Protein Synthesis Inhibitors Flashcards by Stacey Hansen

This typically prokaryotic ribosomal subunit is found in mitochondria of mammalian cells

70S

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Protein synthesis inhibitor that penetrates the mitochondria, leading to extensive toxicity

Chloramphenicol

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Streptomycin is this type of protein synthesis inhibitor

Aminoglycoside (30S inhibitor)

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Neomycin is this type of protein synthesis inhibitor

Aminoglycoside (30S inhibitor)

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Aminoglycosides have this charge

Positively charged

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Aminoglycosides enter bacteria through this

Negatively charged pores

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The entrance of positively charged aminoglycosides into bacteria through negatively charged pores is disrupted by these 2 things

Low pH and metal ions (divalent cations)

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Internalized aminoglycoside changes the permeability of the membrane under these conditions

Aerobic conditions

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The action of internalized aminoglycoside to change membrane permeability is disrupted by this

Low oxygen

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As initial entry into bacteria is via pores, prior use of these increases overall permeability to aminoglycosides and is a synergistic antibiotic action

Cell wall synthesis inhibitors (penicillins)

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Aminoglycosides inhibit this

Protein synthesis - 30S subunit

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Is aminoglycoside action concentration-dependent?

Yes

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Effect of treatment with aminoglycosides that is related to the formation of frozen initiation complex resulting in formation of “streptomycin monosomes” (ribosomes stuck irreversibly on mRNA)

Post-antibiotic effect

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Spectrum of action of Aminoglycosides

Broad
Effective against aerobic gram negative, staphylococci and mycoplasma

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3 mechanisms of resistance against aminoglycosides

Increased degradation of aminoglycosides
Alterations in ribosomal proteins
Altered permeability

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Aminoglycosides concentrate in these 2 structures

Renal and inner ear

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Adverse effect of aminoglycosides that is generally reversible, dose and time related, and additive with other toxic drugs

Nephrotoxic

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Nephrotoxicity, Ototoxicity, and neuromuscular blockage are adverse effects of this

Aminoglycosides

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The distribution of aminoglycosides leads to these two toxicities

Nephrotoxicity, Ototoxicity

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Why does neuromuscular blockage occur with use of aminoglycosides?

Because of decreased acetylcholine release at neuromuscular junction (due to Ca2+ sequestration)

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3 black box warnings of aminoglycosides

Nephrotoxicity, Ototoxicity, Neuromuscular blockage

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Are aminoglycosides safe during pregnancy?

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Type of drugs that may enhance permeability for aminoglycosides, enhancing activity

Cell wall synthesis inhibitors (penicillins, cephalosporins, vancomycin)

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30S inhibitor that is bactericidal at high doses

Aminoglycosides

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30S protein inhibitor that is bacteriostatic

Tetracyclines

Are these short or long acting tetracyclines: Tetracycline, Oxytetracycline

Short acting (half life ~8 hours)

Are these short or long lasting tetracyclines: Doxycycline, Minocycline, Demeclocycline

Long lasting (>12 hours)

MOA of tetracyclines

Bind 30S and block tRNA binding to A site

Selective toxicity of this protein synthesis inhibitor is related to specific energy-dependent transport and accumulation systems found in bacteria

Tetracyclines

Protein synthesis inhibitor that binds to 30S subunit and blocks tRNA binding to A site

Tetracyclines

Tetracyclines oral absorption is impaired by food and metal ions, except for these 2

Doxycycline and minocycline (less polar tetracyclines)

Doxycycline and minocycline are exceptions to this characteristic of tetracyclines

Are NOT impaired by food and metal ions

Tetracyclines are distributed in body tissues and fluids according to this

Lipid solubility (and protein binding)

Short acting tetracyclines are more or less polar?

More Poorest lipid solubility and protein binding

Long acting tetracyclines are more or less polar?

Less polar Best lipid solubility and protein binding

Elimination of tetracyclines

Renal elimination Except doxycycline which is excreted in the feces and may be preferred in patients with renal problems

Doxcycline is an exception to this characteristic of tetracyclines

is NOT renally excreted Is excreted in the feces

Tetracycline that is excreted in the feces and may be preferred in patients with renal problems

Doxycyline

Spectrum of action of tetracyclines

Broad spectrum of action Commonly used for acne and Chlamydia

Tetracyclines have a broad spectrum of action and are commonly used for these 2 conditions

Acne and Chlamydia

Tetracyclines accumulate in these 2 places

Teeth and bone

Should tetracyclines be used during pregnancy?

No Also not in children under 8 years of age Use during pregnancy may result in yellow to brown discoloration of teeth and potential weakening of teeth and bones

Teeth and bone accumulation is characteristic of this protein synthesis inhibitor

Tetracyclines

Photosensitivity is an adverse effect of this protein synthesis inhibitor

Tetracyclines

MOA of chloramphenicol

Binds 50S to prevent peptide bond formation (transpeptidate reaction)

Spectrum of action of chloramphenicol

Broad

Elimination of chloramphenicol

Inactivation by conjugation before excretion Alternative biotransformation pathways are noted in neonates and young children but are inadequate to handle normal dosing regimens

Chloramphenicol is inactivated by this before excretion

Conjugation

Protein synthesis inhibitor that is inactivated by conjugation before excretion

Chloramphenicol

Protein synthesis inhibitor with bone marrow depression and gray baby syndrome as adverse effects

Chloramphenicol

Reversible dose related anemia and idiosyncratic aplastic anemia are adverse effects of this protein synthesis inhibitor

Chloramphenicol

Onset of this may be delayed months after therapy with chloramphenicol is stopped

Idiosyncratic aplastic anemia (not dose related)

Gray baby syndrome involves undeveloped newborn conjugation processes, allowing blood levels to increase, and is associated with this protein synthesis inhibitor

Chloramphenicol

Why does Gray baby syndrome occur?

Undeveloped newborn conjugation processes allow blood levels of chloramphenicol to increase Is potentially fatal

Depression and suicide risk must be assessed with use of this protein synthesis inhibitor

Chloramphenicol

Appropriate use (hospitalize patients and monitor for hematological toxicity) and blood dyscrasias are black box warnings of this protein synthesis inhibitor

Chloramphenicol

Erythromycin is this type of protein synthesis inhibitor

Macrolides

Clarithromycin is this type of protein synthesis inhibitor

Macroldies

Azithromycin is this type of protein synthesis inhibitor

Macrolides

MOA of macrolides

Bind 50S and inhibit translocation

Spectrum of action of macrolides

Broad Relatively few indications

Motility increased in GI tract, arrhythmia risk, cholestatic hepatitis, rash, and eosinophilia are adverse effects of this protein synthesis inhibitor

Macrolides

risk of this is elevated by macrolide inhibition of CYP3A4

Sudden cardiac death risk

Sudden cardiac death risk elevated by this inhibition of CYP3A4

Macrolide

Sudden cardiac death risk elevated by macrolide inhibition of this

CYP3A4

5 adverse effects of macrolides

Motility increased in GI tract Arrhythmia risk elevated by prolonged QT interval Cholestatic hepatitis Rash eOsinophilia

Macrolide indicated for Clostridium difficile-associated diarrhea

Fidaxomicin

Fidaxomicin is this type of protein synthesis inhibitor

Macrolide

Indication of Fidaxomicin

C. difficile

Protein synthesis inhibitor that inhibits bacterial transcription by targeting RNA polymerase sigma

Fidaxomicin

MOA of Fidaxomicin

Targets RNA pol sigma Cidal

Spectrum of action of Fidaxomicin

Very narrow: gram + aerobes and anaerobes, used primarily for C. diff

MOA of clindamycin

Binds 50S to inhibit translocation

Lincosamide antibiotic that binds to 50S ribosomal subunit to inhibit translocation

Clindamycin

Spectrum of action of clindamycin

Narrow gram positive

Pseudomembranous colitis is a black box warning for this protein synthesis inhibitor

Clindamycin

Black box warning for Clindamycin

Pseudomembranous colitis

Look for this in order to determine if Pseudomembranous colitis is caused by C. diff or drug-induced

C. diff toxin

The depletion of this is an important marker for Streptogramin action (Quinupristin-Dalfopristin Combination)

Free tRNA Cidal

Quinupristin-Dalfopristin Combination: Component that disrupts early protein synthesis steps (blocks aminoacyl-tRNA binding)

Quinupristin

Quinupristin-Dalfopristin Combination Component that disrupts later protein synthesis steps to promote premature dissociation of complex

Dalfopristin

The MOA of Quinupristin-Dalfopristin Combination results in this

Decreased free tRNA in cell (cidal)

Quinupristin-Dalfopristin Combination generally binds this ribosomal subunit

50S

2 adverse effects of Quinupristin-Dalfopristin Combination

Joint and muscle pain Hepatotoxicity

Joint and muscle pain, and hepatotoxicity are adverse effects of this protein synthesis inhibitor

Quinupristin-Dalfopristin Combination (bactericidal streptogramin class)

Protein synthesis inhibitor with these limited indications: MRSA, Vancomycin-resistant enterococcus (black box) Complicated skin and skin-structure infections Drug-resistant pneumococci

Quinupristin-Dalfopristin Combination (bactericidal streptogramin class)

Spectrum of action of Linezolid

Narrow gram positive Primary use is vancomycin-resistant enterococcal infections

Reversible bone marrow depression, peripheral neuropathy, and dangerous drug interactions due to inhibition of monoamine oxidase (dangerous hypertension or serotonin syndrome) are adverse effects of this protein synthesis inhibitor

Linezolid

MOA of Linezolid

Binds 50S and blocks formation of functional tRNA-ribosome-mRNA complex that initiates protein synthesis

Peripheral neuropathy is an adverse effect of this protein synthesis inhibitor

Linezolid

Protein synthesis inhibitor that inhibits monoamine oxidase, leading to dangerous drug interactions

Linezolid

Dangerous hypertension or serotonin syndrome (muscle rigidity, hyperthermia, autonomic instability) are results of drug interactions involving this protein synthesis inhibitor

Linezolid

Protein synthesis inhibitor that has concentration dependent actions with postantibiotic activity

Aminoglycosides