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Antibiotic modes of action (Nucleic Acid Synthesis Inhibitors (Quionolones…
Antibiotic modes of action
Cell wall synthesis
Bacteria require a strong and rigid cell wall to prevent lysis. Peptidoglycan synthesis needs to be completed for the synthesis of the cell wall.
Transpeptidase/Penicillin Binding Proteins - enzyme
Beta-lactams bind to transpeptidase preventing cross-linking of peptidoglycan. It is admininstered with a beta-lactamase inhibitor. E.g-
PENICILLIN (BENZYLPENICLLIN)
Glycopeptides bind to the acyl-D-alanyl-D-alanine of NAM residues which also blocks elongation of peptidoglycan backbone. It is for gram positive organisms and can be used for the treatment for MRSA. E.g-
VANCOMYCIN, TEICOPLANIN
Nucleic Acid Synthesis Inhibitors
Quionolones- Inhibits DNA gyrase and topoisomerase enzymes which prevents DNA replication as the DNA needs to be uncoiled for it to replicate. E.g-
CIPROFLOXACIN
Enters the cell via porins
Treatment of intracellular pathogens
Gram positive and gram negative activity. Gram negative: DNA Gyrase, Gram positive: Topoisomerase
Fluoroquinolones inhibit topoisomerase 4. Bactericidal and broad spectrum.
RNA Synthesis Inhibitors
Binds to RNA Polymerase and inhibits initiation of mRNA synthesis so translation cannot take place. Cells die due to the bactericidal activity of the antibiotics. E.g-
RIFAMPICIN
mRNA is not generated.
Antimetabolites
Blocks the enzymes involved in the production of tetrahydrofolic acid. These enzymes are dihydrofolate reductase and dihydropteroate synthase. TNF is needed for DNA nucleotides. E.g-
SULPHONAMIDES
and
TRIMETHOPRIM (CO-TRIMOXAZOLE)
Co-trimoxazole is a combination of trimethoprim and sulphamethoxazole
Synthesis: Dihyropteroate Synthase converts P-aminobenzoic acid into dihydrofolic acid. Then dihyrdrofolate reductase converts dihydrofolic acid into tetrahydrofolic acid. This is essential for purines to produce the DNA nucleotides.
Trimethoprim
- Binds to the active site of dihydrofolate reductase inhibiting the synthesis of THF acid. Bactericidal
Sulphonamides
- Structural analogues of P-aminobenzoic acid so they bind to the first enzyme, dihyopteroate synthase. Bacteriostatic
Protein Synthesis Inhibitors
Aminoglycosides (E.g-
GENTAMICIN
- can be bactericidal depending on the drug levels)/ Tetracycline (
DOXYCYLINE
)- Inhibition of binding of tRNA to 30S ribosomes by reversibly binding to the 30S subunit of ribosomes. Concentration dependent killing.
CHLORAMPHENICOL
- Inhibition binding of tRNA to 50S ribosomes
Macrolides (
CLARITHROMYCIN
),
CLINDAMYCIN
- Inhibition of RNA-dependent protein synthesis to a 50S ribosome
LINEZOLID
- Reversible binding of bacterial 50S ribosome
Binding to the 50S subunit interferes with the elongation process. These protein synthesis inhibitors are considered to be bacteriostatic so they don't kill the bacteria.
DAPTOMYCIN
Binds to the bacterial membranes and causes rapid depolarisation of the membrane potential and potassium efflux, inhibiting synthesis of protein, DNA, RNA and protein conc dependent.
For
ONLY
gram positive bacteria, MSSA, MRSA, Staph epidermidis and inactive for gram negative aerobes
Polymyxin A/Colistin
Outer membrane of gram negative bacteria
Binds to the lipid A portion of LPS displacing the calcium/sodium ions which stabilise the membrane. Leads to leakage of cell contents--> Cell death. Poor activity in gram positive as their cell wall is too thick to enter the cytoplasmic membrane.