Antimicrobial Drugs - Dupre Flashcards

1
Q

Antimicrobial chemical agents

A

Produced by one organism that have some toxic or inhibitory effect on anther organism or cell
CAN be toxic to cells too

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

Acids and alkalis

A

Prevents growth

Denatures proteins by changing pH

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

Heavy metals

A

Inhibit bacterial growth

Denatures proteins

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

Halogens

A

Hypochlorous acid used in pools with chlorine

Oxidize cell components in absence of organic matter

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

Alcohols

A

70% alcohols

Denature proteins when mixed with water

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

Phenols

A

Disrupts membranes, denatures proteins and inactivated enzymes

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

Oxidizing agents

A

Disrupt disulphide bonds and structure of memrbane

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

Alkylating agents

A

Disrupts structure of proteins and nucleic acids

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

Dyes

A

Some interfere with cell replication or block cell wall synthesis

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

Soaps and detergents

A

Lower surface tension

Make microbes accessible to other agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Selective toxicity

A

Using toxic drugs, as long as they are more toxic to your target than to normal tissues
Ie. antimicrobial drugs or anticancer drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Bactericidal

A

Cells are killed

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

Bacteriostatic

A

Growth is arrested

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

Therapeutic window of antibiotics

A

Usually very safe
Large window
Main adverse effects are allergic responses (NOT toxicity) or disturbances of the normal bacterial flora

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

MIC

A

Minimal inhibitory concentration

Takes about 3 days to reach between doses

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

Antibiotics

A

Not the same as antimicrobial drugs

Agent produced by one organism that have some toxic or inhibitory effect on cancer, bacteria etc

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

Bactericidal antibiotics

A

Drugs that cause the death of the bacteria

Required if the patient is immunosuppressed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Bacteriostatic antibiotics

A

Drugs that inhibit the growth of the bacteria
Growth resumes when drug is removed
Success depends on where being an effective immune reposne

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

Features to attack on bacterial cells

A
  1. Completely unique structure (ie. peptidoglycan)
  2. Pathways that are absent in mammalian cells (ie. dihydropteroate synthetase, which produces folic acid which we get from out diet)
  3. Structure that are different between humans and bacterial cells (ie. ribosomes)
  4. Enzymes that differ between humans and bacterial cells
  5. Cellular constituents that are different in microorganisms (ie. lipid ergosterol)
  6. Cellular constituents that are enriched in microorganisms (ie. lipid phosphatiduylethanolamine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Where antibiotics work

A
  1. Cell wall synthesis
  2. Folic acid metabolism
  3. Cytoplasmic membrane structure
  4. DNA gyrase
  5. RNA elongation
  6. DNA-directed RNA polymerase
  7. Protein synthesis (50S or 30S inhibition or tRNA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Structure of bacterial cell wall

A

Peptidoglycan causes structure and rigidity

Protection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Peptidoglycan

A

Fibrous scaffold in the wall

Cross-linked network of polysaccharides (repeats of certain amino sugars) by polypeptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Penicillin-binding protein

A

Enzyme that helps make scaffold in peptidoglycan

At least 6 different types

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

Beta lactamase

A

Enzyme
Causes resistance to drugs, breaks down common penicillin-like drugs
Susceptible drugs have beta lactic group in their structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Porins

A

Protein pores that pierce the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Transpeptidation

A

Step catalyzed by PBPs

Inhibitors: penicillins, cephalosporins, carbepenems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Penicillin

A

Different modifications of core structure
Penicillin V, Amoxicillin
1. Crosses wall into bacterium
2. Binds to PBP - inhibits
3. Peptidoglycan is not made
4. Cell looses rigidity
5. Fluid inside exerts outward pressure: lysis

28
Q

Potential problems of antibiotics

A
  1. Getting across the outer lipid membrane into gram-negative bacteria (this is why many antibiotic work against gram positive instead gram negative, unless the negative have porins)
  2. Interference by beta lactamases
29
Q

Narrow spectrum penicillins

A

Penicillin V ( better than G because G breaks down in acid)

30
Q

Extended spectrum penicillins

A

Amoxicillin

Better absorbed, longer half life

31
Q

Cephalosporins

A

4 generations, each becoming more resistance to beta lactamases, better activity against gram-negative bacteria, better ability to cross into tissue spaces

32
Q

Carbapenems

A

ie. Imipenem
Penicillin-like antibiotics int which the sulphur atom of the penicillin structure is replaced with carbon
Altered spectrum
resistant to beta-lactamases

33
Q

Vancomycin

A

Binding to growing peptide chain

Prevents subsequent ability to crosslink

34
Q

Bacitracin

A

Mixture of cyclic peptides

Works inside the cell to block cell wall synthesis

35
Q

Antibiotics that block protein synthesis

A
Erythromycin and other macrocodes
Tetracyclines
Amino glycosides
Chloramphenicol
Streptomycin
36
Q

Combining antibiotics

A

By blocking different steps, more likely for antibiotics to work overall

37
Q

Streptomycin

A

Amino glycoside
Changes shape of 30S protein
Causes code on mRNA to be read incorrectly

38
Q

Tetracyclines

A

Interfere with attachment of tRNA to mRNA-ribosome complex
Broad spectrum (bacteria, mycoplasma, some protozoa)
Bacteriostatic
Resistance is common
Differ mainly in their pharmokinetics
Chelate divalent metal ions
Absorption affected by milk and antacids
Accumulate in developing bone and teeth
Should not be used in second half of pregnancy and young children
Also cause gastrointestinal irritation (mucosa and flora)

39
Q

Erythromycin

A

Binds to 50s portion, preventing translation moment of ribosome along mRNA
Base is somewhat unstable in acid conditions
Food reduces absorption
Works well against gram positive organism
Generally poor against gram negatives
Useful in penicillin resistant infections

40
Q

Chloramphenicol

A

Broad spectrum
Bacteriostatic
Binds to 50S portion and inhibits formation of peptide bond
Adverse effects: bone marrow disturbances, common interactions with other drugs, gray baby syndrome

41
Q

Macrolides

A

Ie. erythromycin
Work best with gram positive
Bacteriostatic

42
Q

Clarithromyin

A

Chemically modified from erythromycin, with additional methyl group
Improved acid stability
Improved oral absorption
Most active against gram positive anaerobes

43
Q

Azithromycin

A

Further modified from clarithromycin, with additional lactone ring
Excellent tissue penetration
Release from tissue only slowly
Longer half-life
Best activity against gram negative anaerobes
Also acts against spirochetes
Less likely to become involved in drug interactions

44
Q

Aminoglycoside

A

ie. entamicin, streptomycin
Used mostly against gram-negative enteric bacteria
Oral doses are very poorly absorbed
Usually given intramuscularly or intravenously
Ototoxic and nephrotoxic
Hexose ring bonded to amino sugars with glycosidic bonds
Blocks formation of initiation complex
Miscoding in the polypeptide chain
Block of translocation

45
Q

Why are there multiple antibiotics that block protein synthesis?

A
  1. Different chemically, affecting their stability and absorption
  2. Interfere at different sites on the bacterial ribosome, which means they have different therapeutic actions
46
Q

Folic acid

A

Most bacteria make their own
Made from PABA via DHPS
Then reduced from folate to THF by DHFR

47
Q

Sulfonamides

A

Target DHPS

Structure similar to PABA

48
Q

Trimethoprim

A

Blocks DHFR

49
Q

Sulfonamides and trimethoprim together

A

Synergistic bactericidal
More effective than either drug alone
Still works if resistance develops to one drug
At dose ratio 1:5 (gives plasma ratio of 1:20)

50
Q

DNA gyrase

A

Cuts DNA temporarily during DNA unwinding
Bacterial topoisomerase type II
Inhibitors cause replication arrest

51
Q

Fluoroquinolones

A

Block DNA gyrase enzyme
ie. ciprofloxacin
Early drugs were quinolones, but were fluorinated as it made them more useful against systemic infections
Many respiratory pathogens are now resistant

52
Q

Polymyxins

A
Detergent-like properties
Interferes with integrity of bacterial cell membrane
Binds to phosphatidylethanolamine 
Causes disruption of the bacterial cell membrane
Toxic if systemic (we have PE too)
Resistance rarely develops
Hypersensitivity is rare
Used topically
53
Q

Advantages of using antimicrobial drugs in combinations

A

Wider spectrum for mixed infections
Reduced dose for individual agents
Synergism between antibiotics

54
Q

Risks of using antimicrobial drugs in combinations

A

Increased possibility of adverse reactions
Antagonism between antibiotics
Greater risk of antibiotic resistance

55
Q

Septra

A

Combination of sulfamethoxazole and trimethoprim

Both bacteriostatic, together became bactericidal

56
Q

Antibiotic resistance

A
  1. Beta-lactamase
  2. Mutations in proteins
    If antibiotics are used too freely
    Bacteria are agile
57
Q

Bacterial adaptation

A
  1. Reduced entry of the antibiotic into the bacteria
  2. Increased amount of target protein
  3. Lower binding to altered target protein
  4. Enzyme breakdown of the drug
58
Q

Sulfanamide resistance

A
  1. Decreased permeability of the cell membrane
  2. Bacteria produce a form of dihyropteroate synthetase (DHPS) that binds to sulfanamide poorly
  3. Increase production of PABA by the bacteria
59
Q

Trimethoprim resistance

A
  1. Decreased permeability of the cell membrane
  2. Bacteria produce a form of dihyrofolate reductase (DHFR) that binds trimethoprim poorly
  3. Bacteria produce more DHFR
60
Q

Double antibiotic resistance

A

Way to eradicate resistance strain infections
Link two of them: beta-lactam antibiotic with quinolone
If betalactamase is present, quinolone is released, if not, beta-lactam antibiotic does the work

61
Q

Antifungals in oral candidiasis

A

Candidiasis is most common type of oral fungal infection

Oral ketoconazole, oral fluconazole, intravenous amphotericin B

62
Q

Oral ketoconazole

A

Treatment in oral candidiasis

Potentially hepatotoxic

63
Q

Oral fluconazole

A

Treatment in oral candidiasis
Potentially hepatotoxic (alternative to ketoconazole, less toxic)
Azole fungal drug
Works through ergosterol
Less toxic than polyene antifungals
Acts by inhibiting fungal cytochrome P450 (lower affinity for human P450)

64
Q

Intravenous amphotericin B

A

Treatment in oral candidiasis
Significantly toxic and may cause renal damage
Polyene macrolide antibiotics
Lipophilic on one side and hydrophilic on the other, makes pore

65
Q

Ergosterol

A

Main target of antifungals
Lipid in fungal cell membrane (equivalent to our cholesterol)
Antifungals bind and form pores that leak out contents or bind enzymes that important in making ergosterol