug that stops bacterial growth by inhibiting protein synthesis.
    39. 39. Antimicrobial spectrum Gram positive and negative bacteria, ricketsiae.  Highly active against the Salmonella thypi Adverse effects Major adverse effect -Bone marrow depression  Hypersensitivity reaction  Irritative effects like nausea, vomiting, pain on injection  Gray baby syndrome 
    40. 40. Uses Meningitis  variety of bacterial infections, including gram positive, gram negative and anaerobic bacteria.  Mainly for eye infections CHLORAMPHENICOL WARNINGS  People with eyesight problems  People who are sensitive to light (photophobia)  People who have inflamed eyes and a rash on the scalp or face  People with glaucoma
    41. 41. Antifungal Drugs An antifungal drug is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others  These are the drugs used for superficial & deep fungal infections.  Fungal infections occur when the resistance of host is poor.  Fungi easily invade living tissue & 
    42. 42. Classification 1) Antibiotics: a}Polyenes – Amphotericin B, Nystatin,Hamycin, Natamy cin. b}Heterocyclic – Griseofulvin, Benzofuran.
    43. 43. AMPHOTERICIN B (AMB)  They are all insoluble in water and unstable in aqueous medium. • Fungicidal at high conc. • Have high affinity for ergosterol present in fungal cell membrane. • Resistance is rarely noted. • Not effective against Dermatophytes.
    44. 44. Amino glycosides
    45. 45. Definition  Aminoglycosides are a group of antibiotics that are used to treat certain bacterial infections. This group of antibiotics includes at least eight drugs: amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, and tobramycin. All of these drugs have the same basic chemical structure.
    46. 46. Aminoglycoside streptomycin neomycin kanamycin paromomycin spectinomycin gentamicin tobramycin sisomicin amikacin Year 1944 1949 1957 1959 1962 1963 1968 1972 1972 netilmicin 1975 History Source organism Streptomyces griseus Streptomyces fradiae Streptomyces kanamyceticus Streptomyces rimosus Streptomyces spectabilis Micromonospora purpurea Streptomyces tenebrarius Micromonospora inyoensis semisynthetic derivative of kanamycin semisynthetic derivative of sisomicin
    47. 47. Classification ◦ Micromonospora actinomyctes  Gentamicin (gentamicin and netilmicin) ◦ Streptomyces spp.     Streptomycin (streptomycin and dihydrostreptomycin) Kanamycin (kanamycin, amikacin, and tobramycin) Neomycin (neomycin) groups Apramycin
    48. 48. Gentamicin 5-7mg/kg/24hrs  Once Daily Dosing   Target peak 14-20 mcg/ml  Avoid in patients with: • Burns, CF, pregnancy, children, endocarditis or CrCl < 20ml/min
    49. 49. Gentamicin
    50. 50. Tobramycin  Antimicrobial activity and PK properties very similar to Gentamicin • Superior activity against P. aeruginosa • Less active than gentamicin against enterococci  Can be given IV or IM  Dosage and serum levels are same as Gentamicin
    51. 51. Tobramycin
    52. 52. Amikacin  Broadest spectrum of activity • Resistant to aminoglycoside-inactivating enzymes • Less active against enterococci  Similar dosing interval and monitoring  Peak • Life-threatening infection • Serious infection 25-30 mcg/ml 20-25 mcg/ml
    53. 53. Some commonly used aminoglycosides include: amikacin (Amikin®) apramycin capreomycin gentamicin (Garamycin®) kanamycin (Kantrex®) neomycin (Mycifradin®) netilmicin (Netromycin®) paromomycin (Humatin®) streptomycin tobramycin (TOBI Solution®, TobraDex®, Nebcin®)
    54. 54. Excretion Aminglycoside antibiotics are eliminated unchanged by the kidney by glomerular filtration.  Wide inter patient variability in elimination occurs even in patient s with normal creatinine clearances. 
    55. 55. Other Factors Kinetics         Influencing Age Fever Body Weight Gender Obstetric Patients Burn Patients Pediatric Patients Ascites Aminoglycoside
    56. 56. Amphotericin B  It is obtained from Streptomyces nodosus.  Antifungal Spectrum: active against wide range of yeast & fungi.  Uses: can be used for Otomycosis, Systemic mycosis, Oral Vaginal & cutaneous candidiasis.  Reserve drug for resistant cases of
    57. 57. Griseofulvin Mechanism of action :  Mechanism of action binds to microtubules comprising the spindles and inhibits mitosis. incorporates into keratin and protects newly formed skin. 
    58. 58. • Active against most most Dermatophytes but not candida. • Gets deposited in keratin forming cells of skin,hair & nails • Ineffective topically.
    59. 59. Griseofulvin  Extracted from Penicillium griseofulvum.  Uses: used systemically for dermatophytosis.  Adverse Effects: Headache, G.I.T. disturbance, peripheral neuritis, rashes, transiant leukopenia & albuminuria.  Dose: 125-250mg with meals.
    60. 60.  Adverse Effects: -Acute reaction; consists of chills, fever, aches, nausea, dys pnoea & pain all over. -Long term Nephrotoxicity. - C.N.S. Toxicity.
    61. 61. Anti-viral drugs a class of medication used specifically for treating viral infections.  Viruses have no cell wall and made up of nucleic acid components.  Viruses are obligate intracellular parasite 
    62. 62. Anti-viral drugs Certain viruses multiply in the cytoplasm but others do in the nucleus  Most multiplication take place before diagnosis is made  Effective host immune response remains essential for the recovery from the viral infection 
    63. 63. Anti-viral drugs 1.Anti-herpes virus agents  Acyclovir / Ganciclovir 2.Anti-retrovirus  Zidovudine,Dianosine 3.Anti-influenza virus  Amantadine,Rimantadine 4.Nonselective antiviral Drugs Ribavirin ,Lamivudine 
    64. 64. Anti-viral drugs Acyclovir & Congeners :  Valacyclovir is a prodrug of Acyclovir with better bioavailability.  Famciclovir is hydrolyzed to Penciclovir and has greatest bioavailability.  Penciclovir is used only topically whereas Famciclovir can be administered orally.
    65. 65. Anti-viral drugs Mechanism of action of Acyclovir :  All drugs are phosphorylated by a viral thymidine-kinase, then metabolized by host cell kinases to nucleotide analogs.  The analog inhibits viral DNApolymerase  Only actively replicating viruses are inhibited  Aciclovir targets virus-infected cells quite specifically, and this explains the drug`s relatively low toxicity.
    66. 66. Aciclovir (cont.) Therapeutic uses Chiken pox:Acyclovir is the drug of choice :reduces fever,eruption & prevents viceral complication.  Herpes simplex infections of skin, mucous membranes and cornea. 
    67. 67. Zidovudine (AZT) Mode of action HIV virus is an RNA virus capable of including the synthesis of a DNA transcript of its genome, which can then become integrated into the host cell`s DNA, thereby allowing viral replication.  Synthesis of the initial DNA transcript involves the enzyme reverse transcriptase. 
    68. 68. Zidovudine (AZT) cont. Mode of action Zidovudine is a potent inhibitor of reverse transcriptase.  It has relatively specific toxicity for the virus. 
    69. 69. Anti-viral drugs Adverse effects of Acyclovir / Zidovudine  Nausea, vomiting and diarrhea  Nephrotoxicity crystalluria, haematuria, renal insufficiency  Rashes,sweating,emesis and fall in BP occur only in few patients.
    70. 70. What is antimalerial drugs? antimalarial: a medicinal drug used to prevent or treat malaria.  Most antimalarial drugs target the erythrocytic stage of malaria infection, which is the phase of infection that causes symptomatic illness.  The extent of pre-erythrocytic (hepatic stage) activity for most antimalarial drugs is not well characterized. Treatment of the acute blood stage infection is necessary for malaria caused by all malaria species. In addition, for infection due to Plasmodium ovale or P. vivax.  72
    71. 71. INTRODUCTION  TYPES OF MALARIA AND THEIR CAUSES MALARIA IS CAUSED BY 4 SPECIES OF PROTOZOAL PARASITES PLASMODIUM VIVAX PLASMODIUM OVALE PLASMODIUM FALCIPARUM PLASMODIUM MALARIAE 73
    72. 72. LIFE CYCLE OF MALARIAL PARASITE Dr Prashant's www.pharmacology4students.com 74
    73. 73.  MALARIAL PARASITES EXHIBIT A COMPLEX LIFE CYCLE  THEY HAVE ALTERNATING CYCLE OF ASEXUAL DIVISION (SCHIZONY) IN HUMANS  SEXUAL DEVELOPMENT (SPOROGONY) OCCURS IN FEMALE MOSQUITOES. 75
    74. 74. OBJECTIVES AND USE OF ANTIMALARIAL DRUGS  THE AIMS OF USING DRUGS IN A MALARIAL INFECTION ARE  (a)TO PREVENT AND TREAT CLINICAL ATTACK OF MALARIA  (b)TO COMPLETELY ERADICATE THE PARASITES FROM THE PATIENTS BODY  (c)TO REDUCE THE HUMAN RESERVOIR OF INFECTION 76
    75. 75. ANTIMALARIAL DRUGS CLASSIFICATION 4-AMINOQUINOLONES CHLOROQUINE CINCHONA ALKALOID QUININE
    76. 76. CHLOROQUINE    CHLOROQUINE IS A RAPIDLY ACTING SCHIZONTOCIDE. IT BELONGS TO AMINOQUINOLONES Most effective drug and widely used.  MECHANISM OF ACTION  LIKE CHLOROQUINE IT RAISES THE INTRAVASCULAR PH.  IT BINDS TO THE HAEM AND THE COMPLEX DAMAGES MEMBERANES OF THE PARASITE.  RESISTANT ORGANISMS ACCUMULATE LESS MEFLOQUINE  Exact mechanism is unknown. Probably it blocks the enzymatic system responsible for DNA and RNS synthesis. So it inhibits transcription. 78
    77. 77.  QUININE It is the oldest drug, being used from 1633  Can be used orally and parenterally.  79
    78. 78. Mechanism of Action—not clear, many mechanisms are proposed.  1st mechanism—it may depress many enzymatic system  2nd mechanism—it may produce Hbonding between the DNA strands. So there is no separation, no synthesis of mRNA and no transcription.  3rd mechanism—it may poison the protoplasmic parasitic feeding system.  80
    79. 79.  ADVERSE EFFECTS BITTER IN TASTE  NAUSEA  VOMITING  DIARRHOEA  DIZZINESS  ABDOMINAL PAIN AND  SINUS BRADYCHARDIA . GIT—irritates the gastric mucosa producing nausea, vomiting, epigastric pain etc  81
    80. 80. ◦ USES:- MALARIA  CEREBRAL MALARIA  NOCTURNAL MUSCLE CRAMPS  DIAGNOSIS OF MYASTHENIA GRAVIS  SPERMICIDAL IN VAGINAL CREAMS  82
    81. 81. PULMONARY TUBERCULOSIS
    82. 82. General Considerations Tuberculosis is a chronic infection, potentially of lifelong duration, caused by two species of mycobacteria M.tuberculosis and, rarely, M.bovis It was isolated by Robert Koch in 1882 The morbidity and mortality of tuberculosis are high in developing countries.
    83. 83. General Considerations The disease is confined to the lungs in most patients but may spread to almost any part of the body
    84. 84. Etiology • The tubercle bacillus (M.Tuberculosis) is aerobic, non-motil,nonspore-forming, high in lipid content, and acid and alcohol-fast • It grows slowly . • It can’t tolerate heat, but It can live in humid or dry or cold surroundings.
    85. 85. epidemiology A key link of epidemic The source of contagious The route of spread Peoples are easily affected
    86. 86. • Tuberculosis is transmitted by airborne droplet nuclei(containi ng tubercle bacilli )
    87. 87. • Many droplet nuclei are capable of floating in the immediate environment for several hours • Large particles may be inhaled by a person breathing the same air and impact on the trachea or wall of the upper airway
    88. 88. The transmission is determined • The probability of contact with a case of TB • The intimacy and duration of that contact • The degree of infectiouseness of case • The shared environment of the contact
    89. 89. Pathogenesis tubercle bacillus Human immunity
    90. 90. Antituberculosis drugs  First-line ◦ drugs Isoniazid, rifampin, pyrazinamide, eth ambutol and streptomycin  Second-line drugs ◦ Aminosalicylic acid(PAS), kanamycin
    91. 91. Isoniazid  1952, the most active drug for the treatment of tuberculosis  Mechanism of aciton ◦ Inhibit the synthesis of mycolic acid which is essential components of mycobacterial cell walls  Antimicrobial activity ◦ High activity against both extracellular and intracellular tubercle bacilli
    92. 92. Isoniazid  Pharmacokinetics ◦ Diffuse readily into all body fluids and tissues ◦ Metabolized by acetylation  Clinical uses ◦ First choice for all types of tuberculosis
    93. 93. Isoniazid  Adverse reactions ◦ Peripheral neuropathy ◦ CNS toxicity: memory loss, psychosis, seizures ◦ Hepatoxicity: the most frequent, increase in aminotransferase, hepatitis ◦ Allergic reactions
    94. 94. Rifampicin  Antimicrobial activity ◦ Mycobacteria, some G+ and Gcocci, chlamydiae and some virus  Mechanism of action ◦ Bind to β-subunit of bacterial DNAdependent RNA polymerase and inhibit RNA synthesis
    95. 95. Rifampicin  Clinical uses ◦ Tuberculosis and leprosy ◦ Infections caused by stapylococci and other ripfampicin-susceptible bacteria  Adverse reactions ◦ Gastrointestinal disturbance ◦ Liver toxicity: cholestatic jaundice, hepatitis
    96. 96. Ethambutol  Mechanism: ◦ interfering with synthesis of RNAby combination with Mg2+ Used in combination with INH or rifampicin  Adverse effect  ◦ Loss of visual disturbance, optical neuritis, redgreen color blindness
    97. 97. Rationale for the use of antituberculosis drugs Use as early as possible  Drug combination  Appropriate doses  Use regularly and enough time 
    98. 98. LEPROSY:HANSEN’S DISEASE (HD)
    99. 99. CAUSE:Mycobacterium leprae: One of the causative agents of leprosy. As acid-fast bacteria, M. leprae appear red. When a Zehl-Neelsen stain is used.
    100. 100. Kinds of Anti Leprotic drugs:Sulfone :- Dapsone (DDS), Phenazine derivative - Clofazimine, Antitubercular drugs Rifampicin, Ethionamide, Solapsone, Other antibiotics Oflaxacin, Minocycline, Clarithromycin.
    101. 101. Leprosy - one of the few diseases which can be eliminated Leprosy meets the demanding criteria for elimination practical and simple diagnostic tools: can be diagnosed on clinical signs alone; the availability of an effective intervention to interrupt its transmission: multidrug therapy a single significant reservoir of infection: humans.
    102. 102. Why integrate leprosy into the general health services? Integration means to provide ―comprehensive‖ essential services from one service point to improve patients’ access to leprosy services and thereby ensure timely treatment to remove the ―special‖ status of leprosy as a complicated and terrible disease to consolidate substantial gains made to ensure that all future cases receive timely and correct treatment to ensure that leprosy is treated as a simple disease
    103. 103. How to diagnose leprosy Examine skin Check for patches Test for sensation Count the number of patches Look for damage to nerves
    104. 104. Signs of leprosy Pale or slightly reddish patch Definite loss of sensation in the patch Signs of damage to nerves definite loss of sensation in hands/feet weakness of muscles of hands/feet/face visible deformity of hands/feet/face
    105. 105. Classification of Leprosy:Based on the 2 commonly used classifications, leprosy is classified into six types based on the clinical features (Ridley & Jopling classification): Disease Clinical features Indeterminate leprosy:- They are the first type of skin lesions characterized by hypo-pigmented spots. The lesions undergo healing spontaneously Disease Clinical features Paucibacillary (tuberculoid leprosy):- A large red patch with well-defined raised borders or a large hypo pigmented asymmetrical lesion. Lesion is dry and hairless Infectivity is minimal at this stage Loss of sensation is seen Nerves become thick followed by loss of function It either progresses to the borderline stage or spontaneously get cured
    106. 106. Borderline tuberculoid leprosy:- Characterized by small and numerous skin lesions The disease goes back to the tuberculoid stage or progresses to the next stage Borderline borderline leprosy:- Several small, irregular red lesions are seen Moderate sensory loss is seen It either goes back to the previous stage or progresses to the next Borderline lepromatous leprosy:- Several lesions such as plaques, macules, papules, and nodules are seen. Lesions have a characteristic inverted saucer like appearance.
    107. 107. Borderline tuberculoid leprosy:- Characterized by small and numerous skin lesions The disease goes back to the tuberculoid stage or progresses to the next stage Borderline borderline leprosy:- Several small, irregular red lesions are seen Moderate sensory loss is seen It either goes back to the previous stage or progresses to the next Borderline lepromatous leprosy:- Several lesions such as plaques, macules, papules, and nodules are seen. Lesions have a characteristic inverted saucer like appearance.
    108. 108. Disease Clinical features Multibacillary Hansen’s disease (lepromatous leprosy):- Early symptoms: Several lesions such as plaques, macules, papules, and nodules are seen. Nasal congestion, and bleeding is seen Inflammation of the leg and ankles Progressive symptoms: Thickening of the dermis (skin) in the forehead and ear lobes Loss of eyebrows and eyelashes Eye defects such as glaucoma and blindness are seen Nodules in the legs break and form ulcers Enlargement of the breast and sterility occurs in the males Internal infection results in the enlargement of the liver and lymph nodes Loss of sensation in the peripheral nerves. Deformation of the fingers and toes results due to painless repeated trauma.
    109. 109. Treatment:Chaulmoogra oil:Indicated that the oil was the product of a tree Chaulmoogra odorata, which had been described in 1815 by William Roxburgh, a surgeon and naturalist, while he was cataloging the plants in the East India Company’s botanical garden in Calcutta. This tree is also known as Gynocardia odorata. For the rest of the 19th century, this tree was thought to be the source of the oil.
    110. 110. ANTI-PROTOZOAL DRUGS ANTI-AMOEBIC These are drugs used in infection caused by the protozoa E. histolytica
    111. 111. Life cycle of E. histolytica
    112. 112. Therapeutic Classification of Anti-Amebic Drugs I. Luminal Amebicides (Drugs effective in Luminal Infection only) 1. Dichloroacetamides Diloxanide Furoate 2. Halogenated Hydroxyquinolines Idoquinol (Diiodohydroxyquine) 3. Antibiotics: Tetracyclines, Paromomycin 4. Oral Bismuth Salt : Emetine Bismuth Iodide
    113. 113. II. Extra-Luminal Amebicides A: Systemic or Tissue Amebicides 1. Chloroquine 2. Emetines : Emetine, Dehydroemetine B: Mixed Amebicides /Drugs effective in systemic & Intestinal Amebiasis . (Not reliably effective against luminal infections as luminal concentrations are too low for single drug treatment) Nitroimidazoles Metronidazole Tinidazole Secnidazole.
    114. 114. Metronidazole (Flagyl)    Most commonly used Mixed tissue amebicide (Intestinal & extra Intestinal) not reliably effective against amebae in the lumen as luminal concentrations are too low for single drug treatment. Kills only trophozoits in intestinal wall but not the cysts of E. histolytica.
    115. 115. Chemically --- Nitroimidazole
    116. 116. MOA Metronidazole kills protozoa & is bactericidal for anaerobic bacteria. • Metronidazole is a pro drug. It requires reductive activation of the NITRO group. • This occurs in sensitive anaerobic protozoa & anaerobic bacteria by Ferredoxins; which are electron transport proteins. • These proteins can donate electrons to Metronidazole ,which serves as electron acceptor. • The reduced product is cytotoxic, it targets DNA & other biomolecules / proteins, resulting in cell death. Hence it kills the micro-organisms .
    117. 117. Antimicrobial Spectrum Kills anaerobic protozoa & bacteria • Entameba Histolytica (Trophozoits only)  Trichomona Vaginalis  Giardia Lamblia  Clostridia – C . difficile  B. fragilis  Helicobacter pylori. Also toxic to hypoxic / anoxic cells
    118. 118. USES 1. Amebiasis: 2. Trichomoniasis 3. Giardiasis 4.Bacterial vaginosis 5.Eradication of H. Pylori 6.Pseudomembranous enterocolitis
    119. 119. Adverse Effects GIT: Dry mouth, metallic taste --- most common. Nausea, vomiting, abdominal cramps , Diarrhea. Oral thrush--stomatitis Rarely Pancreatitis. Neurotoxicity: Headache, Insomnia, numbness or paraesthesias, weakness , dizziness. Rarely Ataxia, encephalopathy & seizures.
    120. 120. III. OTHER A/E: 1. Disulfiram like action with alcohol. 2. Dysuria ,Dark urine. 3. Mutagenic in bacteria. 4. Carcinogenic in Rodents. 5. Hypersensitivity reactions--- rash, neutropenia IV. Drug interactions - Potentiate Anticoagulant effect of Warfarin. - Metabolism of Metronidazole induced by Phenytoin & Phenobarbitone & Cimetidine may inhibit it. - Metronidazole increases Lithium toxicity.
    121. 121. Contraindications  Patient with active disease of the CNS.  Hepatic Disease/Renal disease, dose adjustment should be done.  Pregnancy/ Nursing Mothers.
    122. 122. Tinidazole : • It is a second- generation Nitroimidazole. • Congener of Metronidazole • It is similar to Metronidazole in spectrum of activity, MOA , absorption , A/E & D/I. • It is also effective against cysts of E.histolytica. • It is longer acting –once daily dose. • Short course– 2gm daily, single dose-- for 3 days. Secnidazole: Longer acting Single 2gm dose is given
    123. 123. Emetines It is another class of drug which acts as antiprotozal and anti amoebic . Source: Emetine --- Alkaloid of Ipecacuanna (Ipecac) Dehydroemetine---Synthetic analog Effective against the trophozoits of Entameba histolytica.
    124. 124. Therapeutic Uses :Limited use: Only when Metronidazole can not be used in :  Severe Amoebic dysentry  Hepatic Amebiasis Dehydroemetine is preferrd– better toxic profile Drug should be used S/C or I/M injection in a supervised setting Never given I/V Used only for minimum period to relieve severe symptoms. Usually 3-5 days.
    125. 125. Adverse Effects Mild when used for 3-5 days, increase with time  Diarrhea .  Central nausea & vomiting  Pain & tenderness at site of injection/ sterile abscess.  Muscle weakness & discomfort.  Minor ECG changes Serious toxicity:  Hypotension, Cardiac arrhythmias, Cardiac failure. Contraindications: Cardiac /renal disease Young children , pregnancy.
    126. 126. Diloxanide Furoate (Luminal amebicide) Dichloroacetamide derivative Pharmacokinetics: Given orally, in gut splits into Diloxanoid & furoic acid. 90% Diloxanoid is absorbed & conjugated to form glucuronide -- excreted in urine MOA: Not understood. Unabsorbed Diloxanoid is directly amebicidal against amebea in lumen but not those in intestinal wall.
    127. 127. Therapeutic uses:  Drug of choice for Asymptomatic Luminal Amoebiasis (cyst passers)  Alongwith tissue amebicide in severe intestinal & extra intestinal amebiasis. Adverse effects  Flatulence  Nausea, abdominal cramps  Skin rashes rarely. Precautions: Pregnancy
    128. 128. ANTIBIOTICS . Paromomycin  Tetracyclines Uses: Luminal amebicides 1. Asymptomatic infection (Carriers). 2. Along with extra luminal amebicides in serious infections. 
    129. 129. Paromomycin sulphate:   An aminoglycoside antibiotic. Not significantly absorbed from the gut. Used as Luminal amebicide.  Less toxic than other agents.  Superior to Diloxanide furoate in clearing asyptomatic infections.  No effect on extra-intestinal amebic infections.  Also used in visceral leishmeniasis paenterally. A/E: Abd. Distress & diarrhea. 
    130. 130. Tetracyclines: Used as Luminal amebicide.  Does not kill bacteria directly but disturbs the symbiosis between normal intestinal flora & E .histolytica . The amebae grow at expense of normal intestinal flora . Tetracyclines are broad spectrum antibiotics & kill these flora leading to death of E .histolytica also. Used in resistant cases. 

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