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Microbiology > Chapter 14- Antimicrobial drugs > Flashcards

Chapter 14- Antimicrobial drugs Flashcards

1
Q

How long have humans been using antimicrobial compounds for?

A

There’s evidence that humans have been exposed to antimicrobial compounds for millenia, not just in the last century. Skeletal remains from 350-550 revealed residue from tetracycline- this suggests that they were performing the fermentation of streptomyces. The resulting beer was used to treat illness, like gum disease and warts. Used fungi from moldy bread or other mold containing products to treat warts

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2
Q

Era of strategic drug discovery

A

The first half of the 20th century

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3
Q

Paul Ehrlich

A

Early 1900s- Paul Ehrlich and his assistant Sahachiro Hata found compound 606- killed Treponema pallidum- sold under the name of Salvarsan to treat syphilis

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4
Q

Alexander Fleming

A

In 1928, Alexander Fleming discovered penicillin, the first natural antibiotic. Staphylococci had been contaminated by a mold which inhibited its growth

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5
Q

Klarer, Mietzsch, and Domagk

A

1930s- Klarer, Mietzsch, and Domagk discovered prontosil- killed streptococcal and staphylococcal infections
The active breakdown product of prontosil is sulfanilamide, which was the first synthetic antimicrobial created. It was the foundation for the development of the sulfa drug family

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6
Q

Dorothy Hodgkin

A

Early 1940s- Dorothy Hodgkin determined the structure of penicillin using X-rays. Scientists could then modify it to produce semisynthetic penicillins

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7
Q

Selman Waksman

A

1940s- Selman Waksman’s research team discovered several natural antimicrobials produced by soil microorganisms

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8
Q

Chemotherapeutic agent

A

A chemotherapeutic agent or drug is any chemical agent used in medical practice- the use of drugs to treat a disease. Can include the drugs used to treat cancer or antimicrobial drugs

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9
Q

Antibiotic agent

A

Considered to be a chemical substance made by a microorganism that can inhibit the growth or kill microorganisms

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10
Q

Antimicrobial agent

A

An antimicrobic or antimicrobial agent is a chemical substance similar to an antibiotic, but may be synthetic

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11
Q

Antibiotic vs antimicrobial

A

An antibiotic usually has one bacterial target, like if a key bacterial enzyme is blocked
Antimicrobial is a broad term but can often mean multiple targets, like membranes and DNA

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12
Q

Selective toxicity

A

Harms microbes but not damaging to the host. Microbes have different physiology than that of eukaryotic cells, like the bacterial cell wall. However. even with selective toxicity, some antibiotics have harmful side effects

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13
Q

Chemotherapeutic index

A

The maximum concentration of antibiotic that is tolerated per kilogram of that person in comparison to the minimum concentration of antibiotic per kilogram that will kill the disease. It is the ratio between the therapeutic dose and the toxic dose. The higher the chemotherapeutic index, the safer the drug

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14
Q

How are antimicrobial drugs classified?

A

Based on the type of organism they affect (antibacterial, antifungal)

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15
Q

Spectrum of activity

A

The range of microorganisms that an antimicrobial agent acts upon

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16
Q

Broad spectrum antimicrobial

A

Will treat a wide range of microorganisms (like gram positive and gram negative bacteria) if the exact agent isn’t known.

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17
Q

In which situations are broad spectrum antimicrobials used? (4)

A
  1. Used as an empiric therapy to cover a wide range of potential pathogens while the patient is waiting for laboratory identification of the pathogen
  2. Can be used for infections caused by more than one microorganism
  3. Also used as prophylaxis before surgery or other invasive procedures
  4. Used when a narrow spectrum antimicrobial was used first and failed to cure the disease
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18
Q

Isoniazid

A

Has a very narrow spectrum and only works against mycobacteria. Inhibits mycolic acid synthesis

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19
Q

Streptomycin

A

Has a wider spectrum and works against mycobacteria and gram negative bacteria

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20
Q

Tetracycline

A

Has a broad spectrum and works against mycobacteria, gram negative and gram positive bacteria, and chlamydias/rickettsias

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21
Q

Narrow spectrum

A

Targets only specific subsets of bacterial pathogens. For eukaryotic diseases, drugs have a narrow spectrum

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22
Q

Ketoconazole

A

only works against fungi

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23
Q

Mefloquine

A

works against protozoa (malaria)

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24
Q

Helminth drugs (2)

A

Niclosamide works against tapeworms and praziquantel works against flukes

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25
Q

Acyclovir

A

An antiviral that is a synthetic analog of the nucleoside guanosine. It is activated by the HSV enzyme thymidine kinase. When added to a growing DNA strand during replication, it causes chain termination, interfering with nucleic acid synthesis. Its specificity for virus-infected cells comes from both the need for a viral enzyme to activate it and the increased affinity of the activated form for viral DNA polymerase compared to host cell DNA polymerase. It is used to treat herpes infections like genital herpes, chickenpox, shingles, mono, and cytomegalovirus infections

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26
Q

Risks of using broad spectrum antibiotics

A

The risk of using broad spectrum antibiotics is that they will target a broad spectrum of their microbiota. Our normal microbiota keeps opportunistic pathogens in check. Broad spectrum antibiotics kill non resistant cells, but the opportunistic pathogen may be resistant to the antibiotic and can survive. Therefore, the drug resistant pathogens proliferate and can cause a superinfection (secondary infection). The opportunistic pathogen is now a majority in the microbiota

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27
Q

C. difficile

A

One example of an opportunistic pathogen. It overgrows as a result of treatment with broad spectrum antibiotics. It can cause colitis

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28
Q

Bacteriostatic

A

Chemical substance that inhibits the growth of organisms- doesn’t kill them. The viable and total cell counts grow exponentially, but then reach a plateau. In a healthy host, these drugs can effective to treat an infection because the immune system will take over

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29
Q

Bactericidal

A

Kills bacteria. Total cell count grows exponentially, then reaches a plateau. Viable cell counts grow exponentially, reach a peak, then decrease exponentially (V shaped graph)

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30
Q

Bacteriolytic

A

Cause the lysis of cells. Both total cell counts and viable cell counts grow exponentially, then decrease exponentially (both have a V shaped graph)

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31
Q

Minimal inhibitory concentration (MIC)

A

The MIC is defined as the lowest concentration of the drug that will prevent the growth of an organism. It is used to determine measure the in vitro effectiveness of an agent. MIC is useful to determine the effectiveness of a single drug against a single organism, and it will differ depending on the organisms involved.

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32
Q

How is MIC determined?

A

It is performed by using different concentrations of the antibiotic in a test tube with a bacteria. The MIC is determined by looking at the tube with the lowest concentration of the antibiotic that does not have growth of the bacteria (the solution remains clear)
If the .5 micrograms per milliliter tube contains growth but the 1.0 micrograms/milliliter tube does not, 1.0 micrograms per milliliter is the MIC

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33
Q

E test

A

A test strip that contains a gradient of an antibiotic that is placed in a lawn of bacteria (bacteria spread over an agar plate). The drug will diffuse out of the strip and travel farther and faster at high concentrations of the drug that at lower concentrations- it kills the surrounding bacteria and creates an upside down pear shape around the test strip

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34
Q

How is an E test used to determine the MIC?

A

Numbers reflect the relative concentrations of antibiotic present at various points within the zone of inhibition. The concentrations along the periphery of the clear zone are equal and reflect the MIC

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35
Q

Kirby-Bauer disk susceptibility test

A

Uses a variety of antibiotic disks on a lawn of bacteria an agar plate. You measure the zone of inhibition surrounding the antibiotic disk. Depending on the size of the zone, you can say that the organism is susceptible to that antibiotic. With bacteria that is resistant to an antibiotic, the zone of inhibition will be extremely small or will not even exist

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36
Q

Can the MIC test or Kirby-Bauer disk susceptibility test determine whether a drug is bacteriostatic or bactericidal?

A

No, neither test can distinguish whether a drug is bacteriostatic or bactericidal

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37
Q

Minimum bactericidal concentration (MBC)

A

Determined by using a tube dilution test and removing the antibiotic. If cells grow in the fresh medium without antibiotic, the drug is bacteriostatic, if cells do not grow, the drug is bactericidal

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38
Q

Attributes of an ideal antimicrobial (8)

A
  1. Solubility in body fluids
  2. Selective toxicity
  3. Toxicity not easily altered-don’t want the toxicity to change once ingested
  4. Non-allergenic
  5. Stability in the body once ingested
  6. Resistance by microorganisms not easily acquired
  7. Long shelf life
  8. Reasonable cost
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39
Q

Dosage

A

Amount of medication given during a certain time interval

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40
Q

How is dosage of medication determined in children vs adults?

A

In children, dosage is based upon the patient’s mass. In adults a standard dosage is used, independent of mass

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41
Q

How is an effective dose of a medication determined?

A

A dosage needs to be determined that allows for the optimum concentration of the drug at the site of infection that does not cause toxicity. Need to take into consideration the half life of the antibiotic

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42
Q

Half life

A

The rate at which 50% of a drug is eliminated from the plasma. It helps to determine how quickly the drug is removed from the body. Longer half life drugs are typically more convenient as they require less doses, but are more of a concern for toxicity.

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43
Q

Route of administration

A

The method used to introduce a drug into the body. An antibiotic that is ingested has to go through your gastrointestinal system, IV antibiotics directly enter the bloodstream, and some medications are intramuscular injections

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44
Q

Determining whether an antibiotic is clinically useful

A

The antibiotic concentration peaks in the serum at a specific time, but the concentration eventually starts to decrease. The second dose of the antibiotic needs to be taken before the serum concentration of the antibiotic dips below the MIC. An antibiotic may need to be taken at a specific time interval depending on this and the half life.

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45
Q

What do clinicians need to consider when prescribing an antibiotic? (3)

A
  1. Whether the organism is susceptible to the antibiotic
  2. Whether the attainable tissue level of the antibiotic is higher than the MIC
  3. The understanding of the relationship between the therapeutic dose and the toxic dose of the drug
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46
Q

Attainable tissue level of the antibiotic

A

The level that the antibiotic reaches in the infected tissue. If the antibiotic never reaches a high enough concentration in the infected tissue, it will not treat the infection. The concentration needs to be higher than the MIC

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47
Q

Therapeutic dose

A

The minimum dose per kilogram of body weight that stops the growth of the pathogen

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48
Q

Toxic dose

A

The maximum dose tolerated by the patient

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49
Q

How do routes of administration affect the concentration a drug reaches in the plasma?

A

IM and oral routes reach comparable peak concentrations in the plasma, but the IM drug reaches its peak slightly sooner. IV drugs peak much sooner (almost immediately) than IM and oral drugs. However, IM and oral drugs remain at a higher concentration for a longer period of time. The concentration of IV drugs decreases almost immediately after their peak

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50
Q

Synergistic drug combinations

A

Synergistic drugs may work poorly when they are given individually but very well when combined (combined effect is greater than additive effect). Example- aminoglycoside and vancomycin

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51
Q

Antagonistic drug interaction

A

The mechanisms of action of antagonistic drugs interfere with each other and diminish their effectiveness. There is also the risk of toxicity due to decreased metabolism and elimination. Example- penicillin and macrolides

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52
Q

Antibiotics that target cell wall synthesis (4)

A
  1. Beta lactams like penicillin, cephalosporins, monobactams, and carbapenems
  2. Polypeptide antibiotics
  3. Cycloserine
  4. Antimycobacterial antibiotics
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53
Q

Antibiotics that target the plasma membrane (2)

A
  1. Polymyxins like polymyxin B and colistin
  2. Lipopeptides like daptomycin
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54
Q

Antibiotics that target the ribosomes (2)

A
  1. 30s subunit like aminoglycosides and tetracyclines
  2. 50s subunit like macrolides, chloramphenicol, and oxazolidinones
55
Q

Antibiotics that target metabolic pathways- antimetabolites (2)

A
  1. Folic acid synthesis, like sulfonamides, sulfones, trimethoprim
  2. Mycolic acid synthesis like isoniazid
56
Q

Antibiotics that target DNA synthesis

A

Fluoroquinolones like ciprofloxacin, levofloxacin, moxifloxacin. They inhibit the activity of bacterial DNA gyrase, which blocks DNA replication. Ciprofloxacin and levofloxacin are effective against a broad spectrum of gram-positive or gram-negative bacteria, and are among the most commonly prescribed
antibiotics used to treat a wide range of infections

57
Q

Mechanisms of antibiotics (6)

A
  1. Cell wall synthesis
  2. Cell membrane integrity
  3. DNA synthesis
  4. RNA synthesis
  5. Protein synthesis
  6. Metabolic pathways
58
Q

Mode of action of antibiotics that target the cell wall

A

Cell walls are a target for selective toxicity because peptidoglycan does not exist in mammalian cells. Antibiotics that target the cell wall affect the synthesis of peptidoglycan. Certain antibiotics inhibit different mechanisms of peptidoglycan/cell wall synthesis

59
Q

Peptidoglycan synthesis

A

Disaccharides NAG and NAM are made in the cytoplasm of the bacterium and join together. Once they are synthesized, they are shuttled across the membrane by a lipid carrier molecule. At the cellular membrane, the disaccharides are assembled into long chains of peptidoglycan. Adjacent chains are linked by peptides from the NAM molecules

60
Q

Cycloserine

A

Inhibits the process of NAG and NAM joining together

61
Q

Bacitracin mechanism

A

Inhibits NAG and NAM being shuttled across the cell membrane. It targets the lipid carrier bactoprenol, ultimately preventing NAG and NAM from being incorporated into the cell wall. Bacitracin is effective against a wide range of bacteria, including gram positive organisms found on the skin, such as Staphylococcus and Streptococcus. It can be toxic to the kidneys, so it is typically given topically.

62
Q

Penicillin, vancomycin, and cephalosporins cell wall mechanism

A

Inhibit the binding of the new disaccharides to the peptidoglycan molecule. Penicillin and vancomycin also inhibit the cross linkage of the peptidoglycan chains

63
Q

Penicillin

A

Penicillin binds to and inhibits penicillin binding proteins, which are responsible for binding disaccharide to pre-existing peptidoglycan. The beta lactam ring of penicillin resembles and substitutes the D-Alanine-D-alanine molecule of the proteins that bind the peptidoglycan chains, so the saccharides can’t bind to each other. Without an intact cell wall, the growing cell eventually bursts due to osmotic effects. Therefore, penicillin is a bactericidal drug

64
Q

Penicillin-binding proteins (PBPs)

A

The enzymes that attach the disaccharide units to pre-existing peptidoglycan and produce peptide cross links are collectively called penicillin-binding proteins (PBPs)

65
Q

Generations of cephalosporins

A

Cephalosporin is a beta-lactam antibiotic that was discovered in nature. Chemists have modified the basic structure of cephalosporin in ways that improve the drug’s effectiveness against penicillin-resistant pathogens and beta lactamases. Each modification is a new “generation” of cephalosporins. There are currently 5 generations of this antibiotic, each generation is more complex

66
Q

Chemical properties of each cephalosporin generation

A

The beta lactam group had only one R group in the first generation, and two groups in the second. The two R groups became more complex as the generations progressed.

67
Q

Bacterial targets of each generation of cephalosporins

A
  1. The first generation had a narrow spectrum and acted mainly against gram positive organisms
  2. Second generation included some gram negative
  3. Third generation included some gram negative and pseudomonads and is an injectable drug
  4. The fourth and fifth generation are oral drugs
68
Q

Bacitracin

A

A large polypeptide antibiotic produced by Bacillus subtilis. Topical application that targets gram positives. Inhibits cell wall synthesis by binding to the lipid carrier molecules. Resistance can occur if the organism has another drug export system that can pump the bacitracin outside of the cell

69
Q

Vancomycin

A

Binds to part of the peptide chain of a newly exported NAM and NAG cell wall precursors. It blocks the cell wall subunits from being incorporated into the peptidoglycan structure. Glycopeptide molecule produced by Amycolatopsis orientalis. It is an important “last line” against antibiotic resistant S. aureus. It is bactericidal against gram positive bacteria and inactive against gram negative bacteria

70
Q

Polypeptide antibiotics (2)

A
  1. Bacitracin
  2. Vancomycin
71
Q

Antimycobacterial antibiotics (2)

A
  1. Isoniazid (INH)
  2. Ethambutol
72
Q

Ethambutol

A

Inhibits incorporation of mycolic acid

73
Q

Beta-lactamase enzyme

A

Some bacteria have inherited a gene encoding the beta-lactamase enzyme. The enzyme will cleave the B-lactam ring structure of penicillin, which is essential for it to substitute for the amino acid in the peptidoglycan cross linkages. Degrading the ring created penicilloic acid, which can’t be used. This is how bacteria have developed resistance to penicillin. Some derivatives of penicillin can block the beta lactamase action

74
Q

Mutations of penicillin binding proteins

A

The penicillin binding protein is altered by a mutation. The enzyme can still synthesize the cell wall but no longer binds to the antibiotic. Peptidoglycan synthesis still occurs and the bacteria become resistance to penicillin

75
Q

Antibiotics that act as detergents (3)

A

Polymyxin, tyrocidine, and platensimycin. Act as detergents and disrupt the structure of the cell membrane by binding to the phospholipids. Target gram negative bacteria. Highly toxic- eukaryotic cells also have cell membranes containing phospholipids. Therefore, they are only used as a last resort

76
Q

Polymyxin B

A

Detergent antibiotic that is a positively charged polypeptide ring that binds to the inner membranes of bacteria. Disrupts phospholipid interactions. Polymyxin is only used as a topical antibiotic due to the damage it causes to cell membranes

77
Q

Detergent antibiotics mode of action

A

Interacts with lipopolysaccharide in the outer membrane of gram negative bacteria, killing the cell through the eventual disruption of the outer membrane and cytoplasmic membrane

78
Q

Platensimycin

A

Detergent antibiotic that is produced by streptomyces platensis and can inhibit cell membrane synthesis. It is bacteriostatic and acts against a wide spectrum of pathogen

79
Q

Gramicidin

A

Cyclic peptide antibiotic that targets the cell membrane. Has 15 alternating D and L amino acids. Inserts into the membrane as a dimer and forms a cation channel so that sodium and potassium ions can freely pass- disrupts the membrane and kills the cell. Only works for gram positive bacteria

80
Q

Antibiotics that affect DNA synthesis (3)

A
  1. Metronidazole
  2. Sulfonamides
  3. Quinolones
81
Q

Metronidazole

A

This drug is activated after being metabolized by microbial protein cofactors ferredoxin found in anaerobic and microaerophilic bacteria such as Bacteroides and Fusobacterium- targets anaerobic organisms only.Aerobic microbes are resistant because they do not possess the electron transport proteins capable of reducing metronidazole. Impacts DNA synthesis

82
Q

Sulfonamides

A

Sulfonamide (sulfa) drugs act to inhibit the synthesis of nucleic acids by preventing the synthesis of folic acid, an important cofactor in the synthesis of nucleic acid precursors. All organisms, including humans, use folic acid to synthesize nucleic acids.

83
Q

How do sulfa drugs impact folic acid synthesis?

A

Bacteria make folic acid from the combination of PABA (a type of benzoic acid), glutamic acid (G), and pteridine (P). With normal folic acid formation, an enzyme utilizes P, PABA, and G and bind to together and result in the synthesis of folic acid. When folic acid synthesis is blocked by sulfanilamide (SFA), SFA replaces PABA in the synthesis process. SFA binds to G, but not to P, meaning that folic acid cannot be synthesized (meaning no nucleic acids)

84
Q

Quinolones

A

DNA gyrase bound to and inactivated by a quinolone will block progression of a DNA replication fork- Ciprofloxacin is an example. Because bacterial DNA gyrases are structurally distinct from their mammalian counterparts, quinolone antibiotics will not affect mammalian DNA replication

85
Q

RNA synthesis inhibitors

A

Rifampin is the best known member of the rifamycin family of antibiotics that selectively binds to bacterial RNA polymerase (which is different from the eukaryotic version) and prevents transcription. Rifampin is used to treat tuberculosis and meningococcal meningitis

86
Q

Macrolides

A

Erythromycin, azithromycin-prevent peptidyltransferase activity and translocation of tRNA from the A site to the P site. Blocks elongation of proteins and inhibits peptide bond formation between specific amino acids. Target the 50S subunit of ribosomes and is bacteriostatic

87
Q

Peptidyltransferase

A

The enzyme that will connect 2 amino acids

88
Q

Oxazolidinones

A

Linezolid- bind to 50S subunit and prevent 70S subunit formation, stopping the initiation complex from forming. They also prevent translocation of the growing protein from the ribosomal A site to the P site. Target the 50S subunit of ribosomes

89
Q

Chloramphenicol

A

Prevents peptide bond formation by inhibiting peptidyltransferase in the 50S subunit. Target the 50S subunit of ribosomes. It is a broad spectrum antibiotic that is natural but can be synthesized. Due to side effects like anemia and suppression of bone marrow production, it has limited clinical use

90
Q

Lincosamides

A

Clindamycin and lincomycin- bind to peptidyl transferase and prevent peptide bond formation from the ribosome. Target the 50S subunit of ribosomes

91
Q

Streptogramins

A

Quinupristin, dalfopristin- bind to 50S subunit and block tRNA entry into the A site while blocking exit of a growing protein from the ribosome. Target the 50S subunit of ribosomes

92
Q

Aminoglycosides

A

Streptomycin, gentamicin- inhibits translocation and causes misreading of mRNA. Target the 30S subunit of ribosomes. They impair the proofreading ability of the ribosomal complex, so proteins are made with incorrect amino acids and the structures of the cell are disrupted. These antibiotics can be damaging to the kidneys, nervous system, and ears

93
Q

Tetracyclines

A

Doxycycline, minocycline- prevent aminoacyl-tRNA entry into the A site during translation, inhibiting protein synthesis. These antibiotics are bacteriostatic. Very broad spectrum. Target the 30S subunit of ribosomes. Side effects can include phototoxicity and liver toxicity with high doses

94
Q

Glycylcyclines

A

Tigecycline- bind to 30S subunit and inhibit the entry of aminoacyl tRNA into the A site, able to function in tetracycline resistant cells. Target the 30S subunit of ribosomes

95
Q

Mechanisms of drug resistance (7)

A
  1. Drug modification or inactivation (beta lactamase)
  2. Blocked penetration
  3. Efflux pumps
  4. Target modification
  5. Target overproduction
  6. Enzymatic bypass
  7. Target mimicry
96
Q

How can bacteria block penetration of antibiotics?

A

By altering porins in the outer membrane. This happens with gram negative bacteria only- gram positive bacteria do not have an outer membrane with porins

97
Q

Efflux pumps

A

Work by altering porins in the outer membrane for gram negative organisms only. Antibiotics are pumped out at a higher rate than they are pumped in

98
Q

Target modification mechanism of antibiotic resistance

A

Mechanism allows a formerly inhibited reaction to occur. The antibiotic is unable to bind to the typical location and therefore can no longer inhibit any processes

99
Q

Target overproduction mechanism of antibiotic resistance

A

Microbe overproduces the target enzyme such there there is a sufficient amount of antimicrobial-free enzyme to carry out the proper enzymatic reaction. So much of the enzyme is produced that even after the antibiotic has all been used, enough enzymes are left to carry out the normal reaction

100
Q

Enzymatic bypass mechanism of antibiotic resistance

A

Microbe develops a bypass that circumvents the need for the functional target enzyme. Circumvents the pathway that was inhibited by the antibiotic

101
Q

Target mimicry

A

Production of proteins that bind and sequester drugs, preventing the drugs from binding to their target. The microbe makes proteins that bind to the antibiotic so it can’t bind to its normal target

102
Q

Clavulanic acid

A

A dummy target compound that inactivates resistance enzymes. It binds and ties up beta-lactamases that are secreted from penicillin resistant bacteria

103
Q

Actions individuals can take to help prevent antibiotic resistance (5)

A
  1. Frequent hand washing
  2. Vaccinations against bacterial diseases
  3. Avoiding use of antibiotics for viral infections
  4. Refusing leftover antibiotics
  5. Take full course of antibiotic prescribed
104
Q

How are pathogenic bacteria impacted throughout typical antibiotic therapy?

A

On day 0 of taking an antibiotic for an infection, you have a typical distribution of bacteria (like bell curve). On either end, you have highly sensitive organisms and highly resistant organisms, and the middle portion is composed of intermediate organisms
By day 3, the highly sensitive organisms have decreased, intermediate organisms have decreased somewhat, but highly resistant organisms haven’t decreased much. Day 6- highly sensitive organisms are virtually gone, intermediate organisms have decreased, but highly resistant organisms have only decreased slightly. If antibiotics are stopped prematurely, the highly resistant organisms will begin growing exponentially and make a resurgence. The infection relapses and is more prone to spread to other hosts. Day 10- end of successful treatment. All 3 types of bacteria are basically gone

105
Q

Double antibiotic therapy against beta lactamase producing bacteria

A

With a single beta lactam antibiotic, the beta lactam ring (C4NO) will break, inactivating the antibiotic. With double antibiotic therapy, the beta lactam antibiotic has a broken ring and is inactivated. However, when the ring is broken, active quinolone is released and the organisms are killed. The double antibiotic therapy is much more effective against beta lactamase producing bacteria

106
Q

Double antibiotic therapy against non beta lactamase producing bacteria

A

When double antibiotic therapy is used against non-beta lactamase bacteria, it is still effective. The organisms are unable to produce beta lactamase and therefore can’t break the beta lactam ring. The beta lactam antibiotic remains active, and the quinolone remains inactive. Therefore, quinolone is not released, and strains resistant to quinolones do not develop

107
Q

2 components of an influenza virus

A
  1. Hemagglutinin- binds to the host membrane receptors for entry by phagocytosis
  2. Neuraminidase- cleaves sialic acid to allow virus particles to escape from infected cells
108
Q

Amantadine

A

Influenza antiviral that prevents the virus from uncoating and exiting the phagolysosome by changing the pH of the phagolysosome

109
Q

Oseltamivir (Tamiflu) and zanamivir (Relenza)

A

Influenza antivirals- neuraminidase inhibitors prevent the virus particles from leaving the cell

110
Q

Antiviral DNA and RNA synthesis inhibitors

A

These drugs chemically resemble normal DNA nucleotides

111
Q

Nucleoside and nonnucleoside reverse transcriptase inhibitors (2)

A
  1. Protease inhibitors
  2. Entry inhibitors
112
Q

Protease inhibitors

A

Target the HIV protease enzyme. Nelfinavir (Viracept) and lopinavir (Kaletra)

113
Q

Entry inhibitors

A

Block virus envelope protein gp120 from binding to the host receptor CCR5. Includes CCR5 inhibitors (maraviroc). Preventing binding prevents the virus from attaching to the cell

114
Q

Polyenes

A

Nystatin, amphotericin B- disrupts membrane integrity of fungi. They bind to ergosterol in the cytoplasmic membranes and create pores. Used for topical yeast infections (nystatin) and systemic fungal infections (amphotericin B)

115
Q

Azoles

A

Imidazoles, triazoles- interferes with ergosterol synthesis of fungi

116
Q

Allylamines

A

Terbinafine, lamisil- interferes with ergosterol synthesis of fungi. Treats athlete’s foot, ringworm, and nail fungal infections

117
Q

Echinocandins

A

Caspofungin- blocks fungal cell wall synthesis

118
Q

Griseofulvin

A

blocks cell division

119
Q

Flucytosine

A

inhibits DNA synthesis

120
Q

Metronidazole

A

causes DNA breakage. Used to treat giardiasis and trichomonas infections

121
Q

Quinine

A

was commonly used in the past, it is now used as a last resort to treat malaria

122
Q

Antimalarials

A

Chloroquine, primaquine- interfere with protein synthesis, specially red blood cells

123
Q

Niclosamide

A

Prevents ATP generation, used to treat tapeworms

124
Q

Praziquantel

A

Alters membrane permeability, used to treat flatworms. It appears to cause an influx of calcium into the parasite, which causes muscle spasms and paralysis

125
Q

Mebendazole and albendazole

A

Interfere with nutrient absorption, used to treat intestinal roundworms. They prevent microtubule formation, which interferes with glucose uptake

126
Q

Ivermectin

A

Causes paralysis of helminths and blocks neuronal transmission so they can no longer feed. Used to treat intestinal roundworms

127
Q

Superinfection

A

A secondary infection in a patient having a pre-existing infection. A superinfection develops when the antibacterial intended for the preexisting infection
kills the protective microbiota, allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection. C. diff is an example

128
Q

Mode of action

A

The way in which a drug affects microbes at the cellular level

129
Q

Cephalosporins

A

Similar to the penicillins, cephalosporins contain a β-lactam ring and block the transpeptidase activity of penicillin-binding proteins. However, the β-lactam ring of cephalosporins is fused to a six-member ring, rather than the five-member ring found in penicillins. This chemical difference provides cephalosporins with an increased resistance to enzymatic inactivation by β-lactamases.

130
Q

How is cephalosporin different from penicillin?

A

It has a similar spectrum of
activity to that of penicillin against gram-positive bacteria but is active against more gram-negative bacteria than penicillin. Another important structural difference is that cephalosporin C possesses two R groups, compared with just one R group for penicillin, and this provides for greater diversity in chemical alterations
and development of semisynthetic cephalosporins. The family of semisynthetic cephalosporins is much larger than the penicillins, and these drugs have been classified into generations based primarily on their spectrum of activity, increasing in spectrum from the narrow-spectrum, first-generation cephalosporins to the broad spectrum, fifth-generation cephalosporins

131
Q

Ribosomes found in animal cells vs bacterial cells

A

Animal cells have 80S ribosomes while bacterial cells have 70S ribosomes

132
Q

Daptomycin

A

A cyclic lipopeptide produced by Streptomyces roseoporus. It works like the polymyxins, inserting in the bacterial cell membrane and disrupting it. However, it specifically targets gram positive bacteria

133
Q

What is the most common mode of action for antifungal drugs?

A

Disruption of the cell membrane. In eukaryotic cells, sterols are used to maintain membrane fluidity and proper cell membrane function. Fungal cells use ergosterol while human cells use cholesterol, so antifungals that target ergosterol synthesis are selectively toxic.

Microbiology (19 decks)

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