Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

835 > Protein Synthesis Inhibitors > Flashcards

Protein Synthesis Inhibitors Flashcards

1
Q

Protein Synthesis Inhibitors

A

Bind to bacterial ribosomes to block protein translation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Bind to 30s Ribosome

A
  • Aminoglycosides

- Tetracyclines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Bind to 50s Ribosome

A
  • Macrolides
  • Lincosamides
  • Streptogramins
  • Oxazolidinones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Aminoglycoside MoA

A

Block initiation complex formation, proofreading, and ribosomal translocation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Aminoglycoside Examples

A
  • Streptomycin
  • Kanamycin
  • Gentamimcin
  • Tobramycin
  • Amikacin
  • Neomycin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Tetracyclines MoA

A

Prevents binding of incoming tRNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Tetracycline Examples

A
  • Tetracycline
  • Doxycycline (Vibramycin/Doryx)
  • Minocycline (Minocin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Macrolide MoA

A

Blocks polypeptide exit tunnel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Macrolide Examples

A
  • Erythromycin
  • Clarithromycin (Biaxin)
  • Azithromycin (Z-PAK, Zithromax)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Lincosamides MoA

A

Binding site overlaps with macrolides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Lincosamides Example

A

Clindamycin (Cleocin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Streptogramins MoA

A

-Binding site overlaps with macrolides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Streptogramins Examples

A

-Quinupristin/Dalfopristin (Synercid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Oxazolidinones MoA

A

Binds 23s rRNA, prevents ribosome assembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Oxazolidinones Examples

A
  • Linezolid (Zyvox)

- Tedizolid (Sivextro)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Aminoglycosides

A
  • Pass Gram “-“ outer membrane via porins
  • Pass inner membrane by oxygen/energy dependent transport (no activity against anaerobes)
  • Irreverisble
  • Bactericidal
  • Used with B-lactams in serious aerobic, Gram “-“ bacteria OR gentamicin with vanco/B-lactam for Gram “+” endocarditis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Aminoglycosides PK

A
  • Efficacy: concentration dependent
  • Synergy with cell wall synthesis inhibitors
  • IV administration
  • Dosing goal: [plasma] = >= 10-12x the MIC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Aminoglycoside Resistance

A
  • Ribosome mutations that prevent binding
  • Aminoglycoside modifying enzymes (AME) - acetylation, phosphorylation
  • Impaired entry: porin deletion/mutation, loss of active transport
  • Efflux pumps
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Aminoglycoside AE

A
  • Reversible nephrotoxicity in 10-20% of patients on treatment >5 days (monitor SCr)
  • Irreversible ototoxicity from destruction of hair cells in cochlea (~10%)
  • NMJ blockage at high doses
20
Q

Aminoglycoside Nephrotoxic Mechanism

A
  • Bind to cytoplasmic membrane of proximal tubular cells, are internalized, and trapped in lysosomes
  • Lysosomes also accumulate myeloid bodies and lead to leaky, damaged membranes
21
Q

Aminoglycoside Monitoring

A
  • Renal function
  • 8th nerve function
  • Peak/trough [serum]
  • Urine specific gravity/protein
  • Serum BUN, creatinine, and CrCl
  • Serial audiograms
22
Q

Garamycin

A
  • Gentamicin

- Isolated from micomonospora sp.

23
Q

Tobramycin

A

-Slightly more active against P. aeruginosa

24
Q

Amikin

A
  • Amikacin
  • Used to treat severe, HA-infections with MDR Gram “-“ bacteria
  • Highly resistance against enzyme inactivation
  • Combined with gentamicin against resistant bugs and is administered IV, IM, or nebulized
25
Q

Neomycin

A

-Topical

26
Q

Streptomycin

A
  • Isolated from streptomyces sp.
  • Widespread resistance
  • Use limited to susceptible tuberculosis, plague, tularemia
27
Q

Tetracyclines

A
  • Generally bacteriostatic

- Can inhibit protein synthesis in mammalian cells partially, but active efflux mechanism prevents accumulation

28
Q

Tetracycline Cell Entry

A
  • Enter Gram “+” by energy-dependent transport protein-carrier mechanism
  • Enter Gram “-“ bacteria by passive diffusion, porins in outer membrane, then energy-dependent tranport at cytoplasmic membrane
29
Q

Tetracycline Resistance

A
  • Active efflux system
  • Acquiring genes that encode for ribosomal protection proteins that block tetracycline binding
  • Antibiotic modification (enzymatic inactivation)
30
Q

Tetracycline PK

A
  • Absorption: oral, avoid dairy products, antacids, iron/zinc preparation, and bismuth subsalicylate or kaolin-pectin
  • Distribution: liver, kidney, spleen, skin. Binds to tissues undergoing calcification (teeth and bones) and crosses the placenta
  • Metabolism/Excretion: don’t use if renally impaired, doxycycline: biles/feces mainly, alternative if there are renal problems
31
Q

Tetracycline AE

A
  • Gastric discomfort, take with nondairy foods
  • Deposition in bone and teeth during growth in children (stunt growth/teeth discoloration)
  • Possible hepatic toxicity with IV use
  • Phototoxicity: more frequent with tetracycline and doxycycline
  • Vestibular problems: dizziness, N/V, most common with minocycline (sometime doxy too)
  • Superinfection by overgrowth of other bacteria like candidiasis, resistant staph in the intestine, or C. diff
32
Q

Macrolides

A
  • Generally bacteriostatic

- Cover mainly atypicals

33
Q

Macrolides PK

A
  • Oral absorption (food interferes)
  • Clarithromycin: short half-life, intra/extracellular
  • Azithromycin: LONG half-life, purely intracellular
  • Erythromycin: used at low-doses to stimulate GI motility in ICU patients
34
Q

Macrolide Resistance

A
  1. Inability to take up antibiotic
  2. Efflux pump
  3. Plasmid-associated eryhtromycin esterase
  4. Decreased affinity of the 50s ribosome due to methylation of the adenine in the 23s bacterial ribosomal RNA (bacterial methylase) => confers macrolide inducible resistance to clindamycin)
  5. Clarithromycin and azithromycin show cross-resistance with eryhtromycin
35
Q

S. Pneumoniae Resistance

A
  • High or low level macrolide resistance
  • High: mutation in ribosome binding site
  • Low: efflux pumps
36
Q

Macrolide AE

A
  • Epigastric distress
  • Ototoxicity at high doses
  • Liver toxicity probably from an allergic reaction
  • Prolongs QT interval
37
Q

Macrolide Interactions

A
  • Inhibits metabolism of many P450s from extensive liver metabolism (Eryth>Clarith)
  • Azithromycin DOESN’T interact with P450s
  • Eliminates intestinal flora that inactivates digoxin, therefore greater absorption/toxicity likelihood with digoxin
38
Q

Difficid

A
  • Fidaxomicin
  • Macrolide for relapsing/recurring C. difficile
  • MoA: inhibits RNA polymerase sigma subunit, inhibits transcription and therefore protein synthesis
  • PO administration, minimal systemic absorption
  • Confined to GI tract largely
  • Metabolism: intestinal hydrolysis to less active metabolite
  • Mostly eliminated in feces
39
Q

Cleocin

A
  • Clindamycin
  • Lincosamide
  • Structurally different from macrolides but mechanistically similar
  • Active against Gram “+” and anaerobes besides C. Diff
  • Used in severe anaerobic infections
  • Also used to treat SSTI from strept and staph and is active against MRSA
  • Toxicity: hepatotoxicity and occasional neutropenia, also causes fever, rash, N/V, and diarrhea
  • Boxed warning: C. diff associated diarrhea/colitis (~6%)
  • DOESN’T penetrate into CNS or intracellular
40
Q

Synercid

A
  • Quinupristin and Dalfopristin (30:70)
  • Two structurally distinct streptogramins that bind to separate sites on 50s ribosome unit
  • Quinupristin: uses same site as macrolides/lincosamides and early inhibits polypeptide elongation and termination of protein synthesis
  • Dalfopristin binds to nearby site and causes a conformational change in 50s unit that enhances the binding of quinupristin and directly interferes with polypeptide-chain formation
  • Synergistically act to inhibits protein synthesis (bactericidal)
  • Used for E. faecium (VRE) and MRSA complication skin infections
41
Q

Synercid Interactions

A
  • Inhibits CYP3A4

- Don’t give with CYP3A4 metabolized drugs that prolong QTc (cyclosporine)

42
Q

Synercid AE

A
  • Phlebitis with IV administration
  • Severe arthralgias/myalgias
  • Hyperbilirubinemia
43
Q

Zyvox

A
  • Linezolid
  • Oxazolidinone
  • MoA: Binds reversibly to 23S rRNA of 50s subunit to prevent ribosome assembly
  • Bacteriostatic
  • Active against Gram “+” including MRSA and E. faecium
  • 100% oral bioavailability
  • No cross resistance since its MoA is distinct
44
Q

Zyvox Toxicities

A
  • Duration dependent: bone marrow suppression/thrombocytopenia/anemia/neutropenia (reversible)
  • Neuropathy
  • Optic neuritis
45
Q

Zyvox Drug Interactions

A

-MAOI: serotonin syndrome may occur when taken with other serotonergic agents (SSRIs)

46
Q

Sivextro

A
  • Tedizolid
  • 2nd generation Oxazolidinone
  • Used for ABSSSI
  • Daily dosing for 6 days vs BID x 10-14 days with Linezolid
47
Q

Bactroban

A
  • Mupirocin
  • Isoleucyl tRNA synthetase inhibitor
  • MoA: Inhibits protein synthesis due to loss of critical amino acid (isoleucine)
  • Active against Gram “+” cocci
  • Used for topical treatment of skin infections like impetigo
  • Also used for intranasal S. aureus
  • Half-life: 17-36 minutes
  • Excreted in urine

835 (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions