Lec. 7: Inhibitors of Cell Wall Synthesis Flashcards
Name three inhibitors of cell wall synthesis.
- Penicillins
- Cephalosporins
- Vancomycin
Which has a thick peptidoglycan layer in their cell wall?
Gram positive
What has LPS in their cell wall structure?
Gram negative
What do both gram positive and gram negative bacteria cell walls have?
Beta-lactamase enzymes and penicillin-binding proteins
Who discovered penicillin?
Alexander Flemming
What two scientist proved the value of penicillin as a drug?
Chain and Florey
What are the names of the two rings (bicyclic) found in Penicillin?
- Thiazolidine ring
2. Beta-lactam ring
What ring and bond does Penicillinase act on?
Ring: Beta-lactam ring
Bond: C-N
What is the name of the penicillin binding protein that binds the strands together to make the cell wall in bacteria?
Transpeptidase - helps form the peptide bridge in peptoglycan cell wall
What are the two main subunits that make up the peptoglycan cell wall?
NAM and NAG
What are the four main classifications of penicillins?
- Natural penicillins
- Anti-staphylococcal
- Extended spectrum
- Anti-pseudomonal
Which classification of penicillins are penicillinase resistant?
Anti-staphylococcal
Give two examples of Natural Penicillins.
- Penicillin G
2. Penicillin V
Give two examples of Anti-staphylococcal penicillins.
- Nafcillin
2. Oxacillin
Which classification of penicillin is considered a beta-lactamase producing staph?
Anti-staphylococcal penicillin
What type of penicillin could be used to treat Streptococcus, Neisseria gonorrhoeae, and Treponema pallidum?
Natural Penicillins; more specifically Penicillin V
What classification of penicillin would be used to treat E. coli?
Extended spectrum penecillin
Give three examples of anti-pseudomonal penicillins.
- Ticarcillin
- Mezlocillin
- Piperacillin
Which classification of penicillin would be used to treat Pseudomonas aeruginosa?
Anti-pseudomonal penicillin
Why would a beta-lactamase inhibitor be given in combination with penicillin?
Beta-lactamase inhibitors are given in combination with penicillin because without the beta-lactam ring, the penicillin (antibiotic) would NOT have anywhere to bind and perform its action.
Name three beta-lactamase inhibitors.
- Clavulanic acid
- Sulbactam
- Tazobactam
Name four beta-lactamase inhibitor/penicillin combinations.
- Augmentin
- Unasyn
- Timentin
- Zosyn
What is the beta-lactamase and penicillin combination that makes up augmentin?
Clavulanic Acid and Amoxicillin
What is the beta-lactamase and penicillin combination that makes up unasyn?
Sulbactam and ampicillin
What is the beta-lactamase and penicillin combination that makes up timentin?
Clavulanic acid and ticarcillin
What is the beta-lactamase and penicillin combination that makes up zosyn?
Tazobactam and piperacillin
What are also referred to as “suicide inhibitors?”
Beta-lactamase inhibitors
Absorption of penicillin is dependent on what two things?
- Acid stability
2. Protein binding
Will the presences of food increase or decrease absorption of penicillin? Name the one exception.
- Decrease
2. Amoxicillin
Distribution of penicillin is good to most body site. Where is its distribution minimal?
CSF
Penicillin is mainly metabolized by ? enzymes.
Hepatic
What is the major site of excretion (90%) of penicillins?
Renal via tubular secretion
Which four penicillins are penicillanse resistant?
- Nafcillin
- Oxacillin
- Cloxacillin
- Dicloxacillin
T or F. All penicillins are considered narrow spectrum drugs.
True
What classification of penicillins have the higher % that are protein bound?
Penicillinase resistant
Which penicillins have the longest half life?
Extended spectrum
List four ways that the bacteria can become resistant to penicillins?
- Production of beta-lactamases
- Inability of penicillins to penetrate site of action
- Inability of penicillins to bind to the penicillin binding protein
- Lack of activation of autolytic enzymes
What are two mechanisms used to effectively treat resistance strains?
- Use beta-lactamase-resistant penicillins
2. Use beta-lactamse inhibitor
What penicillin would be used to treat methicillin-resistant staphylococcal infections?
Vancomycin
What are two acute allergic reactions that can occur in adverse reactions to penicillin?
- Anaphylaxis
2. Bronchospasm
What are some common adverse reactions that occur with penicillins?
- Nausea and vomiting
- Diarrhea
- Adverse effects on plasma electrolyte concentrations
- Neurotoxicity at large doses
- Hypersensitivity reactions (allergic reactions)
If penicillin G reacts with bacterial amidase, what will the product be?
6-Aminopenicillanic acid
If penicillin G reacts with beta-lactamases, what will be the product?
Penicilloic acid
Give three examples that would indicate prophylactic use of penicillin.
- Individual exposed to gonorrhea or syphilis
- Prevention of recurrence of rheumatic fever
- Patients with valvular heart disease that are undergoing surgery OR dental extraction
What is the mechanism of action of cephalosporins?
Inhibition of cell wall synthesis by binding to the bacterial transpeptidase enzyme (similar to penicillin).
What are three mechanisms of resistance of cephalosporin?
Hint: similar to penicillin
- Inability to reach target of transpeptidase enzymes
- Alteration in binding to transpeptidase enzyme
- Hydrolysis by beta-lactamases
T or F. Even 3rd generation cephalosporins are not reliable for organisms producing AmpC-inducible beta-lactamases.
True
What are the three generations of cephalosporins?
- Cephalexin
- Cefaclor
- Cefotaxime
First generation cephalosporins have a similar spectrum to ? and are most active for gram-? cocci.
- Ampicillin
2. Gram-positive
Second generation cephalosporins are most active for gram-? cocci.
Gram-negative
List three characteristics of third generation cephalosporins.
- Act on enteric gram-negative organisms
- Reserve for very serious infections
- Cross the BBB
List three characteristics of fourth generation cephalosporins.
- Increase activity for gram-positive organisms
- Beta-lactamase producing organisms
- Broad spectrum
Give two examples of fourth generation cephalosporins.
- Cefapime
2. Ceftaroline
How many current cephalosporins have activity for Enterococcus?
Zero
Progression from 1st to 3rd generation cephalosporins is marked by what four things?
- Broadening in gram-negative bacterial susceptibility
- Diminution of activity against gram + bacteria
- Increased resistance to beta-lactamase interaction
- Increased capability to enter CSF
How are most cephalosporins absorbed?
Via IV or IM
What generation cephalosporin will penetrate to CSF sufficiently to be useful for treatment of meningitis. Give two examples.
Third generation
- Cefotaxime
- Ceftriaxone
What is the only cephalosporin that does not require extra dose following hemodialysis?
Ceftriaxone
What is the major pathway for excretion of cephalosporins?
Renal Tubular pathway
Is someone more likely to be allergic to penicillin or cephalosporin?
Penicillin
Penicillins can be anaphylactic. How often are cephalosporins anaphylactic?
Rarely
Name five adverse reactions to cephalosporins.
- Sever pain with intramuscular injections
- Diarrhea and GI disturbances
- Phlebitis from IV administration
- Nephrotoxicity at high doses
- There are disulfiram-like effects with alcohol (cephalosporin must contain specific side chain; ex. cefotetan)
What binds to the penicillin binding proteins and inhibits cell wall synthesis?
Carbapenems
What has a beta-lactam ring, has high resistance to beta-lactamase enzymes, and is a potent “suicide” inactivator of beta-lactamase?
Carbapenems
What has the broadest spectrum of any beta-lactam antibiotics and is given IV?
Carbapenems
Carbapenems are administered with ?, which acts as an inhibitor of dehydropeptidase, prevents breakdown and renal toxicity, and is in fixed combination with primaxin.
Cilastatin
Carbapenems are active against what bacteria, has a role in empiric therapy, and is resistant to nosocomial gram-negatives.
Pseudomonas aeruginosa
What carbapenem does not require co-administration with cilastatin and is less likely to cause seizures?
Meropenem
What carbapenem has a longer serum half-life, is used for once a day dosing, and is active for gram-positive organisms and anaerobes?
Ertapenem
What is the mechanism of action of vancomycin?
Inhibits cell wall synthesis at a DIFFERENT site from other beta-lactams
Vancomycin has a ? spectrum that acts against gram-? bacteria and can require resistance by alteration in what binding site?
- Narrow
- Positive
- Peptapeptide binding site
Vancomycin bacteria have become more resistant by substituting D-Ala-D-Ala for what? This causes the vancomycin to spend more time NOT bound to the bacteria b/c of the mutation (3 H bonds vs 2 H bonds)
D-Ala-D-Lactate
Vancomycin does not typically go to the CNS unless what condition is present?
Meninges are inflamed
It is important to look at the patients kidney functions when giving vancomycin because during normal renal function the T1/2 is 4-6 hours, but with renal impairment the T1/2 can be up to what?
Up to 200 hours
“Red man syndrome,” nephrotoxicity, ototoxicity, and phlebitis are all adverse effects of what?
Vancomycin
T or F. No prophylactic use of Vancomycin unless MRSA is highly suspected.
True
What is used as a first line therapy for antibiotic associated colitis?
Metronidazole
If a patient tests positive for methicillin-resistant staphylococcus aureus, then what drug should not be used and what drug should be used?
Should not use vancomycin, but can switch to nafcillin
“Red man syndrome” is associated with vancomycin and caused by release of what?
Histamine