Blood levels criticisms

Vitamin D intoxication causes 25-hydroxy vitamin blood levels to go from a normal of 30—50 ng/mL to 200—400 ng/mL. At this high level, the metabohte can compete with 1 a-25-dihydroxy vitamin for receptors in the intestine and bone and induce effects usually attributed to the dihydroxy vitamin D. Thus, 25-hydroxy vitamin is beUeved to be the critical factor in vitamin D intoxication. Vitamin D2 is metabolized slower than vitamin and thus appears to be less toxic (218). 

Certain antibiotics such as the tetracyclines, streptomycin, neomycin and kanamycin can cripple the tubules if taken in excessive amounts. Toxic damage to the kidneys can affect not only their filtration functions, but can alter the organs control over blood levels of certain critical molecules. A complex biochemical-hormonal system controlling blood pressure and volume, for example, is regulated by the kidneys, so that chronic kidney damage can inflict damage on the... 

Metabolism and elimination are critical in determining medication blood level and longevity of action. Two main categories of metabolic reactions are phase I reactions and phase 11 reactions. Phase 1 reactions are oxidative reactions that involve the cytochrome P450 system, and phase 11 reactions are conjugative reactions. The rate-limiting step for most compounds occurs through phase I metabolism. 

Because lithium is superior to placebo in preventing a relapse once the acute episode has been controlled, duration of treatment, concurrent drug use, ideal blood levels, and method of discontinuation become critical issues. 

It is critical that the blood methanol level be determined as soon as possible if the diagnosis is suspected. Methanol concentrations higher than 50 mg/dL are thought to be an absolute indication for hemodialysis and treatment with fomepizole or ethanol, although formate blood levels are a better indication of clinical pathology. Additional laboratory evidence includes metabolic acidosis with an elevated anion gap and osmolar gap (see Chapter 59). A decrease in serum bicarbonate is a uniform feature of severe methanol poisoning. 

As with most drugs that affect your brain, the rate at which your blood alcohol levels rise also affect your behavior—that is, faster changes in blood alcohol levels produce more dramatic effects on your behavior. As alcohol levels increase, more and more of your brain is turned off by alcohol s enhancement of GABA. Ultimately, when blood levels become too high, neurons critical to controlling your breathing and heart rate are inactivated... 

Toxicity. Serious medication-related adverse effects associated with actual or potential damage to tissues, organs, or the entire body system. Toxicity may be directly related to critically elevated blood levels of a drug and may be acute (as in tricyclic antidepressant overdose) or chronic (as in prolonged, moderately elevated lithium level). A drug may also produce "toxic effects" at therapeutic doses (such as phenothiazine s potential for inducing bone marrow damage, which in turn causes decreased production of white blood cells). 

Prediction of the dissolution rate is another application of NIR. Carbamazepine is used for the treatment of epilepsy and consistent dissolution of the dosage form is critical for therapeutic blood levels of drug. In 1991 dissolution profiles of brand name and generic carbamazepine tablets were compared by Zannikos et al. after storage in high humidity [90]. The calibration was based upon the percentage of drug in solution after one hour in a USP Type II dissolution apparatus. 

A/3 deposition. The model thus confirmed a critical and isoform-specific role for ApoE in (1) Aj8 trafficking and (2)SP formation. Conversely or additionally the binding of ApoE isoforms to tau may affect phosphorylation of that protein and lead to NFT formation (52, 55). The connection between ApoE isoforms, their serum concentration, high intake of dietary cholesterol, and/or high cholesterol blood levels and an increased risk of AD, cardiovascular disease, and longevity is visible and rational but remains to be proved (47). 

There is accumulating data that alterations in cytokine expression play a critical role in enhanced mortality and morbidity in experimental animals. Klein et al. (1993) reported that THC induced cytokine-mediated mortality of mice infected with L. pneumophila. Mice administered two injections of THC, one before and one after a sublethal dose of Legionella experienced acute collapse and death. The THC-induced mortahty resembled cytokine-mediated shock, and acute-phase serum from these animals contained significantly elevated levels of TNF and IL-6. The investigators concluded that THC increased the blood levels of acute-phase cytokines in the infected animals and that these elevated levels, at least in part, accounted for mortalities induced by THC. Newton et al. (1994) demonstrated that drug treatment of mice suppressed Thi anti-Legionella immu-... 

The ahUity to eradicate bacteria from the urine is related directly to the sensitivity of the microorganism and the achievable concentrations of the antimicrobial agent in the urine. Unfortunately, most susceptibifity testing is directed at achievable concentrations in the blood. There is a poor correlation between achievable blood levels of antimicrobial agents and the eradication of bacteria from the urine. In the treatment of lower tract infections, plasma concentrations of antibacterial agents may not be important, but achieving appropriate plasma concentrations appears critical in patients with bacteremia and renal abscesses. 

The properties of solubility and dissolution rate are key to the form selection process. Solubility in this discussion refers to equilibrium solubility, which is important to both process development and formulation activities. The rate of dissolution of drug substance in physiological media often correlates to the rate of attainment of therapeutic blood levels after administration of solid drug product. In such cases the appropriate choice of form is critical to product efficacy. 

---