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Protein synthesis inhibitors Flashcards

1
Q

What are the 3 tetracyclines?

A
  1. Tetracycline
  2. Doxycycline
  3. Minocycline
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2
Q

What is the mechanism of action of the tetracyclines?

A

Tetracyclines concentrate intracellularly in susceptible organisms and bind reversibly to the 30S subunit of the bacterial ribosome.

This action prevents binding of the tRNA to the A site of the mRNA-ribosome complex, inhibiting bacterial ribosome synthesis

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3
Q

What products should tetracyclines be avoided with?

A

Dairy products or other substances that contain divalent and trivalent cations (Mg, Al, Fe) as it decreases absorption

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4
Q

How well do tetracyclines penetrate the CSF?

A

Moderate CSF penetration

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5
Q

What class of antibiotics should not be given with tetracyclines?

A

Beta lactams

Tetracyclines will arrest the growth of bacteria while beta lactams rely on bacterial growth to be effective

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6
Q

Are tetracyclines safe to be given during pregnancy?

A

No. All are Cat D as they cross the placental barrier and concentrate in fetal bones and dentition

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7
Q

What is tetracyclines spectrum of coverage?

A

Broad spectrum of gram-positive, gram-negative, atypical & spirochete bacteria + MRSA

Ineffective against P. aeruginosa & Proteus spp.

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8
Q

What are the 2 bacteria that tetracyclines lack activity against?

A

P. aeruginosa & Proteus spp.

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9
Q

What is the route of administration of tetracycline?

A

PO

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10
Q

What is the route of administration of doxycycline?

A

PO (good oral bioavailability), IV

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11
Q

Which tetracycline has good oral bioavailability?

A

Doxycycline; almost completely absorbed from the GI tract

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12
Q

What is the route of administration of Minocycline?

A

PO

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13
Q

How are the 3 tetracyclines excreted?

A
  1. Tetracycline is primarily eliminated in the kidney
  2. Doxycycline is eliminated in bile & urine
  3. Minocycline is metabolised in the liver before excretion
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14
Q

What 2 mechanisms of tetracycline resistance do glycylcyclines overcome?

A
  1. Efflux pumps
  2. Ribosomal protection
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15
Q

What is the mechanism of action of tigecycline?

A

Binds reversibly to the 30S ribosomal subunit, preventing the binding of tRNA to the A site of the mRNA-ribosome complex thereby inhibiting protein synthesis

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16
Q

What is the route of administration of tigecycline?

A

IV; poor oral bioavailability

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17
Q

Does tigecycline have good oral bioavailability?

A

No

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18
Q

Is tigecycline safe for pregnancies?

A

No, Cat D

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19
Q

Should tigecycline be given for bacteraemia?

A

No, tigecycline has low plasma conc.

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20
Q

How is tigecycline excreted?

A

Biliary/fecal

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21
Q

What is the spectrum of activity of tigecycline?

A

Broad spectrum against gram-positives & gram-negatives

Covers MRSA, VRE, ESBL gram-negs & multidrug-resistant streps

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22
Q

What spp. is tigecycline not active against?

A

Pseudomonas & Proteus spp.

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23
Q

Tetracyclines & tigecyclines are contraindicated in what patients?

A
  1. Pregnant women
  2. Breast-feeding women
  3. Children under 8
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24
Q

What is the mechanism of action of aminoglycosides?

A

Aminoglycosides distort the structure of ribosomes by binding to them and:
1. Block the formation of the initiation complex
2. Cause misreading of the codons
3. Inhibit translocation

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25
What other class of antibiotics exhibits synergism with **aminoglycosides**?
Beta lactams enhance entry of aminoglycosides
26
The uptake of **aminoglycosides** into the inner membrane is mediated by active transport and they are hence unable to be used to treat what kind of bacteria?
Anaerobes since their energy-dependent phase can be inhibited by anaerobic conditions
27
Are **aminoglycosides** bactericidal or bacteriostatic?
Bactericidal
28
How is CSF penetration of the **aminoglycosides**?
Inadequate CSF penetration
29
How are **aminoglycosides** eliminated?
Renal clearance
30
What is the route of administration of **aminoglycosides**?
Parental; poor oral bioavailability
31
What is the spectrum of coverage of **aminoglycosides**?
Mainly aerobic gram-negative bacteria
32
What is the most frequent use of **aminoglycosides**?
Empirical therapy for serious infections such as septicemia, UTI & nosocomial RTI
33
Which **aminoglycoside** is highly nephrotoxic if given parentally?
Neomycin
34
What are the 4 adverse effects of **aminoglycosides**?
PONS 1. Paralysis 2. Ototoxicity 3. Nephrotoxicity 4. Skin rash (hypersensitivity)
35
Are **aminoglycosides** safe to use in pregnancies?
No. Cat D in pregnancy
36
Which **aminoglycoside** should be given synergistically with beta-lactams to treat gram-positive cocci?
Gentamicin
37
What are the 5 aminoglycosides?
1. Gentamicin 2. Tobramycin 3. Amikacin 4. Streptomycin 5. Neomycin
38
What is the preferred **aminoglycoside** against P. aeruginosa?
Tobramycin
39
What other nephrotoxic drugs should not be given with **aminoglycosides**?
1. Vancomycin 2. Amphotericin B 3. NSAIDs 4. NMBAs
40
What groups of patients are **aminoglycosides** contraindicated in?
1. Pregnant patients 2. Myasthenia Gravis 3. Patients with renal dysfunction
41
What is the mechanism of action of **macrolides**?
They bind reversibly with the 50S ribosomal, inhibiting protein synthesis
42
What are some infections that **macrolides** can be used for?
1. RTI due to S. pneumoniae, H. influenzae, Moracella catarrhalis & atypical pneumonia 2. STDs due to N. gonorrhae & Chlamydia 3. H. pylori infection
43
What is the spectrum of coverage of **macrolides**?
Broad spectrum coverage of gram-negative & gram-positives. Covers atypicals
44
What is the route of administation of **macrolides**?
Good oral bioavailability; oral/IV
45
Are **macrolide** CSF penetration good?
No
46
What are the adverse effects when taking **macrolides**?
QT HOG 1. Prolong QT interval 2. Hepatotoxicity 3. Ototoxicity 4. Gastric distress
47
What are the adverse effects when taking **tetracyclines/glycylcyclines**?
PCGS 1. Phototoxicity 2. Calcium deposition 3. Gastric discomfort 4. Superinfection - thrush
48
**Macrolides** induce CYP450 enzymes. True/False?
False Macrolides inhibity CYP450 enzymes
48
What are the 3 **macrolides**?
1. Erythromycin 2. Clarithromycin 3. Azithromycin
49
How are **macrolides** excreted?
Erythromycin & Clarithromycin metabolised hepatically and excreted in bile Azithromycin eliminated largely unchanged in faeces
49
What are the 2 protein synthesis inhibitors that are safe for use in pregnancy?
1. Macrolides 2. Clindamycin
50
What antibiotic has cross-resistance with **macrolides**?
Clindamycin
51
What is the spectrum of coverage of **clindamycin**?
Mostly gram-positive organisms & anaerobic infections
52
What is the main indication of **clindamycin**?
Serious/severe **anaerobic** infections
53
What is the route of administration of **clindamycin**?
Oral/IV/topically
54
How is **clindamycin** eliminated?
Hepatically
55
How is CSF penetration of **clindamycin**?
Poor
56
What is the mechanism of action of **clindamycin**?
Binds to the 50S subunit of the bacterial ribosome, inhibiting protein synthesis
57
Why do **clindamycin** & **macrolides** exhibit cross-resistance?
They both act at sites of proximity
58
What are the 2 main methods of resistance towards **macrolides**?
1. ERM gene expression 2. Efflux pumps
59
What are the adverse effects when taking **clindamycin**?
1. **CDAD** 2. GI effects
60
What is the mechanism of action of **linezolid**?
Binds to the bacteria 23S ribosomal RNA of the 50S subunit, preventing the formation of the initiation complex and hence inhibiting protein synthesis
61
What is the spectrum of coverage of **linezolid**?
Only gram-positive organisms
62
What is **linezolid** route of administration?
Oral/IV
63
How is the CSF penetration of **linezolid**?
Good
64
What is **linezolid** effective against?
Gram-positive strains that are resistant to other agents (MRSA, VRE, VRSA, MDR streps)
65
What are the adverse effects when taking **linezolid**?
1. GI symptoms 2. Bone marrow suppression 3. Seratonin syndrome - due to MAO inhibition 4. Irreversible peripheral neuropathies & optic neuritis
66
What kinds of food and medications should be avoided with **linezolids**?
1. Tyramine-containing foods 2. Serotonergic drugs
67
Is **linezolid** indicated in treatment of catheter-related bloodstream infections?
No

Anti-microbes (9 decks)

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