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Microbiology > Chapter 12: Chemotherapy > Flashcards

Chapter 12: Chemotherapy Flashcards

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1
Q

Chemotherapy

A

treating disease using chemicals

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2
Q

Chemotherapy History

A
  • Folk Remedies: moldy bread, willow bark, foxglove (digitalis active ingredient, plant), Quinine (ingredient in toxic water); used to prevent Malaria)
  • Ehrlich (father of Chemotherapy): Salvarsan, “magic bullet” (prevent syphilis)
  • Sulfa drugs (sulfonamides): Prontosil (1935; red dye); active ingredient Sulfanilamide
  • Antibiotic discovery: Fleming (1928); mold penicillium: active ingredient penicillin; on market 1944
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3
Q

Chemotherapy History: Folk remedies

A
  • moldy bread
  • willow bark
  • foxglove (digitalis active ingredient, plant)
  • Quinine (ingredient in toxic water; used to prevent malaria)
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4
Q

Chemotherapy History: Ehrlich

A
  • Father of Chemotherapy

- Salvarsan; “Magic Bullet” (prevent syphilis)

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5
Q

Chemotherapy History: Sulfa Drugs (sulfonamides)

A

-Prontosil (1935; red dye); active ingredient Sulfanilamide

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6
Q

Chemotherapy History: Antibiotic discovery

A

-Fleming (1928); mold penicillium: active ingredient penicillin; on market 1944

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7
Q

Antibiotics

A
  • substances produced by living organisms that have anti-microbial ability
  • substance produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms
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8
Q

Synthetic Drugs

A

Antimicrobial compounds synthesized in the laboratory through chemical reactions

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9
Q

Semi-Synthetic Drugs

A

Drugs that are chemically modified in the lab after being isolated from natural sources

  • half made in lab/half made naturally
    ex: Penicillin
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10
Q

Example of a Semi-synthetic Drug

A

Penicillin

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11
Q

Characteristics of the ideal Anti-microbial Drug

A
  • Selectively toxic to microbe but nontoxic to host cells
  • Microbicidal rather than microbistatic
  • Relatively soluble; functions even when highly diluted in body fluids
  • Remains potent long enough to act and is not broken down or excreted prematurely
  • Doesnt lead to development of antimicrobial resistance
  • Complements or assists the activities of the hosts defenses
  • Remains active in Tissues + body fluids
  • Readily delivered to the site of infection
  • Reasonably priced
  • Does not disrupt the hosts health by causing allergies or predisposing the host to other infections
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12
Q

Criteria for Evaluation of Antimicrobial Drugs: Spectrum of Activity

A

(range of activity)

  • Broad (extended): start with this first because you don’t know what you have
  • Narrow (limited)
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13
Q

Very Important Criterion for Evaluation of Antimicrobial Drugs

A

resistance not acquired easily

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14
Q

Ketoconazole

A
  • antifungal

- first oral antifungal drug

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15
Q

Mefloquine

A

used for malaria

  • used to treat resistant cases
  • semi-synthetic
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16
Q

Niclosamide

A

used for tapeworms

-destroys scolex and adjoining proglottids of tapeworms

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17
Q

Praziquantel

A

used for flukes + tapeworms

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18
Q

How microbes require resistance

A
  1. Genetic changes (mutation) followed by natural selection = chromosomal resistance
  2. Transfer of R plasmids: transformation; conjugation; transduction= extra-chromosomal resistance
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19
Q

How Microbes Require Resistance: Genetic changes

A

-Genetic changes (mutation) followed by natural selection = chromosomal resistance

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20
Q

How Microbes Require Resistance: Transfer of R plasmids

A

transformation; conjugation. transduction = extra-chromosomal resistance

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21
Q

How to Limit Spread of Resistance

A

Correct these problems:
-misdiagnosis by physician; wrong dosage
-noncompliance by patient (patient doesn’t follow directions); proximity; office visit; hospital workers
>mechanism: natural selection

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22
Q

Mechanisms of Resistance

A 
Drug resistance may take the form of:
-Inactivation of the drug
-Decreased permeability to the drug
-Increased elimination of the drug from the cell
-Change in drug receptors
-Change of metabolic pathway:
>development of enzymes 
>alteration of an enzyme
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23
Q

Strategic Approaches to the use of Chemotherapeutics

A
  • Prophylaxis: drugs are administered to prevent infection in susceptible people
  • Combined Therapy: two or more drugs are given simultaneously, either to prevent the emergence of resistant species or to achieve synergism (use 2 drugs to increase a enhanced microbial affect)
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24
Q

Strategic Approaches to the use of Chemotherapeutics: Prophylaxis

A

drugs are administered to prevent infection in susceptible people

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25
Q

Strategic Approaches to the use of Chemotherapeutics: Combined Therapy

A

two or more drugs are given simultaneously, either to prevent the emergence of resistant species or to achieve synergism (use 2 drugs to increase a enhanced microbial affect)

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26
Q

Synergism

A

use 2 drugs to increase a enhanced microbial affect

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27
Q

Effects of Combining Antimicrobial Drugs

A
  • Synergism (members cooperate and share nutrients)
    e. g. TMP-SMZ
  • Antagonism (some members are inhibited or destroyed by others)
    e. g. Tetracycline (inhibits protein synthesis) and Penicillin (inhibits peptidoglycan which cells need)
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28
Q

Effects of Combining Antimicrobial Drugs: Synergism

A

members cooperate and share nutrients

e.g. TMP- SMZ

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29
Q

Effects of Combining Antimicrobial Drugs: Antagonism

A

some members are inhibited or destroyed by others
e.g.
>Tetracycline (inhibits protein synthesis)
>Penicillin (inhibits peptidoglycan which cells need)

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30
Q

Major Modes of Action of Common Antimicrobial Drugs: Cell Wall Inhibition

A
  • Penicillins
  • Vancomycins
  • Bacitracin
  • Isoniazid
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31
Q

Major Modes of Action of Common Antimicrobial Drugs: Cell Membrane

A

cause loss of selective permeability

-Polymyxins

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32
Q

What Drug causes loss of selective permeability in cell membrane?

A

Polymyxins

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33
Q

Major Modes of Action of Common Antimicrobial Drugs: DNA/RNA

A 
-DNA
>Inhibit replication and transcription
>inhibit gyrase (unwinding enzyme)
*Quinolones (ciprofloxacin)
-RNA
>Inhibit RNA Polymerase
*Rifampin
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34
Q

Which Drug Inhibits RNA Polymerase?

A

Rifampin

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35
Q

What Drug inhibits replication and transcription and also inhibits gyrase for DNA?

A

Quinolones (ciprofloxacin)

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36
Q

Major Modes of Action of Common Antimicrobial Drugs: Protein Synthesis inhibitors acting on Ribosomes

A 
-Site of Action 50S subunit:
>Chloramphenicol
>Erythromycin
>Clindamycin
>Streptogramin (Synercid)
-Site of Action 30S subunit:
>Aminoglycosides
>Gentamicin (treat pseudomonas)
>Streptomycin
>Tetracyclines
-Both 30S and 50S subunits
>blocks initiation of protein synthesis
>Linezolid (Zyvox)
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37
Q

Protein Synthesis inhibitors acting on Ribosomes: Site of action on 50S subunit

A
  • Chloramphenicol
  • Erythromycin
  • Clindamycin
  • Streptogramin (Synercid)
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38
Q

Protein Synthesis inhibitors acting on Ribosomes: Site of action on 30S subunit

A
  • Aminoglycosides
  • Gentamicin (treat pseudomonas)
  • Streptomycin
  • Tetracyclines
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39
Q

Protein Synthesis Inhibitors Acting on Ribosomes: Both 30S and 50S subunits

A
  • blocks initiation of protein synthesis

- Linezolid (Zyvox)

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40
Q

What Drug Blocks Initiation Of Protein Synthesis on Ribosomes?

A

Linezolid (Zyvox)

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41
Q

Major Modes of Action of Common Antimicrobial Drugs: Metabolic Pathways + Products

A

Block pathways and inhibit metabolism

  • Sulfonamides (sulfa drugs)
  • Trimethoprim
42
Q

What Drugs Block pathways and inhibit metabolism on ribomomes?

A
  • Sulfonamides (sulfa drugs)

- Trimethoprim

43
Q

Drugs that act on Cell Wall

A
  • Penicillins
  • Cephalosporins
  • Vancomycin
  • Isoniazid (INH)
  • Bacitracin
44
Q

Drugs that act on Cell Wall: Penicillins

A

-Organic chemical structure includes beta-lactam ring
-Originally isolated from mold Penicillium chrysogenum
-Bactericidal
-Narrow Spectrum
-Problems: allergic reactions and development of bacterial resistance to drug through beta-lactamase (penicillinase)
-Natural:
>Penicillin G (gram +) (requires injection)
>Penicillin V (gram +) (oral administration)
-Semisynthetic:
>Methicillin (used until MRSA)
>Ampicillin (Broad Spectrum)
>Amoxicillin (Broad spectrum; combined with inhibitor penicillinase)

45
Q

Penicillins: Natural Drugs

A

-Penicillin G (gram +) (requires injection)

>Penicillin V (gram +) (oral administration)

46
Q

Penicillin G

A
  • Gram +
  • requires injection
  • natural penicillin drug
  • Narrow Spectrum
  • Best drug of choice when bacteria are sensitive; low cost; low toxicity
  • Disadvantages: can be hydrolyzed by penicillinase; allergies occur; requires injection
47
Q

Penicillin V

A
  • Gram +
  • oral administration
  • natural penicillin drug
  • Narrow Spectrum
  • Good adsorption from intestine; otherwise, similar to Penicillin G
  • Disadvantages: Hydrolysis by penicillinase; allergies
48
Q

Penicillins: Semisynthetic Drugs

A
  • Methicillin (used until MRSA)
  • Ampicillin (Broad Spectrum)
  • Amoxicillin (Broad Spectrum; combined with inhibitor of penicillinase)
49
Q

Methicillin

A
  • used until MRSA
  • Narrow Spectrum
  • Semisynthetic penicillin drug
  • not usually susceptible to penicillinase
  • Disadvantages: poor absorption, allergies; growing resistance
50
Q

Ampicillin

A
  • Broad Spectrum
  • Semisynthetic penicillin drug
  • works on gram (-) bacilli
  • Disadvantages: can be hydrolyzed by penicillinase; allergies; only fair absorption
51
Q

Amoxicillin

A
  • Broad Spectrum; combined with inhibitor of penicillinase
  • For gram (-) infections; good absorption
  • Disadvantages: hydrolysis by penicillinase; allergies
52
Q

Drugs that Act on Cell Wall: Cephalosporins

A

-originally isolated from the mold cephalosporium
-Bactericidal
-Broader spectrum than Penicillin
>Cephalothin (first generation; requires injection)
>Cefixime (third generation; oral administration)

53
Q

Cephalosporins: Cephalothin

A
  • first generation of cephalosporins

- requires injection

54
Q

Cephalosporins: Cefixime

A
  • third generation of cephalosporins

- oral administration

55
Q

Drugs that act on Cell Wall: Vancomycin

A

-used for life-threatening, methicillin-resistant Staphylococcal infections (MRSA) and Enterococcus, except VRE

56
Q

Drugs that act on Cell Wall: Isoniazid (INH)

A

inhibits synthesis of mycolic acid in cell wall of Mycobacterium

57
Q

Drugs that act on Cell Wall: Bacitracin

A

Topical; produced by B. subtilis; component of triple antibiotic ointments

58
Q

Drug That Act on Cell Membrane

A

Polymyxin

  • Gram (-)
  • topical only
59
Q

Drugs that Affect Nucleic Acid Synthesis

A
  • Fluoroquinolones (Ciprofloxacin), (Levaquin)
  • Rifampin: inhibits synthesis of mRNA; used to treat TB and leprosy
  • Chloroquine
60
Q

Rifampin

A
  • drug that affects nucleic acid synthesis
  • inhibits synthesis of mRNA
  • used to treat TB and leprosy
61
Q

Drugs that Inhibit Protein Synthesis

A
  • Aminoglycosides
  • Tetracyclines
  • Chloramphenicol
  • Erythromycin
  • Azithromycin (Z pack)
  • Telithromycin (Ketek)
  • Clindamycin
62
Q

Drugs that Inhibit Protein Synthesis: Aminoglycosides

A

(produced by streptomyces)

  • Streptomycin: narrow spectrum; including Mycobacterium; hearing loss
  • Gentamicin: narrow spectrum; including pseudomonas
  • Neomycin (broad spectrum; topical use)
63
Q

Aminoglycosides: Streptomycin

A
  • produced by streptomyces
  • narrow spectrum
  • including Mycobacterium
  • hearing loss
64
Q

Aminoglycosides: Gentamicin

A
  • produced by streptomyces
  • narrow spectrum
  • including pseudomonas
65
Q

Aminoglycosides: Neomycin

A
  • produced by streptomyces
  • broad spectrum
  • topical use
66
Q

Drugs that Inhibit Protein Synthesis: Tetracyclines

A
  • produced by Streptomyces
  • very broad spectrum
  • drug of choice for Rickettsia, Chlamydia, Propionibacterium
  • Harms microbiota; animal feed additive; harms teeth of children; photosensitive
67
Q

Drugs that Inhibit Protein Synthesis: Chloramphenicol

A
  • produced by streptomyces

- very broad spectrum; possibly toxic

68
Q

Drugs that inhibit protein synthesis: Erythromycin

A
  • Broad Spectrum

- Alternative to Penicillin for penicillin resistant bacterium and in case of penicillin allergy in patient

69
Q

Drugs that Inhibit Protein Synthesis: Azithromycin (Z Pack)

A
  • semisynthetic

- broader spectrum and better tissue penetration than Erythromycin

70
Q

Drugs that inhibit protein synthesis: Telithroycin (Ketek)

A

-semisynthetic

71
Q

Drugs that inhibit protein synthesis: Clindamycin

A

used primarily for intestinal infection by anaerobes

72
Q

Drugs that interfere with Metabolism/ Enzyme Activity

A
  • Sulfonamides

- Trimethoprim

73
Q

Antifungal Drugs

A
  • Amphotericin B
  • Azoles
  • Flucytosine
  • Echinocandins
  • Allylamines
74
Q

Antigungal Drugs: Amphotericin B

A
  • systemic
  • topical
  • Nystatin (topical)
75
Q

Antifungal Drugs: Azoles

A
  • ketoconazole (Nizoral)
  • Fluconazole (Diflucan)
  • Miconazole (Monistat)
  • Itraconazole (Sporanox)
76
Q

Antifungal Drugs: Flucytosine

A

many fungi resistant so combined often with amphotericin

77
Q

Antifungal Drugs: Echinocandins

A

Capsofungin inhibits fungal cell wall (Chitin)

78
Q

Antifungal Drugs: Allylamines

A

-Terbinafine (Lamisil) systemic, topical; inhibits ergosterol

79
Q

Ketoconazole

A
  • one of the first available oral treatments for systemic fungal infections
  • Toxic to liver so now usually replaced with itraconazole or fluconazole
  • Best absorbed at highly acidic levels, so antacids or other causes of decreased stomach acid levels will lower the drugs absorption when taken orally
  • Side affects are sometimes used to treat non-fungal problems. The decrease in testosterone caused by the drug makes it useful for treating prostate cancer and for preventing post-operative erections following penile surgery
80
Q

Anti-parasitic Drugs: Antiprotozoan Drugs

A
  • Quinine
  • Chloroquine
  • Mefloquine
  • Primaquine
  • Metronidazole (Flagyl)
81
Q

Anti-parasitic Drugs: Anti-protozoan Drugs: Chloroquine

A
  • prophylaxis

- suppression of acute cases of malaria

82
Q

Anti-parasitic Drugs: Anti-protozoan Drugs: Mefloquine

A
  • semisynthetic

- used to treat resistant cases

83
Q

Anti-parasitic Drugs: Anti-protozoan Drugs: Primaquine

A

relapsing cases of malaria

84
Q

Anti-parasitic Drugs: Anti-protozoan Drugs: Metronidazole (Flagyl)

A
  • Amobeasis; Giardiasis, Trichomoniasis

- also used for anaerobic bacteria

85
Q

Anti-helminthic Drugs

A

most effective drugs immobilize, disintegrate, or inhibit metabolism of all stages of life cycle

  • Mebendazole
  • Pyrantel, piperazine
  • Niclosamide
  • Praziquantel
  • Ivermectin
86
Q

Anti-helminthic Drugs: Mebendazole

A
  • Broad spectrum
  • intestinal roundworms
  • work locally in intestines to inhibit microtubule of worms, eggs and larvae
  • only active in virus infected cells
87
Q

Anti-helminthic Drugs: Pyrantel, piperazine

A

paralyze muscles of intestinal roundworms

88
Q

Anti-helminthic Drugs: Niclosamide

A

destroys scolex and adjoining proglottids of tapeworms

*only active in virus infected cells

89
Q

Anti-helminthic Drugs: Praziquantel

A

tapeworms + flukes

90
Q

Anti-helminthic Drugs: Ivermectin

A

veterinary treatment for tapeworms and flukes; used for humans for Strongyloidiasis

91
Q

Antiviral Drugs

A

-most antiviral drugs have limited spectrum of activity
-Most are designed to block a step in viral multiplication
>barring penetration into host cell
>Blocking replication, transcription, and/ or translation of viral genetic material
>Preventing the normal maturation of viral particles
-Influenza drugs
-Herpes drugs
-HIV Drugs
-AZT
-Maravoc
-Fuzeon
-Interferons

92
Q

Antiviral Drugs: Influenza Drugs

A

-Amantadine (block entry of influenza virus by interfering with fusion of virus with cell membrane)
-Relenza
-Tamiflu
(both relenza and tamiflu stop the actions of influenza neuraminidase, required for entry of virus into cell)

93
Q

Antiviral Drugs: Herpes Drugs

A
  • Acyclovir (Zovirax); Valacyclovir (Valtrex); Famciclovir (Famvir) (active in only virus infected cells)
  • Ganciclovir (Cytovene) for CMV; an analog of guanine
94
Q

Analog

A

antiviral agents mimic structure of nucleotides

95
Q

Antiviral Drugs: HIV Drugs

A

interfere with action of reverse transcriptase enzyme

96
Q

Antiviral Drugs: Maravoc

A

covers up receptors

97
Q

Antiviral Drugs: Fuzeon

A
  • prevents viral envelope from fusing with host

- prevents binding of viral receptors to cell receptor which blocks fusion of virus with cell

98
Q

Antiviral Drugs: Interferons

A

glycoproteins produced by viral infected cells (Fibroblasts, leukocytes)

99
Q

Actions of Antiviral Drugs

A

antiviral drugs will affect DNA

100
Q

Tests for Microbial Susceptibility To Antimicrobial Agents

A 
-Disk Diffusion Method
>Kirby Bauer Test
>E Test
-Broth Dilution Tests
>Minimum Inhibitory Concentration (MIC)
>Minimum Bacteriocidal Concentration (MBC)

Microbiology (20 decks)

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