Page 854 - Basic _ Clinical Pharmacology ( PDFDrive )

840 SECTION VIII Chemotherapeutic Drugs

data documenting their safety. Oral or intravenously adminis- many potential adverse effects are uncommon, the FDA called for
tered fluoroquinolones have also been associated with peripheral updated warnings for all fluoroquinolones in 2016, stating that
neuropathy. Neuropathy can occur at any time during treatment these agents should be reserved for patients who do not have alter-
with fluoroquinolones and may persist for months to years after native options, particularly in less severe infections such as upper
the drug is stopped. In some cases it may be permanent. Although respiratory infections or uncomplicated cystitis.

SUMMARY Sulfonamides, Trimethoprim, and Fluoroquinolones

Pharmacokinetics, Toxicities,
Subclass, Drug Mechanism of Action Effects Clinical Applications Interactions
FOLATE ANTAGONISTS
• Trimethoprim- Synergistic combination of Bactericidal activity Urinary tract infections • soft Oral, IV • renal clearance (half-life 8 h)
sulfamethoxazole folate antagonists blocks against susceptible tissue infections • bone and • dosed every 8–12 h • formulated in a
purine production and bacteria joint infections • P jiroveci 5:1 ratio of sulfamethoxazole to
nucleic acid synthesis pneumonia • toxoplasmosis trimethoprim • Toxicity: Rash, fever, bone
• nocardiosis marrow suppression, hyperkalemia,
nephrotoxicity
• Sulfadiazine: Oral; first-line therapy for toxoplasmosis when combined with pyrimethamine
• Trimethoprim: Oral; used alone only for lower urinary tract infections; may be safely prescribed to patients with sulfonamide allergy
• Pyrimethamine: Oral; first-line therapy for toxoplasmosis when combined with sulfadiazine; coadminister with leucovorin to limit bone marrow toxicity
• Pyrimethamine-sulfadoxine: Oral; second-line malaria treatment
FLUOROQUINOLONES
• Ciprofloxacin Inhibits DNA replication by Bactericidal activity Urinary tract infections Oral, IV • mixed clearance (half-life 4 h)
binding to DNA gyrase and against susceptible • gastroenteritis • dosed every 12 h • divalent and trivalent
topoisomerase IV bacteria • osteomyelitis • anthrax cations impair oral absorption • Toxicity:
Gastrointestinal upset, neurotoxicity,
tendonitis
• Levofloxacin: Oral, IV; l-isomer of ofloxacin; once-daily dosing; renal clearance; “respiratory” fluoroquinolone with improved activity versus pneumococcus
• Moxifloxacin: Oral, IV; “respiratory” fluoroquinolone; once-daily dosing; improved activity versus anaerobes and M tuberculosis; hepatic clearance results in lower urinary
levels so use in urinary tract infections is not recommended
• Gemifloxacin: Oral; “respiratory” fluoroquinolone

PREP AR A TIONS A V AIL ABLE

GENERIC NAME AVAILABLE AS GENERIC NAME AVAILABLE AS
GENERAL-PURPOSE SULFONAMIDES PYRIMETHAMINE
Sulfadiazine Generic Pyrimethamine Daraprim
SULFONAMIDES FOR SPECIAL APPLICATIONS Pyrimethamine-sulfadoxine Generic, Fansidar
Mafenide Generic, Sulfamylon QUINOLONES & FLUOROQUINOLONES
Silver sulfadiazine Generic, Silvadene Ciprofloxacin Generic, Cipro, Cipro I.V., Ciloxan
Sulfacetamide sodium Generic (ophthalmic)
(ophthalmic) Gemifloxacin Factive
TRIMETHOPRIM Levofloxacin Levaquin, Quixin (ophthalmic)
Trimethoprim Generic, Proloprim, Moxifloxacin Generic, Avelox, others
Trimpex Norfloxacin Noroxin
Trimethoprim-sulfamethoxazole Generic, Bactrim, Septra, others Ofloxacin Generic, Floxin, Ocuflox
(co-trimoxazole, TMP-SMZ) (ophthalmic), Floxin Otic (otic)