Flashcards in Penicillin and Cephalosporin Deck (107):
What is a synonymn for "Inhibitors of Cell Wall synthesis drugs"?
Beta Lactam Antibiotics
What is the specific structure of penicillin?
Beta Lactam ring = 4 membered ring
What is important about beta lactam ring in penicillin?
It is strained and reactive.
What is a cephalosporin?
A fungally derived drug with a beta lactam ring (penicillin is bacterially derived)
What is the character of the beta lactam ring if it is broken?
It doesn't work.
What type of bacteria are cell wall synthesis inhibitors most effective against?
Most are gram positive with some gram negative
What bacteria are Inhibitors of Cell Wall synthesis drugs effective against?
Treponema palidum (syphilis) Actinomycoses
What organisms are Inhibitors of Cell Wall synthesis drugs not effective against?
When are inhibitors of Cell Wall synthesis most effective?
During early infection when bacteria are actively dividing and building cell wall
Why are Cell Wall synthesis inhibitor drugs not as effective in later stage infections?
Construction of bacterial cell wall is slower
What does a bacterial cell wall do?
Encases bacterial cell membrane
What is the character of the cell interior of gram positive bacteria?
What does penicillin inhibit in bacteria?
Inhibits cross linking of cell wall units
What happens when the cell wall has holes punched in it by beta lactam drugs?
Membrane ruptures due to inflow of water to hypertonic cell causing rupture.
What is required on the bacteria to aide the beta lactam drugs?
Bacterial surface enzymes (autolysins) that cleave previously synthesized cell wall
In the absence of bacterial autolysins what Is the character of Beta Lactam drugs bacteriocidal or bacteriostatic?
What are the 3 stages of bacterial cell wall synthesis?
1. Production of cell wall building blocks
2. Precursor carried from inside cell membrane to outside
3. Cross linking of cell wall
Which Beta lactam drug inhibits the production of Cell Wall Building blocks (Stage I)?
Cycloserine (Stage I cell wall synthesis inhibitor) is used in treating what infection?
What 2 beta lactam drugs inhibit the precursors being carried from inside the cell membrane to the outside (Stage II)?
Vancomycin and Bacitracin
What 2 beta lactam drugs stop the cross-linking of the cell wall (Stage III)?
Penicillin and Cephalosporin
How does penicillin inhibit the cross linking of the cell wall?
It is similar to the D-alanyl-D-alanyl terminus of polypeptide side chain of peptidoglycan and occupies D- ala-D-ala substrate site of transpeptide.
Beta lactam antibiotics interfere with what steps of cell wall synthesis?
The final steps
Cell death requires the action of what?
Autolysins act how normally?
They normally nick cell walls for attachment of new peptidoglycan units.
What are 4 ways bacteria can become resistant to penicillin?
1. Lack of accessibility to target
2. Production of penicillinases or beta lactamases
3. Altered penicillin binding protein
4. Drug efflux pumps
What is an example of lack of accessibility to target for penicillin resistance?
Gram negative bacteria having outer membrane inhibiting access to cell wall.
What is the absolute requirement for inhibition of transpeptidase?
Intact beta-lactam ring
What is the difference between penicillinase and beta lactamase?
Penicillinase only breaks down penicillin beta lactam ring.
Beta lactamase breaks down both penicillin and cephalosporin beta lactam ring
How can gram negative bacteria, who have low production of penicillinases still eliminate antibiotics without being swamped?
Gram negative limits access of beta lactam antibiotics to the peptidoglycan cell wall
If an antibiotic binds to Penicillin Binding Protein 2 or Penicillin Binding Protein 3 what will its effects be on the bacteria
Prevents cell division (septum formation) Loss of rod like structure (filament formation)
If an antibiotic binds to Penicillin Binding Protein 1 what will its effects be on the bacteria?
Inhibits cell wall synthesis
Organism undergoes osmotic lysis
If antibiotic binds PBP 2 and PBP 3 is the effect bacteriocidal or bacteriostatic?
If antibiotic binds PBP 1 is the effect bacteriocidal or bacteriostatic?
What stage of cell wall synthesis is PBP 1 involved in?
Cross linking step on stage III of cell wall synthesis
What can PBP 1 do to itself to resist penicillin?
Change affinity for penicillin
What will happen if bacteria increases levels of penicillin binding protein?
It will soak up the penicillin to decrease the effect of penicillin on PBP 1
What else can bacteria do to alter their penicillin binding protein to resist penicillin
synthesize new PBP’s with altered penicillin affinity
What does a drug efflux pump do?
Pumps the drug out once it gets in cell
What is character of broad spectrum penicillin versus narrow spectrum penicillin?
Broad spectrum can be effective against some gram negatives by getting through the outer membrane to attack the inner membrane peptidoglycan
Are penicillins widely distributed or narrowly distributed throughout the body
Where do penicillins not distribute well and therefore cannot be used for treatment in these areas of the body?
What can cause penicillin to reach higher levels in the central nervous system?
What administrative route is most common parenteral route that gives predictable blood level?
What administrative route to use for treatment of severe infection requiring fast action and high blood levels?
How much penicillin is absorbed by oral administration?
How is penicillin eliminated?
How much of penicillin is excreted as active drug?
What is the half-life of all penicillins?
Approximately 1 hr
Why is probenecid used?
It decreases renal excretion of drugs to increase antibiotic plasma concentration during serious infection.
Use of penicillin is limited primarily by what?
Is penicillin one of the more highly toxic or least toxic drugs in medicine?
One of the least toxic
Use of penicillin limited primarily by
What are 5 toxicities associated with penicillin?
3. Anaphylactic shock
4. CNS effects
Staph infections acquired in hospital are usually susceptible or resistant to penicillin?
What respiratory problem increases one’s risk of penicillin hypersensitivity
Would a penicillin hypersensitivity result in anaphylaxis?
No. It would only cause a rash.
What would be the signs of penicillin anaphylaxis?
Fall in BP
What are immediate indicators of anaphylaxis?
dizziness, weakness, sweating, palpitations
After a sensitization dose to penicillin, what are likely symptoms?
Rashes, fever, swollen joints several days after taking penicillin
When would a person be at risk for penicillin to affect CNS?
When the patient has impaired renal function or is infused w/ unusually high dose
What is the risk with long term penicillin therapy
What are 4 General classes of penicillins?
1. Penicillin G(benzylpenicillin)
2. Gastric Acid Resistant Penicillin
3. Penicillinase Resistant Penicillins
4. Broad Spectrum Penicillins
Standard reference penicillin
Penicillin G (benzylpenicillin)
Is penicillin G administered orally?
No. It is inactive at low pH?
Can penicillin G get by penicillinases in bacteria, e.g. against Staph aureus?
No it is penicillinase sensitive.
Is penicillin G broad or narrow spectrum?
Narrow. Gram positive only.
Penicillin G are used in the treatment of what three bacterial infections?
Syphillis, Rheumatic Fever, and Gonorrhea
What is the name for Gastric Acid Resistant Penicillin
)Penicillin V (acid stable)
What is the importance of Penicillin V?
Itcan be given orally and produces higher blood levels than Pen G
How are Penicillin G and Penicillin V similar?
Both are narrow spectrum.
What are 4 Penicillinase Resistant Penicillins
What is the advantage and the disadvantage of Penicillinase Resistant Penicillins
Less susceptible to penicillinases
Is methicillin (penicillinase resistant penicillin) administered orally or intravenously?
Intravenously (it is not absorbed orally)
Is methicillin as effective as Penicillin G against organisms not producting penicillinase?
No. Only 50% as effective as Pen G
Name 3 Broad Spectrum Penicillins.
Are Broad Spectrum Penicillins active against gram negative or gram positive bacteria?
Gram negative (effectiveness is reduced against gram positive)
Are Broad Spectrum Penicillins susceptible to penicillinases?
What is the penicillin-related drug that is front line for tuberculosis treatment?
Which stage of cell wall synthesis does the anti- tuberculosis drug Cycloserine target?
First Stage (Stage I)
What penicillin-related drug is last line of defense treating MRSA and also used in Endocarditis?
What is the only place where vancomycin is administered?
At the hospital
Which stage of Cell Wall synthesis does Vancomycin inhibit?
What intermediate stage cell wall synthesis inhibitor is toxic systemically, but used topically?
Bacitracin is normally paired with what other 2 drugs as a topical ointment (triple-biotic, Neosporin)?
What are 3 agents that can be given in combination with Penicillin or Cephalosporin to increase their activity by breaking down bacterial resistant Beta-lactamase or penicillinase?
Cephalosporins are cell wall inhibitors that are fungally or bacterially derived?
Cephalosporins are resistant to what?
How are cephalosporins and penicillins similar?
Both have beta-lactam rings
What bacteria types are Cephalosporins effective against?
Gram positive and Gram negative
Most cephalosporins are administered intravenously or intramuscularly. Which 2 cephalosporins are administered orally
Cephalexin and Cefaclor
What is the distribution for Cephalosporins?
Well distributed except to CNS
Are most cephalosporins readily metabolized or minimally metabolized?
How are cephalosporins excreted?
What are 2 things that can block cephalosporin excretion in the kidney?
1. Probenecid (med specifically given to decrease excretion to increase drug potency)
2. Renal Failure
What is the factor causing the hypersensitivity in penicillin and cephalosporins?
What is an adverse systemic reaction to cephalosporins?
What are 3 infections against which cephalosporins are used?
What type of infection/situation necessitates the use of cephalosporins?
Gram negative infection that is penicillin resistant
When is Cephalosporin used prophylactically?
During and after surgery for endocarditis.
What are 3 classifications of cephalosporins?
What is the main character of 1st Generation Cephalosporins?
Good against gram positive
Moderate against gram negative
First Generation Cephalosporin that can be administered orally?
What is the character of 2nd Generation cephalosporins?
Good against G-
Not very active against G+
What is the character of 3rd Generation cephalosporins?
Active against gram negative, especially those producing penicillinase
What are 3 ways bacteria can be Cephalosporin resistant?
1. Drug can’t reach target
2. Produce enzyme to disrupt active ring
3. Alter antibiotic binding protein