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19 Cards in this Set

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Inhibition of Nucleic Acid Synthesis: SULFONAMIDES; sulfisoxazole, sulfamethoxazole
BROADSPECTRUM

bacteriostatic, structural analog and competitive antagonist of PABA at DIHYDROPTEROATE SYNTHASE, inhibiting synthesis of folic acid.
Inhibition of Nucleic Acid Synthesis: SULFONAMIDES; sulfisoxazole, sulfamethoxazole -- Pharmcokinetics
Four classes:

oral absorbable, non-absorbable, topical, long-acting

broad distr. crosses BB and placenta
Inhibition of Nucleic Acid Synthesis: SULFONAMIDES; sulfisoxazole, sulfamethoxazole -- Pharmcokinetics -- RESISTANCE
decreased influx
active efflux
increased production of PABA, decrease synthase sensitivity.
Inhibition of Nucleic Acid Synthesis: SULFONAMIDES; sulfisoxazole, sulfamethoxazole -- Pharmcokinetics -- ADVERSE EFFECTS
UT: crystalluria
hemolytic anemia, aplastic anemia, agranulocytosis

Hypersensitivity: STEVENS-JOHNSON syndrom, rashes, fever

Drug Intxn: potentiate effects of oral anticoagulants, sulfonylurea hypoglycemic agents and hydantoin antiseizure drugs
Inhibition of Nucleic Acid Synthesis: BENZYLPYRIMIDINES (trimethroprim)
Broad spectrum, bacteriostatic

selective inhibitor of DIHYDROFLATE REDUCTASE. (There is a mammalian form of this enzyme but less sensitive to inhibition by these drugs).
Inhibition of Nucleic Acid Synthesis: BENZYLPYRIMIDINES (trimethroprim) -- Pharmacokinetics
usually oral, iv with sulfamethoxazole, broad distribution crosses BBB and placenta.

Drug weak base so trapped in prostatic and vaginal fluid.
Inhibition of Nucleic Acid Synthesis: BENZYLPYRIMIDINES (trimethroprim) -- RESISTANCE
decrease influx

increase production of reductase, decreased sensitivity of reductase
Inhibition of Nucleic Acid Synthesis: BENZYLPYRIMIDINES (trimethroprim) -- adverse effects
megaloblastic anemia, leukopenia, granulocytopenia (prevented by simultaneous admin of follic acid).
Inhibition of Nucleic Acid Synthesis: SULFAMETHOXAZOLE + TRIMETHROPRIM
synergism from seq blockade of folate synthesis>> BECOMES BACTERICIDALL instead of bacteriostatic

AIDS PTS have high incidence of adverse effects i.e. CNS disturbance so give folinic acid
Inhibition of DNA replication (Transcription): FLUOROQUINOLONES: ciprofloxacin, levofloxacin
mostly gram neg, some gram positive.

Bactericidal

Inhibits DNA gyrase (Topoisomerase II) in Gram Neg, which prevents relaxation of pos supercoiled DNA req'd for transcription and replication.

Inhibits Topoisomerse IV in Gram Positive, and probably interferes with seperation of replicated DNA into daughter cells during cell division.
Inhibition of DNA replication (Transcription): FLUOROQUINOLONES: ciprofloxacin, levofloxacin - pharmacokinetics
good oral abs, impaired by dairy prod, antacids and divalent and trivalent cations,

broad distr. Clearance via renal
Inhibition of DNA replication (Transcription): FLUOROQUINOLONES: ciprofloxacin, levofloxacin - MECH OF RESISTANCE
decrease influx

decrease affinity for gyrase or topoisomerase IV.
Inhibition of DNA replication (Transcription): FLUOROQUINOLONES: ciprofloxacin, levofloxacin -- Adverse Rxns
Not routine in pregnancy, nursing mothers and children due to cartillage damage

GI: incl pseudomembranous colitis

Drug intxn: increase levels of theophylline
Inhibition of DNA replication (Transcription): NITROIMIDAZOLES; metronidazole
for Anaerobes, can be used for VRE C. difficile, also some aerobic bacteria

Inhibits DNA replication by: nitro group of nitrosohydroxyl amino moiety is reduce by an electron transport protein in anaerobic bacteria, the reduced drug causes strand breaks in DNA. Mammalian drugs unharmed b/c they lack the enzyme to reduce the nitro group of these drugs.
Inhibition of DNA replication (Transcription): NITROIMIDAZOLES; metronidazole -- pharmcokinetics
can be used IV, good oral bioavailability

metabolized by liver CYP3A4 and renal clearance.

reduce dosing in pts with reduced liver fxn.
Inhibition of DNA replication (Transcription): NITROIMIDAZOLES; metronidazole -- adverse effects
leukopenia, seizures and peripheral neuropathy

drug intxn: Barbiturates induce liver enzyme which decreases serum concentration

has disulfuram like rxn, interfering with alcohol metabolism
Inhibition of DNA replication (Transcription): RIFAMYCINS (rifampin, rifaximin)
binds non-covalently to DNA dependant RNA polymerase and inhibits RNA synthesis
Inhibition of DNA replication (Transcription): RIFAMYCINS -- RIFAMPIN
orally absorbed, good CNS penetration, deacylated in liver (ACTIVE METABOLITES).

adv effects: induces CYP3A4, dermatitis, RED ORANGE DISCOLORATION of urin, sweat, feces, tears.
Inhibition of DNA replication (Transcription): RIFAMYCINS -- RIFAXIMIN
for non-invasive E coli (traveler's diarrhea)

also shigella, salmonella, and other enteropathogens

Not absorbed from GI tract, most excreted in feces