Penicillin Drug Development
23 Questions
0 Views

Penicillin Drug Development

Created by
@OutstandingCantor

Podcast Beta

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the mechanism of action of macrolides?

  • Inhibit translation by binding 23S rRNA of the 50S subunit (correct)
  • Disrupt cell wall synthesis
  • Inhibit translation by binding 16S rRNA of the 30S subunit
  • Inhibit DNA replication

    • Which condition is NOT a common adverse effect of lincosamides?

  • Rash
  • Nausea
  • C. difficile infection
  • Acne (correct)

    • Which of the following is true regarding azithromycin compared to erythromycin and clarithromycin?

  • It has almost no interaction potential. (correct)
  • It is ineffective against pneumonia.
  • It has a higher risk of drug interactions.
  • It is a stronger inhibitor of the CYP 450 system.

    • What distinguishes tigecycline from other tetracyclines?

    <p>It covers many Gram-negative bacteria.</p> Signup and view all the answers

    What is a characteristic of the tetracycline class of antibiotics?

    <p>They have long half-lives.</p> Signup and view all the answers

    What is the mechanism of action of linezolid?

    <p>Binds to 23S rRNA of the 50S subunit</p> Signup and view all the answers

    Which of the following is a common adverse effect of linezolid?

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

    What characterizes the action of nitroimidazoles like metronidazole?

    <p>Bactericidal action via DNA damage</p> Signup and view all the answers

    Which fluoroquinolone is primarily renally excreted?

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

    What is a distinguishing feature of tedizolid compared to linezolid?

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

    Which microbial organisms are fluoroquinolones particularly ineffective against?

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

    Which fluoroquinolone is known to be effective against Pseudomonas aeruginosa?

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

    Which drug class poses a risk of serotonin syndrome when combined with certain medications?

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

    Which class of antibiotics is specifically described as having activity against Pseudomonas aeruginosa?

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

    Which adverse effect is associated with vancomycin administration?

    <p>Vancomycin infusion syndrome</p> Signup and view all the answers

    What is the primary mechanism of action for daptomycin?

    <p>Disruption of cell membrane potential</p> Signup and view all the answers

    Which of the following combinations is active against resistant bacteria, including Pseudomonas and Klebsiella pneumonia?

    <p>Meropenem- vaborbactam</p> Signup and view all the answers

    Which cephalosporin generation is primarily eliminated renally and is effective against MSSA and Gram-negative rods?

    <p>1st generation</p> Signup and view all the answers

    Which antibiotic class is primarily used to treat MRSA infections?

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

    What is a significant concern with rifamycins related to drug interactions?

    <p>Induction of CYP450 enzymes</p> Signup and view all the answers

    Which type of penicillin is no longer available as a single agent but is found in combination therapy?

    <p>Antipseudomonal penicillin</p> Signup and view all the answers

    Which antibiotic is known for attacking both Gram-positive and Gram-negative bacteria, but is not absorbed systemically?

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

    Which beta-lactam antibiotic combination is NOT active against Pseudomonas?

    <p>Amoxicillin/clavulanate</p> Signup and view all the answers

    Study Notes

    Penicillins

    • Ureidopenicillin was a type of penicillin, but it is no longer available as a single agent.
    • Ureidopenicillin could penetrate the cell wall of Pseudomonas, which aminopenicillin could not.
    • Ureidopenicillin had additional adverse effects such as thrombocytopenia.
    • All penicillins are susceptible to beta lactamases.

    Penicillin Drug Development

    • There are 5 main types of pencillins:
      • Natural PCNs
      • Anti-staph PCNs
      • Aminopenicillins
      • Antipseudomonal PCNs
      • Penicillin/Beta-Lactamase Inhibitor Combinations

    Penicillin/Beta-Lactamase Inhibitor Combinations

    • There are 3 main types of penicillin/beta-lactamase inhibitor combinations:
      • Piperacillin/Tazobactam (Zosyn®)
      • Ampicillin/Sulbactam (Unasyn®)
      • Amoxicillin/Clavulanate (Augmentin®)
    • These combinations are used to treat Streptococci, MSSA, enterococci, and Gram negative rods.
    • These combinations provide better coverage for Gram-negative rods than the parent drugs alone.
    • They are active against anaerobes.
    • Amp/sulbactam and amox/clav are not active against Pseudomonas.
    • If a bacteria is susceptible to one beta lactam it is susceptible to all antistaphylococcal beta-lactams.

    Cephalosporins

    • There are 5 main types of cephalosporins:
      • 1st generation cephalosporin
      • 2nd generation cephalosporin
      • 3rd generation cephalosporin
      • 4th generation cephalosporin
      • Anti-MRSA Cephalosporin

    1st generation cephalosporin

    • Examples of 1st generation cephalosporins:
      • Cefalozin
      • Cephalaxin
      • Cefadroxil
    • They are eliminated renally.
    • They are useful against MSSA, streptococci and gram-negative rods.

    2nd generation cephalosporin

    • Examples of 2nd generation cephalosporins:
      • Cefuroximine
      • Cefoxitin (Anaerobic activity)
      • Cefotaten (Anaerobic activity)

    3rd generation cephalosporin activity

    • Compared to the 1st and 2nd generation, they have decreased antistaph activity and better antistrep activity.

    4th generation cephalosporin activity

    • Examples of 4th generation cephalosporins are:
      • Cefepime
      • Cefimine
      • Cefopodoimine
    • They are eliminated renally.

    Anti-MRSA Cephalosporin

    • This type of cephalosporin is useful for treating MRSA and MSSA, strep, and Gram-negative rods.
    • They are not useful for treating Pseudomonas.
    • They are susceptible to beta lactamase.

    Cephalosporin/beta-lactamase Inhibitor Combinations

    • These combinations can kill highly resistant bacteria such as Pseudomonas aeruginosa, Klebsiella pneumonia.

    Carbapenems

    • Examples of carbapenems include:
      • Imipenum/cilastin
      • Meropenum
      • Ertapenum
    • They are renally eliminated.
    • Imipenum has a higher seizure risk than other carbapenems.

    Monobactam

    • Aztreonam is the only monobactam drug.
    • It is only active against gram-negative rods, including Pseudomonas.
    • It is renally eliminated.
    • Monobactams are not cross-reactive with other beta-lactam allergies, except ceftazidime and cefiderocol.

    Carbapenem/Beta-lactamase Inhibitor Combinations

    • Examples of Carbapenem/Beta-lactamase Inhibitor Combinations include:
      • Meropenem-vaborbactam
      • Imipenem- (cilastatin)-relebactam
    • They have the same properties as meropenem and imipenem, but with additional activity.

    Glycopeptides

    • Vancomycin is the main glycopeptide drug.
    • It inhibits cell wall synthesis by binding to the terminal of D-ala-D-ala chain of peptidoglycan.
    • It has poor bioavailability.
    • It is widely distributed and eliminates renally.
    • It is active against Gram-positive aerobes and anaerobes, including MRSA.
    • It is used for MRSA infections because it does not kill beta-lactam susceptible staphylococci as quickly as beta-lactams.
    • Beta lactams kill MSSA better than glycopolypeptides.
    • Adverse effects include Vancomycin infusion syndrome, red man syndrome, nephrotoxicity, and ototoxicity.

    Lipoglycopeptide(s)

    • Examples of lipoglycopeptides include:
      • Telavancin (skin/skin and pneumonia from gram-positive structure)
      • Oritavancin (skin/skin infection)
      • Dalbavancin (skin infections and C. difficile)

    Fosfomycin

    • It inhibits monomer production.
    • It is bactericidal.
    • It is renally eliminated.
    • It has moderate bioavailability.
    • It is active against Pseudomonas, staph, and enterococci.

    Cyclic Lipopeptide

    • Daptomycin is a cyclic lipopeptide.
    • It inserts into the cell membrane of Gram-positive organisms leading to cation leak, depolarization, and cell death.
    • It is bactericidal.
    • It has poor absorption and is inactive in the lung.
    • It is excreted renally.
    • It is active against Gram-positive aerobes and anaerobes, including MRSA and VRE.

    Rifamycins

    • Rifamycins block transcription.
    • They are bactericidal.
    • Rifamycins include: Rifampin, Rifabutin, Rifapentine, Rifaximin.
    • They are active against Gram-positive and Gram-negative bacteria as well as mycobacteria.
    • They are strong inducers of CYP450, and enzyme system that metabolizes many drugs.
    • Adverse effects include rash, hypersensitivity, and hepatotoxicity.
    • Rifamycins discolor secretions orange-red.
    • Rifapentine has an extended t½.
    • Rifaximin is not absorbed.

    Protein Synthesis Inhibitors

    • Most are bacteriostatic.
    • They are effective against most bacteria.

    Aminoglycosides

    • Examples of aminoglycosides include:
      • Gentamicin
      • Tobramycin
      • Amikacin
      • Neomycin
      • Streptomycin
      • Plazomicin
    • They inhibit translation by binding to 16S rRNA of the 30S ribosomal subunit causing misreading, leading to cell death.
    • They are bactericidal.
    • They have low bioavailability.
    • They eliminate renally.
    • They have short half-lives.
    • They have excellent activity vs. gram-negative bacteria.

    Macrolides

    • Examples of macrolides include:
      • Erythromycin
      • Clarithromycin
      • Azithromycin
    • They inhibit translation by binding to the 23s rRNA of the 50S subunit of the ribosome..
    • They are bacteriostatic.
    • They achieve high intracellular concentrations.
    • They are highly bioavailable.
    • Macrolide adverse effects include GI disturbances (N/V/D) and rash.
    • They have drug interactions with Erythromycin, Clarithromycin (inhibitors of CYP 450 system).
    • Azithromycin has almost no interaction potential.
    • They are used for pneumonia and URTIs.

    Lincosamides

    • Examples of Lincosamides include:
      • Clindamycin
    • They inhibit translation by binding to the 50S subunit of bacterial ribosomes.
    • They are bacteriostatic.
    • They are active against staphylococci (including some MRSA) and streptococci, anaerobes (but not C.difficile).
    • Adverse effects include C.difficile infection, diarrhoea, abdominal pain, nausea, and rash.
    • They are mainly used for SSTIs, anaerobic infections, and acne.

    Tetracycline

    • Examples of Tetracyclines include:
      • Minocycline, doxycycline
    • They inhibit translation by binding reversibly to 16S rRNA of the 30S ribosomal subunit, blocking tRNA.
    • They are bacteriostatic.
    • They are active against Staphylococci including many MRSA and some strep.

    Other Tetracyclines

    • Examples of modified tetracyclines include:
      • Tigecycline, Eravacycline, Omadacycline
    • They have an expanded spectrum.
    • They have poor absorption.
    • They have very high distribution and low plasma concentrations.
    • They have a long half-life,
    • They are most hepatic elimination.
    • They cover many GNR and GPC including VRE and MRSA.
    • They have good anaerobic coverage.
    • They do NOT cover Staphylococcus or Proteus.
    • Tigecycline has significant adverse effects.

    Nitroimidazoles

    • Examples of Nitroimidazoles include:
      • Metronidazole, Tinidazole
    • They interact with DNA leading to loss in DNA structure and strand breakage.
    • They are bactericidal.

    Oxalidinones

    • Examples of Oxalidinones include:
      • Linezolid, Tedizolid
    • They bind to the 23S rRNA of the 50S subunit, preventing protein synthesis by blocking the formation of the 70S initiation complex..
    • They are bacteriostatic.
    • They are highly bioavailable.
    • Oxalidinones elimination is:
      • Linezolid- Dual hepatic metabolism (not via CYP450) and renal elimination
      • Tedizolid- Hepatic elimination
    • Linezolid is a weak, reversible inhibitor of monoamine oxidase, so be somewhat cautious of antidepressants when taking linezolid.
    • They are effective against Gram-positive aerobes, including staphylococci, streptococci, including MRSA, and enterococci, including VRE.
    • Adverse effects include possibility of serotonin syndrome with some drugs, and bone marrow suppression.

    Fluoroquinolones

    • Examples of Fluoroquinolones include:
      • Ofloxacin, Ciprofloxacin, Levofloxacin, Moxifloxacin,
    • They bind to DNA gyrase (topo II) or topoisomerase IV, leading to DNA breaks.
    • They are bactericidal.
    • They are highly bioavailable.
    • "Respiratory FQs” (aka Antipneumococcal FQs) have good activity vs.S.pneumoniae and include:
      • Levofloxacin, moxifloxacin, gemifloxacin, delafloxacin, gatifloxacin
    • Ciprofloxacin, ofloxacin, and earlier FQs are not antipneumococcal.
    • Ciprofloxacin used in pneumonia caused by GNR.
    • Fluoroquinolones are largely renally excreted, except moxifloxacin (hepatic) and gemifloxacin (dual).
    • Activity varies between drugs.
    • All are active vs Enterobacterales, atypical organisms.
    • Ciprofloxacin, levofloxacin, and delafloxacin are active vs.P.aeruginosa.
    • Ciprofloxacin has poor Gram-positive activity.
    • There are treatment failures with streptococci and staphylococci.
    • Resistance is common in P.aeruginosa and S.aureus, uncommon in streptococci, and very high in E.coli in some parts of the world and country.
    • Adverse effects include:
      • Lower seizure threshold
      • N/V/D
      • Photosensitivity
      • Arthropathy
      • QTc prolongation
      • Elderly: Mental status changes
    • Absorption is reduced drastically with concomitant multivalent cations.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Antibiotics: A Comprehensive Guide PDF

    Description

    Explore the various types of penicillins, including their uses, specific characteristics, and development history. This quiz delves into combinations like Penicillin/Beta-Lactamase inhibitors and their effectiveness against bacteria. Test your knowledge on essential antibiotics and their mechanisms.

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser