Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
86 Cards in this Set
- Front
- Back
|
What are four groups of beta lactams?
|
penicillins, cephalosporins, monobactams, carbapenems
|
|
|
What are four types of penicillins?
|
-penicillin , penicillinase resistant penicillin, aminopenicillins, antipseudomonal penicillins
|
|
|
Describe the side chain differences amongst the different beta lactams?
|
penicillin : 5 sided ring with S at the top
cephalosporin: 6 sided with S at the top carbapenems: 5 sided with C at the top monobactams: no sided ring and side chains |
|
|
What is intact beta lactam needed for? what is the purpose of different side chains?
|
-intact beta lactam is needed for anti-bacterial activity
-enzymes (beta lactamase) inactivate them -side chains effect spectrum of activity and other properties such as half life and acid stability |
|
|
What is the mechanism of action of beta lactam?
|
-inhibits cell wall synthesis; synthesis of peptidoglycan wall requires 30 enzymes;
|
|
|
What kind of peptides are penicillins and what do they do?
|
penicillins are dipeptides (alanine and beta dimethylcysteine) that competitively inhibit cross linkage (transpeptidase) of the cell by looking like Dala-dala and covalently binding to target!
|
|
|
What are the ranges of Staph aureus intracellular osmotic pressure?
|
1013-2.026x10^6 Pa; 75,00-15,000 mm hg or 10-20 atmospheres
|
|
|
What do penicillins bind to?
|
PBP, which is a transpeptidase. Other pbps are necessary for rod-like shape and for maintaining septum formation during division!
|
|
|
Explain the spectra of activity of penicillins?
|
-have to pass through porins in gram negative
-diff penicillins have different sizes and charges -each cell wall target (PBP-penicillin binding protein) is vulnerable to diff penicillins -bacteria: autolysins that remodel cell wall |
|
|
What is spectrum of activity of bacteria for penicillin G?
|
streptococci, enterococci, T. pallidum, B. burgdorferi, N. meningitidis, actinomyces
|
|
|
Which type of penicillin is short acting and what bacteria does it target?
|
-Procaine PenG: targets streptococci, mouth anaerobes, meningococcus, listeria
|
|
|
What type of penicillin is long acting and what bacteria does it target?
|
benzathine is long acting, targeting T. pallidum, rheumatic fever prophylaxis
|
|
|
What is penicillin V potassium?
|
oral
|
|
|
describe penicillin penetration in uninflamed v. inflamed meninges?
|
-poor penetration in uninflamed meninges; some ~5% of serum concentration found in CSF when meninges are inflamed; so able to sue penicillin to treat meningitis when caused by susceptible bacteria
|
|
|
When a patient has lyme disease CNS spread; what penicillin amount do you use, what is serum median peak concentration, what is median range?
|
-penicillin 3 gm (5 million units) q 6 hr
-serum median peak concentration; 37 ug/ml -CSF median 0.5 range 0.3-1.6 ug/ml |
|
|
What is 1 international unit of crystalline penicillin G sodium?
|
0.6 ug
|
|
|
What is 1 mg of penicillin G sodium = (in units)?
|
1667 units
|
|
|
What are three IV forms of penicillinase-resistant pencillins and what is one P.o. type?
|
nafcillin, oxacillin, methicillin
po: dicloxacillin |
|
|
for penicillinase-resistant penicillins, what does it act against?
|
anti-staphylococcal; not hydrolized by penicillinase produced by staph
|
|
|
What are the downfalls of penicillinase resistant penicillins?
|
-less active than penicillin G and adverse side effects include: leukopenia, renal (note: nafcillin has biliary excretion)
|
|
|
What are two types of aminopenicillins and describe their activity:
|
ampicillin, amoxicillin: some gram negative activity
|
|
|
Describe two groups of anti-pseudomonal penicillins:
|
-carboxypenicillins: carbenicillin:
-ureidopenicillins: piperacillin: |
|
|
What is a benefit of piperacillin and a negative of piperacillin (group: ureidopenicillins):
|
-positive is that piperacillin is more active than ticarcillin against P. aeruginosa; gram negative rods and bacteroides
--> but they are inactivated by some of the most common beta lactamases! |
|
|
What are the adverse side effects of penicillins (HAGS)
|
hypersensitivity, anaphylaxis, granulocytopenia, seizures
|
|
|
How many generations of cephalosporins are there?
|
4
|
|
|
what are the three names of diff types of first generation cephalosprins?
|
cephalothin, cefazolin (half life 2 hours); cephalexin
|
|
|
What are the first generation cephalosporins active against?
|
staph, strep, some gram negative
not pseudomonas, poor anaerobic activity -not active against enterococci |
|
|
Second generation cephalosporins: what are the three types:
|
cefoxitin, cefotetan (cefamycin: methoxy at position 7)
cefuroxime |
|
|
What are cefoxitin and cefotetan more active against?
|
-more active against gram negative and anaerobes! (B. fragilis)
|
|
|
Cefuroxime is active against what/
|
-active against ampicillin resistant H. flu and penetrates into CSF!!!!
|
|
|
What are the oral forms of cephalosporins?
|
cefuroxime axetil, cefaclor, cefprozil, loracarbef
|
|
|
What is an important cephalosporin side chain and what is it associated with? (4 associations are important!!!!)
|
-MTT (methyltetrazole-thiomethyl) at position 3: cefamandole, cefotetan, moxolactam, associated with
1.) disulfiram-like reactions 2.) hypoprothrombinemia 3.) inhibition of vit K 4.) bleeding |
|
|
Third generation cephalosporin: what are two important types and what are they good at acting against and what are they less good at acting against? What do they penetrate?
|
-Ceftazidime, cefoperazone (MTT): activity against gram negatives such as Pseudomonas aeruginosa
-less active against gram positives and penetrates CSF |
|
|
Third generation cephalosporins: What is the activity of cefotaxime and ceftriaxone:
|
-good gram negative activity; but not P. aeruginosa; modest gram positive activity
|
|
|
compare half life of cefotaxime and ceftriaxone. Based on this what can you use cetriaxone for?
|
-cefotaxime: (half life is 1.1 hours)
-ceftriaone: (half life is 8 hours): home IV, gonorrhea, and ceftriaxone gallstones |
|
|
What are the oral agent for third generation cephalosporins?
|
oral agents include cefixime and cefpodoxime
|
|
|
Compare CSF concentrations of third generation cephalosporins in blood and in CSF for 2 grams of each. What happens when you increase to 24 gm/day of cefotaxime and 4 gm/day of ceftriaxone? ANY CHANGE IN CSF?
|
-cefotaxime 2 gm: BLOOD is 130 and CSF is 0.7-8
-ceftriaxone 2 gm: BLOOD is 250 and CSF is 3.5 1-18 no difference in relative concentrations if increase |
|
|
What is the fourth generation cephalosporin? What is half life and describe the activity against antibiotics!
|
-cefepime: half life is 2 hours!
-active against gram negatives including P. aeruginosa and gram positives |
|
|
What are all cephalosporins NOT active against (4 things)
|
enterococci, MRSA, listeria, legionella
|
|
|
What is the newest advanced generation cephalosporin and what is it active agianst?
|
ceftaroline is active against MRSA!!!
|
|
|
What is a monobactam and what is it active against?
|
-example is aztreonam: (monocyclic beta lactam) active against gram negative rods including P. aeruginosa
-no activity against gram positive or anaerobes |
|
|
What are three types of carbapenems?
|
imipenem and meropenem and ertapenem (long half life of 4 hours!)
|
|
|
Compare and contrast structures of imipenem and meropenem:
|
imipenem has a hydroxyethyl side chain in trans orientation ; metabolized by a renal enzyme dihydropeptidase and cilastatin inhibits dihydropeptidase
*MEANWHILE: meropenem hydroxyethyl side chain in cis orientation with different side chain on the side ring and NOT hydrolyze by renal dihydropeptidase |
|
|
Describe the activity of carbapenems:
|
broad gram negative coverage:
-imipenem and meropenem are active against pseudomonas aeruginosa but ertapenem is NOT active against it -S. aureus (methicillin susceptible) and streptococci -anaerobes |
|
|
Compare meropenem and imipenem:
|
meropenem has increased gram negative activity and less gram positive activity compared to imipenem
|
|
|
What is an adverse side effect of imipenem?
|
seizures from imipenem
|
|
|
Name the beta lactamase inhibitors:
|
clavulanic acid, sulbactam, tazobactam : used in combination with a beta lactam antibiotic and are NOT antibacterial agents!
|
|
|
What is augmentin and what are the three different dosage forms of it?
|
Amoxicillin and clavulanate (augmentin):
A/C: 250: amox 250 and clav 125 A/C: 500: amox 500 and clav 125 A/C: 875: amox 875 and clav: 125 *Augmentin XR has 2 tablets twice daily: --> each tablet contains amoxicillin trihydrate and amoxicillin sodium 1000 mg and clavulanate 62.5 mg |
|
|
beta lactamase inhibitor: what is in unasyn, timentin, zosyn, and what do you take for P. aeruginosa?
|
unasyn: ampicillin + sulbactam
timentin: ticarcillin + clavulanate zosyn: piperacillin + tazobactam Pip/tazo: 3.375 gm q 6 hours (pip 3 gm and tazo 0.3 gm) but for P. aeruginosa, 4.5 gm q 6 hours OR 3.375 mg q 4 hr |
|
|
Describe the half life of common antibacterial agents: namely the two highest and the two lowest:
|
lowest:
pen G; 0.5 clavulanate: 0.9 ertapenem: 4 ceftriaxone: 8 hours |
|
|
What is an example of a glycopeptide and what is the mechanism?
|
vancomycin: poorly absorbed orally and bactericidal by inhibiting cell wall synthesis and binding to d-ala d-ala
|
|
|
What is the bacterial clinical spectrum for vancomycin:
|
most gram positive bacteria and not gram negatives or anaerobes
-less efficacious against S. aureus than anti staph beta lactams: |
|
|
What are two new problems with vancomycin:
|
VISA and VRSA: vancomycin-intermediate-S. aureus and vancomycin-resistant S. aureus!!!!!
|
|
|
What are side effects with vancomycin:
|
nephrotoxicity was a problem
-nephrotoxicity seen when used in combination with aminoglycoside -red neck (red man syndrome) histamine -ototoxicity and rash! |
|
|
What is fosfomycin:
|
interferes with early step in peptidoglycan synthesis
-active against gram positive and negative bacteria; -USE: oral agent used to treat uncomplicated urinary tract infections |
|
|
What are two polymyxins and what is the mechanism of action?
|
polymyxin B and polymyxin E = colistin
-poor diffisubility and polymyxin are cationic detergents disrupting cell membrane and causing an increase in permeability |
|
|
What is the spectrum of activity for polymyxins:
|
P. aeruginosa and other gram negative except Proteus, Serratia, Providencia, Neisseria!
|
|
|
Why are polymyxins rarely used systemically and what accounts for their resurgence?
|
-nephrotoxic; hence no used systematically
-resurgence in use in hospitals where multi-drug resistant gram negatives |
|
|
What is an example of a lipopeptide and what does it bind to?
|
daptomycin is a cyclic lipopeptide that binds to bacterial membrane and causes rapid depolarization of the membrane potential!
|
|
|
What is lipopeptide/ daptomycin active against?
|
-active against Staphylococci, streptococci and enterococci including vancomycin resistant strains
-does not penetrate well into the lung: (daptomycin is not indicated for treatment of pneumonia) |
|
|
What is an adverse effect of lipopeptide/ daptomycin?
|
myopathy
|
|
|
What antibacteral agents target the ribosome?
|
aminoglycosides, MLS, tetracyclines, chloramphenicol, oxazolidinones
|
|
|
What is the definition of aminoglycosides and give three examples of them:
|
two or more amino acids linked via glycoside linkage to hexose; highly water soluble
three example are gentamicin, amikacin, and tobramycin |
|
|
Which aminoglycoside is topical and which has synergy with penicillin?
|
neomycin b is topical
-streptomycin (TB; enterococcus has synergy with penicillin) |
|
|
Why are aminoglycosides inactive in an anaerobic environment such as an abscess?
|
-because uptake into bacterial cell depends upon electrochemical gradient of inner membrane; this gradient is generated by aerobic metabolism
|
|
|
How do aminoglycosides block protein synthesis?
|
bind to 30 S ribosome and block initiation of protein synthesis, misreading of genetic code and premature termination of translation
|
|
|
What are aminoglycosides active against; what are they synergistic with: what do they inhibit; what do they cause?
|
-active against aerobic gram negative rods
-synergistic with beta lactams -inhibit staph -tularemia, plague -streptomycin Mycobacterium tuberculosis |
|
|
What are the adverse effects of aminoglycosides?
|
-nephrotoxic and ototoxic (auditory and vestibular) neomycin sever nephrotoxicity precludes use as a parenteral agent
-need to monitor level -streptomycin is more ototoxic -neuromuscular block: |
|
|
What does MLS stand for?
|
macrolides, lincosamides, streptogramins (K for ketolides)
|
|
|
what is the structure of a macrolide?
|
14-membered carbon ring with an amino sugar and a neutral sugar
|
|
|
What is the problem with erythromycin and how do newer macrolides overcome this problem?
|
-erythromycin in an aqueous environment in low pH undergoes internal rearrangements and forms inactive compound, whereas newer macrolides are more acid stable!
|
|
|
What is the mechanism of action of a macrolide?
|
inhibits protein synthesis by binding to 50S subunit of a ribosome and is usually bacteriostatic!
|
|
|
Describe the range of bacterial action with macrolides:
|
streptococci, staph, enterococci
-c diphtheriae, mycoplasma, chlamydia, legionella, moraxella -new macrolides against H. flu -helicobacter pyloriclarithromycin in combination with other antimicrobial agents! |
|
|
New macrolides are active against what type of atypical mycobacteria?
|
MAI: mycobacterium avium intracellulare (though resistance may develop on monotherapy)
|
|
|
Describe the adverse side effects of macroldies:
|
adverse effects: GI mainly (nauseau and vomiting)
cardiac arrythmias, clarithromycin metallic taste and erythromycin estolate: cholestatic hepatitis |
|
|
What are lincosamides:
|
lincomycin and clinamycin: an amino acid derivative attached to sulfur containing sugar
-mechanism: same as macrolide |
|
|
lincosamides: what are they active against?
|
active against mostly strep and staph
-most anaerobes including Bacteroides fragillis -good for aspiration pneumonia and adverse effects include diarrhea and C. difficile |
|
|
What are streptogramins?
|
naturally occurring compounds found in combinations
-macrocytic lactone peptolides -quinupristin (streptogramin B) AND dalfopristin (streptogramin A) |
|
|
Describe the mechanism of action of streptogramin:
|
inhibit protein synthesis
-Streptogramin B (Sg B) binds to a ribosome at a site that overlaps with macrolides and lincosamides -streptogramin A (Sg A) binds to ribosome at a nearby site -SgA and SgB are synergistic |
|
|
What are the bacteria covered by streptogramin?
|
streptococci, staphylococci
-enterococcus faecium (but not active against faecalis) |
|
|
List three adverse effects of streptogrammins:
|
arthralgias, myalgias, phlebitis
|
|
|
What are ketolides?
|
14-membered macrolide ring with cladinose at position 3 replaced by keto and 11, 12 carbamate bridge
|
|
|
Where do ketolides bind?
|
bind to ribosome near where macrolides bind (domain V) AND to domain 2 of 23S rRNA
|
|
|
what are ketolides active against?
|
strep, staph, H. flu; ALSO: active against macrolide resistant strep pneumoniae
|
|
|
What are adverse effects of ketolides?
|
visual adverse effects!
|
|
|
a
|
a
|
