Cell Wall Inhibitor Lecture Sep 12 Flashcards
What are the 4 types of beta lactam ABx?
penicillins
cephalosporins
carbapenems
aztreonam
How do all beta lactam abx work?
they bind to the penicillin binding proteins, which are transpeptidases that catalyze the terminal reactions in bacterial cell wall synthesis
this blocks cell wall synthesis and causes a build-up of cell wall precursors which leads to the activation of autolytic enzymes
the cells lyse
Specifically what site do beta lactams bind?
they bind the d-alanyl-d-alanine substrate site ON the transpeptidase, so the dipeptide on the other sugar can’t enter the binding site and undergo the transpeptidase reaction
Are beta lactams bacteriostatic or bacteriocidal?
bacteriocidal
Would swelling be more likely to occur when the cell is in a hypotonic or hypertonic solution?
A hypotonic because the water will want to flow where there are more ions.
What are penicillins active againse?
gram positive organisms
What drug is given in tandem with penicillins to reduce the renal secretion of the penicillin?
probenecid
What are the side effects of penicillins?
seizures, nausea, and diarrhea
Hypersensitivity reactions are very common-mild rash to anaphylaxis
What are the antistaphylococcal penicillins?
aka Penicillinase-resistance penicillins?
Nafcillin
Dicloxacillin
(methicillin no longer used)
What are nafcillin and dicloxacillin reserved for?
Methicillin Sensitive Staphylococci aureus
What three drugs are used as penicillinase inhibitors?
clavulanate (combined with penicillin and amoxicillin)
Sulbactam Icombined with ampicillin)
Tazobactam (combined with piperacillin)
Why is penicillin ineffective against gram negative bacteria?
It is unable to penetrate across the outer membrane of gram negative bacteria.
THe LPS blocks access and the penicillin can’t pass through the porins
What class of penicillins are able to cross the membranes of gram negative bacteria?
Aminopenicillins
AMPICILLIN
AMOXICILLIN
Their R-groups are more water soluble and can therefore pass through the porin channels of the outer membrane.
THis means they can be used to treat influenza, e. coli, listeria and salmonella
THey can still result in hypersensitivity reactions
What additional side effect is associated with the aminopenicillins that is not associated with penicillin?
They’re more likely to cause c. diff because their spectrum is broader
What are the two penicillins used as antipseudomonals?
Ticarcillin
Piperacillin
What combination of the antipseudomonals are given if the bacteria produces beta lactamases?
ticarcillin/clavulanate
piperacillin/tazobactam
What are the symptoms of a penicillin allergy?
What percentage of the population has had an allergic response to a penicillin?
What percent will have a recurrence?
Symptoms include urticaria, angioedema, and anaphylasic (which can be fatal)
3-10% have had a reaction
5_10% will have a recurrence
How does penicillin cause an allergic reaction?
Penicillin and other beta lactams combine with host proteins to form hapten protein complexes that stimulate the immmune system and results in production of specific antibodies to the antigen
What drug should you use if the patient is allergic to penicillin?
Why won’t it cause cross-reactivity?
What is the spectrum?
Use the monobactum AZTREONAM
It won’t cause cross reactivity because it only has only one ring and is therefore less likely to form hapten proteins.
The spectrium is very narry, however, and only covers gram negative rods such as klebsiella, pseudomonas, and serratia
Where are cephalosporins secreted?
in the urine
Describe the 1st generation cephalosporins
CEFAZOLIN
use the same method of action as penicillins
narrow spectrum: gram + cocci
Used for surgical prophylaxis
Do NOT cross the blood brain barrier
Describe the 2nd generation cephalosporins
cefoxitin
cefuroxime
They have better gram - activity than gram +
Used immedately prior to surgery to prevent infection
Don’t cross the blood brain barrier
Can inhibit Vitamin K production to prolong bleeding and will cause a disulfiram-like reaction when coadministered with ethanol
Describe the 3rd generation cephalosporins
Ceftriaxone
Cefotaxime
Ceftazidime
These are used for streptococci and more serious Gram - infections resistant to other beta-lactams
CAN cross the blood brain barrier–used for meningitis
cetriaxone will interact with calcium containing meds to form crystals that precipitate in lungs and kidneys
STRONG association with C. diff
Describe the 4th generation beta lactams
Cefepime
This has the broadest spectrum of the cephalosphorins because it’s a 1st generation combined with a 3rd generation
It’s used against Gram +, gram - (including pseudomonas)
Often used for empiric therapy
