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Dolly Mehta 5-0236

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Presentation on theme: "Dolly Mehta 5-0236"— Presentation transcript:

1 Dolly Mehta 5-0236

2 Non-beta Lactam Antibiotics
Penicilin Vancomycin Cephalosporins Cycloserine Bacitracin Monobactum Carbepenams Beta-lactam inhibitors Tazobactum

3 Gram positive Gram negative

4 N acetylmuramic acid (NAM)
Peptidoglycan N acetylmuramic acid (NAM) NAM L-Ala D-Glu L-Lys N acetylglucosamine (NAG) NAG Penta peptide (Glycine residues)

5 Transpeptidase (TP) Transglycolase (TG) Bactoprenol (C55-carrier) P
BP periplasm NAG NAM NAG NAM NAG NAM NAM NAM NAG NAM NAG NAM NAM NAM Glycosidic bond Peptide cross link Transglycolase (TG) Transpeptidase (TP)

6 cycloserine bacitracin Beta-lactams vancomycin Inhibits TP alanine
D-ala alanine racemase D-ala cycloserine D-ala D-ala-D-ala-ligase D-ala D-ala L-ala D-ala D-ala D-ala D-ala bacitracin UdP NAM Bactoprenol (C55-carrier) P P BP Beta-lactams periplasm vancomycin NAG NAM NAG NAM NAG NAM NAM Inhibits TP NAM NAG NAM NAG NAM NAM NAM

7 Mechanism of Resistance
Inability of agents to penetrate to site of action Production of b-lactamase Increased expression of efflux pumps Elaboration of normal penicillin binding proteins (PBPs)

8 Classification Cephalosporins Penicillins
Natural Penicillins i.e. PenV Extended-Spectrum Penicillins i.e. (Ampicillin/Amoxycillin) Antistaphylococcal Penicillins i.e. Piperacillin Ist generation i.e. Ceftazolin IInd generation i.e. Cefactor IIIrd generation i.e. Cephaoxime IV generation i.e. Cefapime V generation i.e. Cefrazoline

9 Untoward Effects Hypersensitivity ~(0.7%-4%)
Allergy to one penicillin risk to other penicillins/cephalosporins Haptens Penicilloic acid IgE Abs

10 Beta-Lactam & Other Cell Wall- Active Antibiotics
Subclass Clinical Applications/toxicity PENICILLINS  Ampicillin, amoxicillin, ticarcillin, piperacillin Aumentin, Zosyn CEPHALOSPORINS Cephalexin Cefepime Ceftaroline CARBAPENEMS    Imipenem-cilastatin MONOBACTAMS  Aztreonam Beta-lactamase Inhibitors (suicidal inhibitor) Clavulanic Acid, Sulbactam, & Tazobactam GLYCOPEPTIDE  Vancomycin Telavancin Streptococcal and Staph lycoccal infections, meningococcal infections, neurosyphilis, UTI, RTI, addition of beta-lactamase inhibitor restores activity against many -lactamase-producing bacteria Skin and soft tissue infections, urinary tract infections, surgical prophylaxis, improved stability to chromosomal lactamase, active against methicillin-resistant staphylococci, broad gram-negative activity Serious infections such as pneumonia and sepsis Infections caused by aerobic, gram-negative bacteria in patients with immediate hypersensitivity to enicillins No cross-allergenicity with penicillins  Infections caused by gram-positive bacteria including sepsis, endocarditis, and meningitis  C difficile colitis (oral formulation) , Red man syndrome

11 Antibiotics  Protein Synthesis
Aminoglycosides Macrolides Teteracycline Chloramphenicol

12 Protein Synthesizing Machinery
Ribosome mRNA tRNA bacteria has 50S and 30 S subunit which forms 70 S polysome that slides on mRNA has A, P and E sites for binding with tRNA forms template for protein synthesis transcribed from DNA attaches to 30s ribosomes brings amino acids attaches to A, P and E sites of ribosomes

13 Aminoglycosides uac Binds 30S P E A 50s uuu cca cau cca aug cca cau
MET uac Binds 30S P E A 50s uuu cca cau cca aug cca cau 30s

14 Tetracycline uac P E A uac uuu cca cau cca aug cca cau
Pro uac Tetracycline Binds reversibly at 30 S ribosomal RNA Compete with tRNA P E A Met uac uuu cca cau cca aug cca cau

15 Macrolides, Lincosamide
Binds 50S ribosomal RNA Blocks peptide translocation to P site P E A Met Pro uuu cca cau cca aug cca cau

16 Chloramphenicol Binds 50S ribosomal RNA Inhibit peptidyltransferase P
Pro Met gga uuu cca cau cca aug cca cau

17 Oxazolidinones Inhibits ribosomal complex formation P E A 50s
uuu cca cau cca aug cca cau 30s

18 Modification of the ribosomal binding site (Tet)
Mechanisms of Resistance Low affinity of drug for bacterial ribosomes Efflux pumps (Tet, Mac) Intracellular penetration Modification of the ribosomal binding site (Tet) pH Anaerobic conditions (AG) acetylation, phosphorylation, adenylation of OH or NH2 gr (Macrolides, AG) Drug inactivation Metabolites can also compete with the drugs (Mac, AG)

19 Intracellular Penetration
Macrolides, Tetracyclines, chloramphenicol Aminoglycosides a. Energy-Dependent Phase 1 (EDP1) b. Create fissure inducing bacterial damage (EDP2 phase)

20 Clinical Applications Toxicities
Subclass Clinical Applications Toxicities AMINOGLYCOSIDES (gentamicin, streptomycin) TETRACYCLINES (doxyclines, micocyclines, tigecycline) useful in aerobic_Gram negative bacterial infections meningitis, Sepsis, pneumonia, endocardtis Infections caused by mycoplasma, chlamydiae, rickettsiae, some spirochetes  malaria H pylori  acne Nephrotoxic, ototoxicity, muscular blockade: of neuromuscular junction Gastrointestinal upset, hepatotoxicity, photosensitivity, deposition in bone and teeth MACROLIDES (erythromycin, clarithromycin, azrithromycin, Telithromycin)  LINCOSAMIDE  Clindamycin STREPTOGRAMINS Quinupristin-dalfopristin CHLORAMPHENICOL  OXAZOLIDINONES Linezolid Community-acquired pneumonia pertussis corynebacterial and Chlaydial infections Skin and soft tissue infections anaerobic infections Infections caused by staphylococci or vancomycin-resistant strains of E faecium Rarely used in developing Countries Infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci Gastrointestinal upset, hepatotoxicity, QTc prolongation Gastrointestinal upset, C difficile colitis Severe infusion-related myalgias and arthralgias   Dose-related anemia, idiosyncratic aplastic anemia, gray baby syndrome  Duration-dependent bone marrow suppression, neuropathy, and optic neuritis,  serotonin syndrome may occur when coadministered with other serotonergic drugs (eg, selective serotonin reuptake inhibitors)

21 Drug Interactions Erythromycin, Chloramphenicol Linezolid
serotonin syndrome serotonins Cytochrome P450

22 Anti-tubercular and Anti-leprosy agents
Mycobacteria Tuberculosis leprosy

23 Mycobacterial Cell Wall
Mycolic acid Long fatty acids Allow the bacterium to grow dormantly Reside inside macrophages evading host's immune system

24 Mechanism of Action of TB drugs

25 Mechanism of Resistance of TB drugs

26 Subclass Clinical Applications Toxicities Isoniazid (INH)  First-line agent for tuberculosis treatment of latent infection Hepatotoxic, peripheral neuropathy (give pyridoxine to prevent)   Rifampin First-line agent for tuberculosis atypical mycobacterial infections eradication of meningococcal colonization, staphylococcal infections Rash, nephritis, thrombocytopenia, cholestasis, flu-like syndrome with intermittent dosing  Pyrazinamide "Sterilizing" agent used during first 2 months of therapy allows total duration of therapy to be shortened to 6 months Hepatotoxic, hyperuricemia  Ethambutol  Given in four-drug initial combination therapy for tuberculosis until drug sensitivities are known also used for atypical mycobacterial infections Retrobulbar neuritis  Streptomycin Used in tuberculosis when an injectable drug is needed or desirable for drug-resistant strains Nephrotoxic, ototoxicity

27 Drug Interactions of Rifampin
induces Cytochrome P450 Increases elimination of several drugs i.e cyclosporineAnticonvulsants Protease inhibitors

28 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. common in warm, wet areas in the tropics & subtropics.

29 inhibits the utilization of PABA  folic acid metabolism
Multidrug therapy Sulphones (Dapsones) inhibits the utilization of PABA  folic acid metabolism Rifampin Clofazimine binds GC rich DNA; anti-inflammatory

30 Sulphone syndrome: fever, jaundice, malaise
exacerbation of lepromatos leprosy Untoward Effects Dapsone Clofazimine skin discoloration ranging from red-brown to nearly black

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