PCN lecture Flashcards
What is the main diff bw bacterial and mammalian cells
rigid cell wall of peptidoglycan that protects bacterial cells from osmotic rupture
G+ have thick layer, stain purple
G- have thin layer, stain pink, have outer membrane
What is peptidoglycan composed of
a back bone of NAG-NAM, a chain of 4 aa linked to NAM and a peptide bridge that cross links tetrapeptide chain D-gln to D-ala
Process of peptidoglycan formation
- addition of subunits (sugar and 5 aa) assembled in cytoplasm
- transport to cell surface
- cross linking by cleaving terminal stem-peptide aa; performed by transpeptidases or PBP
Where can antibiotics target to ICWS
- transglycosylation (NAG-NAM)
- vancomycin (a glycopeptide), B-lactams
- Transpeptidation (cross link peptides)
- B-lactam (PCN, ceph, Carbapenems, mononbactams)
- NAG –> NAM reduction
- fosfomycin??
- Transport across inner membrane
- Bacitracin
- AA mimicry (pentapeptide chain)
What are the natural PCNs?
*PCN G -IV, IM, oral?
Benzathine PCN - IM
Procaine PCN G -IM
PCN V - oral
What are the extended spectrum PCNs?
*Ampicillin -
Amoxicillin (Amoxil)
Bacampicillin (Spectrobid)
What are the PCNase resistant PCNs aka antistaphylococcal PCNs
*Nafcillin (Unipen), IM/IV
Oxacillin (Prostaphlin), oral
Dicloxacillin (cloxapen), oral
Methicillin (testing only!)
Name all the anti-pseudomonal PCNs
*Piperacillin (Pipracil)
Mezlocillin (Mezlin)
Ticarcillin (Ticar)
Carbenicillin (Geocillin)
How are ICWS bactericidal?
cause cell death due to osmotic lysis
- autolysins cleave peptidoglycan bonds in normal course of cell growth. This combined with agents that inhibit cell wall growth –> no repair –> weakness and lysis
*note: protein synthesis inhibitors (chloramphenical) PREVENT action of ICWS
List the properties of ICWS
G+ activity, spectrum (G-,anaerobic etc), P aeruginosa activity, PCNase resistance, acid resistance, CNS penetration, unique adverse effects, route of admin
list the B lactams
- PCN
- Cephalosporins
- Carbapenems
- Monobactams
list ICWS that are not B lactams
- Vancomycin
- Phosphomycin
- Bacitracin
- Cycloserine
Where do B-lactamases reside?
periplasmic space
where are PCN binding proteins (PBP) located
cytoplasmic membrane
Describe the activity of Natural PCN (remember, PCN G, Benzathine PCN, Procaine PCN G, PCN V)
- highest activity again G+, including anaerobic
- some G-
- inactivated by PCNase/B-lactamase
- not effective against s. aureus
- no antipseudomonal
- renal/kidney elim
- poor CNS penetration
- PCN V is relatively acid resistant
Procaine PCN V - IM is used for..
only syphilis and rheumatic fever
*note: PCN is leading drug for syphylis (spirochete), lost sensitivity for N gonorrhea (now ceftriaxone is DOC for gonorrhea - 3rd gen ceph)
What is PCN G good against
Many things!
- G+ cocci: s pneumo, S. pyogenes (causes of pneumococcal pneumonia)
- Syphilis (spirochetes)
List and describe the activity of PCNase resistant PCNs aka antistaphyloccocal PCNs?
- Nafcillin, Oxacillin, Dicloxacillin, Methicillin (testing only bc toxic)
- lower G+ activity than natural PCN
- PCNase resistant
- some G-
- some acid stable and pro bound (PCN V)
What is the metab and excretion for PCNase resistant PCNs
hepatic metabolism, renal excretion
What is the DOC for PCNase producing s. aureus (MSSA)
PCNase resistant PCNs
*note: more than 20% s. aureus isolates are resistant (MRSA)
What are the PCNase resistant PCNs that can be taken orally
Oxacillin (Prostaphlin)
Dicloxacillin (cloxapen)
How is methicillin resistant s. aureus (MRSA) resistant, meaning what is it’s MOR?
produces alternate PBP that decreases affinity of B lactam antibiotics to PBPs…. thus NO b-lactam can treat MRSA, except CETAROLINE FOSAMIL (unnamed gen of cephalosporins)
identify the extended spectrum PCNs and their activity
- Ampicillin (Omnimen), Amoxicillin (amoxil)
- lower G+ than natural PCN, but extended G-
- no antipseudomonal
- resistance freq develops
- B lactamase susceptible
- acid resistant
How are extended spectrum PCNs excreted
urinary excretion
