FINALS: Anti Infective Drugs (p1) Flashcards
What are the main components of the bacterial cell envelope?
Membranes, proteins, and other structures surrounding the cytoplasm.
What are the stages of bacterial cell wall biosynthesis?
Assembly: Formation of MurNAc and GlcNAc.
Transport: Movement of peptidoglycan units by bactoprenol.
Transglycosylation: Linking peptidoglycan units into chains.
Polymerization: Cross-linking to form two-dimensional sheets.
What are the targets for antibiotic agents in bacteria?
Cell walls and cell membranes.
How do beta-lactam antibiotics affect bacteria?
They are generally bactericidal and most effective against rapidly dividing bacteria, causing swelling, bursting, filamentation, or cessation of viability.
What happens during the cross-linking reaction in cell wall biosynthesis?
The transpeptidase displaces the final D-alanine from the D-ala-D-ala terminus, forming an acyl enzyme intermediate, which couples with the free amino group of the third residue (L-lysine) of an adjacent chain.
What are first-generation cephalosporins active against?
Gram-positive cocci (pneumococci, streptococci, staphylococci), E. coli, Klebsiella pneumoniae, and Proteus mirabilis.
What are the mechanisms of resistance to beta-lactam antibiotics?
Inactivation by beta-lactamases.
Modification of PBPs.
Impaired drug penetration (especially in gram-negative species).
Efflux pumps.
What types of penicillin are resistant to destruction by most beta-lactamases?
Penicillinase-resistant penicillins like oxacillin, cloxacillin, nafcillin, and dicloxacillin.
Name some first-generation cephalosporins.
Cefadroxil, Cefazolin, Cephalexin, Cephalothin, Cephradine, Cephapirin, Cephaloridine.
What are the pharmacokinetics of penicillins like dicloxacillin, ampicillin, and amoxicillin?
They are acid-stable and relatively well absorbed.
Nafcillin has erratic absorption and is not used orally.
Food impairs absorption (except for amoxicillin), so they should be given 1-2 hours before or after meals.
What organisms are resistant to first-generation cephalosporins?
MRSA, Pseudomonas aeruginosa, indole-positive Proteus, Enterobacter, Serratia marcescens, Citrobacter, Acinetobacter, and anaerobes like Bacteroides fragilis.
What is the role of beta-lactamase inhibitors like clavulanic acid, sulbactam, and tazobactam?
They inactivate beta-lactamases and extend the antibacterial activity of penicillins.
What are second-generation cephalosporins active against?
They have broader activity than first-generation cephalosporins and include drugs like Cefaclor, Cefuroxime, and Cefoxitin.
What are some adverse effects specific to certain penicillins?
Procaine Pen G: Pulmonary embolism and acute psychotic reactions.
Oxacillin, Nafcillin: Hepatitis and granulocytopenia.
Pen G Na: Hypernatremia, hyperkalemia, and Jarisch-Herxheimer reaction.
Ampicillin: Pseudomembranous colitis.
What is the clinical use of Cefazolin, a first-generation cephalosporin?
It is the drug of choice for surgical prophylaxis and for streptococcal and staphylococcal infections requiring intravenous therapy. It does not penetrate the CNS, so it cannot treat meningitis.
What are the second-generation cephalosporins?
Cefaclor, Cefamandole, Cefonicid, Cefuroxime, Cefprozil, Loracarbef, Ceforanide, and the cephamycins like Cefoxitin, Cefmetazole, and Cefotetan.
What is the function of efflux pumps in bacterial resistance to beta-lactam antibiotics?
Efflux pumps in gram-negative bacteria transport beta-lactam antibiotics from the periplasmic space back across the outer membrane, reducing the drug’s effectiveness.
What is the mechanism of action for beta-lactam antibiotics?
They inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan chains, which leads to bacterial cell lysis.
What are the adverse effects of penicillins?
Hypersensitivity reactions.
Seizures following rapid IV administration.
Nerve dysfunction with accidental injection into the sciatic nerve.
Superinfection and hepatitis with chronic use.
Gastrointestinal upset (nausea, vomiting, diarrhea).
What are the four types of penicillin based on their spectrum of activity?
Natural penicillins (e.g., Penicillin G, Penicillin V).
Aminopenicillins (e.g., Amoxicillin, Ampicillin).
Penicillinase-resistant penicillins (e.g., Oxacillin, Dicloxacillin).
Antipseudomonal penicillins (e.g., Ticarcillin, Piperacillin).
Which penicillins are preferred for the treatment of severe systemic staphylococcal infections?
Oxacillin and Nafcillin, typically administered via IV infusion.
What are the pharmacokinetics of Penicillin G?
Penicillin G is administered intravenously (IV) due to poor oral absorption and is rapidly excreted by the kidneys. Dose adjustments are necessary in cases of renal insufficiency.
What second-generation cephalosporin is particularly effective against anaerobes?
Cefoxitin, a cephamycin, is effective against anaerobes and is used in certain abdominal infections.
What are beta-lactamase inhibitors, and how do they work?
Beta-lactamase inhibitors (e.g., Clavulanic acid, Sulbactam, Tazobactam) resemble beta-lactam molecules and inactivate beta-lactamases, preventing the destruction of beta-lactam antibiotics and extending their spectrum of activity.
