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Microbiology > Principles of antimicrobial therapy > Flashcards

Principles of antimicrobial therapy Flashcards

1
Q

Targets of drug action

A 
Enzymes
Receptors
Ion channels
Transporters
targets in host cell to later function
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2
Q

Immunity

A

Body’s ability to recognise and remove non-self material

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3
Q

Action of anti-microbial drugs

A

Ability to recognise and destroy non-self cells

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4
Q

What is chemotherapy based on?

A

Selective toxicity

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5
Q

What is selective toxicity?

A

Causes greater harm to micro-organism than host
Anti-microbial drugs must have limited toxicity but good selectivity
To increase efficacy= increase dose but efficacy and toxicity must be balanced

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6
Q

Chemotherapeutic index formula

A

Toxic Dose (lowest)/Therapeutic dose

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7
Q

Chemotherapeutic index meaning

A

The ratio of the minimal effective dose of a chemotherapeutic agent to the maximal tolerated dose

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8
Q

4 types of anti-microbial drugs

A

Anti-bacterial
Anti-fungal
Anti-protozoan
Anti-helminthic

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9
Q

Class I pathways that antimicrobial drugs target

A

Reactions that use glucose/other carbon sources to make ATP/substrates needed for class II reactions

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10
Q

Class II pathways

A

Pathways that use ATP and class I substrates to make small molecules e.g amino acids, nucleotides

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11
Q

Class III pathways

A

Convert small class II molecules into macromolecules e.g proteins, nucleic acids, polysaccharides, peptidoglycan

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12
Q

Name of a class II antimicrobial drug

A

Sulfonamide

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13
Q

What the pro drug of sulfonamide that is metabolized in the body to produce sulfonamide?

A

Prontosil

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14
Q

Sulfonamide mechanism of action

A

Competitive inhibitor of dihydropteroate synthetase
This enzyme normally produces folic acid
Prevent bacterial DNA synthesis and replication

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15
Q

Why can bacteria synthesise folate but humans can’t?

A

Bacteria have the enzyme dihydropteroate synthetase enzyme but humans don’t

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16
Q

What does dihydrofolate reductase catalyse?

A

Formation of tetrahydrofolate from dihydrofolate

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17
Q

What antimicrobial drugs prevent action of dihydrofolate reductase?

A

Trimethoprim
Methotrexate
Pyrimethamine

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18
Q

Mechanism of action of trimethoprim, methotrexate and pyrimethamine

A

(for trimethoprim) Type= antifolate antibacterial agent
Interaction- dihydrofolate reductase
Reversible inhibitor of dihydrofolate reductase
Tetrahydrofolate cant be made which is essential in making thymidine, nucleic acids and proteins (methionine)
so inhibits bacterial DNA synthesis
Killing bacteria

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19
Q

Example of a class III antimicrobial drug

A

Penicillin

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20
Q

What class of drug is penicillin?

A

Beta-lactam

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21
Q

Is penicillin broad/narrow spectrum antibiotic?

A

Narrow spectrum

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22
Q

Examples of Beta-Lactam drugs

A

Penicillins
Monobactams
Carbapenems
Cephalosporins

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23
Q

Bacteria cell wall peptidoglycan synthesis

A

Penicillin binding protein in cell wall e.g transpeptidase enzyme normally catalyses cross linking of peptidoglycan chains by binding to D-ALA D-ALA by transpeptidation reaction

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24
Q

What does beta-lactam do?

A

Inhibits peptidoglycan cell wall synthesis

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25
Beta lactam mechanism of action
Beta-lactam ring mimics D-ALA D-ALA beta lactam forms a covalent bond with amino aciid serine of transpeptidase enzyme This inhibits transpeptidase carrying out the transpeptidation reaction required for peptidoglycan synthesis no cell wall= lysis of bacteria by autolytic enzymes e.g autolysins
26
Antibiotics that inhibit cell wall synthesis
Vancomycin Bacitracin Cycloserine
27
Class III Anti-bacterial drugs can prevent synthesis of what?
Ribosomes
28
Eukaryotic ribosomes
80s Large subunit= 60s Small subunit= 40s
29
Prokaryotic ribosomes
70s Large subunit= 50s (23sRANA) Small subunit= 30s (16sRNA)
30
Why are ribosomes a good target for anti-bacterial drugs?
Bacteria ribosomes are different to eukaryotic ribosomes
31
What drugs target 30s subunit of bacteria ribosomes?
Aminoglycosides | Tetracyclines
32
Mechanism of action of Aminoglycosides
Targets 16sRNA of 30S subunit Irreversibly bind to specific 30S-subunit proteins and 16S rRNA Induces misreading of mRNA incorrect amino acids are inserted into the polypeptide leading to non-functional or toxic peptides halts protein synthesis
33
Mechanism of action of Tetracyclines
Broad spectrum Passively diffuses through porin channels in the bacterial membrane Reversibly binds to the 30S ribosomal subunit preventing the attachment of aminoacyl-tRNA to the ribosomal A site (mRNA-ribosome complex)- in initiation of translation Inhibiting bacterial growth by inhibiting translation
34
Which anti-bacterial drugs target the 50S large subunit of bacterial ribosomes?
Macrolides | Fusidic acid
35
Macrolides mechanism of action
Broad spectrum Bind to 50s subunit- to 23 S rRNA of 50S Preventing the translocation of the elongation factor G (EF-G) from the ribosome Inhibits polypeptide translocation and assembly of 50s subunit.
36
Problem with bacterial ribosome-targeting drugs?
We have the same ribosomes in our mitochondria as bacteria
37
Name of anti-bacterial drugs that target DNA arrangement?
Quinolones
38
Quinolone mechanism of action
Prevents and inhibits DNA gyrase and topoisomerase from supercoiling and unwinding DNA Inhibiting DNA replication
39
Example of a quinolone
Ciprofloxacin
40
Anti-bacterial drugs that target DNA synthesis
Quinolones | Metronidazole
41
Anti-bacterial drug that target RNA polymerase
Rifampicin (inhibits RNA polymerase)
42
Anti-bacterial drug that targets bacteria cytoplasmic phospholipid membrane
Polymyxins
43
Anti-bacterial drugs that target protein synthesis (50s inhibitors)
Erythromycin | Lincomycin
44
Anti-bacterial drugs that target protein synthesis (30s inhibitors)
Aminoglycosides | Tetracycline
45
What are broad-spectrum drugs?
Active against a wider number of bacterial types Used to treat a wide variety of infectious diseases Useful when bacteria agent is unknown but likely to fall within a set of a certain species
46
What are narrow spectrum drugs?
Used for specific infection when causative organism is known
47
Advantage of narrow spectrum over broad spectrum drugs
Narrow spectrum drugs won't kill as many of the normal microorganisms in the body like broad spectrum drugs do so narrow spectrum drugs are less likely to produce GI side effects and/or residual drug reisistant strains
48
What type of bacteria do polymyxins target?
Gram negative bacteria
49
Examples of polymyxins
``` Polymyxin B Polymyxin E (colistin) ```
50
Mechanism of action of polymyxins (colistin)
Colistin binds to LPS and phospholipids in outer membrane of gram-negative bacteria Competitively displaces Ca2+ and Mg2+ from phosphate group of lipids in OM Disrupts outer membrane= lysis
51
What type of bacteria does vancomycin target?
Gram positive bacteria
52
What is streptomycin an example of?
Aminoglycoside | Inhibits protein synthesis (30s)
53
What type of cell wall do mycobacterium have?
Arabinogalactan
54
Anti-bacterial drug that targets gram negative bacteria and mycobacterium
Streptomycin
55
Why are anti-bacterial drugs good?
Clear difference between eukaryotic and bacterial cells | so easier to target bacterial cells
56
Problem with anti-fungal drugs?
Fungi are also eukaryotic cells so little differnece between our cells and fungal cells
57
What can anti-fungal drugs target in fungi?
Cell membrane | Cell division
58
What anti-fungal drug targets fungi cell membrane?
Flucanozole
59
What do fungi have in their cell membrane instead of cholesterol?
Ergosterol
60
Fluconazole mechanism of action
Type- antifungal Interacts- fungal cytochrome P450 dependent enzyme Selective inhibitor of fungal cytochrome P450 dependent enzyme This enzyme normally converts lanosterol to ergosterol Inhibiting ergosterol synthesis Disruption structure and function fungal membrane
61
What anti-fungal drug disrupts cell structure/division in fungi?
Flucytosine
62
Flucytosine mechanism of action
Type- antimetabolite Fluctyosine is converted into fluorouracil (5FU) 5FU is converted into 5-fluorodeoxyuridylic acid (5dUMP) 5dUMP inhibits thymidylate synthase from converting dUMP to dTMP preventing DNA synthesis
63
Anti-viral drugs
Target various stages in virus' life cycle
64
What part of virus' life cycle do anti-viral drugs target?
Entry into host cells Nucleic acid replication Viral protein synthesis Virus exiting host cell
65
Virus life cycle
1. Virus attaches to receptor on host's surface 2. Virus attaches and enters host cell 3. Uncoating of virus 4. Genome replication of virus 4. Protein and RNA synthesis of virus 5. Assembly and maturation 6. Released from host cell by neuraminidase
66
What do anti-viral ion channel blockers do?
Prevent uncoating of virus in host cell
67
What do integrases do?
Allow viral genome to integrate into host cell
68
Anti-viral drugs that inhibit attachment and entry of virus into host cell
Maraviroc | Enfuvirtide
69
Anti-viral drugs that block ion channels
Amantadine | Rimantadine
70
Anti-viral drugs that inhibit DNA/RNA polymerase from being made
Acyclovir | Zidovudine
71
Anti-viral drug that inhibits integrase enzymes
Raltegravir
72
Anti-viral drugs that inhibit proteases
Saquinavir | Ritonavir
73
Antiviral drugs that inhibit neuraminidase
Zanamivir | Oseltamivir
74
What does viral neuraminidase do?
Allows virus to be released from host cell
75
Viral entry inhibitor
Chloroquine
76
Ribavirin and Favipiravir
Inhibit viral RNA dependent RNA polymerase
77
Hydroxychloroquine
Inhibit viral entry
78
Proteolysis
Spread viral proteins
79
Inhibitors of proteolysis
Lopinavir | Ritonavir
80
Ideal drug target
System in the infectious microorganism that doesn't exist or exists in a different form in the host cell
81
Class I biochemical processes
Common in most organisms so not a good target
82
Class II and III
More likely to differ between organisms so a good target
83
What are the mechanisms responsible for resistance of bacteria to anti-microbial drugs?
1. Inactivating enzymes- beta lactamases break down beta lactam antibiotics (e.g monobactams) 2. Decreased drug accumulation by: - Changing surface proteins e.g porins- bulk transporters- allow material to enter cells. Reduce no. of proins= reduce drug uptake into bacteria - Efflux pump- ejects drug out of cell (U-turn) 3. Altering binding site- drug cant bind to it 4. Development of alternative metabolic pathways - e.g sulfonamides and trimethoprim
84
How do bacteria spread resistance?
1. Spontaneous mutation- occurs as cells replicate some bacteria acquired resistance drug eliminates sensitive organisms resistant ones proliferate 2. Gene transfer/ Transferred resistance- transfer of plasmid (extrachromosomal DNA) 3.Pilli of bacteria can also help spread resistance

Microbiology (5 decks)

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