Abx 2 Flashcards
What are the three families of drugs classified as “beta lactams”?
- Penicillins
- Cephalosporins
- Carbapenems
Are beta lactams bactericidal or bacteriostatic?
-bacteriCIDAL
By what mechanism do beta lactam antibiotics work?
-Cell wall formation disruptor
What is the specific target site that to which beta lactams attach in order to kill bacteria?
- PBP site
How long after the development of penicillin as an antibiotic did resistance to the drug appear?
- 10 years
What is the role of peptidoglycans and transpeptidase in the formation of bacterial cell walls, and how do beta lactams alter this?
- PG = backbone of cell wall lattice
- transpeptidase (AKA penicillin binding protein PBP) = create peptide links to stabilize PG backbone
*Beta lactams inhibit Transpeptidase
Are penicillins considered time-dependent or concentration-dependent? Why?
- Time dependent
- must constantly be present at infection site
- therefore, dose 3-4x’s per day
Inhibition of different PBPs produces what changes in the bacterial cell (not specific ones, just what are the different effects they might have)?
- rapid bacterial cell lysis
- slower bactericidal
- long strands
- which PBP it binds determines degree of bactericidal-ness
What is the mechanism by which some Staphylococcus aureus bacteria are resistant to methicillin?
- altered the shape of the PBP-1
- can NOT bind to PBP-2a
2 characteristics of Gram negative bacteria that are different from Gram positive bacteria, and that contribute to Gram negative resistance to beta lactam antibiotics.
- Thick outer (lipid) membrane
- Small porins
Do beta lactamase enzymes destroy all beta lactam drugs?
- Penicillinases
- Cephalosporinases
- or can destroy both
Due to Staphylococcal aureus beta lactamase, which drugs are effective/ineffective?
????
- most penicillins are NOT effective
- Staph beta lactamase does NOT affect CEPHALOSPORINS (nor cross resistance)
- naturally resistant to Beta lactamase = Oxa-, cloxa-, dicloxacillin
- Clavulanic acid
Generally, how are the Gram negative bacterial beta lactamase enzymes different from Staphylococcal beta lactamase?
Do they destroy just penicillins?
Can clavulanic acid block Gram negative’s beta lactamase enzyme?
- destroy a wider range of β lactam drugs
- penicillinases & cephalosporinases in the periplasm!
-Clavulanic acid added to penicillins can counter effect
What is the mechanism by which E. coli is resistant to most beta lactams?
- Beta lactamases right inside the Outer membrane
Why is clavulanic acid considered to be a suicide inhibitor of beta lactamase?
What is the other suicide inhibitor beside clavulanic acid?
- Has Beta lactam ring
- NO anitmicrobial activity
- inactivates Beta lactamase
-Sulbactam
What are the 4 groups of penicillins?
- Natural Penicillins
- Aminopenicillins
- Antistaphyloccal penicillins
- Extended spectrum penicillin
Which penicillins are “natural” penicillins?
- Pen G
Which penicillins are aminopenicillins?
- amoxi-cillin
2. ampi-cillin
Which penicillins are naturally resistant to Staphylococcal beta lactamase?
- oxa-cillin
- cloxa-cillin
- dicloxa-cillin
- methi-cillin
Which penicillins are considered to be “extended spectrum” penicillins?
- pipera-cillin
- ticar-cillin
- carbeni-cilin
**Big Guns— “I can’t afford drugs”
Is penicillin G good against:
- Pseudomonas?
- Gram positives?
- Streptococci?
- All Staphylococci?
- Gram negatives?
Narrow spectrum
- most Strep
- non-penicillinase Staph
- Gram positives
NOT
- Gram Neg
- Pseduomonas
Why isn’t penicillin G available in tablets?
- acid destroys the molecule
* *IV only**
Why are penicillins in general very good for use in urinary tract infections?
-ACTIVELY secreted INTACT into PCT –> highly concentrated in the urine
How is penicillin G dosed that is different from the other beta lactam antibiotics?
-Units/kg
Do penicillins have a long half life or a short half life? How does this translate into frequency of dosage administration? How does that translate into client compliance with medication administration?
- ????
What are the three types of penicillin G?
- Sodium/potassium Pen G–short half lives
- Procaine Pen G
- Benzathine Pen G
What is the purpose of adding a sodium or potassium molecule to penicillin?
-form water soluble to be given IV
What is the purpose of procaine or benzathine added to penicillin?
How long do each last?
- makes it insoluble in H2O
- -> slows release of penicillin from the injection site when given SQ or IM
Procaine = 12-24 hrs Benzathine = 3-5 days
Why can’t procaine or benzathine penicillin be given IV?
- insolubility –> plugs up capillaries
What is the disadvantage of using a benzathine penicillin product versus just “plain” penicillin G?
- greater variable plasma drug concentrations at any given time
2 Aminopenicillins
- Amoxicillin
2. Ampicillin
Why is amoxicillin advantageous over penicillin G for dispensing to clients to use at home?
-not inactivated by acid –> tablet form (PO)
How are aminopenicillins for activating against:
- Gram positives?
- Gram negatives?
- Susceptibility to beta lactamase?
- same spectrum as Pen G
- *PLUS** some Gram Neg
-Very susceptible to Beta lactamases
(Clavulanic acid or sulbactam added)
What is the purpose of adding trihydrate to amoxicillin or ampicillin?
-to produce a slow-release suspension
What is sulbactam used for?
- to overcome β lactamase
4 ‘beta lactamase stable’ or antistaphylococcal penicillins.
- Oxacillin
- Cloxacillin
- Dicloxacillin
- Methicillin
“beta lactamase stable” effective more than penicillin G or aminopenicillins against which bacteria?
-Staphylococcus
Are ‘beta lactamase stable’ penicillins more effective against Gram negatives than penicillin G or aminopenicillins?
-not penetrate outer membrane of Gr –
**Narrow spec
For what purpose are antistaphylococcal antibiotics used in veterinary medicine?
- Staph and Streptococcus mastitis in cattle
- cloxacillin
3 extended spectrum penicillins
- Ticarcillin
- Piperacillin
- Carbenacillin
Which penicillin might be effective against Pseudomonas bacteria?
- extended spectrum penicillins
- Readily penetrates outer membrane Gram NEG
- including Pseudomonas
- Readily penetrates outer membrane Gram NEG
Are extended spectrum penicillins any better against Gram negatives than aminopenicillins?
-Readily penetrates outer membrane
Gram negative
Are extended spectrum penicillins any better against beta lactamase than aminopenicillins?
-susceptible to β lactamase
– clavulanic acid is added
(Timentin = ticarcillin + CA)
With what other antibiotic are ticarcillin, piperacillin, and carbenacillin used to produce a synergistic antimicrobial effect?
-aminoglycosides
For what purpose are extended spectrum penicillins most commonly used in veterinary medicine?
-resistant Gram NEG bacterial infections (small animals)
Why do we care that penicillins are ionized at most body pH?
– less ability to diffuse across cell
- can’t cross BBB, eye, prostate
Given the mechanism by which beta lactams work, why is the short half-life of penicillins a disadvantage?
- drugs need to be on site continuously to be effective
- Need frequent re-dosing
What is the most severe reaction to penicillin drugs? Does it occur more with injectable or oral formulations?
Allergy: Second exposure can result in severe systemic anaphylaxis and death
**associated w/ injectable form! **
-not nephrotoxic, not hepatotoxic
How does a mild hypersensitivity rxn appear in dogs and cats? Why is it important to recognize the mild hypersensitivity reaction to these drugs?
- swollen face
- hives
- *first exposure –> sensitizes immune system
- *second exposure –> severe systemic anaphylaxis and death
Why are oral penicillins not to be used in many lab animal species (Guinea pig, hamster, gerbil, rabbit)?
- Rodents = very susceptible to killing Gram POS gut flora –> clostridium overgrowth –> fatal
What is the issue with Procaine Pen G and its use in race horses?
- local anesthetic properties
* *Regulated – test positive for as long as 2 wks
What does it mean that cephalosporins (and other beta lactams) are “time dependent” drugs?
-Must be at site of infection at the time of division
How do 1st gen differ from 3rd gen cephalosporins as far as their overall spectrum of activity?
1st gen
- Gram +
- β lactamase Staphylococcus (better than amino penicillin)
3rd gen
- Gram - (Pseudomonas)
- LESS effective for Gram +
What does it mean that some cephalosporins are considered “empirical treatment options”?
-
Does beta lactamase affect cephalosporins more or penicillins more commonly?
- more effective than aminopenicillins
- resistance forms similarly (beta lactamases)
Which is more effective against Staphylococcal beta lactamase:
1st generation cephalosporin
or amoxicillin?
-1st gen Cephalosporins
FOUR 1st generation cephalosporins
- Cefadroxil
- Cephapirin
- Cephalexin
- Cefazolin
THREE 3rd generation cephalosporins
- Cefpodoxime = Simplicef®
- Ceftiofur
- Cefovecin = Covenia®
What dosage form (tablets, injectable, ointments, etc.) do most 3rd generation cephalosporins come in?
Which FDA-veterinary-medical-use-approved cephalosporin is the exception to this? trade name? administered?
-injectables
Exception: cefpodoxime (Simplicef®) = PO
What species of bacteria are 3rd generation cephalosporins worse at than penicillin G or aminopenicillins?
-Gram positive (Staph/Strep)
How long does Convenia® supposedly last?
For what condition is it used to treat? dogs and cats? administered?
- 14 days (half life = 5-7days!)
- Tx Dog/cat PyoDerma
- injection
What does it mean that beta-lactams in general have a “high therapeutic index”?
-concentrations widely separated from toxic concentrations
What is the most severe adverse reaction with cephalosporins?
- Allergy or Hypersensitivity, like penicillin
Is there cross-hypersensitivity in patients between penicillin and cephalosporins?
-4X increased risk for hypersensitivity if know to be allergic to penicillin
What carbapenem (“penem”) drug has been used in veterinary medicine?
-Imipenem (Primaxin®)
What is the specific indication (use) for imipenem in veterinary medicine?
- serious infections (Gram Neg Sepsis)
* * broadest spectrum of Beta lactams!
What is the role of cilastin with imipenem use and why does it protect the animal? What happens if cilastin is not used with imipenem?
- inhibits enzymes in renal tubules
- –> prevents nephrotoxicity
Why is it supposedly important that imipenem is a faster bactericidal drug than the other beta lactam drugs?
-Helpful for killing Gram Neg bacteria in blood, releasing harmful endotoxins
