Vivo

• Chemotherapeutic agents


  Any drug used to treat any condition or disease
• Antimicrobial agents


  Any chemical (drug) used to treat an infectious disease, either by inhibiting or by killing pathogens in vivo
• Antibacterial agents


  Drugs used to treat bacterial diseases
• Antifungal agents


  Drugs used to treat fungal diseases
• Antiprotozoal agents


  Drugs used to treat protozoal diseases
• Antiviral agents


  Drugs used to treat viral diseases
• Paul Ehrlich (1854-1915): 'The Father of Chemotherapy'
• Alexander Fleming (1881-1955): 'Accidentally discovered the first antibiotic, Penicillin'
• Howard Walter Florey and Ernst Boris Chain: 'Purified penicillin and demonstrated its effectiveness in the treatment of various bacterial infections'
• Gerhard Domagk: 'Discovered that the red dye Prontosil was effective against streptococcal infection in mice'
• Selman Waksman: 'Isolated streptomycin (the first antituberculosis drug) and subsequently discovered antibiotics such as chloramphenicol, tetracycline, and erythromycin'
• Ideal antimicrobial agent


  • Kills or inhibits the growth of pathogens
  • Causes no damage to the host
  • Causes no allergic reaction in the host
  • Is stable when stored in solid or liquid form
  • Remains in specific tissues in the body long enough to be effective
  • Kills the pathogens before they mutate and become resistant to it
• Mechanisms of action of antimicrobial agents

  • Inhibition of cell wall synthesis
  • Damage to cell membranes
  • Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
  • Inhibition of protein synthesis
  • Inhibition of enzyme activity
• Sulfonamide drugs


  Inhibit production of folic acid (a vitamin) in bacteria that require p-aminobenzoic acid (PABA) to synthesize folic acid
• Sulfa drugs


  Competitive inhibitors that inhibit growth of microorganisms by competing with an enzyme required to produce an essential metabolite
• Bacteriostatic agents


  Inhibit growth of bacteria
• Bactericidal agents


  Kill bacteria
• Narrow-spectrum antibiotics


  Kill either Gram-positive or Gram-negative bacteria
• Broad-spectrum antibiotics


  Kill both Gram positives and Gram negatives
• Penicillins


  β-lactam drugs that interfere with the synthesis of bacterial cell walls and have maximum effect on bacteria that are actively dividing
• Cephalosporins


  Also β-lactam antibiotics that interfere with cell wall synthesis and are bactericidal
• Carbapenems


  Among the most powerful antibacterial agents that target the cell envelope and have excellent activity against a broad spectrum of bacteria
• Glycopeptides


  Target the cell envelope and have excellent activity against most aerobic and anaerobic Gram-positive bacteria
• Tetracyclines


  Broad-spectrum drugs that exert their effect by targeting bacterial ribosomes and are bacteriostatic
• Aminoglycosides


  Bactericidal broad-spectrum drugs that inhibit bacterial protein synthesis
• Macrolides


  Inhibit protein synthesis and are considered bacteriostatic at lower doses and bactericidal at higher doses
• Most antimicrobial agents have some side effects, produce allergic reactions, or permit development of resistant mutant pathogens
• Cells of humans and animals do not synthesize folic acid from PABA; they get folic acid from the food they eat. Consequently, they are unaffected by sulfa drugs
• Penicillins and cephalosporins are referred to as β-lactam drugs because their molecular structure includes a four-sided ring structure known as a β-lactam ring
• The cephalosporins are classified as first-, second-, third-, fourth-, and fifth-generation cephalosporins
• Aminoglycosides are effective against a wide variety of aerobic Gram-negative bacteria, but are ineffective against anaerobes
• Major Categories of Antibacterial Agents

  • Tetracyclines
  • Aminoglycosides
  • Macrolides
  • Fluoroquinolones
• Tetracyclines


  Broad-spectrum drugs that exert their effect by targeting bacterial ribosomes, bacteriostatic, effective against a wide variety of bacteria including chlamydias, mycoplasmas, rickettsias, Vibrio cholerae, and spirochetes such as Borrelia spp. and Treponema pallidum
• Aminoglycosides


  Bactericidal broad-spectrum drugs that inhibit bacterial protein synthesis, major factor limiting their use is toxicity, effective against a wide variety of aerobic Gram-negative bacteria but ineffective against anaerobes
• Macrolides


  Inhibit protein synthesis, considered bacteriostatic at lower doses and bactericidal at higher doses, include erythromycin, clarithromycin, and azithromycin, effective against chlamydias, mycoplasmas, T. pallidum, and Legionella spp.
• Fluoroquinolones


  Bactericidal drugs that inhibit DNA synthesis, the most commonly used is ciprofloxacin, effective against members of the family Enterobacteriaceae and P. aeruginosa
• Multidrug Therapy


  Two or more drugs may be used simultaneously to kill all the pathogens and to prevent resistant mutant pathogens from emerging
• Synergism


  When the use of two antimicrobial agents produces a degree of pathogen killing that is far greater than that achieved by either drug alone
• Antagonism


  When the use of two drugs produces an extent of pathogen killing that is less than that achieved by either drug alone
• Ways Antifungal Agents Work

  • Binding with cell membrane sterols (e.g., nystatin and amphotericin B)
  • Interfering with sterol synthesis (e.g., clotrimazole and miconazole)
  • Blocking mitosis or nucleic acid synthesis (e.g., griseofulvin and 5-flucytosine)