Pharm - inhibitors of nucleic acid synthesis Flashcards
Sulfonamides inhibit ………………
Sulfonamides inhibit Dihydropteroate synthase. The initiating enzyme in bacterial folate synthesis.
We divide this group of drugs into two subgroups. Name the two subgroups?
1 Drugs working on folate
2 Drugs working on enzymes associated with transcripition of replication.
Trimethoprim and pyrimethiamine inhibit ………….
Trimethoprim and pyrimethiamine inhibit Dihydrofolate Reductase - an enzyme that is also found in humans, thereby producing anti-cancer drug-like side effects.
Sulfonamides pharmacokinetics?
1 Hepatically acetylated(rendering the metabolite less soluble)
2 renally excreted metabolites cause crystalluria
3 high protein binding(kernicterus)
“-floxacins” moa?
bactericidal and interfere with DNA synthesis by inhibiting topoisomerase II and IV.
-All “-floxacins” are quinolones.
Sulfonamides origin?
structural analogues of PABA. What is PABA?
Sulfonamides moa?
prevents synthesis of dihydrofolic acid, which is essential in producing THF - a cofactor in nucleic acid synthesis
sulfonamides absorption and distribution?
well absorbed from GI, enters CNS
sulfonamides target organisms?
- most gram negs + some gram pos.
- UTI
- Toxoplasmosis
- recurrent otitis media
sulfamethoxazole + trimethoprim =
synergy(Bactrim/Fansidar)
sulfonamides used in treating ulcerative colitis?
azaine and azulfidine
sulfonamides adverse effects?
- hypersensitivity
- Steven-Johnson syndrome
- Kernicterus in neonates(bilirubin displacement from albumin)
Rifampin co to jest?
RNA inhibitor
Rifampin moa?
binds DNA dependent RNA polymerase @ beta-subunit
Rifampin distribution?
Widely distributed, including CNS
Rifampin target organisms?
gram pos, Neisseria spp., mycobacteria
Rifampin adverse effects?
induces liver enzymes - increased metabolism of anticoagulants, contraceptives ++
Nitrofurantoin moa and area of use?
- bacterial DNA damage by unknown mechanism
- used solely as urinary tract antiseptic against E. coli
Fluoroquinolones generally have the suffix….?
-floxacin
Fluoroquinolones moa?
- inhibit DNA gyrase(topoisomerase II) in gram negs.
- inhibit topoisomerase IV in gram positives.
Fluoroquinolones area of use?
- urinary tract antiseptic( N. gonorrhoeae + MRSA)
- mycoplasma, legionella, chlamydia
Polymyxins moa?
cationic basic polypeptide that disrupt bacterial cell membrane in gram negs
Polymyxins adverse effects?
substantiel nephro and neurotoxicity
Polymyxins areas of use?
- eye/ear drops
- topical administration
Metronidazole target organisms?
anaerobes + anaerobe protozoal parasites
Metronidazole moa?
unknown. possibly metabolite interferes with electron transport system and DNA synthesis
Metronidazole contraindications?
pregnant in first trimester
Daptomycin target organisms?
MRSA and VRE
Daptomycin adverse effects?
may cause myopathy
Linezolid target organisms?
MRSA and VRE
Synercide target organisms?
Multdrug resistent bugs
Synercide is composed of ………
2x streptogranins
Synercide adverse effects?
decreased CYP 3A4 activity = increased potency in other drugs
Which enzymes are inhibited by Sulfonamides and trimethoprim?
Sulfonamides - dihydrofolate synthase
Trimethoprim - dihydrofolate reductase
Cross allergy between Sulfonamides and Thiazides?
No
Sulfonamides adverse effect if administered during pregnancy?
Basal ganglia dysfunction due to spent folate
