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Medical microbiology > Antibiotics > Flashcards

Antibiotics Flashcards

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Biology 101 flashcards USMLE® Step 1 flashcards
1
Q

What do antibiotics do?

A

• Kill or inhibit the growth of other microorganisms to give the bacteria producing the antibiotic a selective advantage

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2
Q

What are most antibiotics derived from and then modified chemically to?

A

• Most derived from natural products by fermentation, then modified chemically to:
○ ≠ pharmacological properties
○ ≠ antimicrobial effect

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3
Q

What does antibiotics plus immunity give?

A

Gives bacterial clearance

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4
Q

What are the principles of antibiotics as therapeutic agents?

A
  1. Selective toxicity

2. Therapeutic margin

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5
Q

What is selective toxicity due to?

A

• Due to the differences in structure and metabolic pathways between host and pathogen

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6
Q

What is therapeutic margin?

A

• Active dose vs. toxic effect

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7
Q

What is a narrow therapeutic index?

A

margin between safe and harmful is small

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8
Q

What is a drug with a wide therapeutic margin?

A

If a drug is very safe and not very toxic

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9
Q

What is minimum inhibitory concentration?

A

concentration of drug needed to be effective

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10
Q

What can vancomycin cause?

A

toxic and can cause hearing damage in high doses

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11
Q

What do we need to make sure when giving antibiotics?

A

○ Need to make sure you give enough antibiotic to reach the MIC but also to not be toxic

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12
Q

What concept is microbacterial antagonism?

A

The concept that one organism can produce a substance that inhibits the growth of another

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13
Q

Where does microbacterial antagonism and why?

A

Happens in the gut as there is a large number of micro-organisms and they are able to co-exist

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14
Q

What do the microorganisms in the gut secrete and what do these secretions do and affect?

A

§ They secrete anti-microbial peptides and other compounds that limit growth of some organisms and prevent over-growth of others so they are able to co-exist

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15
Q

What can some antibiotics mess up and what can this cause?

A

• Some antibiotics completely mess up the homeostatic, commensal organisation of gut or skin flora
§ This can cause disease

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16
Q

When does clostridium difficile over grow microorganism and what is it associated with?

A

§ As the flora is disrupted, one of the microorganisms that overgrows is clostridium difficile
-Associated with diarrhoea outbreaks in hospital ICUs so serious hospital cross-infection risks due to easy spread of spores

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17
Q

What are antibiotics classified by?

A

○ Type of activity
○ Structure
○ Target site for activity

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18
Q

What are the 2 types of activities of antibiotics?

A
  1. Bacteriostatic

2. Bactericidal

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19
Q

What do bacteriostatic antibiotics do?

A

Inhibit bacteria so immune system can come and clear it

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20
Q

When are bacteriostatic antibiotics used?

A

○ Used when the host defense mechanisms are intact

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21
Q

What do bactericidal antibiotics do?

A

Kill bacteria

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22
Q

When are bactericidal antibiotics used?

A

○ Used when the host defense mechanisms are impaired

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23
Q

What are bactericidal antibiotics required in?

A

Required in endocarditis, kidney infection

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24
Q

What are the 2 spectrums of activity of antibiotics?

A
  1. Broad spectrum antibiotics

2. Narrow spectrum antibiotics

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25
Q

What are broad spectrum antibiotics effective against?

A

○ Effective against many types of bacteria

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26
Q

What are narrow spectrum antibiotics effective against?

A

○ Effective against very few types of bacteria

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27
Q

Refinement of cephalosporins over 3 generations

A
  1. First generation cephalosporins
    ○ Not good against gram-negative bacteria
    ○ Good at killing gram-positive bacteria
  2. Second generation cephalosporins
    ○ Better at killing gram negative bacteria
    ○ Lost ability to kill other microorganisms as effectively as before
  3. Third generation cephalosporins
    ○ Not good at killing gram positive bacteria
28
Q

What is the active structure of beta lactam antibiotics?

A

○ Contain beta-lactam rings which is the active structure in the drugs

29
Q

What do some beta lactam antibiotics act as?

A

○ Act as natural competitor substrates to the enzymes that make the bacterial cell wall

30
Q

What do you divide antibiotics into how they work?

A
  1. Cell wall synthesis inhibitors
  2. Protein synthesis inhibitors
  3. DNA/RNA processing inhibitors
  4. Folic acid metabolism inhibitors
  5. Cell membrane damaging drugs
  6. Free radical generators
31
Q

What are cell walls made of and what happens if it can make a cell wall?

A

○ Cell wall is made of peptidoglycan

§ If bacteria can’t make cell wall, it wukk die

32
Q

What do antibiotics that are protein synthesis inhibitors do?

A

Some antibiotics bind to 50s subunit whilst others bind to 30s subunit

33
Q

Why do antibiotics that bind to ribosomes have a good selective toxicity?

A

○ Antibiotics can bind to bacterial ribosomes without affecting eukaryotic ribosomes as they are different in structure

34
Q

What do antibiotics that inhibit DNA/RNA processing inhibit?

A

○ Inhibits either the way in which the bacteria makes its DNA or mRNA

35
Q

Why do antibiotics that are DNA/RNA processing inhibitors, show good selective toxicity?

A

○ Enzymes in bacteria are different to eukaryotic enzymes so these inhibitors show good selective toxicity

36
Q

What do quinolones inhibit?

A

Inhibits DNA gyrase which is a topoisomerase; helps DNA to coil and uncoil when DNA is replicating

37
Q

What is rifampin a key drug in treating?

A

§ Key drug in treating TB

38
Q

What is rifampin used prophylactically for?

A

§ Used prophylactically for meningitis as well

39
Q

What does rifampin target?

A

§ Targets enzyme that makes MRNA (DNA dependent DNA pol)

40
Q

What happens if bacteria cannot make folic acid?

A

○ If bacteria cannot make this, it loses its cofactor for many processes so will die

41
Q

Why are cell membrane damaging drugs toxic to us?

A

○ Bacteria has similar cell membrane to eukaryotes so these drugs are toxic to us – poor selective toxicity

42
Q

What do free radicals damage?

A

Free radicals will damage multiple targets, not just one

-Damages DNA and membranes

43
Q

What do gram positive bacteria have massive structures of?

A

○ Massive structure of peptidoglycan

§ Consisting of cross linked peptides and polypeptides

44
Q

Why are antibiotics able to get inside the bacteria and what do they target?

A

○ Peptidoglycan structure is porous so plenty of antibiotics can get inside to do their job – target enzymes that put together the peptidoglycan structure

45
Q

What do the antibiotics that inhibit cell wall synthesis target?

A

Antibiotics that inhibit cell wall synthesis target enzymes that make the peptidoglycan layer

46
Q

Where does the peptidoglycan layer in gram negative bacteria sit and with what?

A

sits in the periplasmic space with an outer membrane

47
Q

What mechanism do things that have to enter gram negative bacteria use?

A

§ Anything that has to go through it has to use transport mechanism

48
Q

Why can’t many antibiotics be used on gram negative bacteria?

A

Many antibiotics cannot be used on gram negative bacteria because they cannot pass the barrier

49
Q

Peptidoglycan structure

A

• Made of penta-peptides that are crosslinked together and hold the matrix together
§ Matrix has long polysaccharide chain

50
Q

How does bacteria make the structure of peptidoglycan?

A

• Starts by adding precursor monomer of a disaccharide with 5 peptides
§ Last two peptides in the monomer are alanines: D-ALA
• Once the terminal D-Alas are made, it undergoes transport mechanism across cytoplasm membrane by linking it to a lipid transport molecule
• Once monomer is transported, there is attachment of the 5 crosslinking AAs
○ This structrure can then be polymerized in the cell wall by enzymes
○ Enzymes recognize D-ALA, D-ALA and cleave the terminal D-ALA and links it to the penta-peptide

51
Q

What does the vancomycin antibiotic recognise and do?

A

○ Vancomycin for example recognizes the D-ALA, D-ALA and binds to it
§ Once bound, the enzyme cannot get to the structure and make the peptidoglycan

52
Q

What is PBP?

A

this is a cross-linking enzyme

53
Q

What does PBP bind?

A

Enzymes that competitively bind penicillins and cephalosporins

54
Q

What do penicillins and cephalosporins synthesise?

A

○ They synthesise the peptidoglycan

55
Q

Action beta lactam on penicillin and what does this prevent?

A

• beta lactams need to be able to cross the membrane and then bind to and inhibit the PBP
§ This prevents the bacteria from cross-linking

56
Q

What is most bacterias autolytic response when it can’t make peptidoglycan?

A

Most bacteria have an autolytic response; if it cannot make peptidoglycan, it lyses itself

57
Q

What is sulfonamides and what enzyme does it inhibit?

A

Is a folic acid inhibitor and it inhibits dihydropteroate synthetase

58
Q

What is the structure of sulfonamide almost identical to and what effect does it have?

A

○ Sulfonamide structure is almost identical to the PABA molecule which is necessary to make tetrahydrofolic acid
§ If this is not made, the bacteria dies

59
Q

What does trimethoprim block?

A

Trimethoprim blocks dihydrofolate reductase

60
Q

Why does trimethoprim have a good selective toxicity?

A

Humans have this enzyme but it is completely different to the bacterial enzyme so even though it is present, it does not harm the host enzyme

61
Q

When do we use antibiotics?

A
  1. Treatment of bacterial infections

2. Prophylaxis

62
Q

Route of administration of antibiotics for community infections

A

• Community infections are often treated orally by GP

63
Q

Route of administration of antibiotics for serious infections

A

○ hospitalisation - systemic treatment
§ e.g. i/v rapid delivery, high [blood]
○ Often unable to take oral – vomiting, unconscious, poor gut absorption due to trauma
○ i/v with perivascular collapse (e.g. septicaemia )
○ i/m injection - meningitis case

64
Q

Route of administration of antibiotics for topical infections

A

○ Conjunctivitis, superficial skin infections, burns, antiseptic creams, heavy metal ointments

65
Q

What is MIC?

A

• Concentration at which the antibiotic will kill or inhibit the growth of organism

66
Q

What does MIC depend on?

A

• This will depend upon the age, weight, renal and liver function of the patient and the severity of infection

Medical microbiology (14 decks)

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