Term
| Three Steps in the Synthesis of a Bacterial Cell Wall |
|
Definition
1) Formation of Peptidoglycan Monomers (consist of a disaccharide plus a pentapeptide)
2) Polymerization of Monomers
3) Cross-Linking of Polymers by Transpeptidase Enzymes |
|
|
Term
| How are PDG polymers cross-linked? |
|
Definition
|
|
Term
| Penicillins and cephalosporins are what class of drug? |
|
Definition
|
|
Term
| B-lactams' mode of action: |
|
Definition
| inhibit bacterial cell wall synthesis |
|
|
Term
| B-lactams structurally resemble what? |
|
Definition
| resemble penicillin binding proteins (PBP), the substrates for transpeptidases |
|
|
Term
| B-lactams have reversible or irreversible binding? |
|
Definition
| Irreversible-- bind to PBPs & therefore act as suicide substrates |
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|
Term
| PBP vary from bacteria to bacteria, causing ? |
|
Definition
| bacteria vary in their susceptibility to a given B-lactam |
|
|
Term
| Lack of transpeptidase activity in the construction of a bacterial cell wall leads to the realase of ? |
|
Definition
|
|
Term
| Bacteria that are unable to produce autolysin have what type of response to B-lactams? |
|
Definition
bacteriostatic
such mutants are also tolerant to vancomycin, cycloserine, and bacitracin
infrequently encountered clinically |
|
|
Term
| B-lactams that are incapable of producing autolysin are resistant to ? |
|
Definition
| vancomycin, cycloserine, & bacitracin |
|
|
Term
| The absence of cross-linking between bacterial cell wall polymers causes ? |
|
Definition
the bacterial cell wall is structurally weakened --> lysis of the cell in HYPOtonic environments
does NOT happen in HYPERtonic environments (eg, abscess): why we drain abscesses! |
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|
Term
| What environment is required for a bacteria to lyse after a B-lactam is given? |
|
Definition
|
|
Term
| B-lactams are bacteriostatic or bactericidal? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Innate resistance to B-lactams is from what? |
|
Definition
Inability of drugs to penetrate the outer cell membrane of bacteria
hydroPHILIC B-lactams are least susceptible to this form of resistance because they are able to pass through porins in the bacterial cell membranes |
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|
Term
| What type of B-lactam is a bacterium less likely to be innately resistant to? |
|
Definition
| hydroPHILIC, because these B-lactams can more easily pass through porins in the bacterium cell membrane |
|
|
Term
| Acquired resistance of bacterial pathogens to B-lactam drugs is often due to ? |
|
Definition
|
|
Term
| How can B-lactamase production be overcome? |
|
Definition
Using a B-lactamase inhibitor in combination with the B-lactam drug
many different B-lactamases exist, which differ in their binding affinities for a given B-lactam drug |
|
|
Term
| How do B-lactamases work? |
|
Definition
| They cleave the C-N bond of the four membered B-lactam ring |
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|
Term
| Acquired resistance to B-lactams can also arise due to: |
|
Definition
alteration of the PBP target
up-regulation of efflux pumps |
|
|
Term
| When resistance to a B-lactam is due to an altered PBP: |
|
Definition
| a different class of drug must be used for treatment |
|
|
Term
| The resistance seen in MRSA is due to: |
|
Definition
|
|
Term
| The resistance in PRSP is due to: |
|
Definition
|
|
Term
| Various B-lactam drugs differ chemically by: |
|
Definition
| different substituent groups attached to the basic B-lactam structure |
|
|
Term
| Different substituent groups attached to B-lactam drugs affects the drugs': |
|
Definition
ability to penetrate cell membrane porins
susceptibility to B-lactamases
its binding to target enzymes |
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|
Term
| Penicillins are bacteriostatic or bactericidal? |
|
Definition
|
|
Term
| Penicillin is from which mold? |
|
Definition
|
|
Term
| What is the lead compound for all penicillins? |
|
Definition
|
|
Term
| How are semi-synthetic penicillins made? |
|
Definition
| By attaching various R-groups to 6-aminopenicillanic acid (lead compound in penicillins) |
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|
Term
| What does penicillin acylase do? |
|
Definition
| removes the R group from semi-synthetic penicillins to --> 6-aminopenicillanic acid |
|
|
Term
| How many R groups to penicillins have? |
|
Definition
|
|
Term
| Penicillins are available in what forms? |
|
Definition
| oral, IV, repository forms |
|
|
Term
| When can penicillins access the CNS? |
|
Definition
| When the meninges are inflamed |
|
|
Term
| Can penicillins access most tissues? |
|
Definition
| Yes, except for the CNS (but can enter when the meninges are inflamed) |
|
|
Term
| Penicillins are polar or non-polar? |
|
Definition
|
|
Term
| How are penicillins eliminated? |
|
Definition
| excreted by the kidneys (filtered & secreted there) |
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|
Term
|
Definition
| inhibits the tubular secretion of penicillins, elongating their half-life in the body |
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|
Term
| Penicillin drug allergy works by: |
|
Definition
isomerization of the B-lactam ring allows them to bind to proteins in the body
these drug-protein complexes act as the antigen against which penicillin hypersensitivity reactions are directed |
|
|
Term
| How do allergic reactions to penicillin present? |
|
Definition
skin rases
rarely: serum sickness & anaphylaxis |
|
|
Term
| Adverse effects of penicillin include: |
|
Definition
alteration of normal gut flora --> nausea, vomiting, diarrhea
more extreme cases: psuedomembranous colitis & mucositis |
|
|
Term
| Penicillins are also given as Na+ and K+ salts, --> what potential complication? |
|
Definition
| seizures from hypernatermia or hyperkalemia, especially in patients with renal failure |
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|
Term
| How are penicillins classified? |
|
Definition
| spectrum of action & resistance to B-lactamases |
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|
Term
| Penicillin G is active against: |
|
Definition
| Group A Strep, T. palladium (syphilis), some Enterococci, susceptible strains of Pneumococci, Meningococci, and anaerobes |
|
|
Term
| Penicillin G has what type of spectrum? |
|
Definition
|
|
Term
| What drugs are described as very narrow spectrum, penicillinase resistant? |
|
Definition
| methicillin, nafcillin, & oxacillin |
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|
Term
| Methicillin, Nafcillin, and Oxacillin are active against: |
|
Definition
| Staphlococci (except MRSA) |
|
|
Term
| Methicillin isn't used very much because: |
|
Definition
it is nephrotoxic
now we use oxacillin more |
|
|
Term
| Examples of extended-spectrum, B-lactamase susceptible drugs are: |
|
Definition
aminopenicillins (ampicillin, amoxicillin)
carboxypenicillins (ticarcillin)
ureidopenicillins (piperacillin) |
|
|
Term
| ampicillin & amoxicillin are: |
|
Definition
| extended spectrum, B-lactamase susceptible |
|
|
Term
| aminopenicillins include: |
|
Definition
|
|
Term
| aminopenicillins (ampicillin & amoxicillin) are active against: |
|
Definition
E. coli, H. flu, L. monocytogenes, P mirabilis, & Enterococcus
(these drugs are more hydrophilic than other penicillins & are therefore better able to penetrate the outer cell wall of Gram negatives) |
|
|
Term
| Ticarcillin is an example of a: |
|
Definition
|
|
Term
| Ureidopenicillins (piperacillin) are active against: |
|
Definition
many Gram negatives, including K. pneumonia & B. fragilis
(also relatively hydrophilic) |
|
|
Term
| Carboxypenicillins (Ticarcillin) are active against: |
|
Definition
| many Gram negatives, including Psuedomonas & Proteus species |
|
|
Term
| All extended-spectrum B-lactamase susceptible drugs are often used in combination with: |
|
Definition
|
|
Term
| Clavulanic acid, Sulbactam, & Tazobactam are examples of: |
|
Definition
|
|
Term
| B-lactamase inhibitors are used with: |
|
Definition
| extended-spectrum B-lactams (ampicillin, amoxicillin, ticarcillin, piperacillin) |
|
|
Term
| Why are B-lactamase inhibitors used? |
|
Definition
| to extend the spectrum of ampicillin, amoxicillin, ticarcillin, & piperacillin to include B-lactamase producing organisms |
|
|
Term
| What structural component do B-lactamase inhibitors contain that allows them to be efficacious? |
|
Definition
a B-lactam ring
these drugs bind up B-lactamases, thus acting as suicide substrates |
|
|
Term
| B-lactamase inhibitors act as what type of substrate? |
|
Definition
| suicide substrate (for B-lactamase) |
|
|
Term
| The combination of B-lactam + B-lactamase inhibitor is: |
|
Definition
|
|
Term
| What is the lead compound for cephalosporins? |
|
Definition
| 7-aminocephalospranic acid |
|
|
Term
| How many R groups do cephalosporins have? |
|
Definition
|
|
Term
| What do the R groups of cephalosporin influence? |
|
Definition
| hydrophobicity, B-lactamase susceptibility, & target binding properties of the individual cephalosporins |
|
|
Term
| Is there cross-allergenicity between penicillins and cephalosporins? |
|
Definition
There is some cross-allergenicity, but not complete
If a patient has had a severe reaction to penicillin, s/he should not be given a cephalosporin |
|
|
Term
| What side effects are common with cephalosporins? |
|
Definition
|
|
Term
| How are cephalosporins usually administered? |
|
Definition
| parenteral administration |
|
|
Term
| Do most cephalosporins enter the CNS? |
|
Definition
|
|
Term
| How are cephalosporins eliminated? |
|
Definition
|
|
Term
| How are cephalosporins classified? |
|
Definition
| by their antibacterial spectra |
|
|
Term
| Cefazolin is what generation of what drug class? |
|
Definition
| 1st generation cephalosporin |
|
|
Term
| 1st generation cephalosporins (Cefazolin) are active against: |
|
Definition
most Gram + cocci (even penicillinase producing bugs) and E. coli, K. pneumoniae, & P. mirabilis
used for surgical prophylaxis & skin infections |
|
|
Term
| Used for surgical prophylaxis and skin infections: |
|
Definition
| 1st generation cephalosporins (Cefazolin) |
|
|
Term
| Cefuroxime and Cefoxitin are what generation of what class of drugs? |
|
Definition
| 2nd generation cephalosporins |
|
|
Term
| 2nd generation cephalosporins are active against: |
|
Definition
| Gram negative organisms such as H. flu Cefuroxime) and B. fragilis (Cefoxitin) |
|
|
Term
| Cefuroxime is active against: |
|
Definition
H. flu (Gram negative)
(2nd generation cephalosporin) |
|
|
Term
| Cefoxitin is active against: |
|
Definition
B. fragilis (Gram negative)
(2nd generation cephalosporin) |
|
|
Term
| Used for respiratory & mixed anaerobic infections: |
|
Definition
| 2nd generation cephalosporins (Cefuroxime & Cefoxitin) |
|
|
Term
| 3rd & 4th generation cephalosporins are active against: |
|
Definition
| Enteric Gram negative bacilli, including hospital acquired strains that exhibit multiple drug resistance |
|
|
Term
| Cefaperazone is what generation & what class of drug? |
|
Definition
| 3rd generation cephalosporin |
|
|
Term
| Cefepime is what generation & what class of drug? |
|
Definition
| 4th generation cephalosporin |
|
|
Term
|
Definition
|
|
Term
| 3rd & 4th generation cephalosporins (Cefaperazone & Cefepime) are used as empirical therapy for: |
|
Definition
| serious infections, including meningitis & sepsis |
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|
Term
| Aztreonam is an example of a: |
|
Definition
|
|
Term
| How many rings to monobactams have? |
|
Definition
|
|
Term
| How many rings do penicillins have? |
|
Definition
|
|
Term
| How many rings do cephalosporings have? |
|
Definition
|
|
Term
| Are monobactams susceptible to B-lactamases? |
|
Definition
|
|
Term
| What do monobactams (Aztreonam) target in the microorganism? |
|
Definition
PBP 3 of Gram negative bacteria
bactericial against Gram negative aerobes such as E. coli K. pneumoniae, H. flu, Proteus, Salmonella |
|
|
Term
| Aztreonam (a monobactam) is bactericidal against: |
|
Definition
| Gram negatives: E. coli, K. pneumonia, H. flu, Proteus, Salmonella |
|
|
Term
| Monobactam + aminoglycoside = |
|
Definition
|
|
Term
| True/False: Monobactams & aminoglycosides have similar antibacterial spectrums. |
|
Definition
|
|
Term
| Adverse effects of monobactams (Azteronam) include: |
|
Definition
|
|
Term
| Are monobactams cross-allergic with penicillins or cephalosporins? |
|
Definition
|
|
Term
| How are monobactams administered? |
|
Definition
|
|
Term
| How are monobactams eliminated? |
|
Definition
|
|
Term
| What are monobactams used for? |
|
Definition
| serious infections with drug-resistant Gram negative aerobes |
|
|
Term
| Imipenem/Cilastatin, Meropenem, & Ertapenem are examples of: |
|
Definition
|
|
Term
| Carbapenems (Imipenem/Cilastatin, Meropenem, Ertapenem) target: |
|
Definition
|
|
Term
| Carbapenams are bactericidal against: |
|
Definition
| many Gram + and negative organisms as well as some PRSP (but NOT MRSA) |
|
|
Term
| Are carbapenams susceptible to B-lactamases? |
|
Definition
|
|
Term
| Is resistance a problem for carbapenams? |
|
Definition
| not yet; drug use is limited to prevent development of resistance |
|
|
Term
| Adverse effects of carbapenams include: |
|
Definition
| hypersensitivity (partial cross-sensitivity with penicillins), GI disturbances, seizures (esp. in patients with renal failure) |
|
|
Term
| Do carbapenams and penicillins have cross-allergenicity? |
|
Definition
|
|
Term
| How are carbapenams administered? |
|
Definition
|
|
Term
| How are carbapenams elimiated? |
|
Definition
|
|
Term
| What enzyme in the kidney cleaves the B-lactam ring of Imipenem? What is the significance of this? |
|
Definition
dehydropeptidase I
When using Imipenam, Cilistatin must also be given to inhibit dehydropeptidase I |
|
|
Term
| What drug class might we use as prophylaxis in immunocompromised patients? |
|
Definition
|
|
Term
| Carbapenams (Imipenem/Cilastatin, Meropenam, Erapenem) are used to treat: |
|
Definition
| mixed infections & serious infections with organisms resistant to other drugs |
|
|
Term
| Vancomycin & Teicoplanin bind to: |
|
Definition
| the D-ala-D-ala structure in cell wall subunits, inhibiting polymerization of growing PDG chains & blocking cross-linking of the chains |
|
|
Term
| Vancomycin & Teicoplanin inhibit: |
|
Definition
polymerization of PDG chains
also: block cross-linking of the chains |
|
|
Term
| Vancomycin & Teicoplanin are not very useful against: |
|
Definition
| most Gram negatives, because these drugs are too large to pass through the outer cell membrane |
|
|
Term
| Acquired drug resistance to Vancomycin & Teicoplanin is due to: |
|
Definition
| mutation of the D-ala-D-ala structure to D-ala-D-lac |
|
|
Term
| Mutation of the D-ala-D-ala structure to D-ala-D-lac confers resistance to: |
|
Definition
|
|
Term
| Vancomycin & Teicoplanin are bactericidal against: |
|
Definition
|
|
Term
| Adverse effects of Vancomycin & Teicoplanin are: |
|
Definition
flushing due to histamine release (aka red man's syndrome)
ototoxicity --> hearing loss
nephrotoxicity |
|
|
Term
| Red man's syndrome is a side effect of: |
|
Definition
|
|
Term
| Ototoxicity is a risk of: |
|
Definition
|
|
Term
| Why must vancomycin & teicoplanin be administered via IV for systemic treatment? |
|
Definition
| They have low oral bioavailability |
|
|
Term
| How are vancomycin & teicoplanin eliminated? |
|
Definition
|
|
Term
| What is used to treat MRSA and PRSP? |
|
Definition
|
|
Term
| What are vancomycin & teicoplanin used to treat? |
|
Definition
| serious infections with B-lactam resistant Gram + organisms |
|
|
Term
| How does bacitracin work? |
|
Definition
| blocks dephosphorylation of the lipid II carrier that transfers PDG subunits across the plasma membrane |
|
|
Term
| What is bacitracin effectve against? |
|
Definition
|
|
Term
| How is bacitracin administered? |
|
Definition
| Topically only because of nephrotoxicity |
|
|
Term
| This drug is a structural analog of D-alanine: |
|
Definition
|
|
Term
|
Definition
| inhibiting alanine racemase & D-ala-D-ala ligase |
|
|
Term
| Cycloserine is used to treat: |
|
Definition
|
|
Term
| An adverse effect of cycloserine may be: |
|
Definition
|
|
Term
|
Definition
| inhibiting enolpyruvate transferase, an early step in cell wall synthesis |
|
|
Term
| Fosfomycin is active against: |
|
Definition
|
|
Term
|
Definition
| uncomplicated urinary tract infections |
|
|
Term
| This drug is safe to use during pregnancy and is also quite expensive: |
|
Definition
|
|
Term
| The structure of daptomycin includes: |
|
Definition
| cyclic peptide & a lipophilic tail |
|
|
Term
| How does daptomycin work? |
|
Definition
| Molecules of the drug integrate into bacterial cell membranes & then group together, forming a pore & allowing K+ to leak from the cell |
|
|
Term
| Insertion of the lipid tail region of daptomycin is dependent on what? |
|
Definition
|
|
Term
| Daptomycin is bactericidal against: |
|
Definition
| Gram + organisms, including MRSA, VRSA, and VRE |
|
|
Term
| Daptomycin has concentration- or time-dependent killing? |
|
Definition
|
|
Term
| Does daptomycin have a PAE? |
|
Definition
|
|
Term
| Is resistance a problem for daptomycin? |
|
Definition
|
|
Term
| Adverse effects of daptomycin include: |
|
Definition
| GI disturbances, myopathy (monitor CPK) |
|
|
Term
| How is daptomycin administered? |
|
Definition
|
|
Term
| Daptomycin is eliminated: |
|
Definition
|
|
Term
| drugs target bugs at 4 main levels: |
|
Definition
cell wall synthesis
protein synthesis
folate pathway
DNA/RNA |
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|
