CH 9 antibacterial drugs Flashcards
CH 9 anti-DRUG
Inhibitors of cell wall syntehsis
- high selective toxicity–host cells don’t have cell walls
- bacteriocidal
-penicillins, cephalosporins, vancomycin
CH 9 anti-DRUG
Penicillins (B-lactams)
- penicillin, ampicillin, carbenicillin, methicillin, oxacillin
- inhibit transpeptidation enzymes involved in cross-linking the polysacchardie chains of the cell wall
- activate cell wall lytic enzymes
- stimulate formation of holes in the membrane
CH 9 anti-DRUG
penicillin
high activity against gram positive, destroyed by acid and penicillinase
CH 9 anti-DRUG
ampicillin
active against gram + and gram neg., acid stable
CH 9 anti-DRUG
carbenicillin
gram neg. (pseduomonas and proteus), acid stable, not well absorbed by small intestine
CH 9 anti-DRUG
methicillin
penicillinase-resistant but less active than penicillin, acid-labile
CH 9 anti-DRUG
ticarcillin
like carbencillin but more active against pseudomonas
CH 9 anti-DRUG
cephalosporins
- same function as penicillin
- used in patients with penicillin allergies
- broad spectrum
- some can cross blood-brain barrier
CH 9 anti-DRUG
vancomycin
- binds to D-Ala-D-Ala on peptide cross-bridge
- narrow spectrum (staphylococcus, clostridium, bacillus, stertpcoccus, enterococcus
- drug of last resort
- multi-drug resistnat Staph (MRSA-penicilling, ciprofloxacin, methicillin, VRSA-vancomycin)
CH 9 anti-DRUG
protein synthesis inhibtors
- bind to bacterial ribosomes
- bacteriocidal–complete shut down; bacteriostatic–partial shut down
- aminogycosides
- macrolides
- problem–can affect the mitochondrail ribsomes in host bc also has 80S RNA
CH 9 anti-DRUG
aminoglycosides
streptomycin, kanamycin, neomycin, gentamicin
-bind to 30s ribosomal subunit and cause misreading of mRNA
- most effect against gram neg.
- can be toxic to host
- bacteriocidal–frame shift mutations–synthesize wrong AA, causing cell to create reactive oxygen species as stress response bc the bad proteins and leads to apoptosis
CH 9 anti-DRUG
tetracylines
- bind to 30S subunit and inhibit binding of aminoacyl-tRNA
- bacteriostatic–blocks new tRNA, can’t syn. proteins at all, but if chemical goes away bacteria can function again, so much take it long enough to kill bacteria
- broad spectrum
- used to treat acne
CH 9 anti-DRUG
Macrolides
- erythromycin, azithromycin, and clindamycin
- bind to 23S rRNA on 50S ribosomal subunit and prevents transpeptidation reaction
- broad spectrum
- bacteriostatic–blocks transfer of chain to new AA (transpeptidaton)
CH 9 anti-DRUG
Chloramphenicol
- Binds to 23S rRNA and blocks transpeptidation
- broad spectrum
- highly toxic (depresses bone marrow, shuts down cell division–no RBC, WBC, plateltes)–aplastic anemia, low WBC count
- only used in life-threatening cases where no other drug will work
CH 9 anti-DRUG
Metabolic antagonists
- Block metabolic pathways–compet. inhib. of enzyme activity, structurally similar to natural metabolites
- bacteriostatic–if decrease amount of drug, correct substrate can sneak back in
- broad spectrum
- sulfonamides and trimethoprim: inhibit folic acid syn.
- often block folic acid syn. bc humans don’t syn it but obtain it from diet–it is needed for nucleotide syn –> transcription –> translation
CH 9 anti-DRUG
Sulfonamides
- sulfa drugs
- similar to p-aminobenzoic acid (PABA)
- required for syn. of folic acid–precursor for purines/pyrimidines
- inhibit DNA, RNA, and protein syn
- high selective toxicity–humans get FA from diet
- broad spectrum
- rigid structure–fits into active site but inhibits syn.
CH 9 anti-DRUG
Trimethoprim
- inhibits folic acid syn
- competitive inhib. of dihydrofoloate reductase
- can be combined with sulfa drugs
- synergistic drug interaction with sulfa drugs–less of each drug needed bc affects diff steps in pathway
CH 9 anti-DRUG
Nucleic Acid Syn. Inhibitors
- Block DNA replication–inhibit DNA polymerase or other proteins
- Block transcription–inhibit RNA polymerase
- low selective toxicty–NA syn. is similar btwn bacteria and host cells
- quinolones
- Rifampin
CH 9 anti-DRUG
Quinolones
- ciprofloxacin, norfloxacin, levofloxacin
- inhibit DNA gyrase and topoisomerase II
- blocks DNA replication and repair
- broad spectrum
- bacteriocidal– gyrase, unwinds heliz, topoisomearse II–makes cut for unwinding DNA then closes it back
CH 9 anti-DRUG
Rifampin
- Inhibits DNA-dependent RNA polymerase
- Blocks transcription
- bacteriocidal
- more impact on body bc all cells transcribe proteins, not all replicate DNA
CH 9 anti-DRUG
Cell Membrane Disruption
- Polymyxin B
- binds to cell membrane and disrupts structure and permeability
- bacteriocidal
- toxic to host
- topical ointment
