3 - Pharm: Beta Lactams Flashcards
Describe the mechanism of action of the beta lactam antibiotics.
Bactericidal
They are structural analogs of natural substrates that allow them to covalently bind to the active site of Penicillin Binding Proteins (PBPs)
They inhibit bacterial growth by inhibiting transpeptidation reactions that mediate peptide cross-linking in cell wall synthesis
Describe the clinical uses for beta lactamase resistant penicillins
Indicated for staph and susceptible strains of strep and pneumo
Which penicillins are beta lactamase resistant and what are their indications?
“OCD” - oxacillin, cloxacillin, dicloxicillin are indictated for mild to moderate localized staph infections
Naficillin and oxacillin (IV) are both indicated for serious systemic staph infections
Methicillin is indicated for most staph infections except MRSA of course
Which penicillins are known as extended spectrum, and what are their individual indications?
Ampicillin and Amoxicillin have identical spectrum and activity. Indicated for penicillin resistant pneumococci
Ticarcillin and piperacillin - are the antipseudomonals, often given in combo with other antibiotics (aminoglycosides/flouroquinones) for infections outside the urinary tract
Which extended spectrum penicillin would be indicated if you needed excellent oral absorption?
Amoxicillin is better absorbed orally than ampicillin
What penicillin is the drug of choice for Listeria ?
Ampicillin
Which penicillin is most indicated for a pseudomonas infection?
Ticarcillin and Piperacillin are both indicated
Give some examples of drugs that use beta lactamase inhibitors in combination with beta lactams to make a lactamase resistant antibiotic
Inhibitors include: Clavulanic acid, sulbactam, and tazobactam
Amoxicillin + Clavulanic acid = Augmentin
Piperacillin + Tazobactam = Zosyn
How to beta lactamase inhibitors do the job of inhibiting beta lactamases?
They resemble a ring portion of beta lactamases, but lack the functionality. So, they bind the beta lactamase substrates and inhibit the action through competitive mimicry
List some adverse effects of Penicillins
Hypersensitivity (Anaphylaxis, serum sickness, skin rashes) Diarrhea Nephritis Neurotoxicity Hematologic Toxicity Cation toxicity
Describe the possible resistance mechanisms agains penicillins.
Most common - inactivation via beta lactamases
Modification of the PBPs - (e.g. MRSA and penicillin resistant pneumo)
Efflux from Gram negs
What types of bugs are inherently resistant to penicillins? 2 examples
Most gram negatives are resistant due to their outer membrane that acts as a permeability barrier
Most intracellular bugs (e.g. chlamydia) due to certain penicillins’ inability to penetrate mammalian cell membranes
What makes cephalosporins more desirable than penicillins?
They have a broader spectrum of activity
More resistant to beta lactamases
What is the spectrum of activity of the 1st generation cephalosporins?
Gram negatives: “PEcK” - Proteus, E. coli, and Klebsiella Pneumo
Anaerobes: peptococcus and peptostreptococcus
NOT bacteriodes
What is the spectrum of activity of the second generation of cephalosporins?
Active against organisms that inhibit 1st generations PLUS they have extended gram negative activity
What type of bug do the cephamycins have activity against?
anaerobes
Describe some of the clinical uses of the second generation cephalosporins
Cefuroxime - sinusitis, otitis, and lower resp. tract infections
Cefoxitin, cefotetan - mixed anaerobic infections, peritonitis and diverticulitis (INCLUDING bacteriodes <– not covered by 1st gen cephalosporins)
Describe the spectrum of activity of the 3rd generation cephalosporins
Have expanded gram neg coverage compared to 2nd, (cefotaxime, cetriaxone can cross BBB)
Active against beta-lactamase + haemophilus and nisseria
LESS active against gram positives
What are the clinical uses of the third generation cephalosporins?
emperical therapy for sepsis of unknown cause in the immunocomprimised and regular people
treatment of infection where cephalosporins are least toxic drug available
in neutropenic, febrile, immunocomprimised patients
used in combo with aminoglycosides
If cephalosporins appear to be the least toxic drug available, which generation would you prescribe?
Names?
Third
- Cefotaxime
- Ceftazidime
- Ceftriaxone
Which (2) cephalosporins are known as cephamycins?
Both are second gen
- Cefoxitin
- Cefotetan
Describe the clinical role of 3rd generation cephalosporins.
Similar to 3rd gen
Cefepime - more resistant to B-lactamases
Good activity against pseudomonas, staph, and strep
Highly active against haemophilus and neisseria
Penetrates CSF
What drug would you use to treat an infection that is in the CSF?
Cefepime (4th gen cephalosporin)
Describe how cephalosporins are excreted
Most cephalosporins are excreted in the urine
Ceftriaxone - bile
What bugs aren’t generally covered by cephalosporins?
"LAME" Listeria Atypicals (chlamydia, mycoplasma) MRSA Enterococci
Name a drug that has similar action to penicillins, with a spectrum similar to 3rd gen cephalosporins, and is resistant to beta-lactamases?
Aztreonam - can be given to patients who are penicillin allergic
treat pneumonia, meningitis, and sepsis caused by gram negative pathogens
Describe Imipenem
Acts like a penicillin, resistant to beta lactamases
Inactivated by dehydropeptidase in renal tubules (administered with cilastatin to inhibit dehydropeptidase)
Not necessarily safe in penicillin allergic patients
What is the most important side effect of impenem?
MUST MONITOR RENAL FUNCTION
Skin rashes and reactions at infusion sites are also seen
Describe the mechanism of action of vancomycin
Binds the D-Ala-D-ala terminus preventing peptidoglycan elongation and cross-linking
Describe possible mechanisms of resistance to vancomycin?
The terminal D-ala is transformed to D-lactate, which modifies the binding site for vancomycin
- seen in VRSA (vanco resistant staph aureus
Describe the clinical uses of vancomysin
Sepsis or endocarditis caused by MRSA
In combo with cefotaxime or ceftriaxone for the treatment of meningitis caused by highly penicillin-resistant pneumococcus
Very expensive and IV, so generally an antibiotic of last resort
Why are penicillins given PO at least 2 hrs before or after food? Which is the exception?
Absorption is impaired by food
Amoxicillin is the exception to this rule
Give 2 prominent mechanisms of resistance to penicillins
FINISH
