Week 3 Prunuske - Principles of Chemotherapy Flashcards
What do all beta-lactam antibiotics bind to?
Penicillin Binding Proteins (transpeptidases)
What kind of reactions do transpeptidases catalyze?
Terminal reactions in bacterial wall synthesis.
(connects the peptidoglycan chains together via peptide bonds)
What happens when transpeptidase is inhibited?
cell wall precursors builds up >> activates autolytic enzymes
What is the primary mechanism of action of Beta-lactam antibiotics?
- Inhibit cross-linking of the peptidoglycan by transpeptidase
- Weakens cell wall, cell bursts in hypotonic solution
- Bactericidal
What are the main two forms of Penicillin?
- Penicillin V (oral)
- Penicillin G (IV form)
(active against Gram +)
What is the effect of administering Probenecid simultaneously with Penicillin?
decreases renal excretion >> increases time penicillin is in the blood
(impairs renal secretion of weak acids)
Penicillinase cleaves the beta-lactam ring and causes microbial resistance of what drugs?
Penicillins
What two drugs are Penicillinase-Resistant Penicillins?
Nafcillin & Dicloxacillin
(very narrow-spectrum, mainly used to treat MSSA)
Penicillinase inhibitors (a.k.a. beta-lactamase inhibitors) bind to what and allow penicillin to be an effective?
Bind irreversibly to penicillinase.
(ex. Clavulanate, Sulbactam, and Tazobactam)
What class of penicillins are more water soluble and can pass through porin channels?
Aminopenicillins
(wider spectrum, penicillinase-susceptible)
What are the two types of Aminopenicillins? Note: both start with “Am”
Ampicillin & Amoxicillin
What GI condition is Ampicillin associated with?
pseudomembranous colitis
Antipseudomonal penicillins are pretty broad and include what two drugs?
Ticarcillin & Piperacillin
(susceptible to penicillinases)
What drug is resistant to penicillinase and is mainly used in the treatment of MSSA?
Nafcillin
Which drug is administered if a patient is allergic to penicillin?
Aztreonam
(monocyclic beta-lactams, targets gm-)
What is the mechanism of action of Cephalosporins?
inhibit cell wall synthesis by binding to penicillin binding proteins (transpeptidase)
weaken cell wall > autolyse > Bactericidal
How are cephalosporins excreted from the body?
The kidney.
What is unique about the 3rd generation of cephalosporins compared to the 1st & 2nd generations?
3rd generation can cross the blood brain barrier!
1st & 2nd generations cannot cross the blood brain barrier.
What type of prophylaxis are the 1st and 2nd generation cephalosporins used for?
Surgical prophylaxis
What cephalosporin drug is used to treat meningitis?
Ceftriaxone
What spectrums do cephalosporins have?
1st generation: Gram + cocci
2nd generation: gram - > gram +
3rd generation: gram - (resistant to other Beta-lactams)
4th generation: gram +, gram - including Pseudomonas
5th generation: New (MRSA), resistance to penicillinase
What generation of cephalosporins are strongly associated with Clostridium difficile?
3rd generation: Ceftriazone, cefotaxime, ceftazidime, cefdinir
What is the mechanism of action of Carbapenems?
contain beta-lactam ring and bind to penicillin binding proteins
The spectrum of carbapenems is broad, but what condition is still resistant?
MRSA
Carbapenems (Imipenem/cilastatin, meropenem) are administered parenterally, meaning?
IV, IM, SubQ
Why is the carbapenem Imipenem administered with cilastatin?
To decrease cleavage of the beta-lactam ring and to prevent the formation of potentially toxic nephrotoxic metabolite.
What side effects are associated with carbapenems?
GI distress & cross allergic
*check dose with renal dysfunction to prevent seizures
What are some symptoms associated with a penicillin allergy?
nausea, diarrhea, urticaria, angioedema, and anaphylaxis
Hypersensitivity (mild rash to anaphylaxis)
Seizure if CNS penetration
What target of cell wall synthesis does Vancomycin act on?
Transglycosylase - prevents peptidoglycan synthesis
(bactericidal)
What is the spectrum of Vancomycin?
Very narrow, only gram +
MRSA & C.diff
oral vancomycin is poorly absorbed
What are the four mechanisms of resistance that can result in cross-resistance amongst Beta-lactams?
- Expression of beta-lactamases (penicillinases, cephalosporinases, amidases)
- change in the structure of Penicillin Binding Proteins
- Decrease in uptake of the drug (intrinsically resistant)
- Upregulation of efflux pumps
What are possible side effects of Vancomycin?
Red man syndrome (hypersensitivity due to secretion of histamines)
Nephrotoxicity
What reaction does Bacitracin prevent in the elongation of the peptidoglycan cell wall?
dephosphorylation of the bactoprenol carrier.
What is the side of effect of Bacitracin when give IM?
nephrotoxicity
Polymyxin B binds to phosphatidylethanolamine in the membrane leading to what as a result?
Creating holes in the membrane that leads to the release of cellular contents.
What is the spectrum of Polymyxin B?
Gram - bacilli
effective against multidrug resistant microbes such as Pseudomonas and KBC
(Used in combination with other antibiotics to help facilitate entry.)
What is the only listed side effect of Polymyxin B?
Nephrotoxicity
Aggregation and depolarization of a cell occurs when Daptomycin binds to what part of the cell?
Cell membrane
What difficult condition is Daptomycin used to treat?
MRSA + VRSA
What types of microorganisms does Daptomycin treat?
Gram +
(MRSA, vanco-resistant)
What was the only side effect of Daptomycin listed?
reversible organizing pneumonia binds pulmonary surfactant accumulating in pulmonary spaces
