Protein Synthesis Inhibitors
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Questions and Answers

Which of the following antibiotics is classified under ketolides?

  • Erythromycin
  • Clarithromycin
  • Telithromycin (correct)
  • Chloramphenicol

    • Which phase of translation is primarily targeted by most antibiotics?

  • Translation
  • Initiation
  • Termination
  • Elongation (correct)

    • What action of antibiotics inhibits the binding of mRNA during the initiation phase?

  • Hydrolyzing peptides
  • Preventing mRNA from attaching (correct)
  • Blocking the amino acyl acceptor site
  • Impairing mRNA translocation

    • Which of the following amino acids does the peptidyl transferase enzyme primarily act upon during elongation?

    <p>Amino acyl tRNA</p> Signup and view all the answers

    Which term best describes the process where the newly formed polypeptide is released during translation?

    <p>Termination</p> Signup and view all the answers

    In protein synthesis, what is the result of mutation in the translation termination codons UAA, UAG, or UGA?

    <p>Premature chain termination</p> Signup and view all the answers

    Which step involves the formation of the initiation complex during translation?

    <p>The binding of the 30S ribosomal subunit with formyl methionyl-tRNA</p> Signup and view all the answers

    What is the effect of tetracyclines on calcium in bones?

    <p>They bind irreversibly to calcium.</p> Signup and view all the answers

    Which of the following statements about tetracycline resistance is true?

    <p>Efflux transport pumps may contribute to resistance.</p> Signup and view all the answers

    Which is NOT a clinical use of tetracyclines?

    <p>Diphtheria.</p> Signup and view all the answers

    What is the primary mechanism of action of macrolides?

    <p>Blocking aminoacyl translocation on ribosomal RNA.</p> Signup and view all the answers

    Which antibiotic requires enteric coating due to degradation by stomach acid?

    <p>Erythromycin.</p> Signup and view all the answers

    For which of the following infections is doxycycline NOT a typical treatment?

    <p>Corynebacterial sepsis.</p> Signup and view all the answers

    Which of the following is a characteristic feature of macrolides?

    <p>They are derived from Streptomyces erythreus.</p> Signup and view all the answers

    What spectrum of bacterial activity do macrolides primarily target?

    <p>Primarily Gram-positive bacteria and some Gram-negative.</p> Signup and view all the answers

    What is one of the key adverse effects associated with macrolides like erythromycin?

    <p>Hypersensitivity hepatitis</p> Signup and view all the answers

    What is the mechanism by which erythromycin affects drug levels in the body?

    <p>Inhibiting CYP enzymes</p> Signup and view all the answers

    How is Legionella pneumophila most commonly spread to humans?

    <p>Aerosolized water from air conditioning systems</p> Signup and view all the answers

    Which antibiotic is ineffective against Legionella pneumophila?

    <p>Penicillin</p> Signup and view all the answers

    What characteristic of Legionella pneumophila requires special media for laboratory growth?

    <p>Requires special temperature range</p> Signup and view all the answers

    What is a major toxic side effect associated with Chloramphenicol?

    <p>Bone marrow suppression</p> Signup and view all the answers

    In the case of liver disease, what pharmacokinetic adjustment is required for Chloramphenicol?

    <p>No dosage adjustment is necessary</p> Signup and view all the answers

    What is one of the primary clinical uses of Chloramphenicol?

    <p>Rickettsial infections</p> Signup and view all the answers

    Which mechanism of resistance is associated with Chloramphenicol?

    <p>Decreased drug permeability</p> Signup and view all the answers

    What is a serious adverse effect that can occur with prolonged use of Chloramphenicol?

    <p>Aplastic anemia</p> Signup and view all the answers

    What is the cause of Gray Baby Syndrome in infants who are given Chloramphenicol?

    <p>Deficiency in hepatic enzyme activity</p> Signup and view all the answers

    Which type of bacterial activity does Chloramphenicol exhibit?

    <p>Bacteriostatic broad spectrum</p> Signup and view all the answers

    What is the pharmacokinetic profile of Clindamycin?

    <p>High volume of distribution with deep tissue penetration</p> Signup and view all the answers

    Which microorganism is most likely resistant to clindamycin?

    <p>Bacteroides fragilis</p> Signup and view all the answers

    What is the primary adverse effect associated with clindamycin use?

    <p>Diarrhea</p> Signup and view all the answers

    In which clinical situation is clindamycin particularly useful?

    <p>Anaerobic infections caused by Bacteroides</p> Signup and view all the answers

    Which of the following statements about the mechanism of action of Streptogramins is true?

    <p>They bind to the 50S ribosomal subunit.</p> Signup and view all the answers

    Which antibiotic is indicated for vancomycin-resistant Enterococcus faecium infections?

    <p>Quinupristin-dalfopristin</p> Signup and view all the answers

    What is the appropriate dosage form for linezolid?

    <p>Both oral and intravenous</p> Signup and view all the answers

    Which of the following is NOT a mechanism of resistance for clindamycin?

    <p>Efflux pump mediation</p> Signup and view all the answers

    Which condition might require dosage adjustment for clindamycin?

    <p>Hepatic failure</p> Signup and view all the answers

    What is a significant consequence of tetracyclines binding to calcium in bones?

    <p>It results in the formation of tetracycline rings in long bones.</p> Signup and view all the answers

    Which method is responsible for the decreased efficacy of tetracyclines due to bacterial resistance?

    <p>Mutation-induced degradation of the antibiotic.</p> Signup and view all the answers

    Which group of bacteria is primarily susceptible to macrolides?

    <p>Gram-positive pneumococci and some gram-negative bacteria.</p> Signup and view all the answers

    Which clinical situation is NOT typically addressed with doxycycline treatment?

    <p>Corynebacterial sepsis.</p> Signup and view all the answers

    What is the primary mechanism by which macrolides exert their antimicrobial effect?

    <p>Blocking aminoacyl translocation on 50S ribosomal RNA.</p> Signup and view all the answers

    What is the significance of enteric coating in the administration of macrolide antibiotics?

    <p>It protects the drug from degradation by stomach acid.</p> Signup and view all the answers

    Which characteristic of macrolides makes them a suitable substitute for penicillin?

    <p>They are less likely to cause allergic reactions.</p> Signup and view all the answers

    For which of the following conditions are macrolides considered the drug of choice?

    <p>Community acquired pneumonia.</p> Signup and view all the answers

    What is a significant consequence of Chloramphenicol use related to blood cell production?

    <p>Bone marrow suppression leading to aplastic anemia</p> Signup and view all the answers

    In patients with liver disease, how must Chloramphenicol be adjusted due to its metabolism?

    <p>Significant reduction in dosage is required for safety</p> Signup and view all the answers

    What type of antibiotic activity does Clindamycin exhibit?

    <p>Bacteriostatic against both gram-positive and some gram-negative bacteria</p> Signup and view all the answers

    Which of the following is NOT a clinical use of Chloramphenicol?

    <p>Treatment of community-acquired pneumonia</p> Signup and view all the answers

    What mechanism do bacteria utilize to resist Chloramphenicol?

    <p>Production of chloramphenicol acetyltransferase enzyme</p> Signup and view all the answers

    What specific adverse effect is associated with Chloramphenicol in infants, known as Gray Baby Syndrome?

    <p>Cyanosis and cardiovascular instability</p> Signup and view all the answers

    For what reason might Chloramphenicol be considered for use despite its toxicity?

    <p>Useful when penicillin allergies are present</p> Signup and view all the answers

    For which condition is clindamycin contraindicated due to a high risk of a specific adverse effect?

    <p>Clostridium difficile infection</p> Signup and view all the answers

    What is the primary mechanism by which clindamycin demonstrates resistance?

    <p>Cross-resistance with other antibiotics</p> Signup and view all the answers

    In which scenario is clindamycin particularly effective for treating infections?

    <p>Staph infections in patients allergic to penicillin</p> Signup and view all the answers

    What dosage form is commonly administered for severe cases of clindamycin?

    <p>Intravenous injection</p> Signup and view all the answers

    What serious condition may develop due to the administration of clindamycin, especially if used incorrectly?

    <p>Antibiotic-associated colitis</p> Signup and view all the answers

    Which antibiotic class confers cross-resistance with clindamycin?

    <p>Macrolides</p> Signup and view all the answers

    What is the unique aspect of azithromycin's dosing regimen compared to other macrolides?

    <p>It uses a loading dose on the first day.</p> Signup and view all the answers

    Which of the following correctly describes the mechanism of action of ketolides?

    <p>They bind to the 50S ribosomal subunit, similar to macrolides.</p> Signup and view all the answers

    What pharmacokinetic characteristic is particularly notable for telithromycin compared to other antibiotics?

    <p>It inhibits CYP3A4, affecting the metabolism of other drugs.</p> Signup and view all the answers

    What is the primary role of tRNA in the translation process?

    <p>To transport amino acids to the ribosome.</p> Signup and view all the answers

    Which adverse effect is commonly associated with the use of azithromycin?

    <p>Cardiac arrhythmias.</p> Signup and view all the answers

    Which of the following statements accurately describes the pharmacokinetics of tetracyclines?

    <p>Calcium ions can impair their absorption.</p> Signup and view all the answers

    Why might ketolides be preferable for treating macrolide-resistant bacterial strains?

    <p>They have a modified structure providing higher ribosomal affinity.</p> Signup and view all the answers

    What type of antimicrobial activity do tetracyclines exhibit?

    <p>Bacteriostatic against a broad spectrum including anaerobes.</p> Signup and view all the answers

    Which statement best summarizes the pharmacokinetics of chloramphenicol?

    <p>It effectively crosses the blood-brain barrier.</p> Signup and view all the answers

    Which of the following is NOT a characteristic of tetracyclines?

    <p>They enhance the synthesis of bacterial DNA.</p> Signup and view all the answers

    Which condition may require special dosing considerations for tetracyclines?

    <p>Renal failure, except for doxycycline.</p> Signup and view all the answers

    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.
    • 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.

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