C: 8-13 Flashcards
bacterial cell wall synthesis inhibitors
- penicillins
- cephalosporin
- Vancomycin
- Fosfomycin
- Bacitracin
- Carbapenams
- Aztreonam
- Daptomycin - distrupts cell membrane.
All penicillin are derivatives of ——— and contain a ——–
All penicillin are derivatives of —–6-aminopenicillanic acid—- and contain a —-beta lactam ring—-
beta lactam ring is essential for antibacterial activity
penicillin pharmacokinetics
bioavailability, excretion, plasma half life
- subtypes have different resistance to gastric acid & oral bioavalability
- penicillin are POLAR;
- NOT metabolized extensively (unchanged in urine)
- Exceptions: Ampi (excreted mainly in the bile)
forms of Penicillin G
- Procaine
- Benzathine
- administered I.M
- for syphilis
Penicillins cross BBB when?
meninges inflammed
penicillin Parenteral formulations available for injection?
Ampi
Pipera
beta lactam antibiotics have what effect on bacteria?
bactericidal
mechanism of action of penicillin
They act to inhibit cell wall synthesis:
(1) binding of the drug to PBPs on cytoplasmic memb.
(2) inhibition of the transpeptidation reaction (cross-link the peptidoglycan)
(3) activation of autolytic enzymes → lesions in the bacterial cell wall.
resistance mechanism against penicillins
- formation of Beta-lactamases (eg penicillinases):
* solution: beta-lactamase inhibtiors (tazobactam, clauvulanate)
- structural change in PBP
-
changes in porin structures in the (outer cell membrane)
impedes access of penicillin to PBP
Types of penicillin and names
-
Narrow spectrum (penicillinase-susceptible agents)
- Penicillin G:
- streptococcal
- syphilis
- Penicillin V:
- oral for oropharngeal infections
- Penicillin G:
-
Very narrow spectrum (penicillinase-resistant)
- Oxacillin
- staphylo
- Oxacillin
-
wider spectrum (penicillinase susceptible)
- Ampi
- Amoxi
- pipera
clinical use for Very narrow spectrum penicillinase resistance drugs
- Oxacillin
known/suspected staphylococci infections
***NOT active against MRSA, MRSE***
clinical use for wider spectrum penicillinase susceptible drugs
- Ampicillin & amoxicillin
- Streptococcal
- Enterococci
- E-coli
- Hemophilis influenza
- used in combo with clauvulanic acid
- synergistic effects with aminoglycosides
- piperacillin:
-
gram negative rods: (PEK)
- Pseudomonas,
- Enterobacter
- Klebsiella (some species)
- synergistic effects with aminoglycosides
- often used in combo with tazobactam & clauvulanic
-
gram negative rods: (PEK)
Toxicity of penicillin
-
Allergy: (hypersensitivty reactions)
- urticaria, pruritis, fever, joint swelling,
- hemolytic anemia, nephritis, anaphylaxis
- Ampicillin frequently causes maculopapular rash ( which doesnt appear as allergic rxn)
GI symptoms:
Nausea, diarrhea
due to Direct irritation OR overgrowth of gram + organisms or yeast
cephalosporins are derivative of ——- and contain a ——-
- 7-amino.cephalo.sporanic acid
- contain a beta lactam ring
cephalosporin pharmacokinetics
- most are administered parenterally
- major elimination mechanism in renal excretion via active tubular secretion.
- Exception_:_ ceftriaxone excreted mainly in bile
- Most 1st and 2nd G DONT enter CSF even when meninges inflammed
Mechanism of action cephalosporin
- inhibit cell wall transpeptidation
- binds PBPs-→ inhibit cell wall synthesis
Cephalosporins are bactericidal against susceptible organisms.
mechanism of resistance against cephalosporin
- production of other betalactamases that can inactivate cephalosporins.
- decreases in membrane permeability and from changes in PBPs.
- MRSA are also resistant to cephalosporins.
clinical uses of 1st generation cephalosporin
- Cefazolin (parenteral)
- CephaLexin (oraL)
- They are active against gram-positive cocci:
- staphylo
- streptoco
- E.coli and K.pneumoniae
- infections caused by these organisms and surgical prophylaxis
- renal elimination
clinical use for 2nd gen cephalosporin
- *cef.uroxim & cef.oxitin:**
- *(the ones with OXI)**
- less activity against gram + but have an extended gram - coverage
- Ex:
- cefoxitin: anaerobe Bacteroides fragilis
- cefuroxime: H.influenza or M catarrhalis
- short half lives
clinical use for 3rd gen cephalosporin
cef.tazi.dime → pseudomonas
cefo.taxime → PRSP
Ceftriaxone (parenteral) → PRSP, gonorrhea
cefixime (oral) → gonorrhea
- pneumonia, meningitis, gonorrhea
increased activity against gram-negative organisms resistant to other beta lactam drugs
- ability to penetrate the blood-brain barrier (except cefixime).
clinical use for 4th generation cephalosporin
- *cefepime**
- *Ceftaroline**
Ceftolozane +tazobactam
Broad activity
Beta-lactamase-stable
- cefepime: more resistant to beta-lactamases (by gram - )
- combines G + activity of 1stGs with the wider G - spectrum of 3rdGs
- Ceftaroline: (MRS)
- ceftolozane + tazobactam : MRSA
Cephalosporin toxicity
- allergy:
skin rash + anaphylactic shock - penicillin allergic pts can be treated with cephalosporin.
- However in pts with history of anaphylaxis to penicillin SHOULDNT be treated with cephalo
- Pain at I.M injection site
- Phlebitis after I.V
- increase nephrotoxicity of aminoglycosides when adminitered together
Monobactam
- Az.Treo.nam
- beta lactam drug
- resistant to beta-lactamases produced by certain gram - rods
- NO activity against gram + nor ANarobes
- mechanism:
→ Bind to and inhibit cell wall transpeptidatio
→ Inhibitor of cell wall synthesis by binding specific PBP - Synergistic with aminoglycosides
Aztreonam is administered
eliminated?
I.V
eliminated via renal tubular secretion
- half life is prolonged in renal failure
Aztreonam Adverse effects
- GI upset
- headache
- skin rash ( although no cross-alergenicity with penicillins)
