PHAR7 - Antimicrobials Flashcards

1
Q

Define an anti-microbial.

A

Any agent that inhibits or kills one or more type of microorganism. Can be either natural or synthetic.

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2
Q

Define an antibiotic.

A

A substance produced by a microorganism that acts against another microorganism.

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3
Q

What is a bactericidal agent?

A

Any agent with the ability to kill bacteria.

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4
Q

Define a bacteriostatic agent.

A

Any agent that prevents or stops bacterial growth and/or replication. This does not need to necessarily kill the bacteria.

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5
Q

Define a commensal relationship.

A

A symbiotic relationship where one organism is benefitted and the other is unaffected - no harm and no benefit.

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6
Q

Define horizontal gene transfer.

A

Transfer of genetic material from one bacterium to another.

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7
Q

What are the three methods for horizontal gene transfer?

A

Transduction of DNA.
Phage-mediated transfer.
Bacterial conjugation.

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8
Q

What is another word for a microbe?

A

Microorganism.

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9
Q

Define a mutualistic relationship.

A

A symbiotic relationship between two both organisms benefit from the biological interaction.

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10
Q

Define vertical gene transfer.

A

Transfer of genetic material from parent to offspring.

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11
Q

Are microorganisms beneficial or harmful?

A

Both.
Can be beneficial - human development, biological but functions.
Can be pathogenic - infections.

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12
Q

What characteristics may make a microorganism pathogenic?

A

Wrong location.
Wrong activity.
Wrong amounts within a location.

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13
Q

What are the common mechanisms by which microorganisms act when they are pathogenic ?

A

Exhaustion of critical resources. Invasion/killing of cells. Production of harmful toxins.

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14
Q

Are biochemical functions shared between animals and microbes? Elaborate.

A

Some are shared yes however each contain specific biochemical functions that are not possible in the other.

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15
Q

What is the main characteristic that must be obtained when studying antimicrobial pharmacology ?

A

Ensuring that the antimicrobial agent is not harmful to humans.

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16
Q

What are the three main properties of microbes ?

A

Unicellular or multicellular.
Exist as single cells or colonies.
Present in all three domains of life I.e. archaea, bacteria and eukaryote.

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17
Q

Give 7 examples of microbes.

A
Bacteria. 
Fungi. 
Viruses.
Protozoa. 
Helminths. 
Algae.
Prions.
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18
Q

Give an example of a eukaryotic cell with a cell wall. What is this cell wall made of?

A

Fungi. Cell wall mad from chitin.

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19
Q

What is the size of ribosomes in prokaryotic cells?

A

70S

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20
Q

What is the size of ribosomes in eukaryotic cells?

A

80S

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21
Q

Give two classes of non cellular microorganism.

A

Viruses. Prions.

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22
Q

What is the name of the process by which bacteria divide?

A

Binary fission.

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23
Q

What domain of life are bacteria in?

A

Prokaryotic domain of life.

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24
Q

Describe the general structure of a bacterial cell.

A

Cell membrane and cell wall made of peptidoglycans. Limited membrane bound organelles. Ribosomes for protein synthesis. Circular chromosome. Addition DNA in form of plasmids.

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25
Q

What word describes the relationship between bacteria and animals, where the bacteria and animal are both benefitted?

A

Commensal relationship.

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26
Q

What factors can influence pathogenicity of a bacterium?

A

Host immunity.

Translocation.

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27
Q

Give some examples of shapes of bacteria.

A

Rods - bascilli.
Spheres - occi.
Spirals - spirochaetes.
Commas - vibrio.

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28
Q

What polymer makes up the bacterial cell wall?

A

Peptidoglycan.

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29
Q

What are the two classifications of bacteria, based on the layers of peptidoglycan in the call? Describe each type.

A

Gram positive and gram negative.
Gram positive - thick peptidoglycan layer which retains Gram stain.
Gram negative - thin peptidoglycan layer which does not retain Gram stain.

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30
Q

Describe the process for gram staining.

A

Addition of crystal violet dye, followed by iodine solution. Then, an alcoholic wash is required. Following this, it is counter stained with safronin.

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31
Q

What process has resulted in the formation of many different types of bacteria?

A

Evolution.

32
Q

How can different types of bacteria be distinguished from one another?

A

RNA sequencing.

33
Q

Give examples of components and mechanisms in pace to aid the protection of humans against pathogenic bacteria.

A

Skin- physical barrier.
Fluid composition and pH - environment may be harmful to bacteria.
Innate immune system - targets all foreign antigens.

34
Q

What characteristics describe the ideal therapeutic agent?

A

High selectivity for the target organism with little or no adverse effects.

35
Q

What key difference is required for the development of therapeutic agents?

A

Understanding of the biological differences between animals and the target pathogenic microorganisms.

36
Q

What type of compound was used to treat syphillis?

A

Organoarsenic compounds e.g. Salvarsan.

37
Q

How did Ehrlich contribute to the modern drug development programme?

A

Began developing a screening process which took many compounds with similar chemical structures and tested their therapeutic activity.

38
Q

What bacterium causes syphillis infections?

A

Treponema pallidum

39
Q

What are the five mechanisms by which anti bacterial agents target bacteria?

A

Inhibition of genetic material.
Restriction of availability of components of genetically material.
Cell structural integrity compromised.
Growth prevented by cell membrane synthesis inhibition.
Inhibition of protein synthesis.

40
Q

What are the three types of biochemical reactions in bacteria? Give general overview of each.

A
Class I - catabolic process producing metabolic precursors. 
Class II - production of components required for class III reactions 
Class III - anabolic synthesis of various macromolecules e,g. DNA.
41
Q

What are the four main categories of antibacterial agents?

A

Cell wall synthesis inhibitors.
Cell membrane disruptors.
Protein synthesis inhibitors.
Nucleic acid synthesis inhibitors.

42
Q

What is the purpose of the bacterial cell wall?

A

Provides additional layer of strength. Does not control the porous ness of the cell.

43
Q

What are the two mono refs that make the peptidoglycan polymer? State the type of bond that joins the monomers together.

A

N-acetylglucosamine
N-acetylmuramic acid
1-4 beta glycosidic linkage.

44
Q

What gives the cell wall its mesh like structure?

A

Cross linkages form between the polymer strands. This is between the oligpeptides which are Alanyl and alanine residues.

45
Q

Which monomer constituting the cell wall contains the amino acid oligopeptides which form the cross linkages?

A

N-acetylmuramic acid.

46
Q

What class of drug is commonly used as a bacterial cell wall inhibitor?

A

Beta lactam drugs.

47
Q

Discuss the general mechanism of action of beta lactam drugs.

A

Bind covalently to DD-trans peptidase enzymes. Prevents their action of producing cross linkages between the polymer chains. Bacterial cell wall production is inhibited.

48
Q

How do bacteria gain resistance to beta lactam drugs?

A

Bacteria gain ability to produce beta lactamase enzymes. This enzyme breaks down the beta lactam ring of the drug.

49
Q

Give five examples of common beta lactam drugs.

A
Penicillins. 
Monobactams.
Calvulonic acid. 
Cephalosporins.
Carbapenems.
50
Q

What is the most common type of beta lactam drug?

A

Penicillin and penicillin based antibacterial agents.

51
Q

What is the mechanism of action of vancomycin and teicoplanin?

A

Contain multiple OH groups within their chemical structure so are able to form hydrogen bonds with the oligopeptides. Prevents cross linkages formation. Mesh like structure is disrupted. Bacterial cell wall viability is compromised.

52
Q

What are two examples of bacterial cell membrane disrupters?

A

Daptomycin and polymixin.

53
Q

Discuss the mechanism of action of daptomyicn, in disrupting the cell membrane.

A

Daptomycin is amphipathic molecule so can bind to bilayer and localise within it. Daptomycin molecules aggregate. Holes formed within bacterial cell membrane. Depolarisation occurs due to influx of ions and this cannot be reset. Many biochemical processes affected resulting in eventual cell death

54
Q

Discuss the mechanism of action of polymixin, in disrupting the cell membrane.

A

Polymixin binds to lipopolysaccharides found in bacterial cell membrane (gram negative only). Integrity of cell membrane is compromised.

55
Q

Give one potential use of polymixin, which is supported by its low bioavailability characteristic.

A

Bacterial infections in the GI tract. Does not require the drug to be absorbed into the bloodstream.

56
Q

Why is polymixin not commonly used now as a therapeutic agent?

A

Found to have multiple side effects in addition to its therapeutic effect. Many pharmaceutical drugs now have the same therapeutic effect with fewer side effects.

57
Q

What characteristic bacterial protein synthesis process makes it possible to develop specific antibacterial agents?

A

Bacterial ribosomes (as with all prokaryotic ribosomes) are different to eukaryotic ribosomes. Drugs can be made to target bacterial ribosomes solely, without affecting eukaryotic/host protein synthesis.

58
Q

What are the respective subunits of eukaryotic and prokaryotic ribosomes?

A

Eukaryotic - 40S and 60S. Ribosome is 80S.

Prokaryotic - 30S and 50S . Ribosome is 70S.

59
Q

Give examples of drugs which target the 30S subunit of the ribosome.

A

Tetracyclines — tetracycline, doxycycline, lymecycline

Aminoglycosides - gentamycin, neomycin, tobamycin

60
Q

Give examples of drugs which target the 50S ribosomal subunit.

A

Macrolides - erythromycin, spiramycin, telithromycin.
Chloramphenicol.
Fusidic acid.

61
Q

Discuss the process by which DNA is formed from PABA in bacterial cells.

A

PABA converted to folate by dihydropteroate synthetase.
Folate converted to tetrahydrofolate by dihydrofolate reductase.
Tetrahydrofolate converted into thymidylate.
Used to make DNA.

62
Q

Which two drugs can be used to target the synthesis of DNA in bacterial cells? Give brief overview of their mechanism of action.

A

Sulfonamides - block dihydropteroate synthetase enzyme from binding to PABA as it is similar in structure to PABA.
Trimethoprim - blocks dihydrofolate reductase enzyme from binding to folate/folic acid, as it is similar in structure to folate/folic acid.

63
Q

Why are nucleic acid synthesis inhibitors considered as bacteriostatic agents?

A

Prevent bacterial growth and replication however do not kill the bacteria.

64
Q

What is the role of topoisomerase II enzymes in DNA replication?

A

Uncoils any supercooling ensuring that all DNA undergoes replication.

65
Q

What is the name of topoisomerase II enzymes in bacteria?

A

DNA gyrase

66
Q

What drug is used to inhibit DNA gyrase and what is its mechanism of action?

A

Quinolones. Inhibit the DNA gyrase enzyme. Prevents gene translation and replication. Bacteriostatic agent.

67
Q

Give examples of quinolone drugs.

A

Ciprofloxacin. Norfloxacin. Nalidixic acid.

68
Q

What drug is used as an antibacterial agent to inhibit RNA synthesis? Discuss its mechanism of action.

A

Rifampicin or rifampin. Inhibition of bacterial DNA dependent RNA polymerase enzymes.

69
Q

What are the four mechanisms by which bacteria gain resistance ?

A

Target modification.
Innate resistance.
Drug efflux.
Drug inactivation.

70
Q

Discuss target modification as a way of resistance development.

A

The target of the antibacterial agent becomes modified which prevents the intended therapeutic effect.

71
Q

Discuss innate resistance as a method of bacterial resistance.

A

Specific process is in place within the cell which means the bacterial cell is resistant to the drug.

72
Q

Discuss drug efflux as a method for antimicrobial resistance.

A

Less drug within the bacterial cell means the intended therapeutic effect is lowered. Lower drug dosages promote the development of resistance.

73
Q

Discuss drug inactivation as a method of antimicrobial resistance.

A

Bacteria inactivated for sequestered the antibacterial agent e.g. via enzymes. This prevents the drug having the intended therapeutic effect.

74
Q

What are the three methods by which resistance is developed within a bacterial population?

A

Inherent resistance of cells.
Mutation and selection of resistance cells.
Horizontal gene transfer causing resistance mechanism in cell.

75
Q

Discuss three ways by which cells may have an inherent resistance to antibacterial agents.

A

Degradation of the antibacterial drug.
Cell is impervious to the drug - antibacterial agent unable to enter the cell at all.
Antibacterial drug can not evoke therapeutic effect on that target.

76
Q

Give three scenarios that drive antimicrobial resistance when considered mutations and their selection.

A

Insufficient bacterial population control.
Incomplete /unnecessary use of antibiotics.
Low level chronic exposure to antibacterial agent.

77
Q

Give an overview of how mutations and their selections, can result in resistance within a bacterial population.

A

Random mutation occurs which gives resistance to some bacteria (not all bacteria undergo the same mutation). These have a selective advantage so survive. Replicate and pass on the resistance mutation. Eventually, all the bacteria will contain the resistant mutation.