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PMP-201 > Antibiotics - drug classes and mechanisms > Flashcards

Antibiotics - drug classes and mechanisms Flashcards

1
Q

prokaryotic cells

A

Bacteria

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2
Q

eukaryotic cells

A

fungi (yeasts/ mounds)
parasites (protozoa)

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3
Q

acellular

A

viruses
prions

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4
Q

Difference with human cells compared to prokaryotic

A

Without a nucleus (different DNA arrangements)
* Without membrane-bound organelles
* Simple organisation and smaller
* Different components (cell walls, glycocalyx, sex pili,
fimbriae, flagella)
* Different compositions of ribosomes (70s vs 80s)

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5
Q

Antimicrobial chemotherapy

A

Drugs to treat infectious diseases, having selective
toxicity against the pathogens involved, while damaging the host as little as possible

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6
Q

antibiotics to treat

A

bacterial infections

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7
Q

Selective toxicity

A

Ability of drug to kill or inhibit pathogen while damaging host as little as possible
* Degree of selective toxicity is expressed by the therapeutic index

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8
Q

Therapeutic index

A

Ratio of toxic dose to therapeutic dose
The larger the index, the safer/better the agent

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9
Q

Therapeutic dose

A

▪ drug level to treat/resolve an infection

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10
Q

Toxic dose

A

drug level that is toxic for the host

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11
Q

Spectrum of activity

2 types

A

narrow spectrum drugs

broad spectrum drugs

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12
Q

Narrow-spectrum drugs

A

effective only against a limited
variety of bacteria
✓When the microorganism is identified
✓Minimise the disruption of normal
flora

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13
Q

Broad-spectrum drugs

A

Target and inhibit many kinds of
bacteria (e.g. Gram+ and Gram-)
✓Serious bacterial infections by an
unidentified organism
✓Infection with multiple bacteria

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14
Q

Bacteriostatic

A

Prevent bacterial
growth (no killing)
* Reversible effect
* Bacterial clearance
depends on the
immune system

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15
Q

Bactericidal

A

Kill the target
bacteria
* Irreversible effect
* Appropriate in poor
immunity

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16
Q

How to measure effectivness of antimicrobial drugs?

A
  • Minimal inhibitory concentration (MIC)
  • Minimum bactericidal concentration (MBC)
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17
Q

MIC

A

lowest concentration of drug that
prevents the visible growth of the pathogen
* It varies against different bacterial species (spectrum of activity)
* Indicator for assessing bacterial drug resistance

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18
Q

MBC

A

lowest concentration of drug
that kills the pathogen

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19
Q

Calculation for effectiveness of antimicrobial drugs?

A

MBC / MIC

20
Q

Ratios that determines if drug is bactericidal or bacteriostatic

A

Bactericidal = MBC/MIC ratio <4

Bateriostatic = MBC/MIC ratio <10

21
Q

Antimicrobial Activity Can Be Measured by Specific Tests

A

✓Dilution Susceptibility Tests
✓Disk Diffusion Tests (Kirby-Bauer Method)
✓The Etest

22
Q

1) Dilution Susceptibility Tests
STEP by STEP

A

Used to determine MIC and MBC values.
* Inoculating media with different concentrations
of a drug and fixed number of bacteria.
* Broth or agar with lowest concentration
showing no growth is MIC.
* MBC is ascertained when tubes that show no
growth are then cultured into fresh medium
lacking antibiotic.
* The lowest antibiotic concentration that fails to
support the microbe’s growth is the MBC.

23
Q

2) Disk Diffusion Tests
➢Disk Diffusion Tests (Kirby-Bauer test)

A

Disks impregnated with different antibiotics
are placed on agar plates inoculated with a
microbe.
* Antibiotic diffuses from disk into agar,
establishing concentration gradient.
▪ Higher concentrations near the disk

24
Q

What does Measurement of the clear zones diameter
(no growth) around disks compared to a
standardized chart show?

A

susceptibility or resistence

25
Q

the diameter in disks diffusion tests correlates with

A

MIC

26
Q

Wider clear zone indicates that a microbe
is more ______ to that antibiotic

A

susceptible

27
Q

Narrower clear zone indicates drug
_______

A

resistance

28
Q

3) The Etest

A

Bacterial is inoculated on agar, then Etest® strips are
placed on the surface.
* Etest® strips contain a gradient of an antibiotic.
* Intersection of elliptical zone of inhibition with strip
indicates MIC
17
* Sirirat/Shutterstock

29
Q

Gram-Positive Cell Walls

A

Thick peptidoglycan
(including teichoic acids)

30
Q

Gram-Negative Cell Walls

A

Thin peptidoglycan
* Outer membrane (LPS, porins)

31
Q

Peptidoglycan formation:

A

Bacterial transpeptidase (or penicillin-binding
proteins) form peptide cross-link bridges between
tetrapeptide of NAMs of peptidoglycan strands

32
Q

MoA of B-Lactam

A

β-Lactams bind to and block transpeptidases (PBP), mimicking the substrate
* β-Lactams block the transpeptidation of peptidoglycan strands
* Prevent the synthesis of complete cell walls, leading to lysis of bacteria
▪ Only effective against bacteria reproducing
* Activates enzymes to break down peptidoglycan

33
Q

B-Lactam role

A
  • block NEW cell wall formation
  • bacterial lysis
34
Q

1) Inhibitors of Cell Wall Synthesis: β-Lactam antibiotics

A

ontaining a β-lactam ring — core structure
▪ Essential for bioactivity
β-lactam ring
* Same mechanism of action:
▪ Blocking the formation of peptide bridges between peptidoglycan chains
▪ Bactericidal effect and high therapeutic index
▪ Some resistant bacteria produce β -lactamase (penicillinase, more common
in Gram-negative bacteria) which hydrolyses and inactivate the ring.

35
Q

1) β-Lactam antibiotics subclasses

A

Penicillins
Cephalosporins
Carbapenems
Monobactams

36
Q

Natural Penicillins – the first antibiotics

A

Penicillin G

Penicillin V

37
Q

Penicillin G
(Benzylpenicillin)

A
  • Narrow (most Gram +ve
  • Parenteral
    (degraded by stomach acid pH)
  • Very low (easily inactivated by
    bacterial beta-lactamases
38
Q

Penicillin V
(Phenoxymethylpenicillin)

A
  • Narrow (most Gram +ve)
  • Oral
    (Resistant to acid pH
  • Very low (similarly)
39
Q

Bacterial β-lactamases cut the β-lactam ring
to _______ antibiotics of this class

A

inactivate

40
Q

Semisynthetic Penicillins

A
  1. Antistaphylococcal penicillins
  2. Aminopenicillins (Broad-spectrum penicillins)
  3. Antipseudomonal penicillins (Extended broad-spectrum)
41
Q

Antistaphylococcal penicillins - Penicillinase-resistant penicillins

EXAMPLE

A

Flucloxacillin – acid-stable (oral and iv)
▪ Bulkier side chains – Resistant to β-lactamase of Staphylococci
▪ Retain a narrow-spectrum activity (not active against Gram-)

42
Q

Aminopenicillins/Broad-spectrum penicillinsAminopenicillins/Broad-spectrum penicillins

A

Ampicillin (oral)
➢ Amoxicillin (oral)
❖ the most prescribed
antibiotic in the UK
Brand name
(Generic)
Antibiotic
(generic)
Β-lactamase
inhibitor
Augmentin
(Co-amoxiclav)
Amoxicillin clavulanic acid
▪ Amoxicillin is also combined with Flucloxacillin in co-fluampicil (Magnapen)
▪ Active against Gram-negative (e.g. E. coli, Salmonella spp)
o Hydrophilicity allows passage through porins of outer membrane in Gram-negative only)
▪ combined with beta-lactamase/penicillinase inhibitor
o inactivating bacteria producing β-lactamases
o beta-lactamase inhibitors do not have anti-bacterial activity

43
Q

Antipseudomonal penicillins – extended broad-spectrum
➢ Piperacillin, Ticarcillin
* Only available in combination with the beta-lactamase inhibitors

A

Piperacillin, Ticarcillin
* Only available in combination with the beta-lactamase inhibitors

44
Q

Penicillins: Adverse effects

A
  • hypersensitivity
  • check for any allergies before (mild/ mod/ severe rash)
  • GI distress, diarrhoea + nausea
45
Q

Contraindications: of penicillin

A

hypersensitivity and history of hepatic impairment

Penicillin resistance
➢Mainly due to the production of β-lactamases to cleave the β-lactam ring
➢Mutations changing the transpeptidase conformational structure

PMP-201 (34 decks)

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