EXAM #4: ANTIBIOTICS II Flashcards
Describe the composition of peptidoglycan.
Peptidoglycan is composed of repeating monomers of NAM-NAG-pentapeptide
What is NAM?
N-acetylmuramic acid
What is NAG?
N-acetylglucosamine
What is the function of the Penicillin-Binding Proteins?
Forming peptidoglycan by creating the NAM-NAG bonds
What category of antibiotics inhibit the PBPs?
Beta-Lacam antibiotics
What drugs are part of the B-Lactam family of antibiotics?
Penecillin
Cephalosporins
Monobactams
Carbapenems
Are the B-Lactams bacteriostatic or bactericidal?
Bactericidal
What enzyme can cause drug resistance in the B-Lactams?
Beta-Lactamase, which hydrolyzes the Lactam ring that is integral to this class of antibiotics
List the antibiotics that fall into the PCN family.
PCN G PCN V Amoxicillin Methicillin Nafcillin Oxacillin Ampicillin Piperacillin Ticarcillin Azlocillin
All end in “cillin”*
What are the key adverse effects seen with the PCN family of antibiotics?
Hypersensitivity
If a patient has a severe reaction to a PCN-type antibiotic, what should you be concerned about?
Hypersensitivity to ALL Beta-Lactam drugs, not JUST the PCNs
What is unique about the drug Methicillin?
This is a synthetic PCN-type drug that is RESISTANT to Beta-Lactamase
What PCN-type drugs are narrow spectrum?
PCN G PCN V Methicillin* Nafcillin* Oxacillin*
*Note that all three are “v. narrow spectrum” and are ALL resistant to Beta-Lactamase
What PCN-type drugs are broad spectrum?
Ampicillin Amoxicillin Piperacillin Ticarcillin Azlocillin
What is the utility of Beta-Lactamase inhibitors?
- Side-setting drug resistance mechansim
- These drugs can be CO-ADMINISTERED with PCN-type drugs
What is the hallmark Beta-Lactamase inhibitor?
Clavulanic acid
How is Clavulinc acid commonly administered?
Co-administration with Amoxicillin as AUGMENTIN
If a patient has a mild hypersensitivity reaction to PCN-type drugs, what family of drugs should you consider?
Cephalosporins
Generally, how do the Cephalosporins differ from the PCN-type drugs?
More resistant to Beta-Lactamase
What is the key adverse reaction to the Cephalosporins?
Hypersensitivity
What is the theme in terms of specificity/generation in the Cephalosporins?
- There are 4 generations - 1 is narrow (gram positive only)
- 4 is the broadest (gram positive and negative)
What is the theme in Cephalosporin generations and CNS penetration?
3rd and 4th generation Cephalosporins penetrate the BBB
What are the first generation Cephalosporins?
Cefazolin
What are the 2nd generations cephalosporins?
Cefotetan
Cefaclor
Cefuroxime
What are the 3rd generation Cephalosporins?
Ceftriaxone
Cefotaxime
Cefdinir
Cefixime
What is the 4th generation Cephalosporin?
Cefepime
What is the MOA of the monobactams?
PBP inhibitor
What is the only drug in the monobactam family?
Aztreonam
What are the important features to remember about Aztreonam?
- Gram negative ONLY
- Penetrates the BBB
- Beta-lactamase resistance
What is the key adverse effect seen with Aztreonam?
Mild hypersensitivity
What is the MOA of the Carbapenems?
PBP inhibitors
What is the spectrum of activity in the Carbapenems?
Both gram negative and positive
Generally, when are the Carbapenems used?
Life-threatening infections
What are the unique features of the Carbapenems?
- Resistant to Beta-Lactamase
- Susceptible to Carbamenemase
List the drugs that fall into the Carbapenem family.
Doripenem
Imipenen
Entapenem
Meropenem
What are the key side effects seen with the Carbapenems?
GI disturbances
What family of antibiotics does Vancomycin fall into?
Glycopeptide antibiotic
What is the MOA of Vancomycin?
- Prevents elongation of the peptidoglycan cell wall
- Binds to the pentapeptide and sterically inhibits pentapeptide linkage
- Specific target is the D-ala/ D-ala
**Note it is NOT binding to the PBP but IS still a Beta-Lactam antibiotic
What is Vancomycin commonly used to treat?
Gram + bacteria e.g. MRSA
What should you remember about Vancomycin and the CNS?
- Poor CNS penetration
- However, still a good first choice to treat meningitis
What is the key adverse effect seen with Vancomycin?
Red Man Syndrome
- Flushing
- Red neck
What is the MOA of Bacitracin?
Blocks incorporation of amino acids and nucleic acids into the cell wall of the bacteria
Inhibits the building of the building blocks that are used to create the cell wall
What is the specificity of Bacitracin?
Both gram positive and negative
What is unique about Bacitrain?
Commonly included in TOPICAL preparations (OTC)
What type of drug is Fosfomycin?
Cell wall synthesis inhibitor
Similar to Bacitracin
What is the specific MOA of Fosfomycin?
Prevents the synthesis of UDP-NAM–disaccharide (a component of peptidoglycan)
What is Fosfomycin commonly used to treat?
UTIs
What is the general MOA of protein synthesis inhibitor antibiotics?
Bind and inhibit the bacterial ribosome–70S
In general, are the protein synthesis inhibitors bactericidal or bacteriostatic?
Bacteriostatic
What are the two subunits of the bacterial ribosome?
50S and 30S
Review the steps of protein synthesis.
1) charged tRNA binds to the A site of the ribosome
2) Peptide bond formation between amino acid in A site and growing chain
3) Newly uncharged tRNA exits
4) Longer amino acid chain translocates into the P site
What class of antibiotics are the Aminoglycosides?
Protein synthesis inhibitors
List the aminoglycosides?
Streptomycin Gentamicin Kanamycin Amikacin Tobramycin Neomycin
How are aminoglycoside antibiotics commonly used?
In combination with Beta-Lactams for SERIOUS gram negative infections
What part of the bacterial ribosome is inhibited by the aminoglyocisdes?
30S subunit by preventing the tRNA molecules from entering the A site
What are the key adverse effects associated with the Aminoglycosides?
1) Nephrotoxicity
2) Ototoxicity
How do the Aminoglycosides differ from the general pattern of the protein synthesis inhibitors?
Generally BACTERICIDAL
What antibiotic class are the Macrolides?
Protein synthesis inhibitors
List the Macrolides.
Erythromycin
Clarithromycin
Azithromycin
What is the target of the Macrolides?
50S subunit–disrupts the translocation of the growing amino acid chain from the A site to the P site to allow for a new amino acid to enter
What are the key side effects associated with the Macrolides?
GI disturbances
How do the Macrolides alter GI physiology?
Motilin receptor agonists
What class of antibiotic are the Tetracyclines?
Protein synthesis inhibitors
What subunit of the bacterial ribosome do the Tetracycline block?
30S
What is the specific MOA of the Tetracyclines?
The drug blocks the A site of the ribosome to prevent the charged tRNA from entering
What nutrient interaction do you need to remember about the Tetracyclines?
- Binds Ca++
- Will result in GROWTH of calcified tissue
*Don’t use in growing kids or pregnant women
What are two additional adverse effects that need to be remembered about the Tetracyclines?
1) Disrupt the normal flora (more than the other drugs)
2) Cause photosensitivity
