Antibiotic Drug Classes Flashcards
At the most basic level, antimicrobial agents act through what four distinct major mechanisms of actions?
Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of folic acid biosynthetic pathways Inhibition of DNA/RNA synthesis
Penicillins belong to a class of antibiotics known as ____
β-lactams (others include carbapenems and cephalosporins)
What are some examples of narrow-spectrum penicillins?
Oxacillin, Nafcillin
What are some examples of aminopenicillins?
Ampicillin, Amoxicillin
What are some examples of broad-spectrum penicillins?
Piperacillin.
What is the mechanism of action of penicillins?
- The first is the binding to penicillin-binding proteins.
2. The second is the destruction of the bacterial cell wall.
T or F. Virtually all bacteria contain penicillin-binding proteins
T. Different bacteria have different amounts and different types of penicillin-binding proteins. For example, Escherichia coli has seven types, and Staph. aureus has four.
Different penicillin-binding proteins have different affinities for β-lactams, and therefore different bacteria will demonstrate different sensitivities to β-lactams
How do B-lactams work?
by inhibiting transpeptidases, the enzymes that cross-link peptidoglycan molecules in bacterial cell walls. Cross-linking these molecules gives strength to the cell wall. Weak walls typically leads to lysis.
Are gram-positive or negative bacteria susceptible to B-lactams? Why?
Gram-positive bacteria have a thick peptidoglycan layer. They are therefore sensitive to β-lactams.
Gram-negative bacteria have a thinner peptidoglycan layer, but external to this layer is a lipopolysaccharide layer. This lipopolysaccharide layer protects the peptidoglycan layer from β-lactam activity, and therefore gram-negative bacteria are significantly more resistant to β-lactams.
What are β-Lactamase inhibitors?
these are added to some β-lactam antibiotics to overcome resistance caused by β-lactamase. Although β-lactamase inhibitors do contain a β-lactam, they are not toxic to the bacteria; they merely bind to β-lactamase.
What are some examples of β-lactamase inhibitors?
Clavulanic acid (added to amoxicillin) Tazobactam (added to piperacillin)
What are the positives and negatives of narrow-spectrum B-lactams?
Narrow-spectrum penicillins contain a larger molecule on the penicillin molecule side chain that confers steric hindrance: the inability to twist the molecule into other stereoisomers. This results in these penicillins being resistant to β-lactamase but at the same time restricts their spectrum of activity (thus they are said to be narrow-spectrum agents).
What are aminopenicillins used for?
Aminopenicillins have an added amino group (NH2) that makes the molecule more hydrophilic and thus able to cross the lipopolysaccharide layer more easily. Therefore aminopenicillins have greater activity against gram-negative bacteria.
What are the uses of broad-spectrum penicillins?
Broad-spectrum penicillins are modifications of aminopenicillins: nitrogen and carbon atoms are added to the molecule. This increases the range of bacteria that are sensitive to the antibiotic. These penicillins are usually co- administered with a β-lactamase inhibitor because they are β-lactamase sensitive (a common example is “Pip/Tazo,” which is piperacillin and tazobactam).
How does the drug aztreonam differ from penicillins and cephalosporins in its structure and function?
Unlike the penicillins and cephalosporins, which contain a thiazolidine ring attached to the β-lactam ring, aztreonam is a monobactam. The β-lactam ring contains a sulfonic acid group that gives aztreonam its activity. Like the penicillins and cephalosporins, aztreonam is mainly bactericidal and inhibits bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall.
How do Carbapenems (brand: Imipenem) differ structurally from penicillins?
The 5-membered ring at its core contains a carbon atom, rather than a sulfur atom.
What are the uses of Imipenem?
a) more efficient penetration through the bacterial cell wall,
b) resistance to bacterial enzymes. Imipenem has a high degree of stability in the presence of beta-lactamases, and is itself a potent inhibitor of beta-lactamases from certain gram-negative bacteria that may be inherently resistant to many beta-lactam antibiotics
c) affinity for all bacterial PBPs. Imipenem has a broader spectrum of activity than do many other beta-lactam antibiotics.
Imipenem is often given in combination with Cilastatin. Why?
Cilastatin is a reversible, competitive inhibitor of dehydropeptidase-1 (DHP-1), an enzyme found in the brush border of the proximal tubular cells of the kidneys that breaks down imipenem to inactive metabolites. By inhibiting this enzyme, cilastatin prevents the renal metabolism of imipenem, which results in an increase in urinary concentrations of imipenem from 15—20% to 60—70% and minimizes the nephrotoxicity observed when imipenem is administered alone. Cilastatin has no antimicrobial activity, nor does it interfere with imipenem’s actions
T or F. IN GENERAL, gram-positive activity
is lost with each successive drug generation of cephalosporins, whereas activity against gram-negative organisms is gained.
T
What are first generation cephalosporins use for?
useful in treating skin infections (which are commonly Streptococcus or Staphylococcus)
What are some common first generation cephalosporins and their uses?
Cefazolin is used commonly for surgical prophylaxis.
Cephalexin (1st gen; oral drug) is the most commonly prescribed cephalosporin for outpatient use.
What are second generation cephalosporins used for?
good for mild gram-negative Bacteroides infection (anaerobic), which can occur with intraabdominal infections.
They are used less commonly for severe infections because third-generation cephalosporins are more efficacious.