Antifungal agents

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Antifungal agents

• Problem eukaryotic drugs harm mammalian hosts
  too
• 4 drug groups
• Macrolide polyene antibiotics
• Griseofulvin
• Synthetic azoles
• flucytosine

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Macrolide polyene

• MOA bind fungal membranes, increase permeability
  (fungal membranes have sterols)
• Examples
• Amphotericin B mimic lipids, most versatile
  effective, topical systemic treatments
• Nystatin topical treatment
• Structure steroid
• Applications
• Candida, ringworm,
• histoplasmosis, cryptococcus

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Other antifungals

• Griseofulvin
• Application stubborn cases of dermatophyte
  infections, nephrotoxic
• Synthetic azoles Application broad-spectrum
  Examples ketoconazole, clotrimazole, miconazole
  Structure complex ring structure
• Flucytosine MOA/Structure analog of cytosine
  Application cutaneous mycoses or in combination
  with amphotericin B for systemic mycoses

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Antifungal drugs
Azoles
Flucocytozine
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Antiprotozoan drugs

• Malaria is caused by Plasmodium spp.
• Antimalarial drugs quinine (cinchona tree)
  chloroquinine, primaquine (synthetic quinolines)
  mefloquine (semisynthetic)
• Used as prophylaxis and treatment some used to
  treat various stages or species

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Other antiprotozoan drugs

• Metronidazole (Flagyl) Entamoeba, Giardia,
  Trichomonas
• Quinicrine (quinine-based)
• Sulfonamides, tetracyclines (antibiotics)

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Antihelminthics

• Flukes, tapeworms, roundworms
• Large animals, similar to human physiology
• Drugs block reproduction, or (better yet)
  immobilize, disintegrate, or inhibit metabolism
  of worms (all stages)

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Antihelminthics

• mebendazole, thiabendazole- broad-spectrum
  inhibit function of microtubules, interferes with
  glucose utilization disables them
• pyrantel, piperazine- paralyze muscles
• niclosamide destroys scolex
• Praziquantel tapeworms, flukes
• Ivermectin heartworm, stronglyoides,
  oncocercosis

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Antiviral drugs 3 MOA

• Block _________________________
• Fuzeon blocks HIV
• Amantidine blocks influenza entry and release
  (blrocks fusion and uncoating)
• Block __________________________
• Acyclovir herpesviruses binds viral DNApol
• AZT thymine analog HIV RT inhibitor
• Prevent _______________________
• Protease inhibitors HIV inactivate enzyme

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Interferon

• IFN is a human cytokine, naturally produced by
  cells (leukocytes) as part of the immune response
• It is the natural antiviral mechanism in your
  body! (also anticancer)
• recIFN can be used therapeutically
• Shorten herpes healing time
• Reducing colds and warts
• Slowing cancer progress treating rare cancers
• Treating HepC, papillomavirus, Kaposis sarcoma

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Four Mechanisms drug resistance

• Drug inactivation penicillinases
• Decreased permeability to drug or increased
  elimination of drug from cell
• Change in metabolic patterns
• Change in drug receptors

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Mechanisms drug resistance
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Selection for drug resistance
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Human behavior that leads to drug resistance

• Doctors over-prescribing antibiotics
• asking for antibiotics when they are not needed
  (viral infections)
• failing to finish an antibiotic prescription
• saving the unused medication and taking it later
  for another illness
• taking antibiotics before symptoms arise simply
  to avoid getting sick

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Other factors that lead to microbial drug
resistance

• Hospital setting Lots of Abt being used,
  weakened (sick and easy to infect) hosts
• MRSA last resort was vancomycinnow there are
  VRSA!
• Resistance in food animals on antibiotic regimens
  (these microbes are also in the meats we eat)
• Resistance spreads rapidly both geographically
  (exporting foods) and within populations
  (transformation, conjugation, etc.)
• Viruses have rapid mutation rate (HIV)

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Side effects of drugs

• Toxicity to organs liver (detox), kidney
  (excretion sulfonamides), GI (kills flora), bone
  marrow (anemia, chloramphenicol), nervous system
  (aminoglycosides), Teeth/bones (tetracycline)

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• Allergic responses true penicillin allergy is
  to benzlpenicilloyl (product of metabolism of
  Pen)
• Suppression and alteration of microflora