8. Penicillins Flashcards
List the Basic Penicillins.
- Penicillin G: given IV
- Penicillin V: oral
- Penamecillin: prodrug, metabolized into benzylpenicillin.
List the Staphylococcus B-Lactamase Resistant Penicillins (Anti-Staphylococci).
- Oxacillin
- Nafcillin
- Methicillin
- Cloxacillin
- Dicloxacillin
- Flucloxacillin
List the amino-penicillin ESP (Extended Spectrum Penicillins).
- Ampicillin
- Amoxicillin
List the ureidopenicillin ESP (Extended Spectrum Penicillins)/ (Anti-pseudomonal).
- Piperacillin
- Ticarcillin
What are the side effects of Penicillin therapy?
Penicillins are generally non-toxic and can be used in pregnancy.
- Allergy: T1 HS rxn; may be cross-reactive with cephalosporins
- Epileptic seizures: (↓ BBB pen → only at high serum levels, as in ↓ kidney function)
- Hematological reactions: drug-induced AI hemolytic anemia (via anti-penicillin IgG binding RBC surfaces)
- Morbilliform rash - sometimes occurs if given during viral infection (EBV, etc.)
- (Interstitial nephritis - mononuclear infiltrate)
What are the indications of basic penicillins?
- Gram + cocci: used to be good for staph, now 99% staph are resistant; still good against Streptococci (esp. S. pyogenes)
- Good for Pasteurella multocida (pet bites), Actinomyces (and other Gram + anaerobes in general, i.e. C. perfringens, oral strep, etc.); Leptospira; Borrelia; Treponema
- Syphilis; fever after cat/dog bite; upper respiratory infections (otitis, tonsillopharyngitis); soft tissue infections (Staph/Strep)
- Gram - cocci: good for Neisseria only (most meningococci, some gonococci)
- NOT effective for: Enterococci, Gram - rods (H. flu, E. coli, salmonella), Gram - anaerobes (B. fragilis, etc.)
How are the kinetic parameters of penicillins?
- Penetrate CNS, eye + prostate only in inflammation (compromised barrier)
- Does not enter abscesses
- Cross placenta + enter breast milk
- Excreted via kidney unchanged
What is the route of administration for penicillin G?
Penicillin G - gastric acid unstable → IV only
List the cell wall synthesis inhibitors.
- B-lactams (penicillins, cephalosporins, carbapenems, monobactams)
- Glycopeptides
- Others
What spectrum does Extended-Spectrum Penicillins cover?
Spectrum: similar spectrum to basic penicillins (Staph, Strep), plus activity against…
- Gram - rods - E. coli, Shigella, Salmonella etc. causing GI infections, UTIs, etc.Gram - rods often produce beta-lactamases, so ESPs are often combined with beta-lactamase inhibitors (Topic C-10) in these cases. B-Lase inhibitors have 100x ↑ affinity for B-Lase than the abx themselves and thus competitively inhibit it
- Gram - anaerobes (B. fragilis, often multi-resistant + causes abdominal infections: peritonitis, etc.)
- Enterococci (about 50%, many are multi-resistant); Listeria and some lower respiratory tract infections; Borrelia in early stages
What are the indications for Staph B-Lactamase Resistant Penicillins/ Anti-staphylococci penicillins?
They have larger R groups that inhibit B-lactamase binding so are generally good against Staph (except MRSA), but weaker against Strep than basic penicillins.
What are the indications for penicillin G?
- Rheumatic fever
- mitral endocarditis (S. viridans/bovis)
- intrapartum group B strep prophylaxis (agalactiae)
- IM form for syphilis (primary, secondary or early latent)
- Neisseria meningitis
What is the route of administration of Penicillin V?
Penicillin V - acid stable → oral admin.
What is Penamecillin?
Penamecilline is prodrug metabolized by esterases into benzylpenicillin.
What are the indications for Penicillin V?
DOC for group A strep (strep throat, rheumatic fever)
What are the kinetic parameters like for Penicillin V?
- Poor bioavailability
- 4x/day dosing
- Narrow spectrum
What is the route of administration of Oxacillin?
Oxacillin has good oral absorption and it is often combined with aminoglycoside (gentamicin) in severe, life threatening infections (osteomyelitis, endocarditis, etc.)
What is the route of administration of Nafcillin?
Nafcillin is only parenterally administered.
What are the indications for Methicillin?
Methicillin is no longer used because of nephrotoxic side effects and is therefore only used for diagnostics.
What are the indications of anti-staphylococci penicillins?
- Oral admin: mild or moderate localized skin / soft tissue infections (folliculitis, impetigo, abscesses) by methicillin-sensitive Staph.
- IV admin: severe systemic Staph infections such as tricuspid endocarditis or osteomyelitis.
What is the resistance mechanism behind the anti-staphylococci penicillins?
Resistance occurs when Staph have altered PBPs + thus ↓ beta-lactam binding.
What are the side effects of aminopenicillins?
- Aminopenicillins can cause dysbacteriosis due to effect on GI bacteria (potentially pseudomembranous C. difficile colitis)
- (rash, or in serious cases Stevens-Johnson syndrome)
- often combined with aminoglycoside (ampicillin + gentamicin) for severe cases
What is the route of administration of Ampicillin?
Ampicillin is parenteral admin; often w/ sulbactam B-Lase inhibitor.
What are the indications for Piperacillin?
Piperacillin is good for P. aeruginosa and resistant nosocomial infections.
What is the MOA of Beta-Lactams?
- Beta Lactams all inhibit peptidoglycan synthesis by transpeptidase rxn inhibition.
- They bind to PBPs which are the transpeptidase enzymes themselves → bactericidal effect.
- Generally ineffective against intracellular bacteria.
- Generally low toxicity and ok in pregnancy.
What is the resistance mechanism behind Beta-Lactams?
- Beta Lactamases - break down the abx molecules (penicillin > cephalosporins > carbapenems > monobactams). Extended Spectrum B-Lactamases - more effective + even break down carbapenems
- Altered PBPs - conveys resistance against all B-lactam abx via ↓ binding. ex: MRSA - resists all the staph B-lactamase-resistant penicillins
- Permeability Decrease - reduced or absent pores in cell (ex: Gram negatives)
- Efflux Pump - less common
What are the indications of Ticarcillin?
Ticarcillin is a carboxypenicillin, also good for P. aeruginosa, with clavulanate.
Which are the broadest spectrum penicillins?
Ureidopenicillins are the broadest spectrum penicillins.
What are the pharmacokinetic paramters of Piperacillin?
- Parenteral admin only
- Often combined with gentamicin or tobramycin
- Also often w/ tazobactam B-Lase inhibitor
What are the indications of ampicillin?
- severe anaerobic infections (aspiration pneumonia, Enterococcus, Listeria meningitis)
- accumulates in gallbladder → can be good for cholecystitis
What is the route of administration of Amoxicillin?
Amoxicillin is orally administrated, often w/ clavulanic acid, a B-Lase inhibitor.
What are the indications of Amoxicillin?
- common for Strep pharyngitis
- sinusitis, otitis media and pneumonia by Strep, H. flu, etc.
- dental surgery prophylaxis - against oral anaerobes in pts with endocarditis risk
- (part of H. pylori triple therapy; also for Borrelia)
- (prophylaxis against encapsulated microbes in asplenia )
What are the side effects of Amoxicillin?
- Hepatotoxicity (common with amox + clav).
- common cause of morbilliform rash when given during EBV.
