Antibiotic Mechanisms Flashcards
Fosfomycin: Describe MOA and common uses.
Cell wall synthesis inhibitor
Blocks synthesis of polypeptide monomers by irreversibly binding to the enzyme involved.
a. It readily accumulates to therapeutic levels in urine→ Used to treat lower UTI’s.
Bacitracin: Describe MOA and common uses.
Cell wall synthesis inhibitor
Blocks transfer of peptidoglycan monomer Out of the cell by blocking the dephosphorylation and subsequent reactivation of lipid II.
a. Broad spectrum, acts on both Gram positive and negative. Systemic use limited by nephrotoxic side effects.
b. Mainly used in combination (neomycin and polymixins).
Glycopeptides (Vancomycin): Describe MOA and common uses.
Cell wall synthesis inhibitor
a. MOA: sequester peptidoglycan monomers and block cell wall synthesis. They do this by binding to the terminal amino acids of the peptidoglycan monomer.
b. Used as last resort for treatment of drug resistant bacteria (ex: MRSA) or those with allergies to alternatives.
c. Vancomycin poorly absorbed when given orally and must be given by IV except when given for C. Dif infections.
Glycopeptdes (Telavancin): Describe MOA and common uses.
Cell wall synthesis inhibitor
semi-synthetic variant of Vancomycin (addition of long acyl tail).
(1) Blocks cell wall synthesis same way as vancomyin, but binds to Lipid II as well as the peptidoglycan monomer.
(2) Also works by secondary mechanism: depolarization of the cell membrane if Lipid II present (ie bacteria in growth media).
(3) Effective in bacteria resistant to vancomycin in vitro, not indicated for that use.
(4) Enhanced binding at site of bacterial cell division (septum) compared to Vancomycin.
B-Lactams: describe general MOA
Cell wall synthesis inhibitor (most common type of AB used)
β-lactams inhibit cell wall synthesis by blocking Cross-Linking between peptidoglycan polymers. The targets of β-lactams are called Penicillin Binding Proteins (PBP’s). Modification to core β-lactam structures alters spectrum of activity and resistance susceptibility. Penicillin acts like amino acid and covalently binds to enzyme→ Dead end complex form. Resistance: Break β-lactam ring. Change in PBP.
Penicillin G: Describe MOA and common uses.
Cell wall synthesis inhibitor (B-lactam)
only natural penicillin used clinically, has best effect
(1) Given by injection (acid sensitive) to treat wide array of Gram positive and some Gram negative.
(2) Penicillin G is susceptible to β-lactamases that render it inactive.
Amoxicillin: Describe MOA and common uses.
Cell wall synthesis inhibitor (B-lactam)
most widely used semisynthetic penicillin
(1) Broader spectrum than penicillin G because it can penetrate gram negative outer membrane better.
(2) Amoxicillin less susceptible to acid degradation→ can be taken orally.
(3) Susceptible to β-lactamases. Often formulated in combination with β-lactamase inhibitors (ex: clavulanic acid). Brand name for this combination: Augmentin.
Penicillinase-Resistant Penicillins: Describe MOA and common uses.
Cell wall synthesis inhibitor (B-lactam)
Aim to make the drug’s β-lactam ring resistant to β-lactamases.
(1) Resistance can result from expression of altered PBP’s.
(2) Narrower spectrum compared to other β-lactams (Gram positive bacteria only).
Oxazolidinones (Linezolid): Describe MOA and common uses.
Protein synthesis inhibitor (bacterostatic)
prevent initiation complex formation by binding 50S site.
Tetracyclines: Describe MOA and common uses.
Protein synthesis inhibitor (bacterostatic)
block tRNA binding to the A site (broad spectrum antibacterials). Stops elongation of peptide by binding 30 S site.
Aminoglycoside: Describe MOA and common uses.
Protein synthesis inhibitor (bacterostatic)
“lock” the ribosome in the initiation phase and bind irreversibly (bactericidal agents).
Cholramphenicaol and Lincosamides (Clindamcin): Describe MOA and common uses.
Protein synthesis inhibitor (bacterostatic)
overlapping binding sites that inhibit transfers of nascent polypeptide chain. Block amino acid transfer from P site to A site. (50 S).
Macrolides (Ertyromycin, Azithromycin) and Streptogramins: Describe MOA and common uses.
Protein synthesis inhibitor (bacterostatic)
Prevent translocation of tRNA carrying nascent polypeptide change from A site to P site. The combination of quinupristin/dalfopristin increases quinupristin affinity 100-fold.
Sulfonamides and Trimethoprim: Describe MOA and common uses.
Metabolic inhibitors (Bacterostatic)
Inhibitors of folate metabolism
(1) These are always used together to minimze resistance of emergence and for their synergistic effect to Prevent Tetrahydrofolic acid production at 2 different steps.
(2) Treats lower UTI’s.
Fluoroquinolonejs (Ciprofloxacin, Moxifloxacins): Describe MOA and common uses.
DNA replication inhibitors/DNA damage agents (Bactericidal)
a. Fluoroquinolones inhibit DNA gyrase and topisomerases and Block DNA replication
(1) Ex: Ciprofloxacin and Moxifloxacin: broad spectrum AB’s with good oral bioavailability. Widely used for UTI and STD’s.
(2) MOA: Prevent unwinding of DNA→ Prevent DNA replication.
