Injury to plasma membrane

1

• Injury to plasma membrane
• Polymoxins
• useful against G- bacteria
• One of very few antibiotics used against G-
  Pseudomonas
• Seldom used except as a topical treatment.
• Five varieties designated A, B, C, D and E with B
  and E the most commonly prescribed
• May be combined with bacitracin and neomycin and
  a non-prescription antiseptic ointment
• (neosporin)

2
Inhibitors of Protein Synthesis

• Aminoglycosides
• amino acids linked by glycoside bonds
• 1st to have significant activity against G-
  bacteria
• Have some serious side effects like damage to the
  auditory nerve and kidneys
• Use has been declining
• Streptomycin
• best known aminoglycoside
• Used as alternative treatment for tuberculosis
• very toxic and resistant strains are rapidly
  emerging
• Neomycin
• available over the counter as a topical ointment
• Gentamicin
• effective against Pseudomonas infections

3

• Tetracyclines
• Group of broad spectrum antibiotics produced by
  Streptomyces
• Effective against most G- and G bacteria
• Penetrate body tissues easily
• Especially valuable against intracellular
  rickettsia and chlamydias
• Used to treat UTIs, pneumonias and as an
  alternative treatment for syphilis and gonorrhea.
  
• Common animal feed additive
• Oxytetracycline, chlortetracycline and
  tetracycline are the 3 most commonly used

4

• Chloramphenicol
• broad spectrum but serious toxicity issues
• suppression of bone marrow activity
• very simple chemical structure so it is easier to
  make than isolate form Streptomyces
• inexpensive so its used when cost is an issue
• Microlides
• spectrum of activity similar to penicillin
• often used as an alternative to penicillin
• Erythromycin , azoithromycin , clarithromycin
• Ketolides
• new generation of semisynthetic macrolides
• Developed to fight antibiotic resistant bacteria

5
Inhibitors of Nucleic Acid Synthesis

• Rifamycin
• Best known is rifampin
• Inhibits RNA synthesis
• Used in treatment of tuberculosis and leprosy
• Penetrate tissues so they are capable of reaching
  cerebrospinal fluid and abscesses
• Unusual side effect - urine, saliva, sweat and
  tears turn orange-red
• Quinolones and fluoroquinolones
• Broad spectrum
• Inhibits DNA gyrase
• Adversely effect the development of cartilage so
  use is limited among children and pregnant women
• Urinary tract infections
• Ciprofloxacin effective against anthrax

6
Anti-metabolites

• Sulfonamides
• Inhibit folic acid synthesis
• Broad spectrum
• Used to treat UTIs and to control infections in
  burn patients
• Commonly used in a combination
• synergism
• has a broader spectrum and reduces the risk of
  resistance

PABA
Sulfa Drug
PAS
7

• Anti-mycobacterium antibiotics
• Effective against acid-fast Mycobacterium
• Isoniazid
• Inhibits mycolic acid synthesis
• very effective against Mycobacterium tuberculosis
• Ethambutol
• Inhibits incorporation of mycolic acid
• Mycobacteria acquire resistance quickly
• Typically used with isoniazid and rifampin

8

• Antifungal drugs
• Agents affecting membranes
• Fungi have different sterols than animals
• Ergosterol vs cholesterol
• Imidazoles and triazoles
• Synthetic fungicides
• Topical treatment for dermatomycoses and Candida
  yeast infections
• Polyenes
• Amphotericin B
• Used to treat systemic infections like
  Aspergillosis
• Numerous and sever side effects
• Nystatin
• Effective topical treatment for Candida yeast
  infections

9

• Agents affecting cell walls
• fungal cell walls contain unique compounds
• B-glucan
• Echinocandins
• valuable in fighting Aspergillus, Candida and
  Pneumocystis infections
• Agents inhibiting nucleic acid synthesis
• work on specific enzymes lacking in mammalian
  cells
• Flucytocine
• Uracil analog inhibits protein synthesis
• Treats Candida infections

10

• Other antifungals
• commonly used for superficial mycosis and
  dermatomycoses
• Griseofulvin
• Given orally then reaches target site through
  sweat
• Inhibits cell division
• Tolnaftate (Tinactin)
• Action not clear
• Terbinafine (Lamisil)

11

• Antiprotozoan drugs
• Quinine
• Used to treat malaria
• isolated from a Peruvian tree largely replaced
  with synthetic versions
• Mechanism of action is unknown
• Metronidazole
• effective against Trichomonas and Girardia
• Damages DNA
• Side effect black, hairy tongue
• Causes birth defects passed in breast milk

12

• Antihelminthic drugs
• Piperazine
• Neurotoxin that paralyzes roundworms
• May cause convulsions in children
• Niclosamide
• Interfers with carbohydrate metabolism
• Treatment of tapeworms
• Mebendazole
• Blocks uptake of glucose by roundworms
• Causes birth defects

13

• Antiviral drugs
• CDC estimates that 60 of all infectious diseases
  are caused by viruses
• Annually 90 of people suffer from a viral
  infection
• There are very few antiviral drugs
• toxicity to host and rapid mutation rate
• Targets include various points in viral
  replication

14

• Purine and pryimidine analogs
• Results in an increased mutation rate
• Idoxuridine and trifluridine
• Thymine analog
• Ribavirin
• Guanine analog
• Acyclovir
• Guanine analog
• Reduces frequency and severity of herpes
  outbreaks

15

• Anti-retrovirals
• Zidovudine
• Interfers with reverse transcriptase
• Stimulate Immune System
• Leukocyte activity
• Interferon
• Anti-viral proteins prduced by host cell
• production can be stimulated to prevent spread of
  virus