Topic 6B Flashcards
What are antibiotics
may be either bactericidal or bacteriostatic. Antibiotics work through five different mechanisms of action.
What is inhibition of cell wall synthesis
the primary component of the bacterial cell wall is peptidoglycan, which is
synthesized by the transpeptidase, penicillin binding protein (PBP). PBPs can be inhibited by beta-lactam antibiotics.
Inhibition of PBPs weakens the cell wall, resulting in osmotic lysis during bacterial growth. Inhibiting PBPs also enhances the effect of murein hydrolases, which degrades peptidoglycan to permit cellular elongation or division. Since PBPs are only required during growth, stationary/dormant cells can not be killed by these antibiotics.
Cell wall inhibitors are all bactericidal and include: beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), vancomycin, cycloserine, and bacitracin.
What is the drug penicillins
are derived from 6-aminopenicillinic acid, which contains the 4-membered β-lactam ring, allowing them to act as transpeptidase (PBP) inhibitors.
Natural penicillins are synthesized by the fungi, penicillium chrysogenum, as part of a mixture of related compounds.
Biosynthetic penicillins are synthesized by adding side-chain precursors to the fungi which shifts the reaction towards
benzylpenicillin, also known as Penicillin G, the most important product.
Semisynthetic penicillins are synthesized by naturally produced by fungi, and then chemically modified by the
addition of a side chain. Example: amoxicillin.
What is Benzylpenicillin
- Penicillin G is more effective against gram-positive bacteria due to slow porin uptake through the gram-negative bacteria’s outer membrane. Side chain modifications can increase uptake, but lowers its effectiveness against gram-positive bacteria.
Aqueous Penicillin G is administered intravenously.
Procaine Penicillin G slows drug metabolism and acts as an anesthetic for large intramuscular injections. Benzathine Penicillin G greatly slows metabolism of the drug, resulting in long bioavailability.
What are the limitations of penicillin G
Penicillin G can cause anaphylaxis in 0.5% of patients.
Penicillin G is hydrolyzed by stomach acid, preventing oral formulations.
Penicillin G is hydrolyzed by bacterial beta-lactamases (a defensive bacterial enzyme).
• Can prevent this by adding aromatic rings, containing many methyl or ethyl groups, for steric hindrance.
• Can also prevent this by co-administering a beta-lactamase inhibitor, such as clavulanate.
What is penicillin V
modification of amine group limits hydrolysis by stomach enzymes, allowing for oral formulations.
What is cephalosporins
derived from natural compounds of cephalosporium (fungi) and streptomyces (bacteria).
They contain the 4-membered β-lactam ring attached to a 6-membered ring and has two substitutable groups.
Depending on their substituents, five iterations of cephalosporins have been created:
• The 1st generation is only effective against gram-positive cocci.
• The 2nd generation is only effective against H. influenzae and B. fragilis.
• The 3rd generation is only effective against gram-negative bacilli.
• The 4th generation is effective against both gram-positive cocci and gram-negative bacilli which produces ESBL.
• The 5th generation is effective against gram-positive cocci, gram-negative bacilli, and MRSA
What is carbapenems
derived from natural compounds of the bacteria streptomyces cattleya.
They resemble a heavily modified penicillin, but still contain the β-lactam ring attached to a 5-membered ring. Carbapenems are broadly effective against both gram-positive and gram-negative bacteria.
Carbapenems are only given as a drug of last resort to prevent resistance!
The carbapenem, imipenem, is usually co-administered with cilastatin to inhibit kidney dehydropeptidase.
What is monobactams
similar to carbapenems, also contains the contain the β-lactam ring. Very resistant to beta-lactamase! Monobactams are highly effective against gram-negative bacteria.
Monobactams are ineffective against gram-positive bacteria and anaerobic bacteria.
What is vancomycin
a glycopeptide antibiotic that blocks the transpeptidase (PBP) binding site on the tetrapeptide chain, preventing pentaglycine chain cross-linking. Vancomycin does not contain a β-lactam ring!
Vancomycin is highly effective against gram-positive bacteria. It is also effective against MRSA!
Telavancin is a synthetic derivative of vancomycin which inhibits cell wall synthesis, inhibits protein synthesis, and
disrupts the cell membrane (3 mechanisms of actions in one!)
What is cycloserine
a D-alanine analog that inhibits formation of the D-alanyl-D-alanine dipeptide, preventing cross-linking.
What is bacitracin
- a cyclic polypeptide that interferes with dephosphorylation of bactoprenol, a lipid carrier which transports NAG and NAM across the cell membrane during the synthesis of peptidoglycan.
Bacitracin is extremely toxic so it can only be used topically.
What is inhibition of protein synthesis
the bacterial 70S ribosomes are composed of 50S and 30S subunits, whereas the human 80S ribosomes are composed of 60S and 40S subunits. Antibiotics which inhibit protein synthesis target either the 50S or 30S subunits, resulting in selective toxicity.
What is aminoglycosides
30S inhibitor; inhibits initiation complex formation and triggers misreading of mRNA (frame shifts). Aminoglycosides are highly effective against gram-negative bacteria. They are bactericidal.
Aminoglycosides are poorly absorbed from the GI tract, so they can not be administered orally.
Aminoglycosides can not cross the blood-brain barrier, so they require intrathecal administration for meningitis.
Aminoglycosides require O2-mediated transport for entry into bacteria cells, so they are ineffective against anaerobes.
What is tetracycline
30S inhibitor; a large structure with four rings and 3 substitutable groups.
Tetracyclines are broad spectrum against many types of bacteria; however, they are only bacteriostatic.
Tigecycline is a tetracycline derivative with even broader activity, including effectiveness against MRSA & VRE!
