Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology III > Antimocrobials and Selective Toxicity > Flashcards

Antimocrobials and Selective Toxicity Flashcards

1
Q

What are antibiotics?

A

Agents produced by one organism that have a toxic or inhibitory effect on another organism or cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List 9 types of antibiotics

A
  • Acids and alkalis (eg. benzoic acid in food)
  • Heavy metals (inhibits bacteria growth)
  • Halogens (eg. hypochlorous acid)
  • Alcohols
  • Phenols
  • Oxidizing agents: Disulfide bonds (membrane structure)
  • Alkylating agents: Protein/nucleic acid structure
  • Dyes: Cell replication

Soaps and detergents such as sodium and alkalis can kill many bacterias and viruses along with mechanical scrubbing. when

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How do soaps and detergents act as antimicrobial chemical agents?

A

Lower surface tension and make microbes accessible to other agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do surfactants act as antimicrobial chemical agents?

A

Dissolve lipid membranes and denature proteins. Will deactivate enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do phenols act as antimicrobial chemical agents?

A

Disrupt cell membranes, denature proteins and inactivate enzymes. Phenols are not impaired by organic matter like halogens are.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are bacteriostatic and bacteriocidal drugs?

A

Bacteriostatic drugs arrest growth (reconfiguration, the proteins are temporarily denatured) and bactericidal drugs kill bacteria cells (proteins are permanently denatured).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Discuss the safety of antibiotic drugs

A

Antibiotics are generally very safe and have a very wide therapeutic window! The ED50 (dose at which 50% experience antibacterial effect) is well before (100 times smaller than) the TD50 (dose at which 50% experience toxic effects)

Adverse effects most commonly due to allergic response (penicillins, sulfonamides), rather than toxicity. Also disturbance of normal flora can cause antibiotic-associated diarrhea (erythromycin, tetracycline)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Contrast antibiotics and antimicrobial drugs

A

Antibiotics are produced by one organism that have a toxic or inhibitory effect on another organism or cell (eg. bacteria, fungi or cancer cells). Antibiotics can be antimicrobials when they are antibacterial/antifungal. But they can also be anticancer, and therefore would not be antimicrobials.

Antiinfectives are antimicrobials AND antivirals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why are antibiotics administered with successive high doses?

A

They must be given at a high enough dose above the MIC (minimal inhibitory concentration) so that the antibiotic is effective in killing cells and not allowing them to come back.

It is given successively (concentration undulates in serum) so that toxicity levels are not reached, but it is more important that the drug is given over the MIC, as antibiotics have a high TD50.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do bactericidal and bacteriostatic antimicrobials differ in regards to immune response?

A

Bactericidal

  • Kill bacteria
  • Required if patient is immunosuppressed

Bacteriostatic

  • Inhibit bacterial growth
  • Growth resumes after drug
  • Success depends on there being an effective immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are 6 prokaryotic features that antibiotics can target?

A
  • Unique structures (eg. peptidoglycan complex)
  • Unique pathways (eg. dihydropteroate synthetase to make folic acid)
  • Organelle structures (eg. differing ribosomal subunits)
  • Differing enzymes (eg. dihydrofolate reductase and DNA gyrase)
  • Cellular constituents (ergosterol lipids in fungi)
  • Cellular constituents that are enriched in microorganisms (eg. lipid phosphatidylethanolamine), but also present in human cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the difference between gram-positive and gram-negative bacteria?

A

Gram-positive cells are thicker peptidoglycan cell wall (which antibiotics try to destroy), lacking an outer membrane with porins and lipopolysaccharide phospholipids.

Positive cells also have beta-lactamase, which also confers resistance.

Gram negative cells have penicillin binding protein, which is the enzyme that helps make the peptidoglycan scaffold.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is transpeptidation? How is this used for antibiotics?

A

A chemical reaction (as the reversible conversion of one peptide to another by a protease) in which an amino acid residue or a peptide residue is transferred from one amino compound to another.

Beta-lactam antibiotics (incl. penicillin derivatives). Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

There are 6 different classes of penicillin binding proteins (PBPs), these catalyze transpeptidation needed for cell wall biosynthesis (linking together polysaccharides by short peptide chains).

What are the 3 main transpeptidation inhibitors?

A

Beta lactam drugs

  • Penicillins
  • Cephalosporins
  • Carbapenems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are penicillins?

A

Different modifications of a core structure (6-aminopenicillanic acid).

An amidase reacts to sub different R groups on to this structure (yielding Penicillin G, dicloxacillin etc.).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which Penicillin like antibiotics:

  • Attack the bacterial cell wall?
  • Are beta lactam antibiotics
  • Are penicillins
A

Attack the bacterial cell wall?
- All of the bellow and vancomycin and bacitracin)

Are beta lactam antibiotics
- Penicillin V, amoxicillin, cephalosporins and carbapenems

Are penicillins

  • Penicillin V
  • Amoxicillin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the seven steps of penicillin mediated bactericide?

A
  1. Cross cell wall into bacterium through. Easy with gram-positive, but can’t get through outer lipid membrane of gram-negative unless through porin
  2. Bind to PBP
  3. Stop PBP from working
  4. Peptidoglycan not made
  5. Cell loses rigidity
  6. Fluid inside exerts outward pressure
  7. Bacterium lysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does beta lactamase present a problem for penicillin mediated bactericide?

A

These enzymes break down many common penicillin like drugs.

Susceptible drugs have a beta lactam ring group in their structure.

If beta lactamase is present, the beta lactam ring containing drug will not work and the bacterium will be resistant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give an example of a narrow spectrum penicillin and a extended spectrum penicillin. How do these differ? Which is preferred?

A

Narrow spectrum: gram positive
- Penicillin V

Extended spectrum: gram positive and negative. Better drug: wider spectrum, better absorbed, longer half life.
- Amoxicillin

Differ in their:

  • Sensitivity to beta lactamases
  • Pharmacokinetics
  • Spectrum of action
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the pharmacokinetics of Penicillin G and amoxicillin.

A

Penicillin G is acid labile, therefore penicillin V is preferred.

Amoxicillin has a longer half life Penicillin V or G

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What can be done about beta lactamases?

A
  1. Using a beta-lactamase resistant antibiotic (eg. Nafcillin), which are sometimes called penicillinase-resistant.
  2. Combining with a beta lactamase inhibitor (eg. Clavulanate). Clavulin is Clavulanate plus amoxicillin.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Of these three, which are best at resisting beta lactamase?

  • Cephalosporin
  • Penicillin
  • Carbapenem
A

Worst

  • Penicllin
  • Cephalosporin (especially 4th generation, which are better against gram negative bacteria)
  • Carbapenem
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are carbapenems?

A

Eg. Imipenem

These are penicillin like antibiotics in which the sulfur atom of the penicillin structure is replaced with a carbon.

They have an altered spectrum and are resistant to beta lactamase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do Vancomycin and Bacitracin act as bactericides?

A

Vancomycin

  • Binds to growing peptide chain
  • Prevents ability to crosslink through this binding

Bacitracin

  • A mixture of cyclic peptides
  • Works inside the cell to block cell wall synthesis
25
Q

List some antibiotics which can inhibit bacterial protein synthesis

A
  • Macrolides (eg. erythromycin)
  • Tetracyclines (eg. tetracycline)
  • Aminoglycosides (eg. gentamicin)
  • Chloramphenicol
26
Q

What are the two subunits of a bacterial ribosome?

How can protein synthesis be inhibited by:

  • Chloramphenicol
  • Erythromycin
  • Tetracyclines
  • Streptomycin
A

50S and 30S

Chloramphenicol: Bacteriostatic, binds 50S portion and inhibits formation of peptide bond

Erythromycin: Binds 50S portion, prevents translocation of ribosome along mRNA

Tetracycline: Interferes with tRNA attachment

Streptoycin: Changes 30S shape to cause incorrect mRNA reading

27
Q

Describe chloramphenicol.

A

Binds 50S portion of ribosome and inhibits formation of peptide bond

  • Broad spectrum
  • Bacteriostatic

Adverse effect: Bone marrow disturbances, interactions with other drugs, gray baby syndrome (vomiting, flaccidity, hypothermia, gray colour, collapse)

28
Q

Describe erythromycin and the macrolide antibiotics

A

Macrolides work best against gram positive microorganisms. Binds 50S portion, prevents translocation of ribosome along mRNA

  • Bacteriostatic
  • Unstable in acid
  • Poor against gram negative
  • Useful in penicillin resistant infections
29
Q

Clarithromycin is another macrolide. How is it different from erythromycin?

A
  • Additional methyl group
  • Improved acid stability
  • Improved oral absorption
  • Still most active against gram positive anaerobes
30
Q

Azithromycin is another macrolide. How is it different from erythromycin and clarithromycin?

A
  • Additional lactone ring
  • Excellent tissue penetration
  • Released from tissue slowly
  • Longer half life (about 3 days)
  • Has the best activity against gram negative anaerobes of all the macrolides
  • Acts against spirochetes
  • Less likely to become involved in drug interactions
31
Q

Describe the aminoglycosides, sites of toxicity and their administration method

A

Eg. streptomycin, gentamicin

  • Have a hexose ring to which is linked various amino sugars (by glycosidic links)
  • Used mostly against gram negative, enteric bacteria.
  • Oral doses are poorly absorbed
  • Usually given intramuscularly or intravenously

All are ototoxic (ear) or nephrotoxic (kidney)

32
Q

Describe the mechanism of action of aminoglycosides

A
  1. Block the formation of the initiation complex
  2. Cause miscoding in the polypeptide chain
  3. Block translocation
33
Q

Describe tetracyclines

A

Broad-spectrum drugs that are active against bacteria, mycoplasma and some protozoa

  • Bacteriostatic
  • Resistance is common
  • They chelate divalent metal ions (like calcium), which can lead to adverse effects and absopriton in bone and teeth. - -
  • Absorption affected by milk and antacids, it should not be used in second half of pregnancy or in young kids

Other adverse effects: Mucosa irritation and disturbance of normal flora

34
Q

If macrolides, tetracyclines and aminoglycosides all block protein synthesis in bacteria, why are they different in use?

A
  1. They’re chemically different, which affects things like their stability and absorption.
  2. They interfere at different sites on the bacterial ribosomes, which means they have different therapeutic actions.
35
Q

Describe the folic acid synthesis pathway and two places where it can be inhibited.

A
  1. p-aminobenzoic acid (PABA) is converted to hydrofolic acid by dihydropteroate synthase (DHPS) in bacteria. THis can be inhibited by sulfonamides (compete with PABA, competitive inhibitor)
  2. Dihydrofolic acid is converted to tetrahydrofolic acid by dihydrofolate reductase (DHFR) in both bacteria and humans. This can be inhibited by trimethoprim.
  3. Tetrahydrofolic acid can be converted to purines. This process is NEEDED in bacteria to make DNA.

Sulfonamides and trimethoprim are synergistic bactericides

36
Q

Dihydrofolate reductase is a major enzyme target for toxic drugs. It reduces folate to tetrahydrofolic acid (THF).

Give three cell targets and their respective drugs that target DHFR.

A

Bacteria - Trimethoprim

Protozoa - Pyrimethamine

Cancer cell - Methotrexate

37
Q

Why are sulfamethoxazole (a sulfonamide) and trimethoprim combined in Septra to block the folic acid pathway?

A
  • More effective than either drug alone
  • Still works if resistance to one drug develops
  • Used at a dose ratio of 1:5, which gives a plasma ratio of 1:20 (optimal for the drugs)

Sulfamethoxazole and trimethoprim are both bacteriostatic separately. Together, they are bactericidal.

38
Q

What is DNA gyrase?

A

Bacterial topoisomerase type II

DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-strand DNA is being unwound by helicase. This causes negative supercoiling of the DNA. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, norfloxacin, levofloxacin and ciprofloxacin.

39
Q

What happens when DNA gyrase is inhibited?

A

Replication arrest in bacteria.

Fluoroquinolones block DNA gyrase (eg. ciprofloxacin).

Non fluorinated quinolones couldn’t reach antibacterial levels systemically.

Overuse has led to widespread resistance and many respiratory pathogens are now resistant!

40
Q

What are Polymyxins? What are their mechanism of action?

When are they toxic??

What is their advantage?

What is the only used polymyxin?

A

Molecules that have detergent like properties and which disrupt the bacterial cell membrane by binding to phosphatidylethanolamine (PE) in the cell membrane.

Human cells have PE and therefore these agents are toxic if given systemically.

Advantages

  • Resistance is rare
  • Hypersensitivity (allergy) is rare

Use is restricted to polymyxin B used topically.

41
Q

List four drugs that attack the bacterial cell wall (memorize this list)

A
  • Penicillins
  • Cephalosporins
  • Vancomycin
  • Bacitracin
42
Q

List three drugs that block bacterial protein synthesis (memorize this list)

A
  • Macrolides
  • Tetracyclines
  • Aminoglycosides
43
Q

List three drugs that interfere with DNA processes (memorize this list)

A
  • Fluoroquinolones
  • Sulfonamides
  • Trimethoprim
44
Q

What are three advantages and three risks of using antimicrobial drugs in combinations?

A

Advantages

  • Wider spectrum for mixed infections
  • Reduced dose for individual agents
  • Synergism between antibiotics (more effective combined)

Risks

  • INcreased possibility of adverse reactions
  • Antagonism between antibiotics (reduced effect overall)
  • Greater risk for antibiotic resistance
45
Q

What happens when chloramphenicol and aminoglycosides are combined in antibiotic therapy?

A

Antagonism

46
Q

List four synergistic antibiotic combinations

A
  • Cell wall synthesis inhibitors and aminoglycosides
  • Beta-lactam drugs with beta-lactamase inhibitors
  • Beta-lactams that act on different PBPs
  • Sulfonamides and trimethoprim (eg. Septra)
47
Q

Give five mechanisms of antibiotic resistance

A
  • Decreased entry into cell
  • Efflux pumps
  • Bypass pathways or increased amount of target protein
  • Lower binding affinity with target protein
  • Enzymatic degradation
  • Altered target site
48
Q

What are three possible explanations for sulfonamide resistance?

A
  • Decreased permeability of the cell membrane
  • Production of a form of dihydropteroate synthetase that binds the sulfonamide poorly
  • Increased production of PABA by the bacteria
49
Q

What is double antibiotic resistance?

A

A way to eradicate resistant-strain infections.

Eg. attaching a quinolone to a beta lactam antibiotic. if beta lactamase breaks lactam ring, quinolone is released and kills/suppresses cell. If lactam ring is not broken, than the beta lactam antibiotic can kill or suppress the cell, while quinolone is not released.

50
Q

Describe three treatments to oral candidiasis

A
  1. Oral ketoconazole can be used, but is potentially hepatotoxic
  2. Oral fluconazole is an alternative to ketoconazole that is less hepatotoxic
  3. Intravenous amphotericin B may be considered, but it is significantly toxic and may cause renal damage (only used in severe cases)

These all target ergosterol

51
Q

How do amphotericin B and fluconazole kill fungus?

A

Both target ergosterol

Amphotericin B binds ergosterol and forms pores in the cell membrane

Fluconazole inhibits enzymes that are important in making ergosterol

52
Q

Ergosterol is to fungi what ___ is to humans

A

cholesterol

53
Q

How do azoles work as antifungals?

A

Inhibit conversion of lanosterol to ergosterol.

Less toxic than the polyene antifungals (eg. amphotericin B)

Acts by inhibiting fungal cytochrome P450 enzymes, has a lower affinity for human P450 enzymes.

54
Q

How does terbinafine work as an antifungal?

A

Inhibits conversion of squalene to squalene epoxide (which is converted to lanosterol, which is converted to ergosterol)

55
Q

How does flucytosine work as an antifungal?

A

Works in nucleus

56
Q

How do amphotericin B and nystatin work as antifungals?

A

form pores in fungal cell membrane (but not chitinous wall)

The cell wall can be taken down by inhibiting beta glucan synthase with echinocandins

57
Q

What is amphotericin B?

A

A polyene macrolide antibiotic.

It is large and is lipophilic on one side (binds to ergosterol) and hydrophilic on the other (creates inside of pore)

58
Q

Describe amphotericin B toxicity.

A

Can bind to human cell membranes with cholesterol (much more weakly than to ergosterol).

This can lead to nephrotoxicity.

59
Q

The more selective the mechanism is, the more wide the therapeutic window is. Of the three main selective toxic classes of drugs, which are most selective and which are least selective?

A 
Most selective 
 - Antibacterials 
 - Antifungals
 - Anticancer
Least selective

Pharmacology III (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions