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Which of the following antibiotics is classified under ketolides?
Which of the following antibiotics is classified under ketolides?
Which phase of translation is primarily targeted by most antibiotics?
Which phase of translation is primarily targeted by most antibiotics?
What action of antibiotics inhibits the binding of mRNA during the initiation phase?
What action of antibiotics inhibits the binding of mRNA during the initiation phase?
Which of the following amino acids does the peptidyl transferase enzyme primarily act upon during elongation?
Which of the following amino acids does the peptidyl transferase enzyme primarily act upon during elongation?
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Which term best describes the process where the newly formed polypeptide is released during translation?
Which term best describes the process where the newly formed polypeptide is released during translation?
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In protein synthesis, what is the result of mutation in the translation termination codons UAA, UAG, or UGA?
In protein synthesis, what is the result of mutation in the translation termination codons UAA, UAG, or UGA?
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Which step involves the formation of the initiation complex during translation?
Which step involves the formation of the initiation complex during translation?
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What is the effect of tetracyclines on calcium in bones?
What is the effect of tetracyclines on calcium in bones?
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Which of the following statements about tetracycline resistance is true?
Which of the following statements about tetracycline resistance is true?
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Which is NOT a clinical use of tetracyclines?
Which is NOT a clinical use of tetracyclines?
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What is the primary mechanism of action of macrolides?
What is the primary mechanism of action of macrolides?
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Which antibiotic requires enteric coating due to degradation by stomach acid?
Which antibiotic requires enteric coating due to degradation by stomach acid?
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For which of the following infections is doxycycline NOT a typical treatment?
For which of the following infections is doxycycline NOT a typical treatment?
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Which of the following is a characteristic feature of macrolides?
Which of the following is a characteristic feature of macrolides?
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What spectrum of bacterial activity do macrolides primarily target?
What spectrum of bacterial activity do macrolides primarily target?
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What is one of the key adverse effects associated with macrolides like erythromycin?
What is one of the key adverse effects associated with macrolides like erythromycin?
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What is the mechanism by which erythromycin affects drug levels in the body?
What is the mechanism by which erythromycin affects drug levels in the body?
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How is Legionella pneumophila most commonly spread to humans?
How is Legionella pneumophila most commonly spread to humans?
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Which antibiotic is ineffective against Legionella pneumophila?
Which antibiotic is ineffective against Legionella pneumophila?
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What characteristic of Legionella pneumophila requires special media for laboratory growth?
What characteristic of Legionella pneumophila requires special media for laboratory growth?
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What is a major toxic side effect associated with Chloramphenicol?
What is a major toxic side effect associated with Chloramphenicol?
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In the case of liver disease, what pharmacokinetic adjustment is required for Chloramphenicol?
In the case of liver disease, what pharmacokinetic adjustment is required for Chloramphenicol?
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What is one of the primary clinical uses of Chloramphenicol?
What is one of the primary clinical uses of Chloramphenicol?
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Which mechanism of resistance is associated with Chloramphenicol?
Which mechanism of resistance is associated with Chloramphenicol?
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What is a serious adverse effect that can occur with prolonged use of Chloramphenicol?
What is a serious adverse effect that can occur with prolonged use of Chloramphenicol?
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What is the cause of Gray Baby Syndrome in infants who are given Chloramphenicol?
What is the cause of Gray Baby Syndrome in infants who are given Chloramphenicol?
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Which type of bacterial activity does Chloramphenicol exhibit?
Which type of bacterial activity does Chloramphenicol exhibit?
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What is the pharmacokinetic profile of Clindamycin?
What is the pharmacokinetic profile of Clindamycin?
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Which microorganism is most likely resistant to clindamycin?
Which microorganism is most likely resistant to clindamycin?
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What is the primary adverse effect associated with clindamycin use?
What is the primary adverse effect associated with clindamycin use?
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In which clinical situation is clindamycin particularly useful?
In which clinical situation is clindamycin particularly useful?
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Which of the following statements about the mechanism of action of Streptogramins is true?
Which of the following statements about the mechanism of action of Streptogramins is true?
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Which antibiotic is indicated for vancomycin-resistant Enterococcus faecium infections?
Which antibiotic is indicated for vancomycin-resistant Enterococcus faecium infections?
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What is the appropriate dosage form for linezolid?
What is the appropriate dosage form for linezolid?
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Which of the following is NOT a mechanism of resistance for clindamycin?
Which of the following is NOT a mechanism of resistance for clindamycin?
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Which condition might require dosage adjustment for clindamycin?
Which condition might require dosage adjustment for clindamycin?
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What is a significant consequence of tetracyclines binding to calcium in bones?
What is a significant consequence of tetracyclines binding to calcium in bones?
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Which method is responsible for the decreased efficacy of tetracyclines due to bacterial resistance?
Which method is responsible for the decreased efficacy of tetracyclines due to bacterial resistance?
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Which group of bacteria is primarily susceptible to macrolides?
Which group of bacteria is primarily susceptible to macrolides?
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Which clinical situation is NOT typically addressed with doxycycline treatment?
Which clinical situation is NOT typically addressed with doxycycline treatment?
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What is the primary mechanism by which macrolides exert their antimicrobial effect?
What is the primary mechanism by which macrolides exert their antimicrobial effect?
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What is the significance of enteric coating in the administration of macrolide antibiotics?
What is the significance of enteric coating in the administration of macrolide antibiotics?
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Which characteristic of macrolides makes them a suitable substitute for penicillin?
Which characteristic of macrolides makes them a suitable substitute for penicillin?
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For which of the following conditions are macrolides considered the drug of choice?
For which of the following conditions are macrolides considered the drug of choice?
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What is a significant consequence of Chloramphenicol use related to blood cell production?
What is a significant consequence of Chloramphenicol use related to blood cell production?
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In patients with liver disease, how must Chloramphenicol be adjusted due to its metabolism?
In patients with liver disease, how must Chloramphenicol be adjusted due to its metabolism?
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What type of antibiotic activity does Clindamycin exhibit?
What type of antibiotic activity does Clindamycin exhibit?
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Which of the following is NOT a clinical use of Chloramphenicol?
Which of the following is NOT a clinical use of Chloramphenicol?
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What mechanism do bacteria utilize to resist Chloramphenicol?
What mechanism do bacteria utilize to resist Chloramphenicol?
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What specific adverse effect is associated with Chloramphenicol in infants, known as Gray Baby Syndrome?
What specific adverse effect is associated with Chloramphenicol in infants, known as Gray Baby Syndrome?
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For what reason might Chloramphenicol be considered for use despite its toxicity?
For what reason might Chloramphenicol be considered for use despite its toxicity?
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For which condition is clindamycin contraindicated due to a high risk of a specific adverse effect?
For which condition is clindamycin contraindicated due to a high risk of a specific adverse effect?
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What is the primary mechanism by which clindamycin demonstrates resistance?
What is the primary mechanism by which clindamycin demonstrates resistance?
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In which scenario is clindamycin particularly effective for treating infections?
In which scenario is clindamycin particularly effective for treating infections?
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What dosage form is commonly administered for severe cases of clindamycin?
What dosage form is commonly administered for severe cases of clindamycin?
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What serious condition may develop due to the administration of clindamycin, especially if used incorrectly?
What serious condition may develop due to the administration of clindamycin, especially if used incorrectly?
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Which antibiotic class confers cross-resistance with clindamycin?
Which antibiotic class confers cross-resistance with clindamycin?
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What is the unique aspect of azithromycin's dosing regimen compared to other macrolides?
What is the unique aspect of azithromycin's dosing regimen compared to other macrolides?
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Which of the following correctly describes the mechanism of action of ketolides?
Which of the following correctly describes the mechanism of action of ketolides?
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What pharmacokinetic characteristic is particularly notable for telithromycin compared to other antibiotics?
What pharmacokinetic characteristic is particularly notable for telithromycin compared to other antibiotics?
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What is the primary role of tRNA in the translation process?
What is the primary role of tRNA in the translation process?
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Which adverse effect is commonly associated with the use of azithromycin?
Which adverse effect is commonly associated with the use of azithromycin?
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Which of the following statements accurately describes the pharmacokinetics of tetracyclines?
Which of the following statements accurately describes the pharmacokinetics of tetracyclines?
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Why might ketolides be preferable for treating macrolide-resistant bacterial strains?
Why might ketolides be preferable for treating macrolide-resistant bacterial strains?
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What type of antimicrobial activity do tetracyclines exhibit?
What type of antimicrobial activity do tetracyclines exhibit?
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Which statement best summarizes the pharmacokinetics of chloramphenicol?
Which statement best summarizes the pharmacokinetics of chloramphenicol?
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Which of the following is NOT a characteristic of tetracyclines?
Which of the following is NOT a characteristic of tetracyclines?
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Which condition may require special dosing considerations for tetracyclines?
Which condition may require special dosing considerations for tetracyclines?
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Study Notes
Protein synthesis inhibitors
- Tetracyclines
- All end in “cycline”
- Bind to calcium in bone irreversibly
- Highly fluorescent molecules
- Mechanisms of Resistance:
- Decreased intracellular accumulation
- Mutation of proteins that block tetracycline binding
- Mutation of enzyme that degrades drug
Macrolides
- Include erythromycin, clarithromycin, azithromycin
- All end in “mycin”
- Source: Streptomyces erythreus and semisynthetic
- Mechanism of action:
- Binds to 50S ribosomal RNA
- Blocks aminoacyl translocation reactions
- Blocks formation of initiation complexes
Chloramphenicol
- Only one of its kind
- Mechanism of action:
- Binds to 50S ribosomal subunit
- Blocks peptide bond formation
- Pharmacokinetics:
- Large Vd
- Inactivated by Phase II in the liver
- Renal disease does not require dose adjustment
- Liver disease requires dose adjustment
- Clinical uses:
- When penicillin is contraindicated
- For rickettsial infections
- For children when tetracyclines cannot be used
- Adverse Effects and ADRs:
- Bone marrow suppression
- Aplastic anemia
- Gray Baby Syndrome
Lincosamides
- Include clindamycin only
- Source: Streptomyces lincolnensis
- Mechanism of action:
- Bind to 50S subunit
- Identical to erythromycin and other macrolides
- Pharmacokinetics:
- No dosage adjustment for renal failure
- Antimicrobial activity:
- Gram pos and neg
- Streptococci, staphylococci, pneumococci
Streptogramins
- A combination of two streptogramins: quinupristin-dalfopristin
- Same mechanisms as clindamycin
- IV dosing
- Elimination is fecal
- Used for vanco resistant strains of E faecium
Oxazolidinones
- Include linezolid only
- Gram pos staph, strep, enterococci, and gram pos rods
- Mostly bacteriostatic
- Binds 50s ribosome, inhibits protein synthesis
- Used often for vancomycin resistant infection
- Given po or iv, does not interact with CYP 450 enzymes
mRNA and Protein Synthesis
- mRNA is a sequence of codons, each containing 3 nucleotides, which represent 1 amino acid.
- During translation, the ribosome attaches to the mRNA's start codon (AUG).
- tRNA, with its attached amino acid, binds to the corresponding codon on the mRNA, forming complementary base pairs with the tRNA anticodon.
- Each of the 20 amino acids has its own unique tRNA.
- The ribosome moves along the mRNA, adding amino acids to the growing polypeptide chain.
Tetracyclines
- Structure/Source: Discovered in 1946 from Streptomyces species, including semisynthetic variations like chlortetracycline, oxytetracycline, demeclocycline, methacycline, doxycycline, and minocycline.
- Mechanism of Action: Bind to the 30S subunit of the bacterial ribosome, preventing aminoacyl-tRNA from binding to the acceptor site on the mRNA-ribosome complex.
- Pharmacokinetics: Absorption varies by type, ranging from 30 to 100% bioavailability. Absorption is hindered by calcium ions due to chelation formation, therefore avoid taking with dairy products. Primarily excreted renally, requiring dosage adjustments based on creatinine clearance (except for doxycycline, which is the preferred option in renal failure).
- Antimicrobial Activity: Broad-spectrum bacteriostatic, effective against gram-positive, gram-negative bacteria, anaerobes, rickettsiae, chlamydiae, and mycoplasmas. All tetracyclines possess identical antimicrobial activity, but resistance patterns might influence their usage.
- Clinical Uses: Drugs of choice for Mycoplasma pneumoniae, chlamydiae, rickettsiae, and some spirochetes. Used in combination to treat Helicobacter pylori and acne. However, many applications have been abandoned due to increasing resistance.
- Adverse Effects and ADRs: Tetracyclines bind to calcium deposited in teeth and bones, with absorption being irreversible. This has been observed in 3,500-year-old mummies, exhibiting tetracycline rings in their long bones. Tetracycline dosing is used to measure bone growth.
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Mechanism of Resistance:
- Decreased intracellular accumulation due to impaired influx or an increase in efflux (active transport pump).
- Mutation leading to the expression of proteins that block tetracycline binding to the ribosome subunit.
- Mutation leading to the expression of an enzyme that degrades the drug.
- Clinical uses limited in lower extremity infections to mostly doxycycline and minocycline. Uses also include MRSA infections. Doxycycline (po) used for Lyme disease. For use with staph and strep infections in patients with penicillin allergies.
Macrolides
- Structure/Source: Erythromycin, azithromycin, and clarithromycin. Derived from Streptomyces erythreus (1952), including semisynthetic derivatives (azithromycin, clarithromycin). Named for the presence of a macrolide ring.
- Mechanism of Action: Binds to the 50S ribosomal RNA, blocking aminoacyl translocation reactions and the formation of initiation complexes.
- Pharmacokinetics: Stomach acid destroys macrolides, so enteric coating must be used. Excretion is mainly via bile; dosage adjustment for renal failure is not required. Can be administered orally or intravenously.
- Antimicrobial Activity: Active against gram-positive bacteria like pneumococci, streptococci, staphylococci, corynebacteria, mycoplasma, legionella, Chlamydia, Helicobacter, and listeria. Also effective against some gram-negative bacteria, including Neisseria.
Azithromycin
- Most active against gram-positive pathogens (Staph and Strep) with limited gram-negative activity.
- Unique dosing form known as "Z-Pak®".
- Pharmacokinetics: 500mg (2 x 250mg tablets) on day 1 followed by 250mg (1 x 250mg tablet) on days 2-5.
- Cpmax on day 1: 410 ng/mL.
- Cpmax on day 5: 240 ng/mL.
- AUC on day 1: 2600 ng.h/mL.
- AUC on day 5: 2100 ng.h/mL.
- Dosing:
- Day 1: 2 x 500mg oral dose.
- Day 2-5: 1 x 250mg oral dose per day (up to four days).
- Once-a-day dosing improves patient compliance.
Ketolides
- Structure/Source: Telithromycin is the only approved ketolide, derived from erythromycin (semisynthetic).
- Mechanism of Action: Same as macrolides.
- Pharmacokinetics: Similar to macrolides.
- Antimicrobial Activity: Similar to macrolides.
- Clinical Uses: Used for macrolide-resistant strains. The modified structure makes them poor substrates for the efflux pump and they bind with higher affinity for the ribosome subunit binding site.
- Adverse Effects and ADRs: Similar to macrolides.
- Mechanism of Resistance: To be determined, as it's a new drug class.
Telithromycin
- Administered once a day orally.
- Excreted primarily via bile and urine.
- Inhibits the CYP3A4 enzyme.
Chloramphenicol
- Structure/Source: Discovered in 1947 from a soil sample in Venezuela, originating from Streptomyces venezuelae.
- Mechanism of Action: Reversible binding to the 50S subunit of the bacterial ribosome, inhibiting peptidyl transferase.
- Pharmacokinetics: Available as oral tablets, a 1g oral dose produces plasma levels of 10-15 ug/mL. Large volume of distribution, penetrating into CNS and reaching similar concentrations as plasma. Inactivated into metabolites via phase II in the liver. Renal disease does not require clearance correction (as 90% of inactive metabolites are excreted renally), but liver disease does.
- Antimicrobial Activity: Bacteriostatic broad spectrum against aerobic and anaerobic gram-positive and gram-negative bacteria.
- Clinical Uses: Use limited due to resistance and toxicity. Used when penicillins are contraindicated due to allergy or for rickettsial infections (Rocky Mountain spotted fever) in children where tetracyclines cannot be used.
-
Adverse Effects and ADRs:
- Bone marrow suppression of red cell production after 1-2 weeks of dosing.
- Aplastic anemia (idiosyncratic), occurring in 1/24,000 to 1/40,000 patients who receive the drug.
- Inhibits various CYP450 enzymes, prolonging the half-life of other drugs.
-
Mechanism of Resistance:
- Mutations that make organisms less permeable to the drug.
- Mutation selection for the production of chloramphenicol acetyltransferase, a plasmid-encoded enzyme that inactivates the drug.
Gray Baby Syndrome
- Occurs in infants, manifesting as decreased red blood cells, cyanosis, and cardiovascular collapse.
- Premature neonates have deficient levels of hepatic glucuronosyltransferase, which is responsible for inactivating chloramphenicol into inactive metabolites.
Lincosamides
- Structure/Source: Clindamycin is the only lincosamide, derived from Streptomyces lincolnensis.
- Mechanism of Action: Bind to the 50S subunit, similar to erythromycin and other macrolides.
- Pharmacokinetics: Administered orally or intravenously. Relatively high volume of distribution, penetrating most tissues. No dosage adjustment needed for renal failure.
- Antimicrobial Activity: Effective against gram-positive and gram-negative bacteria, including streptococci, staphylococci, and pneumococci.
- Clinical Uses: Used to treat severe anaerobic infections caused by bacteroides and other anaerobes.
- Adverse Effects and ADRs: Skin rashes, impaired liver function, antibiotic-associated colitis due to C. difficile, often fatal. Treat with metronidazole.
-
Mechanism of Resistance: Confers cross-resistance to macrolides.
- Mutation in the ribosomal receptor binding site.
- Enzymatic inactivation of the drug.
- Mutation altering the receptor by inducing methylase.
Clindamycin
- Most commonly reported adverse effect is diarrhea (up to 20% of patients). Diarrhea resolves after stopping the drug.
- Dosing: 600-900mg every 8 hours intravenously or intramuscularly, or 150-300mg three times daily orally.
- No dosage adjustment is required for reduced creatinine clearance as the drug is eliminated hepatically. Hepatic failure requires dosage adjustment.
Streptogramins
- Quinupristin-dalfopristin is a combination of two streptogramins, sharing the same mechanisms as clindamycin.
- Administered intravenously and mainly eliminated via feces.
- Can treat vancomycin-resistant strains of Enterococcus faecium.
Linezolid
- An oxazolidinone antibiotic, active against gram-positive bacteria like staph, strep, enterococci, and gram-positive rods.
- Mostly bacteriostatic.
- Binds to the 50S ribosome, inhibiting protein synthesis.
- Often used for vancomycin-resistant infections.
- Administered orally or intravenously, does not interact with CYP450 enzymes.
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Description
This quiz covers the key concepts of protein synthesis inhibitors, including tetracyclines, macrolides, and chloramphenicol. Learn about their mechanisms of action, clinical uses, and mechanisms of resistance. Perfect for students studying pharmacology and microbiology.
