Therapeutic Notes

Y = yes, N = no) Sulfonylureas Brand (mg) Nonetderty Elderly Dose (mg) (mg/day) Action Metabolism or Therapeutic Notes... 

Stubbs CM. Medication in the elderly. Therapeutic Notes 186. Wellington, Australia Department of Health, April 14,1982. 

The therapeutic iadication (TI) is antiulcer, unless otherwise noted. 

Toxicological studies have demonstrated that there are no important problems with fluconazole. Therapeutic doses of fluconazole may cause enzyme induction in the Hver. This suggests that interactions with other dmgs cannot be excluded. The side effects are similar to those of itraconazole and include nausea, headache, and vertigo. Occasionally, increased Hver enzymes may be noted. Like itraconazole, fluconazole is contraindicated during pregnancy. 

Mexifitene is well absorbed from the GI tract and less than 10% undergoes first-pass hepatic metabolism. In plasma, 60—70% of the dmg is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.5—2.0 lg/mL. The plasma half-life of mexifitene is 10—12 h in patients having normal renal and hepatic function. Toxic effects are noted at plasma concentrations of 1.5—3.0 lg/mL, although side effects have been noted at therapeutic concentrations. The metabolite, /V-methy1mexi1itene, has some antiarrhythmic activity. About 85% of the dmg is metabolized to inactive metabolites. The kidneys excrete about 10% of the dmg unchanged, the rest as metabolites. Excretion can also occur in the bile and in breast milk (1,2). 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

Note The three reagents should be applied as quickly as possible after each other. In combination with the Ry value, and with UV detection before application of the reagent sequence this procedure allows the identification of therapeutic quantities of thiazide diuretics and methyldopa in urine together with a series of other therapeutic agents. Mobile phase residues e. g. acetic acid, should be completely removed from the chromatograms before application of the reagent sequence. 

Howe et al. 2008). Of note, more than 30 other severely ill patients with two types of SCID have received therapeutically effective gene therapy without clinical or molecular evidence of major side effects in prolonged follow-up. 

All musical composers work with the same set of notes, but the geniuses put the notes together in an extraordinarily beautiful way. Synthetic chemists all have available to them the same elements. The successful medicinal chemist will combine atoms such that amazing therapeutic effect is achieved with the resulting molecule. The computational chemist s goal should be to help the medicinal chemist by providing information about structural and electronic requirements to enhance activity, namely, information about which regions of compound space are most propitious for exploration. 

A cautionary note must still be added, however problems of toxicity remain and these must be overcome before widespread therapeutic usage is feasible. 

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