mode of action of antibiotics Flashcards

1
Q

2 essential requirements of antibiotics:
1. Must cause disruption to a – or process that is essential for – and — of the microorganism
2. Must cause— harm to the host
organism
In other words…. they must be —
examples:
* If the antibiotic target is present in the bacteria but
absent in human cells
* The antibiotic target may be present in human cells
but the antibiotic cannot bind as easily to it

A

structure
growth and survival
minimal
selectively toxic

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2
Q

importance:
* Some antibiotics may have a narrow
— : Although they can kill bacteria, they are also toxic to— and may cause unwanted –.
* Some antibiotics must be carefully– to
ensure they are therapeutic but not excessively – ( aka —).

A

arrow therapeutic index
human cells
side effects
monitored
Therapeutic drug monitoring

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3
Q

mechanisms of action of anti bacterials:
1-Cell wall synthesis inhibitors-
bactericidal agents that target
and lyse — in cell
wall ex: — (e.g. penicillins,
cephalosporins, carbapenems) — (e.g. vancomycin) – (e.g. colistin)
2- binds to calicum channel in cell as –
3- — sythesis as Quinolones , Metronidazole
4- rna synthesis as —-
5- —- as. Trimethoprim
Sulphonamides
6- protein synthesis 30S ribosomes as — , —
7- protein synthesis 50s ribosomes as
— (e.g. clarithromycin)
—- (e.g. clindamycin)
— (e.g. linezolid)

A

peptioglycan
beta lactams
glycopeptides
polymyxin
daptomycin
dna synthesis
rna sythesis
antimetabolites
Aminoglycosides (e.g.
gentamicin) and Tetracycline
macrolids
lincosamides
oxazolidiones

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4
Q

modes of attack:
1. Breach their walls:
—– agents
2. Hack into their information centres
- —
- Inhibit — synthesis or –
3. Disrupt their factories
- inhibitors of— & —

A

cell wall active
antimetabolites
inhibit rna synthesis or dna replication
nucleic acid and protein sythesis

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5
Q

1- breach their walls:
Bacteria need a strong and functional
cell wall to prevent —
* If they cannot synthesise – correctly, the
cell wall is compromised
* Agents that disrupt the process of peptidoglycan synthesis – bacteria

Remember
➢different locations of cell wall in Gram+ and Gram-
➢the cell wall is thicker in Gram –

A

cell lysis
peptidolyclan
kill
+ve

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6
Q

-peptidoglycan synthesis:
Building of cross linked chains is
catalysed by specific enzymes – —- or —
- mode of action of cell wall active agent:
A: b-lactams bind – to – preventing cross linking.
B: Glycopeptides bind to – preventing –

A

transpeptidase or penicillin
binding proteins PBP’s
directly
transpeptidase
side chain
cross linking

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7
Q

1- beta lactams are defined by the presence of —- , the prevent cross linking of peptidoglycan structure by inhibiting — and bacteria die by —
the four main types are: —
- however :
* Many bacteria (Gram + and Gram-) can produce enzymes that destroy the b–lactam ring of these antibiotics
* b–lactamases are large group of enzymes that include : — ( – ) and –
* – antibiotic + — inhibitor ensures activity , inhibitor so antibiotic remains active
2- glycopeptides :
* Vancomycin bind to — of
NAM residues and blocks — of
peptidoglycan backbone.
* Gram- — organisms only (eg used for
treatment of — infections)
– — size means it cannot pass the outer
membrane of Gram- – , therefore no Gram- – activity
- the action of vancomycin:
Inhibits cell wall crosslinking but in a different way to penicillins
Binding of Vancomycin to – (d-ala-d-ala)of the tetra-peptides that extend from the M sugars, causes – hindrance that disrupts crosslinking

A

four membered b lactam ring
transpeptidase (PBP)
lysis
penicillin , cephalosporins , carbapems , monobactams
Extended spectrum b-lactamases ESBL
carbapenemase
b lactam n b lactamase ( check examples slide 16)
acyl-D-alanyl-D-alanine
elongation
+ve
MRS
large
-ve
-ve
amino acids
steric

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8
Q

2- hack into info centres :
A: nucleic acid synthesis inhibitors:
* Bacteria need to replicate their
DNA and need to transcribe it
to – to specify the correct
sequence of amino acids to
make proteins and enzymes
required for survival and
growth
* Agents that disrupt these
processes cause –
- Remember that DNA gyrase/topoisomerase catalyses DNA
— . This unravelling of supercoiled DNA is a necessary activity for DNA replication to take place
- Negative supercoiling – catalysed by — -relaxes the supercoils by nicking ( – ) the DNA at
specific points so that replication can take place.

A

mRNA
cell death
supercoilling
dna gyrase
cutting

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9
Q

quinlones:
* Inhibit the bacterial — and —
enzymes, thereby inhibiting— as supercoils cannot be unraveled.
* Enter cells easily via – & therefore are sometimes used to treat — pathogens
* Gram- and Gram+ activity.
– For G-ve bacteria — is the main target,
whereas — is the main target for G+ve
bacteria.
* Example: –

A

dna gyrase and topoisomerase IV
dna replication
poris
intracellular
dna gyrase
topoisomerase iv
ciprofloxin

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10
Q

2- hack into their info centres
b: rna synthesis inhibitors:
( Remember functional – is required to generate messenger RNA from the DNA sequence during transcription)
* Rifampicin binds– and inhibits initiation of – synthesis thus – is not formed and – cannot
take place
* Cells cannot make – and – -> results in –
* Gram- – are not susceptible to
rifampicin due to decreased uptake of
hydrophobic antibiotic

A

rna polymerase
rna polymerase
mRA
mRNA
translation
proteins n enzymes
cell death
-ve

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11
Q

2- hacking into info centre
c: antimetabolites as —- and — (Co-trimoxazole)
* Bacteria make— (THF) which they incorporate into DNA nucleotides
* The metabolic pathway for THF synthesis involves a number of key enzymes
* If these enzymes are – , bacteria cannot make – and hence the nucleotide bases they need for– are not made.
-Remember bacterial genetics, structure of DNA, need nucleotides
- so basically antimetabolites block enzymes required for
the synthesis of — ,precursor to some
nucleotides in DNA

A

sulphonamides and trimethoprim
tetrahydrofolate
inhibited
THF
dna replication
tetrahydrofolic acid

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12
Q

3- distrust their factories - agents that inhibit protein sythesis:
* Remember that bacteria must make the proteins they need to survive and they do this in the process of
translation which takes place at the ribosome and requires – RNA (carries amino acids) and – RNA (specifies the amino acid to be inserted based on triplet codon).
- mRNA Translation
mRNA is — by ribosomes and transfer RNA (tRNA) molecules to specify the exact sequence of amino acids in a protein

A

transfer n messenger
decoded

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13
Q

mechanism of action of protein synthesis inhibitors:
There are many ways by which the translation process
can be disrupted to prevent protein synthesis:
* Inhibition of binding of tRNA to 30S ribosome
– — (eg gentamicin)
– — (eg doxycyline)
* Inhibition of binding of – to – Ribosome
– Chloramphenicol
* Inhibition of RNA-dependent protein synthesis at 50S
ribosome
– — (eg clarithromycin, azithromycin),
– —
* Binding to bacterial 50S ribosome
– –

A

aminoglycosides
tetracycline
tRNA to 50s
macrolide
clindamycin
linzeoid

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14
Q

novel classes - daptomycin:
Mechanism of action
* Binds to — & causes rapid— of the membrane potential, inhibiting synthesis of —, –,— &—
concentration-dependent
* — activity
Spectrum of activity
* Gram – Bacteria only including antimicrobial resistant strains (e.g., –,—)

A

bacterial membranes
deplorizarion
dna rna protein
bactericidal
+ve
mrsa vre

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15
Q

Search for new targets and approaches, eg cell membrane, virulence factors - There is a need to identify new targets with modes
of action that are different from those available
currently.
1- Host defence peptides (HDP)
* – modes of action including cell membrane—
* may have — effects in addition to –
2- Anti-virulence therapy
* Reduce the – of the organism, – target infection sites.
* E.g Inhibitors of siderophores– target iron metabolism
3- Bacteriophages
* Naturally occurring – that specifically kill –
* May have very specific host range for targeted therapy

A

multiple
deplorizarion
immune-regulatory
anti microbial
virulence
selectively
viruses
kill bacteria

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