Therapeutic dose

White cell contamination of a platelet product can induce GvHD. It is beUeved that GvHD can be minimized by a contamination of less than 5 X 10 white cells per therapeutic dose of platelets, ie, 3-5 x 10. Blood cell separation technology is directed toward consistentiy achieving this goal. 

Clinically Efficacy. It is evident from the mechanism of action of antihistamines and the etiology of allergic diseases that antihistamines in no sense achieve a cure of the patient s allergy. After the adrninistration of a therapeutic dose, a temporal blockade of the effects of histamine is obtained. Whereas classical antihistamines needed at least twice daily adrninistration, for most of the more recently introduced agents adrninistration once daily is sufficient. 

Once the steady-state concentration is known, the rate of dmg clearance determines how frequendy the dmg must be adininistered. Because most dmg elimination systems do not achieve saturation under therapeutic dosing regimens, clearance is independent of plasma concentration of the dmg. This first-order elimination of many dmgs means that a constant fraction of dmg is eliminated per unit time. In the simplest case, clearance can be deterrnined by the dose and the area under the curve (AUC) describing dmg concentration as a function of total time ... 

An hplc assay was developed suitable for the analysis of enantiomers of ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory dmg (NSAID), in plasma and urine (59). Following the addition of racemic fenprofen as internal standard (IS), plasma containing the KT enantiomers and IS was extracted by Hquid-Hquid extraction at an acidic pH. After evaporation of the organic layer, the dmg and IS were reconstituted in the mobile phase and injected onto the hplc column. The enantiomers were separated at ambient temperature on a commercially available 250 x 4.6 mm amylose carbamate-packed chiral column (chiral AD) with hexane—isopropyl alcohol—trifluoroacetic acid (80 19.9 0.1) as the mobile phase pumped at 1.0 mL/min. The enantiomers of KT were quantified by uv detection with the wavelength set at 254 nm. The assay allows direct quantitation of KT enantiomers in clinical studies in human plasma and urine after adrninistration of therapeutic doses. 

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. 

In long-term treatment, the thia2ides may produce hypokalemia, hyperglycemia, hypemricemia, and a 5% increase in plasma cholesterol indapamide has been shown not to increase plasma cholesterol or Hpids at therapeutic doses (21—23). The decrease of plasma potassium, ie, hypokalemic effect, is dose-dependent, and can be avoided if high doses are avoided (24,25). Thia2ides can cause hyponatremia in patients with large water intake while on the dmg (26,27) hyponatremia may be associated with nausea, vomiting, and headaches. 

Except for the addiction HabiUty of some of the narcotic antitussives, side effects for most of the centrally acting compounds are relatively few and mild at therapeutic doses. QuaUtative comparisons of both side effects and pharmacological profiles have been summarized for many of the compounds described above (97). 

It follows that drugs that selectively inhibit COX-2 should cause fewer side effects than those that inhibit both COX-1 and COX-2. At therapeutic doses, all currently available NSAIDs, with the excqrtion of celecoxib, etoricoxib, lumiracoxib and parecoxib (the prodrug of valdecoxib), are non-selective and inhibit both COX isoforms. 

The use of quinine can cause cinchonism at full therapeutic doses. Cinchonism is a group of symptoms associated with quinine, including tinnitus, dizziness, headache, gastrointestinal disturbances, and visual disturbances. These symptoms usually disappear when the dosage is reduced. Other adverse reactions include hematologic changes, vertigo, and skin rash. 

The patient is monitored carefully vital signs are taken frequentiy, and die patient is placed on a cardiac monitor while the drug is being titrated to a therapeutic dose The dosage may be increased more rapidly in hospitalized patients under close supervision. 

Pharmacokinetics concerns the fate of a dmg in the body at the approximate therapeutic dose range, while toxicokinetics assesses behaviour at the higher dose levels associated with toxic effects. The fate of a dmg is dictated by the rates of ... 

Administration of sufficient doses of an opioid antagonist after only a single therapeutic dose of morphine results in withdrawal phenomena (Bickel et al. 1987 Heishman et al. 1989 Jones 1979). Some degree of physical dependence... 

A rebound sleep disturbance has been found after only 7—10 days of treatment with therapeutic doses of triazolam (Greenblatt et al. 1987). Others have described a withdrawal syndrome after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine (Conell and Berhn 1983). Rebound insomnia may occur with zolpidem. 

The toxic mechanism of action of these various jellyfish venoms is complex. The cardiotoxic reaction seems to focus on calcium transport and is blocked by the prior or post administration of therapeutic doses of verapamil (7J). In neuronal tissue, Chrysaora venom induces large cationic selective channels which open and close spontaneously. These channels are permeable to Na , Li, K, and Cs but not and the channels are present in spite of the treatment with sodium and potassium inhibitors such as tetrodotoxin and tetraethylammonium (14). 

It is perhaps not surprising that, even after taking into account pharmacokinetic differences between these drugs, the therapeutic doses of the SSRIs do not parallel their Ki for inhibition of 5-HT reuptake. For instance, citalopram is about a thousand times more selective than fluoxetine for inhibition of 5-HT uptake, and yet their clinically effective doses are similar. In short, not only is their selectivity for the 5-HT transporter in vitro a poor predictor of their efficacy in vivo but it has to be questioned whether any of these compounds actually work by blocking 5-HT uptake alone. 

There are a number of side-effects of opiates that are due to their actions on opiate receptors outside the central nervous system. Opiates constrict the pupils by acting on the oculomotor nucleus and cause constipation by activating a maintained contraction of the smooth muscle of the gut which reduces motility. This diminished propulsion coupled with opiates reducing secretion in the gut underlie the anti-diarrhoeal effect. Opiates contract sphincters throughout the gastrointestinal tract. Although these effects are predominantly peripheral in origin there are central contributions as well. Morphine can also release histamine from mast cells and this can produce irritation and broncho-spasm in extreme cases. Opiates have minimal cardiovascular effects at therapeutic doses. 

Bis(thiosemicarbazones) [89-97] and AT-heterocyclic thiosemicarbazones comprise two interesting series of experimental chemotherapeutic agents. 2-formylpyridine thiosemicarbazone, the first of the latter series to be examined for biological activity, showed mild antileukemic activity against 1-1210 tumor in mice [98]. However, it was found to be toxic at the therapeutic dose levels which led to synthesis of other aromatic and heterocyclic thiosemicarbazones as potential agents [80, 99, 100]. However, the only active anticancer compounds besides glyoxal bis(thiosemicarbazones) were the iV-heterocyclic thiosemicarbazones [101], 2 formyl-3-hydroxypyridine thiosemicarbazone [102] and... 

Gold is used therapeutically in chronic inflammations as rheumatic arthritis (Ishida and Orimo 1994). The dose is given in the form ofa gold complex, such as gold sodium thiomalate and Auranofin toxic effects due to overdoses may appear. The most common method to monitor the therapeutic dose in serum or urine is GF-AAS. 

So you see, according to our thinking, some of these drugs are more dangerous because the toxic doses are so very close to the behaviorally active therapeutic doses. 

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