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B&B Protein Synthesis Inhibitors Flashcards

1
Q

Protein Synthesis Inhibitors

A 
Aminoglycosides
Macrolides
Tetracyclines
Chloramphenicol
Clindamycin
Linezolid
Streptogramins
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2
Q

Bacterial Protein Synthesis

A

DNA inside cytoplasm which must be transcribed to RNA by RNA polymerase (target of Rifampin for tuberculosis)

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3
Q

To initiate protein synthesis

A
  1. Initiate Process: Ribosomal subunits have to bind mRNA
    - 50s subunit and 30s subunit
  2. Add tRNA
  3. Add peptides, translocate
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4
Q

Antibiotics that work on initiation process

A

Aminoglycosides/Linezolid

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5
Q

Antibiotics that block tRNA addition

A

Tetracyclines

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6
Q

Antibiotics that block addition of peptides and translocation

A

Chloramphenicol
Macrolides
Clindomycin

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7
Q

Aminoglycosides

A 
Gentamicin
Neomycin
Amikacin
Tobramycin
Streptomycin
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8
Q

Aminoglycosides

A

Block protein synthesis initiation

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9
Q

Aminoglycoside MOA

A

Block initiation of protein synthesis

  • Primarily bind 30S
  • Misreading of genetic code
  • Bacteria cannot divide, produce cellular proteins
  • Cell death (bactericidal)
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10
Q

Aminoglycosides require what for transport into cells

A

O2

Not effective against anaerobes

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11
Q

Do aminoglycosides affect eukaryotic cells?

A

No (different ribosomes)

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12
Q

Are aminoglycosides transported into eukaryotic cells?

A

No. Therefore they are not effective against IC organisms like Rickettsia and Chlamydia

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13
Q

Aminoglycosides are usually used

A

in combination but can be used along for serious gram (-) infections

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14
Q

Streptomycin

A

Aminoglycoside used for tuberculosis in combo w/ other drugs

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15
Q

Neomycin

A

Given prior to bowel surgery
Poorly absorbed (stays in gut)
Often given with erythromycin
Decrease colonic bacteria

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16
Q

Aminoglyosides are often added to what drug

A

Beta-lactams

Synergistic effects: Combo effective than one drug alone

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17
Q

Endocarditis Tx

A

Vancomycin/Gentomycin

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18
Q

Newborn meningitis Tx due to Listeria

A

Ampicillin/Gentamycin

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19
Q

Pseudomonas Tx for CF patients

A

Pip/Tazo + tobramycin

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20
Q

Resistance to aminoglycosides

A

Bacteria acquire Aminoglycoside Modifying Enzymes
Bacteria acquired enzymes that modify drug structure
Modified structure binds poorly to ribosomes
Phosphorylation (mediated by aminoglycoside kinase)
Adenylation/acetylation (mediated by transferases)

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21
Q

Aminoglycosides: Adverse S/E

A 
Ototoxicity: 8th CN
-Hearing loss, balance problems
Nephrotoxicity:
-5-10% of drug taken up by proximal tubule cells
-Serum creatinine will rise
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22
Q

Rare S/E of aminoglycosides

A

Neuromuscular blockade

  • Can limit/block release of Ach at NMJ
  • Usually occurs when levels are high or pre-existing neuromuscular disease
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23
Q

Can you give aminoglycosides to pregnant women?

A

No. Pregnancy Class D. Renal and Ototoxicity in fetus.

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24
Q

Aminoglycosides: plasma level monitoring

A

Trough level: just before next dose

Peak level: short time after dose

25
High aminoglycoside trough =
High risk for toxicity
26
Low aminoglycoside peak =
Less effective therapy
27
Macrolides
Azithromycin, Clarithromycin, Erythromycin
28
MOA Macrolides
Bind 50s ribosomal subunit and block process of translocation: tRNA binds A site Ribosome RNA catalyzes peptide bonds (peptidyl transferase) Ribosome advances along mRNA tRNA moves to P site Block tRNA movement to P site (translocation) Promote tRNA dissociation May also block peptidyl transferase
29
Macrolides
Cover many gram (+) cocci, especially strep Some gram (-) coverage Concentrated inside macrophages, other cells Effective against IC pathogens -Chlamydia (obligate) -Legionella (facultative)
30
Common uses of Macrolides
Community Acquired Pneumonia -Azithromycin covers Strep, H. flu, Atypicals -Good for penicillin allergic patients Chlamydia Infections -Azithromycin (safe in pregnancy) -Often co-administered with Ceftriaxone (gonorrhea)
31
Erythromycin
Macrolide Binds to motolin receptors in GI tract Stimulates SM contraction Can be used in GI motility disorders
32
Clarithromycin
Part of triple therapy for H. pylori
33
Macrolide Resistance
Bacteria methylate location of macrolide binding, which is 23S rRNA = component of 50S ribosome
34
Macrolides: Adverse Effects
Nausea, diarrhea, abdominal pain (motility) -Erythromycin is worst offender Prolonged Qt on EKG (prolonged K+ blocking) -Erythromycin is also worst offender Acute cholestatic hepatitis -Increased AST/ALT/Alk Phos (out of proportion)/Bilirubin -Case reports with Azithromycin -Contraindicated with h/o cholestatic jaundice or hepatic dysfunction Rash -Maculopapular allergic reaction
35
P450 enzyme inhibitors
Will raise serum levels of P450 metabolized drugs | Theophylline, Warfarin
36
Tetracyclines
Tetracycline, Doxycycline, Demeclocycline, Minocycline
37
Tetracyclines MOA
Transported into bacterial cells Binds 30S ribosome Prevents attachment of tRNA
38
Demeclocycline
``` Tetracycline Not used as an antibiotic ADH antagonist Given in SIADH Causes nephrogenic DI to reverse SIADH ```
39
Doxycycline
Most commonly used member of tetracycline family Accumulates IC Covers many unusual/atypical bacteria -most zoonoses -chlamydia Acne Vulgaris Tx (also minocycline) -Covers propionibacterium acnes in follicles
40
Tetracyclines
``` Absorption impaired by minerals and antacids Cations chelate drug -Calcium, magnesium (antacids) -Iron -Dairy ```
41
Tetracyclines resistance
Decreasing influx or increasing efflux from cells Plasmid-encoded transport pumps Different from many other antibiotics -No alteration of drug by bacteria
42
Tetracycline Adverse Effects
GI distress (common) -Epigastric pain, N/V, anorexia Photosensitivity -Red rash or blisters from sun
43
Tetracycline Adverse Effects
Discolors teeth of children | Inhibits bone growth in children due to calcium chelation
44
Can you use tetracyclines if you are pregnant?
No. They cross placenta and accumulate in fetus bones and teeth.
45
Chloramphenicol
Inhibits peptidyl transferase: 50s ribosomal subunit -tRNA binds A site -Ribosome RNA catalyzes peptide bonds (peptidyl transferase) -Ribosome advances along mRNA -moves tRNA to P site Chloramphenical blocks peptidyl transferase
46
Chloramphenicol is rarely used due to
toxicity and resistance
47
Chloramphenical
Broad coverage of gram (+), gram (-) and atypicals Can be used in pregnancy instead of doxycycline -Rickettsia (RMSF), Ehrlichia -Only in 1st/2nd trimester -3rd trimester: gray baby syndrome
48
Chloramphenical
Used for meningitis - Covers Neisseria - less effective than alternative drugs
49
Chloramphenical Adverse Effects
Anemia: bone marrow suppression | Aplastic anemia: Idiosyncratic, Irreversible, fatal
50
Gray baby syndrome
``` Babies lack liver UDP-glucuroynyl transferase Required for drug metabolism/excretion Skin turns ashen, gray Hypotension Often fatal ```
51
Clindamycin
Binds 50s ribosome - 23s rRNA component - Prevents translocation - Same as macrolides
52
Clindamycin Resistance
23s rRNA = component of 50s ribosome - Location of macrolide binding - methylation of this site causes resistance - same as macrolides
53
Clindamycin
Covers some gram (+) -Staph, viridans Strep, Strep pyogenes, S. pneumonia Covers many anaerobes -Clostridium perfringens -Mouth anaerobes: Fusobacterium, Prevotella, Peptostreptococcus
54
Main use of Clindamycin
Main use is to cover anaerobes "above the diaphragm" -Aspiration pneumonia -Lung abscesses -Oral infections (mouth anaerobes) Lots of resistance to Clindamycin in B. fragilis -Anaerobic infections "below the diaphragm" -Metronidazole
55
Clindamycin Adverse Effects
``` Classic cause of c. difficile infection -Up to 10% of pts -Pseudomembranous colitis -C. difficile overgrowth -Massive, watery diarrhea Antibiotic-associated diarrhea -Milder than c. diff infection -Changes in GI flora -Less absorption of solutes causes osmotic diarrhea -Stops when drug discontinued ```
56
Linezolid
Binds to 50s ribosome Blocks initiation Main use: Vancomycin resistant enterococcus (VRE) -Epidemics in hospitals -Usually occurs in patients with prior antibiotic treatment
57
Linezolid S/E
Weak monoamine oxidase (MAO) inhibitor Can cause serotonin syndrome High risk when given SSRIs Fever, confusion, agitation, hyperreflexia
58
Streptogramins
``` Quinupristin/Dalfopristin -Block protein synthesis 50s ribosome -Used together for sequential protein synthesis block -Synercid (quinupristin/dalfopristin) Used for Vancomycin resistant bacteria -VRSA -VRE ```
59
Which protein synthesis inhibitor is not bacteriostatic?
Aminoglycosides: Bacteriocidal | -Misread proteins travel to cell membrane and increase permeability

ID Review (23 decks)

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