Antibacterial Drugs PDF

10/18/2024 1 2 ANTIMICROBIAL DRUGS...

10/18/2024 1 2 ANTIMICROBIAL DRUGS  Antibacterial ANTIMICROBIAL Antivirals DRUGS   Antifungal Antibacterial  Antiprotozoal 1 2 3 4 CLASSIFICATIONS OF ANTIBACTERIAL DRUGS ANTIBACTERIAL AGENTS  Cell wall synthesis inhibitors  Bactericidal drugs (Kill)  Additive effects (Summative)  Protein synthesis inhibitors  Bacteriostatic (Stops growth)  Antagonistic effects (Opposing)  Nucleic acid synthesis inhibitors Severely ill and immunosuppressed …inhibition of growth induced by a patients with bacterial infections  Miscellaneous bacteriostatic drug results in an overall should be treated with bactericidal reduction of efficacy when the drug is antibiotics combined with a bactericidal drug… 3 4 1  10/18/2024 5 6 CELL WALL SYNTHESIS INHIBITORS  Bactericidal CELL WALL SYNTHESIS INHIBITORS  Cause a structurally deficient cell wall  B-lactam drugs  Vancomycin 5 6 7 8 Inhibit DD-transpeptidase (penicillin- binding proteins) BETA LACTAMS PENECILLINS  Penicillins Resistance Penicillinases (Beta lactamases)  Cephalosporins Structural changes of PBPs or porin  Carbapenems channels  Monobactams Gram positives are more sensitive to penicillins than gram negative organisms 7 8 2  10/18/2024 9 10 CLASSIFICATION OF PENICILLINS NATURAL PENICILLINS  Natural penicillins  Penicillin V (oral)  Anti-staphylococcal penicillins  Penicillin G (parenteral)  Aminopenicillins  Gram positive. Gram negative cocci. Anaerobes. Spirochetes.  Anti-pseudomonal penicillins  Penicillinase sensitive 9 10 11 12 ANTI-STAPHYLOCOCCAL AMINOPENICILLINS PENICILLINS  Methicillin, Nafcillin, Oxacillin, Cloxacillin ….  Ampicillin, Amoxicillin  Narrow spectrum, Penicillinase resistant  Extended spectrum, Penicillinase sensitive  DOC for staphylococci  Gram negatives (H Influenza, E Coli, Proteus, Salmonella, Shigella)  Methicillin Resistant Staphylococcus Aureus (Modified PBPs) 11 12 3  10/18/2024 13 14 ANTIPSEUDOMONAL PENICILLINASE INHIBITORS PENICILLINS  Piperacillin, Ticarcillin  Sulbactam  Extended spec, Penicillinase sensitive Tazobactam  ? Augmentin  Gram negative rods (Pseudomonas, Enterobacter, Klebsiella)  Clavulanic acid 13 14 15 16 ADVERSE EFFECTS OF PENICILLINS  GIT distress  Structurally and functionally related to  Hypersensitivity penicillins CEPHALOSPORINS  Cross allergic reactions with cephalosporins  First, second, third, fourth generations Pseudomembranous colitis, a severe inflammation of the inner lining of the large intestine, manifests as an antibiotic-associated colonic inflammatory complication. The disease most commonly results from a serious Clostridium difficile infection 15 16 4  10/18/2024 Generation Example Coverage First Cephalexin, Cefazolin Gram positive cocci (staph, strep) 17 18 Gram negative rods (Proteus, E Coli, ADVERSE EFFECTS OF CEPHALOSPORINS Klebsiella) Second Cefuroxime (crosses the BBB) Hemophilus Influenza, Enterobacter, Neisseria Third Ceftazidime (Pseudomonas) Less gram positive.  Hypersensitivity reactions (Cross-reactions with penicillins) Ceftriaxone (Gonococcus) Extended gram-negative coverage (Citrobacter, Serratia, Providentia)  Disulfiram-like reactions (Alcohol intolerance) Fourth Cefepime Pseudomonas and gram-positive  Nephrotoxicity concerns (except ceftriaxone) None of the 4 generations of cephalosporins are active against MRSA. 17 18 19 20 CARBAPENEMS MONOBACTAMS  Imipenem and meropenem  Aztreonam  Administered IV or IM  Resistant to beta-lactamases. Cover most gram positive, gram negative and anaerobic organisms  None is active against MRSA  Active against most gram-negative bacteria but has no activity against gram positive organisms  Imipenem is compounded with CILASTATIN to protect it from metabolism by renal dehydropeptidase  High levels of imipenem may provoke seizures  No cross allergenicity with other beta lactam drugs  Relatively non-toxic but can cause phlebitis and skin rash Cilastatin (Dehydropeptidase inhibitor) 19 20 5  10/18/2024 21 22 VANCOMYCIN  Inhibits peptidoglycan polymerization (d-alanyl-d-alanine portion of cell PROTEIN SYNTHESIS membrane)   Effective against most gram positives (including MRSA) Intravenous vancomycin is commonly used to treat sepsis INHIBITORS  Oral vancomycin is used to treat gastrointestinal infections with C. difficile  Infusion related adverse effects (phlebitis, flushing) Resistance due to modification  Dose related ototoxicity & nephrotoxicity of the D-Ala-D-Ala binding site of the peptidoglycan building block in which the terminal D- Ala is replaced by D-lactate. 21 22 23 24 PROTEIN SYNTHESIS INHIBITORS AMINOGLYCOSIDES  Target translation  Streptomycin, Tobramycin,  Nephrotoxicity and Ototoxicity Gentamycin, Amikacin (Prolonged intake, Elderly, renal  Act on the 30s or 50s ribosomes insufficiency, Overdose)  Block initiation complex formation,  P-Site (Aminoglycosides) mRNA misreading, Breakup of  Inhibit calcium uptake   A site (Tetracyclines) polysomes (Bactericidal) neuromuscular paralysis (Respiratory  Peptidyl transferase (Chloramphenicol) paralysis, Myasthenia gravis)  Bind irreversibly on the 50s subunit and inhibit translocation, Peptide exit tunnel  Gram negative rods, gram positive (Macrolides, Clindamycin) cocci, mycoplasma  Resistance (Ribosome alteration, Efflux pumps, Drug modifying enzymes) 23 24 6  10/18/2024 25 26 TETRACYCLINS MACROLIDES  Prevent the (aminoacyl) tRNA  Doxycycline has a better oral  Block translocation  Azithromycin less active against gram positives. More active against from entering the acceptor site. bioavailability, longer duration Haemophilus influenza and of action and eliminated to a  Erythromycin is active against chlamydia spp.  Gram Negative Rods susceptible strains of gram-positive lesser extend in urine than organisms, especially pneumococci,  Gram Positive Cocci, Gram tetracycline streptococci, staphylococci and  +++ Gastric Upset Positive Bacilli, corynebacteria.  All except azithromycin (CP450  Gastric discomfort inhibitors)  Anaerobes, Mycoplasma  Bind to calcium and deposited  Clarithromycin more active against  Rickettsia, Spirochetes & in bones and teeth haemophilus influenza, helicobacter pylori and intracellular organisms Chlamydia (chlamydia)  Clindamycin (MRSA)  Linezolid (MRSA, VRSA) 25 26 27 28 QUINOLONES  Topoisomerase II (DNA NUCLEIC ACID Supercoiling) SYNTHESIS INHIBITORS Nalidixic acid Fluroquinolones  Topoisomerase IV  DNA synthesis inhibitors (Quinolones) (Separation of newly  RNA synthesis inhibitors (Rifamycins) replicated DNA)  Folic acid synthesis inhibitors (Trimethoprim and sulfonamides) 27 28 7  10/18/2024 29 30 GENERATIONS TOXICITY 1) Nalidixic acid (nonfluorinated quinolone, gram negative  Common adverse effects are nausea, vomiting and diarrhea organisms, UTIs).  Articular cartilage erosion (Avoid in children) 2) Ciprofloxacin (Aerobic gram-negative. Moderate activity against gram positive bacteria)  Ingestion of fluroquinolones with dietary supplements containing iron or zinc can reduce their absorption 3) Levofloxacin (…increased activity against gram-positive bacteria) 4) Moxifloxacin (…activity against anaerobic) 29 30 31 32 TRIMETHOPRIM AND SULFAMETHOXAZ  Cotrimoxazole is a bactericidal and “ OLE broad spectrum METRONIDAZOLE ”  Bacteria (MRSA, Norcardia, E coli…)  Forms toxic free radical metabolites that damage DNA.  Fungi (Pneumocytis jiroveci)  Protozoa (Toxoplasma gondi)  Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, c difficile).  Folic acid deficiency (megaloblastic) anemia  Disulfiram-like reaction with alcohol Cotrimoxazole= Trimethoprim + Sulfamethoxazole  Metallic taste 31 32 8  10/18/2024 33 THANK YOU. 33 9