Drugs Used in the Treatment of Infectious Diseases

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Drugs Used in the Treatment of Infectious Diseases

• Pharmacology 49.222
• Bill Diehl-Jones RN, PhD
• Faculty of Nursing and Department of Zoology

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Agenda

• Zen Review
• Antibiotics
• Antiviral Agents
• Antifungal Agents
• Antihelminthic Agents

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Antimicrobial Agents
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The Problem

• Many chemicals are lethal to bacteria
• Cyanide works really well!
• However, these are lethal to the host
• The solution is to find substances that attack
  pathways or structures found in bacteria
  (prokaryotes) but not in humans (eukaryotes)

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Antibacterial AgentsBasic Mechanisms of Action
Nucleic Acid Inhibitors (Rifampin)
Metabolic Inhibitors (Sulfonamides)
Cell Wall Synthesis Inhibitors (ß-lactams,
Vancomycin)
Protein Synthesis Inhibitors Tetracycline,
Aminoglycosides
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So where do antibiotics come from?

• Natural products
• Eg Penicillin
• Found in secretions of soil bacteria, fungi
• Semi-synthetic products
• Natural products that are chemically modified
• Completely synthetic products
• Sulfa drugs

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Categories of Antibiotics

• Sulfa Drugs
• Beta Lactams
• Aminoglycosides
• Tetracyclines
• Macrolides
• Lincosamides
• Streptogramins

• Fluoroquinolones
• Polypeptides
• Rifampin
• Mupirocin
• Cycloserine
• Aminocyclitols
• Glycopeptide
• Oxazolidinones

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Sulfa Drugs

• First antibacterial agent
• How it works
• Bacteria need to synthesize FOLIC ACID from
  para-aminobenzoic acid (PABA)
• Sulfa drugs are PABA analogues they compete with
  PABA
• What is it used for
• Concentrates in urine used for urinary tract
  infections
• Also used in treating pneumonia, upper
  respiratory tract infections

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Clinical Notes on Sulfa

• Allergies to sulfa drugs are common
• Combines with other molecules to activate immune
  system
• May present as rash may cause anaphylaxis
• Numerous drug-drug interactions

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Beta-Lactams

• Include
• Penicillins (eg Penicillin G)
• Ampicilin
• Cephalosporin (Cefonicid)
• How they works
• Inhibit cell wall synthesis (effective on
  dividing bacteria
• Indications
• Meningococcal, Streptococcal infections

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Clinical Notes on Beta-Lactams

• Allergies are common

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Aminoglycosides

• Include
• streptomycin, kanamycin, gentamycin
• How they work
• Bind to ribosomes, interfere with protein
  synthesis
• Indications
• Acinetobacter, Enterobacter, Pseudomonas
  infections
• Eg endocarditis, septicemia

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Clinical Notes on Aminoglycosides

• Toxicity
• Aminoglycosides can be OTOTOXIC and Nephrotoxic
• Worsened by diuretics, NSAIDS
• Serum levels should be monitored
• They can enhance bacteriocidal activity of
  beta-lactams

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Tetracyclines

• Include
• Chlortetracycline, oxytetracyclin
• How they work
• Bind to ribosomes, inhibit protein synthesis
• Indications
• Haemophylus, Strep, Chlamydia, Nisseria
• Common uses acne, respiratory tract infections

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Clinical Notes on Tetracyclines

• Tetracycline should be taken 1 hour before food,
  to prevent binding/reduced absorption
• Should not be taken with Tums, Rolaids
• Also binds to the drug
• May enhance activity of coumadin
• Precautions?

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Macrolides

• Include
• Erythromycin, clarithromycin
• How they work
• Bind to ribosomes, block protein synthesis
• Indications
• Common uses Pertussis, bronchitis, diptheria,
  acne

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Clinical Notes on Macrolides

• Erythromycin should not be taken with the
  following
• Seldane, prupulsid, hismanal
• Contraindicated with liver disease
• Generally considered safe for breast-feeding
  mothers

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Discussion

• How are antibiotics chosen?
• What are some of the therapeutic issues?

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Antibiotic Resistance

• Intrinsic Resistance
• Some bacteria are more resistant to antibiotics
  than others (eg gram positive are less
  susceptible to polymixins than others)
• Acquired Resistance
• Many bacteria acquire resistance
• Eg Shigella resistance to ampicillin grew from
  32 to 65 in ten years

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How Does Resistance Develop?

• Bacteria acquire genes encoding proteins that
  protect them from antibiotics
• Can occur by mutation, or acquired from bacteria
  already resistant

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Why Does Antibiotic Resistance Develop?

• Over-use of antibiotics
• Prophylactic use of Antibiotics
• Full course of antibiotics not taken
• Overuse in livestock industry

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Hospital Superbugs

• VRE
• Vancomycin-resistant Enterococcus
• Potential alternative drugs
• teicoplanin, ciprofloxacin
• MRSA
• Methicillin-resistant Staphylococcus aureus
• Potential alternative drugs
• Vancomycin, linezolid
• Multiple Drug-Resistant Tuberculosis
• Usually due to too short duration, inadequate dose

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Can nursing interventions reduce the spread of
antibiotic resistance?
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Future Prospects

• Over a dozen new antibiotics are reaching the
  clinical trial stage, including
• Modified, already existing antibiotics
• New beta-lactams, macroilides, modifications of
  vancomycin
• Totally new antibiotics
• Urea Hydroxyamates (block translation)
• Heteroaromatic polycycles (HARP block
  transcription)

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Antiviral Agents

• General Considerations
• Different types of viruses
• Different drugs are required
• Only a few types of viruses respond to drugs

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Examples of Antiviral Agents

• Drugs for RSV
• Amantidine
• Herpes/Cytomegaloviruses
• Acyclovir, vidarabine
• HIV
• Didanosine
• Hepatitis, Leukemias, Kaposiss Sarcoma
• Interferon

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Antifungal Agents

• Fungal disorders
• Candidiasis, ring worm, athletes foot
• How they work
• MOST alter cell membrane permeability
• Can be systemic/topical

• Four Groups
• Polyenes
• Azoles
• Fluorinated pyrimidines
• Miscelanious

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Polyene Antifungal Drugs

• Examples
• Amphotericin B (good for Blastomyces)
• Nystatin (good for Candida)
• Griseofuvin (good for Tinea if otherwise
  unresponsive)
• Watch
• Amphotericin B can cause anemia, hypokalemia

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Azole Antifungal Drugs

• Example
• Fluconazole (used for candidiasis)
• Clotimazole (as above also for Tinea (foot
  fungus))

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Antihelminthics

• So, what are helminths?
• Cestodes (tapeworms)
• Nematodes (pinworn, common roundworm)
• Trematodes (liver flukes)
• Prototype drug Mebendazole
• Good for mixed helminth infections
• Damages microtubules in worm gut cells, but not
  in humans
• Watch interactions with anticonvulsant drugs