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lolmyi > L13: Antibiotics > Flashcards

L13: Antibiotics Flashcards

1
Q

What are most antibiotics derived from?

A

→ natural products of fungi and bacteria - soil dwellers
→natural products by fermentation

then are chemically modified

→synthetic antibiotics are produced too

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2
Q

Why are antibiotics chemically modified?

A

→ increase pharmacological properties ie can they survive in the stomach
→increase antimicrobial effect

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3
Q

What is an example of a totally synthetic antibiotic?

A

→sulphonamides

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4
Q

What are natural products of fungi and bacteria derived from?

A

→- soil dwellers natural antagonism and selective advantage

→kill or inhibit the growth of other microorganisms

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5
Q

Why is there selective toxicity in antibiotics?

antibiotic has selective toxic effect against organism that is being treated and minimum effect on host

A

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

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6
Q

Why is selective toxicity difficult in viruses?

A

→viruses are intracellular

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7
Q

What are the principles of selective toxicity?

A

→differences in structure and metabolic pathways between host and pathogen
→Harm microorganisms, not the host
→Target in microbe, not host (if possible)
→selective toxicity Difficult for viruses (intracellular), fungi and parasites
→Variation between microbes
→effect on commensals

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8
Q

What is therapeutic margin?

A

→active dose (MIC) vs toxic effect

THERE IS NO SAFE DRUG - in balance

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9
Q

What types of drugs have narrow therapeutic margins?

A

→toxic drugs e.g. aminoglycosides, vancomycin, ototoxic, nephrotoxic

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10
Q

Why is microbial antagonism important?

inhibition of one bacterial organism by another

A

→Maintains flora

→Limits growth of competitors and pathogens

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11
Q

What happens with loss of flora?

A

→bacterial or pathogen overgrowth

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12
Q

Example of a disease cause by loss of flora

A

→Antibiotic Associated Colitis i.e. pseudomembranous colitis

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13
Q

Which bacteria can cause pseudomembranous colitis?

A

Clostridioides difficile

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14
Q

Which antibiotics most commonly cause (antibiotic associated) colitis?

A

→Fluoroquinolones
→clindamycin,
→broad-spectrum lactams

these antibiotics affect gut flora thus causes over growth of the bacteria Clostridioides difficile

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15
Q

What conditions cause immunosuppression?

A

→cancer chemotherapy,
→transplantations,
→myeloma,
→leukaemias,

→HIV with low CD4

→Neutropenics, 
→asplenics, 
→renal disease, 
→diabetes,
→ alcoholics
→babies and elderly
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16
Q

How are antibiotics classified?

A

→Type of activity e.g. bactericidal and bacteriostatic

→Structure

→ Target site for activity

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17
Q

What are bactericidal antibiotics?

A

→Kill bacteria

→Used when the host defense mechanisms are impaired

→Required in endocarditis, kidney infection

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18
Q

Describe bacteriostatic antibiotics

A

→Inhibit bacteria (at a certain concentration) eg tetracyclin

→Used when the host defence mechanisms are intact

→Used in many infectious diseases

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19
Q

What might a bacteriostatic antibiotic become if dose is increased?

A

→bactericidal if dose is increased

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20
Q

Examples of broad spectrum antibiotics:

antibiotics that are effective against many types

A

→Cefotaxime

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21
Q

Example of narrow spectrum antibiotics:

effective against very few types

A

→Penicillin G

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22
Q

What are cephalosporins now (third-generation) most effective against?

A

→gram negatives

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23
Q

What are basic penicillins active against?

A

→streptococci,
→pneumococci,
→meningococci,
→treopnemes

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24
Q

Which bacteria are resistant against basic penicilin?

A

→Staphylococcus aureus thus need a different type of penicillin to kill it

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25
What type of natural substance does penicilin have?
→Beta-lactams
26
What are anti-staphylococcal penicillin?
→narrow spectrum, →G+ves, →beta-lactamase resistant (enzyme that breaks down penicillin produced by S. aureus) → less potent than PenG → not MRSA (type of bacteria resistant to several antibiotics)
27
Compare Pen G and Pen V
Pen G - benzylpenicillin →not acid stable (cannot give orally) →thus administered i/v or i/m →good for some G-ves as well as G+ves Pen V - phenoxymethylpenicillin →oral (more acid-stable than penG) →less active G-ves, → same activity with G+ves as in PenG
28
What are broader spectrum penicillins?
→Spectrum of activity is similar to basic penicillins but also includes some Gram-negative organsims and also enterococci
29
What are anti-pseudomonal penicillin?
→extended spectrum beta-lactam antibiotic →also G+ve, G-ve, anaerobes
30
Example of anti-pseudomonal penicillin
→piperacillin
31
What are beta-lactam/lactamase inhibitors?
→Spectrum like amoxicillin plus activity against some Gram-negatives and Staph aureus
32
What are pseudomonal?
→a major cause of lung infections in people with cystic fibrosis. →thrive in moist environments and equipment
33
What are the molecular structure classifications of antibiotics?
``` →nalidixic acid →ciprofloxacin →erythromycin →tetracycline →vancomycin →streptomycin(aminoglycosides) ```
34
What are beta lactams?
→Structural mimics of natural substrates for enzymes ``` beta lactams antibiotics are antibiotics that have a beta lactic ring including: →penicillins, →cephalosporins →sulbactam →carbapenem →monobactam ```
35
Why is the beta-lactam ring structure important?
→Without B lactam there will be no antimicrobial property → b lactam ring is the active structure in penicillin →stop bacterial growth by inhibiting PBPs (penicillin-binding proteins) that are indispensable for the cross-linking process during cell wall biosynthesis
36
Which antibiotics have beta lactams?
``` →penicillins, →cephalosporins →sulbactam →carbapenem →monobactam ```
37
What are carbepenams?
→effective antibiotic agents commonly used for the treatment of severe or resistant bacteria
38
What are the bacterial targets for common antibiotics? | modes of actions of bacteria?
``` →cell wall synthesis →DNA →folic acid metabolism →cell membrane →protein synthesis- 50S and 30S →DNA and RNA processing- DNA Gyrase, DNA-directed RNA polymerase → generation of Free radicals ``` Thus many targets for selective toxicity
39
Is tetracycline bactericidal or bacteriostatic?
→bacteriostatic has anti-inflammatory effects; broad-spectrum thus used widely in community
40
How do antibiotics reach membrane of gram negatives?
→porins in outer membrane mediate the passive diffusion of antibiotics these bacteria have an impermeable barrier thus certain pores allow for entrance to periplasmic space and thus inhibit PEPTIDOGLYCAN SYNTHESIS ENZYMES
41
What are the sites of action of inhibitors of bacterial cell wall synthesis?
→cytoplasm- synthesis of cell wall precursors (MONOMERS) e.g. cycloserine →cytoplasmic membrane- synthesis of cell wall subunits attached to lipid carriers (DIMERS TO CHAIN FORMATION) e.g. vancomycin and bacitracin →cell wall- new wall unit attachment to growing peptidoglycan (CROSS LINKING) e.g. beta lactams (penicillin)
42
What are D-alanines?
→incorporated by PBPs (Penicillin-binding proteins) into peptidoglycan
43
How does cycloserine inhibit bacteria cell wall synthesis?
→inhibits incorporation of alanine into cell wall precursor
44
How does vancomycin inhibit bacteria cell wall syntesis?
→bind to terminal D-ala D-ala residues to prevent incorporation of subunit into peptidoglycan
45
How does bacitracin inhibit bacteria cell wall synthesis?
→prevents dephosphorylation of phospholipid carrier which prevents regeneration of carrier to continue synthesis
46
How do penicillin and cephalosporins (beta lactams) inhibit bacteria cell wall synthesis?
→inhibit enzymes which catalyse cross linking (PBPs) induction of autolytic enzymes causing bacteria to die as cannot make peptidoglycan structure.
47
Which bacteria is resistant against penicillin?
→mycoplasma pneumoniae | →have sterol packed cell membrane (not peptidoglycan thus use other antibiotics that target elsewhere in the bacteria)
48
What type of antibiotics are folic acid synthesis inhibitors?
→bactericidal | →broad spectrum
49
What are the targets of folic acid synthesis inhibitors?
→PABA | →dihydrofolate reductase- human DHFR is less inhibited hence selective toxicity
50
How do aminoglycosides inhibit protein sythesis?
→Binding fmet t-RNA Initiation complex formation | →streptomycin
51
How does gentamycin inhibit protein synthesis?
→Translocation of fmet t-RNA | to P site
52
How does tetracycline inhibit protein synthesis?
→Competition with new Aminoacyl t-RNA at the A site
53
How does chloramphenicol inhibit protein synthesis?
→Blocks formation of peptide bond peptidyl transferase | →Bind to 50S ribosome
54
How do erythromycin and fusidic acid inhibit protein sythesis?
→Block translocation of peptidyl t-RNA
55
What 2 infections can antibiotics be used prophylaxis (to prevent bacterial infection)?
→meningitis | →tuberculosis
56
How is antibiotic given in a meningitis case?
→i/m injection
57
Which conditions are antibiotics given topically?
``` →conjunctivitis →superficial skin infections →antiseptic creams →burns heavy metal ointments ```
58
What does minimum inhibition concentration depend on?
→age →weight →renal and liver function →severity of infection →susceptibility of the organism to the antibiotic →properties of the antibiotic i.e. is it enough to give a concentration higher than MIC (minimum inhibitory concentration) at the site of infection -NOT JUST BLOOD MIC levels vary between different antibiotics
59
What are the two pharmacodynamic properties of antibiotics killing activity?
→time-dependence | →concentration-dependence = max or area above MIC
60
Why are antibiotic combinations used?
→life-threatening infections e.g. endocarditis, septicaemia →Polymicrobial infections →Less toxic doses →synergy eg. penicillin and gentamicin →reduce antibiotic resistance e.g. Tuberculosis
61
What is microbial antagonism?
Inhibition of one bacterial organism by another
62
what is dysbiosis?
outgrowth of certain organisms due to antibiotics disrupting the flora Normal microbiota prevent outgrowth of pathogens
63
Clinical features of antibiotic associated colitis (pseudomembranous colitis by bacteria C. difficile)?
→Ulcerations - inflammations →Severe diarrhoea → serious hospital cross-infection risks
64
How is Clostridium difficile (bacteria) spread?
→ via endospores (spores)
65
what 2 factors allow fro bacterial clearance?
antibiotics and immunity
66
Example of basic penicillin
benzylpenicillin (PenG), penicillin V
67
Examples of and MOA of antibiotics targeting cell wall synthesis
→penicillins → cephalosporins → cycloserine →vanomycin
68
Examples and MOA of antibiotics targeting folic acid metabolism: Folate is made in bacteria; humans consume folate
Synergetic effect (given together): →trimethoprim →sulphonamides
69
Examples and MOA of antibiotics targeting cell membrane:
→colistin (hugely toxic in human c=membranes thus only given if bacteria is multi drug resistant e.g. e.coli →daptomycin
70
Examples and MOA of antibiotics targeting protein synthesis - 50s inhibitors:
→erythromycin →chloramphenicol (toxic drop so used topically as eye drops) →clindamycin →linezolid
71
Examples and MOA of antibiotics targeting protein synthesis - 30s inhibitors:
``` →tetracycline - bacteriostatic effect →spectinomycin →streptomycin →gentamicin (toxic thus measure concentration to prevent overdosing) →tigecycline →doxycycline (modern tetracycline) ```
72
Examples and MOA of antibiotics targeting DNA and RNA processing:
→Quinolones- inhibits DNA Gyrase by targeting DNA replication and mRNA synthesis → Rifampin- blocks ability of bacteria to produce mRNA binds to and inhibits bacterial DNA-directed RNA polymerase
73
What is the enzyme that acts like DNA gyrase in humans?
topoisomerase IV
74
Examples of antibiotics that generate free radicals:
→METRONIDAZOLE - used to treat anaerobic infections (deep ulcers, abscesses etc.) →NITROFURANTOIN -treating simple infections thus decreases toxicity; good anti-microbial effects These AB generate free radicals once inside the bacteria
75
Why is the germination of free radicals helpful in killing bacteria?
Free radicals kill many of the bacterial structures thus killing the bacteria
76
Are the enzymes making peptidoglycan the same in both gram positive and gram negative bacteria?
NO! Different antibiotics required to treat the 2 types of bacteria even though in both cases u are targeting the peptidoglycan (cell wall synthesis antibiotics)
77
What are PBPs?
Penicillin-binding proteins or transpeptidase involved in the synthesis of peptidoglycan - enzyme cross-line sub-units of peptidoglycan to form peptidoglycan dimers which then exist as peptidoglycan.
78
How are community infections administered antibiotics?
→Orally by GP
79
How are serious infections, which have lead to hospitalisation, administered antibiotics?
→systemic treatment via I/v I/v is rapid delivery and high [blood] I/v when unable to take orally e.g. vomiting, consciousness, poor gut absorption due to trauma
80
Does MIC levels vary between different antibiotics?
YES

lolmyi (31 decks)

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