MOA for drugs Flashcards
B lactams
Bind to PBP and inhibit cell wall synthesis
Monobactam
Bind to PBP-3 in gram negative and inhibit cell wall synthesis
FQ
Bactericidal
inhibition of DNA synthesis by binding to and inhibiting bacterial topoisomerases
DNA gyrase (topoisomerase II) - removes excess positive supercoiling in the DNA helix
Quinolones form a stable complex with DNA and DNA gyrase which blocks DNA replication
Primary target in gram negative bacteria
Topoisomerase IV - Essential for separation of interlinked daughter DNA molecules
Quinolones interfere with separation of daughter cells
Primairy target for many gram positive bacteria
Macrolides
Bacteriostatic
Inhibit protein synthesis by reversibly binding to the 50s ribosomal subunit
induce dissociation of peptidyl transfer RNA from the ribosome during the elongation phase
Vanc
Bactericidal
Inhibits cell wall synthesis and assembly at the second stage by binding firmly to D-ala-D-ala portion of the cell wall precursors to prevent cross linking
Streptogtram - synercid
Developed in response to the need for antibiotics with activity against resistant gram positive bacteria, namely VRE
Two semi-synthetic pristinamycin derivatives
30:70 ratio Quinupristin/Dalfopritisn
OXazolidinone
Bacterostatic
Oxazolidinones bind to the 50S ribosomal subunit near the surface interface of the 30S subunit, producing inhibition of the 70S initiation complex for protein synthesis
Inhibit protein synthesis
Lipopeptide - daptomycin
Rapid Bactericidal
Daptomycin binds to bacterial membranes and inserts its lipophilic tail into the cell wall to form a transmembrane channel –> leakage of cellular contents and rapid depolarization of the membrane potential leading to inhibition of protein, DNA, and RNA synthesis, resulting in bacterial cell death.
Lipoglycopeptides - tela, orita, dela
All lipoglycopeptides interfere with the polymerization and cross- linking of peptidoglycan by binding to the D-Ala-D-Ala terminus. The lipid side chain anchors the drugs to the cell membrane and concentrates the drug at the site of action.
Oritavancin and telavancin (not dalbavancin) also appear to bind to bacterial membranes and insert their lipophilic tails into the cell wall to form a transmembrane channel (like daptomycin) causes leakage of cellular contents and rapid depolarization of the membrane potential leading to inhibition of protein, DNA, and RNA synthesis, resulting in bacterial cell death.
Aminoglycosides
Aminoglycosides irreversibly bind to the 30S ribosomal subunit (some to 50S subunits), which results in a disruption in the initiation of protein synthesis, a measurable decrease in protein synthesis, and misreading of messenger RNA
rapidly bactericidal in a concentration-dependent manner
Tetracyclines
Tetracyclines and tetracycline analogs inhibit bacterial protein synthesis by reversibly binding to the 30S ribosome, blocking binding of amino-acyl tRNA to the acceptor (A) site on the mRNA-ribosomal complex. This prevents the addition of amino acid residues to the elongating peptide chain and inhibits protein synthesis.
Polymixin
Polymyxins are cationic detergents that bind to the anionic lipopolysaccharide molecules of the outer cell membrane of Gram-negative bacteria causing displacement of calcium and magnesium, which normally stabilize the cell membrane. This action leads to changes in cell wall permeability, leakage of cellular contents, and subsequent cell death.
Polymyxins display concentration-dependent bactericidal activity.
Clindamycin
Clindamycin inhibits protein synthesis by exclusively binding (reversibly) to the 50S ribosomal subunit.
Metronidazole
damage bacterial DNA (inhibit nucleic acid synthesis) and subsequently cause cell death – metronidazole is rapidly bactericidal in a concentration-dependent manner.
towards anaerobic and microaerophilic bacteria is due to the presence of electron transport components such as ferredoxins within these bacteria. Ferredoxins are small Fe-S proteins that donate electrons to metronidazole to form a highly reactive nitro radical anion.
TMP/SMX
Sulfamethoxazole: a sulfonamide that competitively inhibits the incorporation of p-aminobenzoic acid (PABA) into folic acid by inhibiting dihydropteroate synthetase, which inhibits the formation of dihydrofolic acid
Trimethoprim: competitively inhibits the activity of bacterial dihydrofolate reductase to prevent the reduction of dihydrofolate to tetrahydrofolate
Together, these two agents produce sequential inhibition of the synthesis of folate, which is necessary for microbial production of DNA, producing a synergistic bactericidal effect against many Gram-positive and Gram-negative aerobic bacteria that may not be present with each agent alone.
