Drugs Flashcards
What is the mechanism of action of beta lactam antibiotics?
- Inhibit cross-linking of peptidoglycan by transpeptidase
- Beta lactam antibiotics bind to Penicillin Binding Protein (the transpeptidase that catalyzes the terminal reactions in bacterial cell wall synthesis)
- This weakens the cell wall so that when water enters through osmosis it bursts
- Bactericidal
What is the generic name for general penicillin?
What is it’s mechanism? What is it’s spectrum? Why is it’s half life an issue?
- Penicllin V (oral) or G (IV)
- Inhibits cross linking of peptidoglycan by transpeptidase (makes cell wall weak and kapooowi!)
- Narrow: Gram +
- Short half life, but coupling it with probenecid impairs renal secretion and increases the half life
What are penicillinases?
Enzymes that certain bacteria produce (Staph and Gonorrhea that inactivate penicillans by breaking their beta-lactam ring
What are penicillinase-resistant penicillins? What is their mechanism? What is their spectrum?
- Nafcillin and Dicloxacillin
- Have the same mechanism as penicillin but have larger R group so resistant to penicillinases
- Narrow, Gram +
- Treat MSSA (Staph aureus)
What are penicillinase inhibitors? What is the mechanism by which they work?
- Clavulanate, Sulbactam and Tazobactam
- Clavulanate, when combined with penicillin, binds irreversibly to penicillanse allowing penicillin to be an effective drug.
Why is penicillin unable to penetrate some gram negative membranes?
Lipopolysaccharides (endotoxin) block antibiotics and dyes form entering the cell
What are aminopenicilins?
- Ampicillin and Amoxicillin
- Mechanism: More water soluble so can pass through pore channels. Same mechanism as penicillin but inactivated by many beta lactamases
- Gram + AND Gram - (influenza, e. coli, listeria, salmonella)
- Ampicillin with Sulbactam, Amoxicillian with Clavulanate
- Ampicillin is associated with c. diff
What are antipseudomonals?
- Ticarcillin, piperacillin
- Mechanism: Same as penicilian, inhibits cross linking by transpeptidase, ineffective if penicillinase is expressed
- BROAD- Gram + and - including pseudomonas
- Tic with clav, pip with tazo
What drug should be used if a patient is allergic to penicillins? How do penicillins cause allergic reactions?
- Aztreonam
- Binds to polypeptide binding protein
- Gram - rods
- Bind with proteins in your body to form a hapten protein. This stimulates the immune system and results in the production of specific antibodies against this antigen.
What are cephalosporins and what is the mechanism by which they work?
- Beta lactam drugs that are less sensitive to penicillinases but can still be inactivated by beta lactamases
- Have the same mechanism of action–inhibit cell wall synthesis by binding to PBP
- Excreted by kidneys, dosage may need to be altered if there is renal insufficiency
- Bactericidal
What is the first generation cephalosporin?
- CEFAzolin
- Gram + cocci
- Surgical prophylaxis
- Doesn’t cross BBB–not good for CNS infections?
- Prevents cross-linking by binding to PBP
What is the second generation cephalosporin?
- CEFOXitin, CEFURoxime
- Gram - and weaker Gram +
- Use immediately before surgery to prevent infection
- Don’t cross BBB
- Inhibits vitamin K production to prolong bleeding
- Cause a disulfiram like reaction when coadministered with ethanol
- Prevents cross linking by binding to PBP
What is the 3rd generation cephalosporin?
- CEFTriaxone, CEFOtaxime
- Gram - infections resistant to other beta lactams
- Prevents cross liking by binding to PBP
- Can cross BBB, good for meningitis treatment
- Ceftriaxone–can react with Ca containing meds to form crystals that precipiatate in lungs nad kidneys
- Associated with C.Diff
What is 4th generation cephalosporin?
- CEFEpime
- Broadest spectrum: Gram + and - including Pseudomanas
- Prevents cross linking by binding to PBP
What is the 5th generation cephalosporin?
- MRSA DESTROYER!
- Prevents cross-linking by binding to PBP 2a present in MRSA that has low affinity for other beta lactams
- Skin and soft tissue infections
What are carapenems?
- IMIpenem/CILAstatin, MEROpenem
- Mechanism: contains beta lactam ring and binds to PBP, has low susceptibility to beta lactamases
- Broad spectrum, Gram + and -, but MRSA resistant
- Imipenem is adminstered with cliastatin to decrease inactivation of drug by renal dehydropeptidase I and prevent the formation of a potentially toxic nephrotoxic metabolite
Which drugs are beta-lactams and what characteristics do they share?
- Penicillins, cephalosporins and carapenems
- Bacterialcidal
- All bind to PBP (transpeptidases that catalyze terminal reactions in bacterial cel wall synthesis
- Side effects: Hypersensitivity (mild rash to anaphalaxis, Seizure (high doses of beta lactams associated with renal dysfunction, and super infection
What are the mechanisms of resistance against beta-lactamases?
- Beta lactamases–drugs that cleave beta lactam rings that are found in most antibiotics
- Changing the structure of pBP
- Decrease in uptake of the drug
- Efflux pumps
What is vancomycin?
- NOT a beta lactam, has a different target in cell wall synthesis–Binds with high affinity D alanyl D alanine terminus of cell wall precursor inhibity the realse from the bactoprenol carrier, prevents peptidoglycan syntesis
- Gram + (Esp. MRSA and c. diff)
- Bactericidal
- Orally is oorly absorbed
- Enterococci are resistant–change d alanyl site and prevent vancomyacin from binding
What is bacitracin?
- NOT a beta lactam
- Gram +
- Prevents the dephosphorylation of bactoprenol carrier (needed for elongation of peptidoglycan wall–peptide can’t cross from inside to outside the cell)
- Usually topical, nephrotoxic when given systematically
What is polymyxin B?
- Creates holes in the membrane by binding to phosphatidylethanolamine
- Narrow: Gram negatie (Often multi-drug resistant)
- Side effects: nephrotoxicity
What is Daptomycin?
- Depolarizes the membrane of gram + bacteria
- Bactericidal
- Treats gram + organisms (MRSA)
