Antibiotics 2 Flashcards
what does penicillin inhibit?
PBP
what is the chemical structure of a NAM subunit?
peptide side chains with 1 proximal L-alanine and 2 distal D-alanines
what does PBP do?
binds peptide side chains to form a cross link with the removal of 1 D-alanine
how does penicillin inhibit PBP?
enters the active site of PBP and reacts with the serine group which is important for activity
how does penicillin permanently block the active site of PBP?
the beta lactam ring of the penicillin is opened and it remains covalently linked to PBP
what bacteria does penicillin treat?
strep and staph, Neisseria, anaerobes, spirochetes
what are the pharmacokinetics of penicillin G?
acid labile, widely distributed, rapid renal excretion
how are some bacteria resistant to penicillin?
does not pass gram negative cell envelope very well and degraded by beta lactase enzymes
what are beta lactamase enzymes?
produced by bacteria and provide resistance to beta lactam antibiotics
how does beta lactam enzymes degrade beta lactam antibiotics?
break open the lactam ring via hydrolysis
what antibiotics are penicillinase resistant?
methicillin and oxacillin
what antibiotics have a broad spectrum?
amoxicillin and ampicillin
what antibiotics are antipseudomonas?
azlocillin and piperacillin
how is penicillin G administered?
requires injection
how is penicillin V administered?
can be taken orally
what are the natural penicillins?
pen V and pen G
what are the semisynthetic penicillins?
oxacillin and ampicillin
what are the clinical uses of penicillins?
pneumonia, meningitis, staph infections, syphilis, urinary tract infections
what are the adverse reactions to penicillins?
hypersensitivity, immediate anaphylaxis
what is augmentin?
combination of clavulanic acid and amoxycillin
what does clavulanic acid do?
acts as a beta lactam inhibitor
what is the mechanism fo augmentin?
acts as a competitive and reversible inhibitor of beta lactamase enzymes
what are the adverse reactions of cephalosporins?
hypersensitivity, thrombophlebitis and nephrotoxicity
how are cephalosporin variants produced?
modification of the side chain at position 7 and substituents on position 2 of the ring
what are the first generations of cephalosporins?
cephalosporin, cephalexin, cephradine
how are second generations of cephalosporins produced?
removal of methyl group
what are the second generation cephalosporins?
cefaclor and cefuroxime
how are third generation cephalosporins produced?
R1 and R2 groups changed ao that it is stable without refrigeration
what are the third generation cephalosporins?
cefotaxime and ceftriaxone
what are the most active cephalosporins against E.coli?
third generation
what cephalosporins have increased activity against pseudomonas aeruginosa?
third generation
what does third generation cephalosporins have decreased activity against?
gram-positive staphylococci
what are the fourth generation cephalosporins?
cefepime and cefipriome
how is a fourth generation cephalosporin created?
quaternary N-methyl pyrrolidine (NMP) at R1
what is different about fourth generation cephalosporins?
improved resistance to beta lactamase and penetration of outer membrane of gram negative bacteria, extended spectrum
what causes fourth generation cephalosporins to have minimal beta lactamase activity?
rapid periplasmic penetration and high PBP access
what drug resistant bacteria is fourth gen cephalosporins effective against?
enterobacter and klebsiella
what does isoniazid do?
inhibits cell wall synthesis due to no mycelia acid synthesis
what is mycolic acid?
alpha-alkyl-beta-hydroxy long chain fatty acids
how can resistance to isoniazid occur?
mycobacterial enzyme called peroxidase so depletion of peroxidase causes resistance
how are neuropathic side effects of isoniazid ameliorated?
by co-administration of B6
how does isoniazid lead to blocked fatty acid synthesis?
activated by KatG which catalyses the formation of INH-NAD complex, which then binds tightly to enoyl-aceyl carrier protein reductase which becomes inactive so no fatty acid synthesis
how does blocked fatty acid synthesis lead to a damaged cell wall?
no mycolic acid synthesis
what is rifampicin used to treat?
mycobacterium infections including tuberculosis and leprosy
how does rifampicin inhibit RNA synthesis?
inhibits the bacterial dependant RNA polymerase
what 3 drugs cause inhibition of protein synthesis?
chloramphenicol, tetracycline and streptomycin
how does chloramphenicol work?
binds to the 50s subunit and inhibits formation of peptide bond
how does tetracycline work?
interfere with attachment of tRNA to the mRNA-ribosome complex
how does streptomycin work?
changes shape of the 30s subunit, causing the mRNA to be read incorrectly
how are drugs that inhibit protein synthesis achieve selective toxicity?
due to translational events differing in eukaryotes and prokaryotes
how large are eukaryotic and prokaryotic ribosomes?
eukaryotic = 80s and prokaryotic = 70s
what antibiotics act on 50s subunits?
chloramphenicol, lincosamides, erythromycin and fusidic acid
what are the 2 subunits of a prokaryotic ribosome?
50s and 30s
what antibiotics act on the 30s subunit?
ahminoglycosides and tetracyclines
what is the target for ahminoglycosides?
fmet binding and initiation complex
what is an example of an amino glycoside?
streptomycin
what is the target of tetracycline?
binding of tRNA to the available aminoacyl site on the 50s subunit
what is the target for chloramphenicol and lincosamide?
the formation of a peptide bond
what is the target for erythromycin?
translocation of peptidyl tRNA so removal of tRNA molecule prevented
why might erythromycin be prescribed?
when someone is allergic to penicillin
what does sulfamindes and trimethoprim do?
prevents formation of pyrimidine and purine
what drugs are inhibitors of DNA replication? how?
quinolone as prevent action of DNA gyrase
what drugs are inhibitors of RNA polymerase? how?
rifampicin as prevents RNA synthesis
what are the 4 types of antiviral inhibitors?
protease inhibitors, entry inhibitors, reverse transcriptase inhibitors and non-nucleotide reverse transcriptase inhibitors
what type of inhibitor is acyclovir?
nucleoside reverse transcriptase inhibitors
how is acyclovir prodrug action increased?
after metabolisation, acyclovir-GTP has 100x higher affinity for viral polymerase
how does acyclovir prevent viral replication?
incorporation into viral DNA causes premature chain termination
what is target site alteration?
the target site is altered by reducing the affinity for the antibiotic without impairing cellular function
what is the two types of target site alteration?
cell wall synthesis and protein synthesis
how is target site altered in cell wall synthesis?
shift in amino acid sequence in PBP reduces the affinity for penicillin
how is target site altered in protein synthesis?
shifts in amino acid sequence of ribosomal proteins reduces the affinity for erythromycin and tetracycline
how is the access to target site modified to gain antibiotic resistance?
ability of antibiotic to enter bacterial cell and gain access to target site is impaired
what are the mechanisms of antibiotic resistance?
target site modification, access to target site modified, inactivation of antibiotic and efflux
how does the cell wall lead to resistance in terms of access to target site being modified?
alterations of the composition of bacterial membrane can reduce permeability for antibiotic
what is inactivation of antibiotic?
antibiotics is inactivated by enzymes produced by bacteria
how is cell wall synthesis involved in inactivation of antibiotic?
beta lactamase inactivates penicillin by catalysing lactam ring cleavage
how is protein synthesis involved in inactivating an antibiotic?
amino glycoside modifying enzymes and chloramphenicol transferases prevent disruption of protein synthesis by modifying the structure of the antibiotic
what is efflux?
the antibiotic enters the bacteria but rapid expulsion lowers the cytoplasmic concentration
