Intro to antibacterial agents Flashcards
What is meant by bacteristatic?
Antibiotics that inhibit bacterial growth, ie protein synthesis inhibitors.
What is meant by bactericidal?
Antibiotics that kill bacteria, ie cell wall-active agents
What is the minimum inhibitory concentration?
Minimum concentration of antibiotic at which visible growth is inhibited.
What is antimicrobial synergism?
Activity of two antimicrobials given together is greater than the sum of their activity if given separately.
Give a clinical example of synergism.
β-lactam/aminoglycoside combination therapy of streptococcal endocarditis.
What are possible antibiotic targets?
- Cell wall
- Protein synthesis
- DNA synthesis
- RNA synthesis
- Plasma membrane
What is the bacterial cell wall made of?
Peptidoglycan - Polymer of glucose-derivatives, N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG)
Give example of antibiotics that inhibit cell wall synthesis.
β-lactams
Glycopeptides
(also cycloserine and fosfomycin)
Why are the beta-lactam antibiotics so-called?
Because they have a beta -lactam ring structure.
What was the first beta-lactam antibiotic?
Benzylpenicillin (penicillin G). Acid labile so must be delivered parenterally.
What was the first oral antibiotic?
Phenoxymethylpenicillin (penicillin V)
Describe the beta lactam ring
Four members - CCCN
How do beta lactams work?
Interfere with function of “penicillin binding proteins” - transpeptidases enzymes involved in the peptideoglycan cross-linking.
Give examples of classes of beta lactams.
Penicillins (relatively narrow spectrum), cephalosporins, carbapenems, monobactams (broad spectrum).
What kind of ribosomes do bacteria possess?
70s (30s+50s)
How do aminoglycosides such as gentamicin inhibit protein synthesis?
- Bind to 30S ribosomal subunit
- Mechanism of action not fully understood
How to macrolides (erythromycin), lincosamides (clindamycin) and the streptogramins work?
- Bind to 50S ribosomal subunit
- Blockage of exit tunnel
- Inhibit protein elongation
How do tetracyclines inhibit protein synthesis?
- Bind to 30S ribosomal subunit
- Inhibit RNA translation
- Interfere with binding of tRNA to rRNA
How do oxazolidinones inhibit protein synthesis?
- Inhibits initiation of protein synthesis
- Binds to 50S ribosomal subunit
- Inhibits assembly of initiation complex
- May also bind to 70S subunit
How do trimethoprim and the sulfonamides inhibit DNA synthesis.
- Inhibit folate synthesis - folic acid is a purine synthesis precursor
- Trimethoprim inhibits dihydrofolate reductase
- Sulfonamides inhibit dihydropteroate synthetase
How do the quinolones and flouroquinolones (ciprofloxacin) inhibit DNA synthesis?
Inhibit one or more of two related enzymes -DNA gyrase and topoisomerase IV
Involved in remodelling of DNA during DNA replication
Supercoiling/strand separation
How do RNA synthesis inhibitors like rifampicin work?
- RNA polymerase inhibitor
- Prevents synthesis of mRNA
How does the plasma membrane agent daptomycin work?
- Cyclic lipopeptide
- Inserts lipophilic tail into cell membrane resulting in depolarisation and ion loss
- Effective in Gram-positives only
What are the specific adverse effects associated with aminogylcosides?
- Reversible renal impairment on accumulation
- Therapeutic drug monitoring indicated
