Lecture 10 Flashcards

1
Q

What is Colistin?

A
  • It is a last-resort antibiotic
  • It is increasingly used as a ‘last-line’ therapy to treat infections caused by multi-drug resistant Gram-negative bacteria
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2
Q

Antimicrobial Chemotherapy

A
  • Antimicrobial drugs must be administered in the proper dose and at the correct dosing intervals
  • Immune system competence of host body is critical
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3
Q

What are potential issues with therapy?

A
  • Drug delivery and retention
  • Correct activity spectrum
  • Toxic side effects
  • Development of resistance
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4
Q

What is Antimicrobial Chemotherapy? What are the types of parasites?

A

Drug treatment of parasitic infections in which the parasites are destroyed or removed without injuring the host.

Parasites: bacteria, viruses, protozoa, fungi and worms

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5
Q

Who developed the concept of antimicrobial chemotherapy?

A

Paul Ehrlich in 1906

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6
Q

What are the important microorganisms involved in infectious diseases?

A

Bacteria
Viruses
Fungi
Protazoa
Helminths
(look at slide 11 for examples)

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7
Q

What is the proper use of antimicrobial drugs?

A
  • Diagnosis
  • Removal of barriers to cure
  • Necessity of chemotherapy
  • Selection of appropriate drug
  • Combinations of antimicrobials
  • Chemoprophylaxis and preemptive suppressive therapy
    (look at slide 12)
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8
Q

What are the general problems with antimicrobial drugs?

A
  • Opportunistic infection
  • Allergic reactions
  • Treatment failure
    (look at slide 13)
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9
Q

The relationship between humans and microorganisms is affected by factors such as?

A
  • Natural distribution of microorganisms
  • Microbial pathogenicity
  • Susceptibility to infection
    (look at slide 15)
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10
Q

What is the classification of antimicrobial drugs?

A
  1. Mode of action in target organism
  2. Site of action in target organism
  3. Type of organism against which they are active
  4. Spectrum of antimicrobial activity
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11
Q

What is a bacteriostatic and bactericidal?

A
  • Bacteriostatic: the arrest of bacterial growth. kills pathogens, if at all, only at much higher conc.
  • Bactericidal: killing of bacteria
    at high conc. some bacteriostatic drugs become bactericidal. Kills pathogens at levels 2-4 times the MIC
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12
Q

What are some types of antimicrobial drugs?

A
  • Antibacterial drugs
  • Antiviral drugs
  • Antifungal drugs
  • Antiprotozoal drugs
  • Anthelminthic drugs
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13
Q

What are the different sites in a target organism?

A
  • Cell wall
  • Cytoplasmic membrane
  • Protein synthesis
  • Nucleic acid metabolism
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14
Q

What is the spectrum of antimicrobial drugs?

A
  • Narrow-spectrum drugs
  • Broad-spectrum durgs
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15
Q

What are some examples of cell wall synthesis inhibitors?

A
  • Penicillins
  • cephalosporins
  • bacitracin
  • vancomycin
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16
Q

What agents are highly suitable since human host cells lack a cell wall?

A

Anti-bacterial agents that inhibit cell wall synthesis are highly suitable. Cell wall synthesis inhibitors, bactericidal on growing or multiplying bacteria.

17
Q

What is the Inhibition of peptidoglycan synthesis?

A

Penicillins
- Inhibition of transpeptidation and thus no proper cross-linking of peptidoglycan via binding and inhibition
of penicillin-binding proteins (PBP)

Cephalosporins
- Inhibition of transpeptidation and thus no proper cross-linking of peptidoglycan

Bacitracin
- Inhibition of regeneration of lipid carrier due to blocking its de-phosphorylation

Vancomycin
- Inhibition of transport and release of peptidoglycan building blocks through the plasma membrane

18
Q

What are penicillins?

A
  • They are beta-lactam antibiotics
  • Their parent substance in Penicillin G (benzyl-penicillin)
  • Obtained from cultures of mold fungi Penicillium notatum
  • Disrupts cell wall synthesis by inhibiting transpeptidase
  • Bactericidal effect: since cell wall prevents rupture of the bacterial plasma membrane from a high internal osmotic pressure, cell wall defects cause bacterial cells to swell and burst
  • It requires injection
  • Has potential adverse effects such as hypersensitivity, neurotoxic effects, anaphylactic shock
19
Q

What are the disadvantages of Penicillin G?

A
  • Cleavage of beta-lactam ring by gastric acid
  • Cleavage of beta-lactam ring by bacterial enzymes (beta-lactamases)
  • Narrow anti-bacterial spectrum (mostly against gram+ bacteria)
20
Q

What are penicillin derivatives?

A
  • Penicillin V
  • Oxacillin
  • Amoxicillin
  • Amoxicillin plus clavulanic acid
21
Q

What are the advantages of penicillin derivatives?

A

Penicillin V
- Acid resistance (permits oral administration)

Oxacillin
- Penicillinase resistance (suitable for therapy of penicillinase-producing staphylococci)

Amoxicillin
- Extended activity spectrum, also including many gram-negative bacteria

Amoxicillin in combination with Clavulanic Acid
- Protection against destruction by penicillinase

22
Q

Estimation of antimicrobial activity levels is a crucial procedure to what?

A
  • Determine which agents are most effective against a particular pathogen of interest
  • Estimate the proper therapeutic dose
23
Q

Some idea of the effectiveness of a chemotherapeutic agent against a pathogen can be obtained from determining what? need to know

A
  1. MIC - Minimal Inhibitory Conc.
    • lowest conc of a drug that prevents the growth of a particular pathogen
  2. MLC - Minimum Letal conc.
    • lowest conc of drug that kills the pathogen
24
Q

What are the two established methods that are often used to determine the level of antimicrobial activity?

A
  • Mueller-Hinton broth dilution susceptibility assay
  • Kirby-Bauer disk diffusion assay
25
Q

Dilution susceptibility test

A

look at slide 25

26
Q

What is the Kirby Bauer method?

A
  • The antibiotic-impregnated disk is placed on agar previously inoculated with a test bacterium.
  • Disk picks up moisture, and the antibiotic diffuses radially outward through the agar
  • Production of an antibiotic concentration gradient
    (look at slide 26)