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43 Cards in this Set
- Front
- Back
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Glycopeptides
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Vancomycin, Teicoplanin
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1. spectrum of action
VANCO |
1)Bacteriostatic against G+ cocci, bactericidal against G+ rods (including penicillinase producers and methicillin-resistant strains)
NOT effective against G- used orally to treat AB-resistant pseudomembranous colitis and stapylococcal enterocolitis, and esp. MRSA in pneumonia |
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2. mechanism of action
VANCO |
2)Binds to D-ala-D-ala terminus of murine monomer and inhibits murine polymer synthesis by blocking attachment of repeating disaccharide units to pre-existing cell wall.
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3. pharmacokinetics
4. Distribution 5. Drug interactions VANCO |
3-5. poorly absorbed from GI. Primarily renal elimination. No cross resistance or cross allergenicity w other antibiotics.
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6. Resistance
7. Toxicity and adverse effects VANCO |
6. Bacteria aquire ability to replace terminal D-ala with D-lactate (van HAX genes)
7. Hypersensitivity, neprhotoxicity, neutropenia, skinflushing or rash "red man syndrome" |
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Whats different about Teicoplanin? (from vanco)
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extended half life, 1X/day dosing. NO/less pain or tissue necrosis after IM injection. Less nephro/oto toxicity
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Name the β-lactams
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Penicillins, cephalosporins, Carbacepham, Carbapenems, Monobactam
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About natural Penicillins...
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G and V. From fungus and semisynthetic derivatives. Come closest to the ideal of full antibacterial spectrum with low toxicity, esp some newer derivatives.
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Penicillin chemistry
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Strong organic acids.
Ionized at physiological pH. Bc free acids are poorly soluble, they are frequently provided as Na+ or K+ salts. A 6-aminopenicillanic acide nucleus composed of a thiazoldiline ring fused to a beta-lactam ring |
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Why is Ring B important?
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Ring B is:
1. the active center of the antibiotic, 2. the site of action of bacterial enzymes (βlactamases and penicillinases) 3. the site of formation of the "major" antigenic determinants of the penicillins |
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Alterations in the R group change what properties of the penicillin molecule?
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1. Acid stability
2. Sensitivity to penicillinase activity 3. Antibacterial spectrum 4. Potentcy |
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1. Spectrum
2. Mechanism (& site) of Action (PENICILLIN) |
1. Full spectrum (except when resistant)
2. (Peni/Cephalo)Inhibition of the synthesis of crosslinks between the repeating disaccharide subunits of the bacterial cell wall. These antibiotics are structural analogues of the D-ala-D-ala substrate for the transpeptidase and form a covalent complex which is inactive. These ABs bind to PBPs that catalyze or participate ion a variety of rxs necessary for the synthesis & maintenence of the cell wall. β Lactam Abs also activate/disinhibit autolytic enzymes which normally fxn to break down the cell wall during cell growth and division. |
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Penicillin G is absorbed...?
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ORALLY. is also ACID-LABILE. oral=max blood levels at 45-60 min, IM= w/i 15 min
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Elimination of Penicillin G...?
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renal secretion of unmetabloized drug. short serum half life. In renal failure this can increase to 10 hrs; dose must be altered.
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Why are liver generated metabolites of Penicillin G important?
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Although they lack anitbacterial activity, they are important for generation of hypersensitivity.
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How do we maintain blood levels of Penicillin G for extended periods of time?
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1) delay absorption from IM sites by adding organic bases such as procaine or benzathine. (penicillin G + benzathine= still tx of choice for syphilis)
2) Administer probenecid- a competitive blocker of tubular secretion of organic acids |
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What are the 4 mechanism of beta-lactam resistance?
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1- ↓ affinity of PBPs through mutation and recombination
2- ↓ cell wall permeability 3- ↑ activity of β lactamases 4- energy dependent efflux pumps |
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Penicillinase/β-lactamase resistant Penicillins (3)
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Methicillin
Nafcillin Cloxacillin These resist hydrolysis by exocellular β-lactamases produced by S Aureus and S Epidermis |
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How does bug become resistant to Methicillin?
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Related to failure to bind to PBPs.
Methicillin resistant bugs are likely to be resistant to other penicillins and cephalosporins. |
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What are the extended range penicillins?
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Ampicillin, Amoxicillin
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What is the spectrum of extended range penicillins?
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They have ↑ spectrum due to better penetration of G- outer membrane and/or decreases the susceptibilityto G- penicillinases.
It IS however MORE susceptible to G+ penicillinases active against E Coli, P mirabilis, H influenzae, Salmonella, Shigella, Neisseria |
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What are the anti-pseudomonal Penicillins?
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1- Carboxylated derivatives: CARBENICILLIN, TICARICILLIN
2- N-acyl derivatives: PIPERICILLIN |
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Name the suicide inhibitors of β-lactamases
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Clavulinic Acid (clavulanate)
Sulbactam Tazo bactam |
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Name β-lactamase inhibitor/penicillin combination drugs
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Augmentin= Clavulanate + amoxicillin
Timentin= Ticaricillin + clavulanate Unasyn= ampicillin + sulbactam Zosyn= Pipericillin + Tazobactam |
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What are the adverse effects of Penicillins?
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CV overload due to salts
Diarrhea inhibition of GABA Coag defects allergic rxs (metabolites) |
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What about testing for Penicillin hypersensitivity?
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Skin testing is often used. Challenge with the major determinant (pre-pen) will predict about 95% of IgE-mediated hypersensitivity. soooo, even a neg test doesn't guarantee the absence of an anaphyllactic response
RAST is used to detect penicilloyl-specific IgE ab wo skin testing, results comparable to skin testing. |
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Whats so speial about the Cephalosporins?
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Broad spectrum (even G- bacilli) w a higher degree of resistance to G+ penicillinases.
3rd generation are good for pulmonary, urinary, surgical and bone issues. |
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What are the major 1rst gen cephalosporins?
Whats thier problem? |
Cephalexin
Cephazolin Cephadroxil Cephadrine Good activity against G+, moderate activity against G- Not effective against MRSA, not DOC for active infection (No CNS penetration) but may be DOC for surgical prophylaxis |
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What are the 2nd generation Cephalosporins?
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Cefotexan
Cefotetan Cefuroxime Cefuroxime axetil Carbacepham (not a true cephalosporin) |
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What is different about the 2nd gen cephalosporins from the first?
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Increased activity against G-, decreased activity against G+
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What are the major 3rd generation cephalosporins?
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GOOD PENETRATION OF CNS
Cefotaxime- G- enterics Cefpodoxime- UTIs & URIs Ceftazidime- P Aerug & MDR G- Ceftriaxone- DOC for N. gonrrhrea & B. Burgdorferei |
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What is the major 4th generation cephalosporin?
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Cefepime
Pseudomonas and G- better than 3rd gen against G+ due to resistance to chromosomally encoded Beta-lactamases |
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What are some of the adverse effects of Cephalosporins?
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Vit K def (& upset stomach)due to eradication of the GI flora
Nephrotoxicity Allergy in pts allergic to penicillins |
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What is Locarbef?
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Carbacepham- a cephalosporin derivative w activity comparable to that of cefaclor or Augmentin
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What are the Carbapenems?
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Imipinem
Meropenem Ertapenem Aztreonam |
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Imipenem?
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Extremely broad spectrum.
Resistant to B-lactamases. Given in combination with cilastatin (a dipeptidase inhibitor) as PRIMAXIN to avoid rapid hydrolysis by renal tubule dipeptidase. |
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Meropenem?
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Does not require cliastatin to acheive therapeutic concentrations. Less nephrotoxic than imipenem
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Ertapenem?
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longer plasma half-life permitting once daily dosing
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Aztreonam?
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Excellent activity against G-, poor activity against G+
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What are the Lipopeptide antibiotics?
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They are CELL MEMBRANE POTENTIAL INHIBITORS
Daptomycin (Cubicin) |
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What about daptomycin?
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Used for tx of complicated skin structure infections by aerobic, G+ organisms.
Bactericidal against vancomycin resistant enterococci. Injection only |
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Daptomycin mechanism?
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Binds to bacterial membranes and forms membrane channels (in a Ca+ dependent manner) leading to rapid membrane depolarization thus inhibiting protein, RNS and DNA synthesis.
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Daptomycin side effects?
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irritation at site of injection, skeletal muscle pain and weakness, increase in CPK, renal failure
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