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Chapter 12: Chemotherapy Flashcards

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
Strategic Approaches to the use of Chemotherapeutics: 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)
26
Synergism
use 2 drugs to increase a enhanced microbial affect
27
Effects of Combining Antimicrobial Drugs
- 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)
28
Effects of Combining Antimicrobial Drugs: Synergism
members cooperate and share nutrients | e.g. TMP- SMZ
29
Effects of Combining Antimicrobial Drugs: Antagonism
some members are inhibited or destroyed by others e.g. >Tetracycline (inhibits protein synthesis) >Penicillin (inhibits peptidoglycan which cells need)
30
Major Modes of Action of Common Antimicrobial Drugs: Cell Wall Inhibition
- Penicillins - Vancomycins - Bacitracin - Isoniazid
31
Major Modes of Action of Common Antimicrobial Drugs: Cell Membrane
cause loss of selective permeability | -Polymyxins
32
What Drug causes loss of selective permeability in cell membrane?
Polymyxins
33
Major Modes of Action of Common Antimicrobial Drugs: DNA/RNA
``` -DNA >Inhibit replication and transcription >inhibit gyrase (unwinding enzyme) *Quinolones (ciprofloxacin) -RNA >Inhibit RNA Polymerase *Rifampin ```
34
Which Drug Inhibits RNA Polymerase?
Rifampin
35
What Drug inhibits replication and transcription and also inhibits gyrase for DNA?
Quinolones (ciprofloxacin)
36
Major Modes of Action of Common Antimicrobial Drugs: Protein Synthesis inhibitors acting on Ribosomes
``` -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) ```
37
Protein Synthesis inhibitors acting on Ribosomes: Site of action on 50S subunit
- Chloramphenicol - Erythromycin - Clindamycin - Streptogramin (Synercid)
38
Protein Synthesis inhibitors acting on Ribosomes: Site of action on 30S subunit
- Aminoglycosides - Gentamicin (treat pseudomonas) - Streptomycin - Tetracyclines
39
Protein Synthesis Inhibitors Acting on Ribosomes: Both 30S and 50S subunits
- blocks initiation of protein synthesis | - Linezolid (Zyvox)
40
What Drug Blocks Initiation Of Protein Synthesis on Ribosomes?
Linezolid (Zyvox)
41
Major Modes of Action of Common Antimicrobial Drugs: Metabolic Pathways + Products
Block pathways and inhibit metabolism - Sulfonamides (sulfa drugs) - Trimethoprim
42
What Drugs Block pathways and inhibit metabolism on ribomomes?
- Sulfonamides (sulfa drugs) | - Trimethoprim
43
Drugs that act on Cell Wall
- Penicillins - Cephalosporins - Vancomycin - Isoniazid (INH) - Bacitracin
44
Drugs that act on Cell Wall: Penicillins
-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
Penicillins: Natural Drugs
-Penicillin G (gram +) (requires injection) | >Penicillin V (gram +) (oral administration)
46
Penicillin G
- 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
Penicillin V
- Gram + - oral administration - natural penicillin drug - Narrow Spectrum - Good adsorption from intestine; otherwise, similar to Penicillin G - Disadvantages: Hydrolysis by penicillinase; allergies
48
Penicillins: Semisynthetic Drugs
- Methicillin (used until MRSA) - Ampicillin (Broad Spectrum) - Amoxicillin (Broad Spectrum; combined with inhibitor of penicillinase)
49
Methicillin
- used until MRSA - Narrow Spectrum - Semisynthetic penicillin drug - not usually susceptible to penicillinase - Disadvantages: poor absorption, allergies; growing resistance
50
Ampicillin
- Broad Spectrum - Semisynthetic penicillin drug - works on gram (-) bacilli - Disadvantages: can be hydrolyzed by penicillinase; allergies; only fair absorption
51
Amoxicillin
- Broad Spectrum; combined with inhibitor of penicillinase - For gram (-) infections; good absorption - Disadvantages: hydrolysis by penicillinase; allergies
52
Drugs that Act on Cell Wall: Cephalosporins
-originally isolated from the mold cephalosporium -Bactericidal -Broader spectrum than Penicillin >Cephalothin (first generation; requires injection) >Cefixime (third generation; oral administration)
53
Cephalosporins: Cephalothin
- first generation of cephalosporins | - requires injection
54
Cephalosporins: Cefixime
- third generation of cephalosporins | - oral administration
55
Drugs that act on Cell Wall: Vancomycin
-used for life-threatening, methicillin-resistant Staphylococcal infections (MRSA) and Enterococcus, except VRE
56
Drugs that act on Cell Wall: Isoniazid (INH)
inhibits synthesis of mycolic acid in cell wall of Mycobacterium
57
Drugs that act on Cell Wall: Bacitracin
Topical; produced by B. subtilis; component of triple antibiotic ointments
58
Drug That Act on Cell Membrane
Polymyxin - Gram (-) - topical only
59
Drugs that Affect Nucleic Acid Synthesis
- Fluoroquinolones (Ciprofloxacin), (Levaquin) - Rifampin: inhibits synthesis of mRNA; used to treat TB and leprosy - Chloroquine
60
Rifampin
- drug that affects nucleic acid synthesis - inhibits synthesis of mRNA - used to treat TB and leprosy
61
Drugs that Inhibit Protein Synthesis
- Aminoglycosides - Tetracyclines - Chloramphenicol - Erythromycin - Azithromycin (Z pack) - Telithromycin (Ketek) - Clindamycin
62
Drugs that Inhibit Protein Synthesis: Aminoglycosides
(produced by streptomyces) - Streptomycin: narrow spectrum; including Mycobacterium; hearing loss - Gentamicin: narrow spectrum; including pseudomonas - Neomycin (broad spectrum; topical use)
63
Aminoglycosides: Streptomycin
- produced by streptomyces - narrow spectrum - including Mycobacterium - hearing loss
64
Aminoglycosides: Gentamicin
- produced by streptomyces - narrow spectrum - including pseudomonas
65
Aminoglycosides: Neomycin
- produced by streptomyces - broad spectrum - topical use
66
Drugs that Inhibit Protein Synthesis: Tetracyclines
- produced by Streptomyces - very broad spectrum - drug of choice for Rickettsia, Chlamydia, Propionibacterium - Harms microbiota; animal feed additive; harms teeth of children; photosensitive
67
Drugs that Inhibit Protein Synthesis: Chloramphenicol
- produced by streptomyces | - very broad spectrum; possibly toxic
68
Drugs that inhibit protein synthesis: Erythromycin
- Broad Spectrum | - Alternative to Penicillin for penicillin resistant bacterium and in case of penicillin allergy in patient
69
Drugs that Inhibit Protein Synthesis: Azithromycin (Z Pack)
- semisynthetic | - broader spectrum and better tissue penetration than Erythromycin
70
Drugs that inhibit protein synthesis: Telithroycin (Ketek)
-semisynthetic
71
Drugs that inhibit protein synthesis: Clindamycin
used primarily for intestinal infection by anaerobes
72
Drugs that interfere with Metabolism/ Enzyme Activity
- Sulfonamides | - Trimethoprim
73
Antifungal Drugs
- Amphotericin B - Azoles - Flucytosine - Echinocandins - Allylamines
74
Antigungal Drugs: Amphotericin B
- systemic - topical - Nystatin (topical)
75
Antifungal Drugs: Azoles
- ketoconazole (Nizoral) - Fluconazole (Diflucan) - Miconazole (Monistat) - Itraconazole (Sporanox)
76
Antifungal Drugs: Flucytosine
many fungi resistant so combined often with amphotericin
77
Antifungal Drugs: Echinocandins
Capsofungin inhibits fungal cell wall (Chitin)
78
Antifungal Drugs: Allylamines
-Terbinafine (Lamisil) systemic, topical; inhibits ergosterol
79
Ketoconazole
- 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
Anti-parasitic Drugs: Antiprotozoan Drugs
- Quinine - Chloroquine - Mefloquine - Primaquine - Metronidazole (Flagyl)
81
Anti-parasitic Drugs: Anti-protozoan Drugs: Chloroquine
- prophylaxis | - suppression of acute cases of malaria
82
Anti-parasitic Drugs: Anti-protozoan Drugs: Mefloquine
- semisynthetic | - used to treat resistant cases
83
Anti-parasitic Drugs: Anti-protozoan Drugs: Primaquine
relapsing cases of malaria
84
Anti-parasitic Drugs: Anti-protozoan Drugs: Metronidazole (Flagyl)
- Amobeasis; Giardiasis, Trichomoniasis | - also used for anaerobic bacteria
85
Anti-helminthic Drugs
most effective drugs immobilize, disintegrate, or inhibit metabolism of all stages of life cycle - Mebendazole - Pyrantel, piperazine - Niclosamide - Praziquantel - Ivermectin
86
Anti-helminthic Drugs: Mebendazole
- Broad spectrum - intestinal roundworms - work locally in intestines to inhibit microtubule of worms, eggs and larvae * only active in virus infected cells
87
Anti-helminthic Drugs: Pyrantel, piperazine
paralyze muscles of intestinal roundworms
88
Anti-helminthic Drugs: Niclosamide
destroys scolex and adjoining proglottids of tapeworms | *only active in virus infected cells
89
Anti-helminthic Drugs: Praziquantel
tapeworms + flukes
90
Anti-helminthic Drugs: Ivermectin
veterinary treatment for tapeworms and flukes; used for humans for Strongyloidiasis
91
Antiviral Drugs
-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
Antiviral Drugs: Influenza Drugs
-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
Antiviral Drugs: Herpes Drugs
- Acyclovir (Zovirax); Valacyclovir (Valtrex); Famciclovir (Famvir) (active in only virus infected cells) - Ganciclovir (Cytovene) for CMV; an analog of guanine
94
Analog
antiviral agents mimic structure of nucleotides
95
Antiviral Drugs: HIV Drugs
interfere with action of reverse transcriptase enzyme
96
Antiviral Drugs: Maravoc
covers up receptors
97
Antiviral Drugs: Fuzeon
- prevents viral envelope from fusing with host | - prevents binding of viral receptors to cell receptor which blocks fusion of virus with cell
98
Antiviral Drugs: Interferons
glycoproteins produced by viral infected cells (Fibroblasts, leukocytes)
99
Actions of Antiviral Drugs
antiviral drugs will affect DNA
100
Tests for Microbial Susceptibility To Antimicrobial Agents
``` -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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