Beta-Lactam Antibiotics Flashcards
List important components to the structure of the penicillin. 3 things
4 membered nitrogen containing compound
sulfur containing 5 membered ring
then R group coming off of the amine(where you can make substitutions
what is so significant about the R-group on the Beta lactam ring and where is the site of hydrolysis by acid or B-lactamase
R-group determines stability to acid or B-lactamase hydrolysis
what is the structure and the list some components of the cephalosporin.
Six membered sulfur containing ring
4 membered nitro containing ring
R group in two locations
- off of the sulfur containing ring
- of of the nitro group
What is the structure and list some components about Carbapenems
5 membered ring that is not sulfur containing; sulfur instead comes off of the ring(formamidine)
4 membered nitro containing ring
what is the structure and list the components of the monobactems
no other ring coming off of the 4 membered nitro containing ring
sulfate and nitro group coming off the 4 membered nitro containing ring
what are the 4 types of penicillins?
Penicillin G (Pen V is the oral prep)
Acid-stable or Antistaphylococcal (isoxazolyl)(ox, clox and icloxacillin, methicillin)
Extended-Spectrum (amoxicillin, ampicillin)
Antipseudomonal or ureido penicillins (piperacillin)
list the different types of acid stable or antistaphylococcal penicillins
methicillin, oxacillin, cloxacillin, dicloxacillin
what are the different types of extended spectrum penicillin
amoxicillin and ampicillin
what are the types of antipseudomonal or ureido penicillin
piperacillin, carbenicillin, and ticarcillin
what are some organisms that penicillin G or the oral type penicillin V is used against?
use it against gram + bacteria
use it against non b-lactamase staph and strep
obligate anaerobes like actinomyces and clostridia
Treponium palidum(syphillis)
meningococcal and used to be good for neiserria gonorhea
what do you want to use acid stable or antistaphylococcal penicillins (meth-, oxa-, cloxa-dicloxacillin) against
against penicillanase producing staphylococcus aureus
what is extended spectrum (ampicillin and omaxicillin) used against
use against gram neg p mirabilis, H influenzae, E.coli, listeria moncytogens, salmonella shigella, and enterococcus faecalis
what is the antipseydomonal or ureido penicillins used against
pseudomonas aeruginosa, K pneumonia, serratia marcescens, and gram - rods
in peptidoglycan synthesis, what strands need to be crosslinked
NAM(N-acetyl muramic acid) and NAG(N-acetyl glucosamine) need to be crosslinked
What is the mechanism of B-lactams
All of the β-lactams interfere with this process of crosslinking during peptidoglycan synthesis. This causes faulty linkage in the peptidoglycan and thus the structural integrity of the bacterial cell wall is compromised and so ultimately the bacterium die
what are the requirements for B-lactams to be efficient and work properly
- Growing cultures are required
- Peptidoglycan cell wall producing bacteria
- Irreversibly inhibit the transpeptidation reaction
- Osmotic pressure causes the bacterial cell to burst-bactericidal
- activate autolysins in some organisms
what are autolysins
The β-lactams activate autolysins in bacteria. Many organisms including bacteria are most vulnerable when they are dividing. So the autolysins are there for use by the bacteria so that they can open up their cell walls and then reseal them during cell division. So β-lactams can interfere with this process by activating autolysins and this contributes to their bactericidal activity.
list the mechanisms of resistance for B-lactams
- B-lactamse breaks B-lactam ring (chromosomal or plasmid)
- Reduced binding to penicillin binding proteins; methicillin resistant staph aureus
- Decreased access to gram neg organisms via down regulationof porins
- Increased efflux pumps found in some gram neg organism
a few gram negative bacteria can confer resistance to B-lactams by
down regulation of porins: Gram negative bacteria require pores in their outer membrane so that things can get in and out but they can modify the size to inhibit the entry of antibiotics like β-lactam.
efflux pumps:A few Gram negative organisms have very active efflux pumps. So in this case the β-lactam gets into the periplasmic space between the inner membrane and the outer membrane but it can’t be concentrated at a high enough level to perform its actions effectively
if patient is suspected of having meningitis what penicillin would you use
extended spectrum penicilin; ampicillin or amoxicillin against listeria monocytonges
what are the orally active penicillins
Pen V, ampicillin, amoxicillin, and all of the isoxozolyl
which ones are given IV
pen G, piperacillin, and methicillin
what is the definition of time dependent killing
plasma levels should be greater than the MIC for at least 70% of every 24 hrs…particularly gram - penicillin exhibits this
explain penicillins metabolism and its renal excretion if any
excreted via urine unchanged because there is no metabolism also it can be pumped(proximal tubule) and filtered through the renal system.
can penicillin penetrate the CSF
no but it can during times of inflammation early during its onset before the meninges have healed
what are the adverse effects of penicillins
rashes and anaphylaxis due to hypersensitivity
ampillicin can cause a maculopapular rash because of chemical reaction in skin not allergic
seizures with high doses due to penicillin interfering with GABA: neurotoxicity
nephritis
diarrhea because normal gut flora disrupted
platelet dysfunction
false positive for urinary glucose
cation toxicity
what side effect does methicillin cause
nephritis
what side effect does ticarcillin cause
platelet dysfunction and cation toxicity
which penicillins cause cation toxicity
ampicillin, ticarcillin, and piperacillin
what is augmentin composed of and what is the side effect.
Augmentin is composed of amoxicillin and clavulanic acid(which is a beta lactamase inhibitor). The combination will effectively deal with penicillinase producing organism. However it can also cause a false positive for urinary glucose.
what are the different adjunct medications given with penicillin
Probenecid and penicillin
Augmentin: (Clavulanic acid and amoxicillin)
why do we give probenecid with penicillin
because it will decrease the rate of excretion of the penicillin by acting at the organic acid pump in the proximal tubule of the kidney, making penicillin rely only on glomerular filteration for its excretional methods
what are the three different types of beta lactamase inhibitors?
- Clavulanic acid
- Tazobactam
- Sulbactam
The mechanism of action, resistance, pharmacokinetics and adverse effects is similar to penicillin for cephalosporins except for what?
- Third generation cephalosporins are more resistant to beta lactamases
- There is a disulfiram-like effect when taken with alcohol
what is the structure of cephalosporins
What are the first generation cephalosporins
Cafazolin
What are the second generation cephalosporins
- cefamandole
- cefonicid
- cefotetan
what are the third generation cephalosporins
- Cerfoperzone
- Ceftriaxone
- Cefixime
- Ceftazidime
what are the fourth generation?
Cefepime
Which cephalosporins cause the disulfiram-like effect (Hypoprothrombinemia)? and what is this effect?
2nd generation cefamandole, cefotetan, cefonicid and 3rd generation cefoperazone
when some cephalosporins are taken with alcohol, you have a very serious adverse reaction to the drug. There’s changes in blood pressure, sweating, nausea, and vomiting. This occurs because if you drink alcohol and take that particular cephalosporin at the same time, you wind up with a lot of acetaldehyde which is a toxic compound.
specifically how does second generation cefamandole play in the disulrifam like effect
has a tetra imidazole sulfur-containing entity and this is the part of the drug that inhibits acetaldehyde dehydrogenase. Acetaldehyde dehydrogenase normally converts acetaldehyde into acetic acid
what is the spectrum of treatment from the 1st generation cephalosporins
mostly against gram + including the anaerobic streptococci
but also gram - PEcK
what is the spectrum of treatment for 2nd generation cephalosporins
same as first gram positive and negative but with the addition of h. influenzae
and used to treat sinustis, otitis, and pneumonia
what is third generation cephalosporins used against
Efective against gram-negative bacteria and used to treat serious gra-negative infections
specifically the third generation cephalosporin ceftazidime is used to treat
pseudomonal
fourth generation is used to
treat gram + and negative and serious gram-negative infections like meningitis, pseudomonas, enterobacter infections
which cephalosporin would you use to treat gonorrhea
ceftriaxone and cefixime
cefixime is taken how
orally
Meningitis due to pneumococci and meningococci and h influenzae but not listeria monocytogenes is treated by
3rd generation cephalosporins
what would you use for empiric therapy of sepsis of unknown origin in both immunocompetent and immunocompromised hosts
3rd generation cephalosporins
what are the four different types of carbapanems
imipenem, meropenem, doripenem, dertapenem
2nd generation have effects similar to
amoxicillin and ampicillin because they go against h. influenza and ecoli
3rd generation are given
parenterally thats why they are given in the hospital
. These drugs are usually reserved for a seriously ill patient where you don’t know what the etiological agent for the infection is yet. If you don’t treat the patient, there will be serious sequelae and even death. So you treat the patient
4th generation
carbapanems are given and can enter
parenterally and CSF
carbapenems are effective against
gram +, Gram _ aerobic and anerobic cocci and bacilli
carbapenems are wide spectrum and can be used
in treatment of hospital acquired resistant infections
monotherapy for septicemia, neutropenic fever, intra-abdominal, lower respiratory tract, genitourinary, gynecological, skin and soft tissue, and skin and bone infections in patients who cannot tolerate a cephalosporin
if i am a patient who is prescribed cefazolin for bone infection but cannot take it because of toleration
you can take a carabapenem
what are the adverse effects
NVD, skin rashes, infusion site reactions; imipenem is convulsant at high doses(prolly cuz of CSF)
what type of carbapenem is used to treat bacterial meningitis
meropenem
monotherapy for septicemia, neutropenic fever, intra-abdominal, lower respiratory tract, genitourinary, gynecological, skin and soft tissue, and skin and bone infections in patients are treated with
Carabapenem
What is the only monobactam
Aztreonam
what drug spectrum is similar to aztreonam
aminoglycosides
aztreonam targets
gram negative aerobic bacteria
aztreonam works against
gram-negative rods(Klebsiella, pseudomons, serratia). it has no activity against gram-positive bugs or anaerobes
adverse effects of aztreonam
injection site reactions; pain
the aztreonam is fitered and secreted by
the kidney
aztreonam can be used as an alternative to
aminoglycosides, penicillins and cephalosporins
summary for aztreonam
Is a part of the monobactem B-Lactams
- used to treat aerobic gram negative bacterial infections
- It is not effective against gram positive or anaerobes
- Given parenterally to patients; pain associated with the injection
- This drug also penetrates well into the CSF without inflammation
- Used as an alternative to aminoglycosides, penicillins, or cephalosporins
