7th week

• Chemotherapeutic drugs (antibiotics)


  Antimicrobial drugs that can selectively kill microorganisms without harming the patient's normal cells
• Chemotherapeutic drugs


  • They have capabilities
  • The most important point in selection is determining the microorganism causing the disease
  • Gram staining and culture are used to identify the microorganism
• Selective action of chemicals


  Differences between microorganism cell and human/mammalian cell in structure and biochemical mechanisms
• Penicillins and cephalosporins


  • Most selective as the cell wall affected is not found in human and other eukaryotic cells
  • Some drugs have low toxicity on mammalian cells due to low selectivity
• Bacteriostatic chemotherapeutic drugs


  • Sulfonamides
  • Chloramphenicol
  • Tetracyclines
  • Erythromycin
  • Clindamycin
  • Miconazole
  • Etambutol
• Bactericidal chemotherapeutic drugs


  • Penicillins
  • Cephalosporins
  • Aminoglycosides
  • Vancomycin
  • Rifampin
  • Fluoroquinolones
  • Amphotericin B
  • Polymyxins
• MIC (Minimum Inhibitory Concentration)


  Quantitative indication of bacteriostatic potency of antimicrobial drugs, measured in liquid culture. The smaller the value, the more effective the drug.
• MBC (Minimum Bactericidal Concentration)


  Indicator of the bactericidal effect of antimicrobial drugs, measured as the minimum concentration that kills more than 99.9% of bacteria in liquid culture.
• Antimicrobial spectrum


  • Narrow-spectrum: Effective on only one or a few bacteria
  • Extended-spectrum: Effective against gram-negative and gram-positive bacteria
  • Broad-spectrum: Effective against a large number of bacteria and microorganisms
• Mechanisms of action of antibacterial chemotherapeutics

  • Inhibitors of cell wall synthesis
  • Those that inhibit intermediate metabolism in bacteria
  • Those that inhibit nucleic acid synthesis
  • Protein synthesis inhibitors
  • Those that increase the permeability of the cytoplasm membrane
• Inhibition of bacterial cell wall synthesis and activation of autolytic enzymes

  1. Beta-lactam antibiotics bind to penicillin-binding proteins, preventing transpeptidation and activating autolytic enzymes to destroy the cell wall

  2. Causes leakage of small molecules from the cytoplasm, having a bactericidal effect
• Increasing cytoplasm membrane permeability

  Polymyxins, amphotericin B, nystatin, ketoconazole, fluconazole, daptomycin
• Inhibition of protein synthesis in bacterial ribosomes

  Tetracyclines, aminoglycosides, macrolides, clindamycin, chloramphenicol
• Disruption of DNA and RNA synthesis

  Fluoroquinolones, rifampicin, mitomycin, actinomycin, doxorubicin, daunorubicin
• Antimetabolite effect


  Prevent synthesis of necessary substances for bacterial metabolism, e.g. sulfonamides, trimethoprim, PAS, sulfones, isoniazid, ethambutol, chloroquine
• Bacteria sooner or later acquire resistance to chemotherapeutic drugs
• Types of resistance


  • Natural resistance: Some bacteria species are not affected at all
  • Acquired resistance: Initially effective but bacteria become unaffected over time
  • Cross-resistance: Resistance to one drug confers resistance to another with similar structure or mechanism
• Mechanisms of acquired resistance

  1. Disruption of porin structure decreasing drug permeability

  2. Secretion of enzymes that break down the drug

  3. Synthesis of insensitive enzymes

  4. Modification of the drug in the cell

  5. Decreased drug uptake

  6. Decreased binding of the drug to its target
• Concentration-dependent lethal effect


  When concentrations of some antimicrobials are increased 4-64 times, the rate of bacterial destruction increases significantly. These are administered as bolus infusions to quickly destroy pathogens.
• Post-antibiotic effect


  Suppression of microbial proliferation even when drug concentration falls below MIC, e.g. with aminoglycosides and fluoroquinolones
• Clinical situations for prophylactic antibiotic use

  • Protection of people with rheumatic heart disease
  • Pre-treatment before dental procedures with prosthetic devices
  • Prevention of meningitis and tuberculosis in contacts
  • Prevention of infection before some surgeries
  • Prevention of fetal infection in HIV-positive pregnant women
• Antibiotics not requiring dose adjustment in organ failure

  • Chloramphenicol
  • Erythromycin
  • Lincomycin
  • Clindamycin
  • Rifampin
  • Cephalothin, cefoperazone
  • Isoniazid (rapid acetylators)
  • Sulfadimidine
  • Pefloxacin
  • Doxycycline, minocycline
  • Cloxacillin, dicloxacillin, nafcillin
• Antibiotics requiring dose adjustment in organ failure

  • Penicillin G
  • Amoxicillin
  • Ampicillin
  • Lincomycin
  • Isoniazid (slow acetylators)
  • Ofloxacin
  • Ethambutol
  • Co-trimoxazole
• Nephrotoxic antibiotics


  • Aminoglycosides
  • Tetracycline and oxytetracycline
  • Cephaloridin
  • Long-acting sulfonamides and paraaminosalicylic acid
• Cell wall synthesis inhibitors

  • Beta-lactams: Penicillins, cephalosporins, other beta-lactams

  Carbapenems

  Monobactams

  Beta-lactamase inhibitors
• Penicillins


  • Strong bactericide
  • Low toxicity
  • Increasing risk of resistance
• Those whose elimination is mostly from the kidneys but have little or no nephrotoxic effect

  • Pen G
  • Amoxicillin
  • Ampicillin
  • Lincomycin
  • Isoniazide (in slow acetylators)
  • Ofloxacin
  • Etambutol
  • Co-trimoxazole
  • carbenicillin
  • ticarcillin
  • cefazolin
  • moxolactam
  • Polymyxin B
  • vamcomycin
  • flucytosine
  • colistin
• Nephrotoxic effects, most of which are eliminated from the kidneys

  • Aminoglycosides (Gentamicin, kanamycin, streptomycin)
  • Tetracycline and oxytetracycline
  • Cephaloridin
  • Long-acting sulfonamides and paraaminosalicylic acid
• Cell wall synthesis inhibitors

  • Non-beta-lactams
  • Beta-lactam group drugs
  • penicillins
  • Cephalosporins
  • Other beta lactams
  • Carbapenems
  • Monobactams
  • Beta-lactamase inhibitors
• Penicillins


  • Strong bactericide
  • Their toxicity is low
  • Increasing risk of drug resistance
  • They are natural or semi-synthetic antibiotics
• 1. aminopenicilic acid (6-APA)


  The basic structure in penicillins
• If the beta-lactam ring of 6-APA is opened by an enzyme called beta lactamases (penicillinase), penicillic acid is formed from the substance, so that penicillins are converted into penicilloid acid derivatives
• R group


  Determines the drug's resistance to enzymatic or acid hydrolysis and also affects its antibacterial spectrum
• Mechanism of Action of Penicillin

  1. They act by inhibiting cell wall synthesis

  2. Beta-lactam antibiotics bind to penicillin-binding proteins (PBP, transpeptidase), which is the last step of cell wall synthesis (necessary for its health), prevent transpeptidation (cross-link formation), and activate autolysins (degrading enzyme, murein hydrolase) in the cell wall, resulting in cell lysis. So it breaks down
• It is bactericidal, therefore it is ineffective against mycobacteria, protozoa, fungi and viruses that do not have a bacterial wall
• PEP side chains are cross-linked in the final step of peptidoglycan synthesis. Penicillin blocks this process
• Penicillins


  • Natural Penicillins: Penicillin G, Benzathine Penicillin G, Procaine Penicillin G, Penicillin V
  • Broad spectrum: Ampicillin, amoxacillin
  • Antipseudomonal penicillins: carbenicillin, ticarcillin, Mesocillin, azlocillin, piperacillin
  • Antistaphylococcal (Penicillinase-resistant) penicillins: Methicillin, nafcillin, oxacillin, dicloxacillin
• Penicillin Resistance


  • Beta lactamase activity
  • Decrease in drug permeability in the outer cell membrane
  • The drug is expelled by the pump
  • Binding of penicillin-binding proteins
• Absorption of penicillins


  • Most types of penicillin are not absorbed through the gastrointestinal tract and therefore are not used orally
  • It is penicillin V that is used orally (orally)
  • They are used on an empty stomach, amoxicillin (full) is used
• Pharmacokinetic properties of penicillins

  • Pen V, amoxicillin, ampicillin orally
  • Procaine and benzathine pen G, which are depot forms
  • They are administered i.m. and are present in the blood at low levels for a long time (long duration of action) as they are gradually introduced into the circulation