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Protein Synthesis Inhibitors Flashcards

(49 cards)

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1
Q

30S Inhibitors:

A

Aminoglycosides (bactericidal)

Tetracyclines (bacteriostatic)

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2
Q

50S Inhibitors:

A

Chloramphenicol, Clindamycin (bacteriostatic)
Erythromycin (macrolides) (bacteriostatic)
Linezolid (variable)

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3
Q

Oxazolidinones:

A

Linezolid

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4
Q

Linezolid: mech

A

Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.

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5
Q

Linezolid: uses

A

Gram+ species including MRSA and VRE

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6
Q

Linezolid: tox

A

Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome

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7
Q

Linezolid: MOR

A

point mutation in ribosomal RNA

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8
Q

Aminoglycosides:

A

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

“Mean” (aMINoglycoside) GNATS caNNOT kill anaerobes

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9
Q

Aminoglycosides: mech

A

Bactericidal
Inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation. Require O2 for uptake; therefore ineffective against anaerobes.
“A initiates the Alphabet”

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10
Q

Aminoglycosides: uses

A

Severe gram - rod infections. Synergistic with beta-lactam antibiotics.
Neomycin for bowel surgery

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11
Q

Aminoglycosides: tox

A

Nephrotoxicity (especially when used with cephalosporins), Neuromuscular blockade, Ototoxicity (especially when used with loop diuretics). Teratogen.
Streptomycin - worst for ototoxicity

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12
Q

Aminoglyclosides: MOR

A

Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
Amikacin is more resistant, so broadest spectrum.

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13
Q

Tetracyclines:

A

Tetracycline, Doxycycline, Minocycline, Tigecycline

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14
Q

Tetracyclines: mech

A

Bacteriostatic
Binds 30S and prevents attachment of aminoacyl-tRNA; limited CNS penetration.
Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit its absorption in the gut.

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15
Q

Tetracyclines: uses

A

Borrelia burgdorferi (DOC), M. pneumoniae. Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne.

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16
Q

Tetracyclines: tox

A

GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Contraindicated in pregnancy (cross placenta and found in breast milk)
Outdated Tetracyclines –> Fanconi syndrome

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17
Q

Tetracyclines: MOR

A

decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps

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18
Q

Macrolides:

A

Azithromycin, Clarithromycin, Erythromycin

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19
Q

Macrolides: mech

A

Inhibit protein synthesis by blocking translocation (“macroslides”); bind to the 23S rRNA of the 50 S ribosomal subunit. Bacteriostatic.

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20
Q

Macrolides: uses

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A 
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram + cocci (streptococcal infections in patients allergic to penicillin). Corynebacteria
Tx and Px of Bordetella Pertussis
21
Q

Macrolides: MOR

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A

Methylation of 23S rRNA-binding site prevents binding of drug.

22
Q

Chloramphenicol: mech

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A

Blocks peptidyltransferase at 50S ribosomal subunit. Blocks peptide bond formation.
Bacteriostatic

23
Q

Chloramphenicol: uses

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A

Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain Spotted Fever (Rickettsia rickettsii).
Limited use owing to toxicities but often still used in developing countries because of low cost.

24
Q

Chloramphenicol: tox

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A

Anemia (dose dependent), aplastic anemia (dose dependent), gray baby syndrome (in premature infants because they lack the liver UDP-glucuronyl transferase)

25
Chloramphenicol: MOR
Plasmid-encoded acetyltransferase inactivates the drug.
26
Clindamycin: mech
Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic
27
Clindamycin: uses
``` Anaerobic infections (Bacteroides, Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Group A Streptococcal (GAS) infection. Treats anaerobes ABOVE the diaphragm vs. metronidazole (anaerobic infections BELOW diaphragm) ```
28
Clindamycin: tox
Pseudomembranous Colitis (C diff), fever, diarrhea
29
Clindamycin MOR:
Mutations in 50S subunit, modification of binding site by enzyme methylase. Bacteria resistant to clindamycin - usually resistant to Erythromycin
30
Sulfonamides:
Sulfamethoxazole (SMX), Sulfisoxazole, Sulfadiazine
31
Sulfonamides: mech
Inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase (mammals don't have this). Bacteriostatic.
32
Sulfonamides: uses
Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
33
Sulfonamides: tox
Hypersensitivity rxn, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (warfarin, phenytoin)
34
Sulfonamides: MOR
Altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or Increased PABA synthesis
35
Sulfasalazine:
Ulcerative colitis and IBD Luminal flora metabolize sulfasalazine to produce 5-ASA, which remains in the lumen and has topical anti-inflammatory and immune modulating properties
36
Silver sulfadiazine:
Standard topical treatment to prevent infection in burns. OTC. Ag is important anti-microbial.
37
Sulfadoxine:
Malaria prophylaxis - usually combined (Plasmodium falciparum) w/pyramethamine
38
Trimethoprim: mech
Inhibits bacterial dihydrofolate reductase (DHFR). Bacteriostatic. DHFR in bacteria is 100,000x more sensitive than human enzyme
39
Trimethoprim: uses
Used in combination with sulfonamides (TMP-SMX), causing sequential block of folate synthesis. Combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis TMP penetrates prostate -> prostatitis
40
Trimethoprim: tox
Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid) Hyperkalemia (blocks Na+ reimport --> inhibits K+ excretion) TMP: Treats Marrow Poorly
41
Fluoroquinolones:
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, enoxacin (fluoroquinolones), nalidixic acid (a quinolone).
42
Fluoroquinolones: mech
Inhibit DNA gyrase (topoisomerase II) (gram - target) and topoisomerase IV (gram + target). Bactericidal. Must not be taken with antacids
43
Fluoroquinolones: uses
Gram - rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram+ organisms.
44
Fluoroquinolones: tox
GI upset, superinfections, skin rashes, HA, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnant women, nursing mothers, and children under 18 years old due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people >60 years old and in patients taking prednisone. Fluoroquinolones hurt attachments to your bones.
45
Fluoroquinolones: MOR
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps. (Qnr) Quinolone resistance proteins shield target enzyme from drug Resistance to one = resistance to all
46
TMP-SMX: mech
Bactericidal Dosing schedule based on TMP (more potent) Dual inhibition of folate pathway Active against wide range of bacteria and some protists UTIs - E. coli, Enterococcus faecalis
47
Metronidazole: mech
Forms free radical toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.
48
Metronidazole: uses
Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides (DOC), C. Diff). Used with proton pump inhibitor and clarithromycin for "Triple therapy" against H. Pylori Treats anaerobic infection BELOW the diaphragm vs clindamycin (anaerobic infections ABOVE diaphragm)
49
Triple therapy against H. Pylori:
Metronidazole, Clarithromycin, PPI

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