Toxic blood concentrations

Schulz, M. and Schmoldt, A., Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics, Pharmazie, 58, 447 -74, 2003. 

Toxic blood concentrations of some drugs (e.g. thioridazine) are not significantly higher than dierapeutic concentrations. This is not generally true of liver concentrations which, in postmortem specimens, may be over ten times higher than those obtained from patients on dierapeutic dose regimens. Liver analysis in these cases will provide a more certain indication of a fatal overdose. 

Toxicity. Blood concentrations greater than 0.2 pg/ml of flurazepam or 0.5 pg/ml of V-desalkylflurazepam may be toxic, and blood concentrations greater than 0.5 pg/ml of flurazepam may be fatal. 

Toxicity. Blood concentrations greater than about lOpg/ml may be toxic or lethal. 

Toxicity. Blood concentrations in the region of 0.1 pg/ml produce abnormal behaviour and concentrations of about 0.3 pg/ ml or more cause severe toxic symptoms which may be followed by death although there is considerable intersubject variation. Many deaths have been due, not to the toxic effects of phencyclidine itself, but to the effects of irrational behaviour caused by the drug. In 53 cases of death reported in the literature as not directly due to phencyclidine, blood concentrations ranged from 0.01 to 2.1 pg/ml (mean 0.36) in 22 of these cases urine concentrations ranged from 0.1 to 10.6pg/ml (mean 2.1) alcohol was also present in a number of these cases. 

Methemoglobinemia has been reported with benzocaine, Cetacaine (a mixture of benzocaine, butyl aminobenzo-ate, and tetracaine), cocaine, lidocaine, novocaine, and prUocaine. Acquired methemoglobinemia can result from exposure to chemicals that contain an aniline group, such as benzocaine and procaine, or to those that are transformed to metabolites that contain an aniline group, such as lidocaine and prilocaine. Toxic blood concentrations of local anesthetics, aberrant hemoglobin, and NADH-methemoglobin reductase deficiency are critical... 

In spite of the extensive knowledge about different kinds of consequences of an intoxication with OP.v, data on toxic blood concentrations are non-existent for most of the substances. When known, the values vary strongly between the respective OP.v. For example, the toxic and comatose-fatal (see case report) blood concentrations of parathion are in the ranges 10-50 and 50-80 ng mf, respectively. In contrast, higher concentrations of... 

The therapeutic and toxic blood concentrations of several hundred drugs and xenobiotics have recently been published [1], This may help in determining critical cases of narrow therapeutic index. The rationale of TDM was proven first for phenytoin treatment of epileptic patients. In other words, it was shown that the side effects were reduced and the seizure control was improved if instead of applying standard doses (based on the body weight of the patients) the dosages were... 

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

No effect on food intake or growth. Blood and tissue lead levels elevated, but no overt signs of lead toxicity. Lead concentrations (controls vs. dosed birds) were 0.6 vs. 1.3 mg/kg FW in blood, <0.1 vs. 7 mg/kg DW in liver, and <0.1 vs. 30 mg/kg DW in kidney... 

Lundquist, P. and B. Sorbo. 1989. Rapid determination of toxic cyanide concentrations in blood. Clin. Chem. 35 617-619. 

Cyclosporine is not recommended for Crohn s disease except for patients with symptomatic and severe perianal or cutaneous fistulas. The dose of cyclosporine is important in determining efficacy. An oral dose of 5 mg/kg/ day was not effective, whereas 7.9 mg/kg/day was effective. However, toxic effects limit application of the higher dosage. Dosage should be guided by cyclosporine whole-blood concentrations. 

It has been shown that all doses of arsenic trioxide are characterized by different toxicokinetics parameters. Arsenic compounds have long half-times and the tendency to accumulate in the body. The excretion rate decreased with decreasing blood concentration. The present study confirms the ability of toxicokinetic models to improve the study of various toxic substances and to estimate the Biological Threshold Limit Values. 

Figure 2-1 Toxic blood level concentration as a function of route of exposure. Wide variations are expected as a result of rate and extent of absorption, distribution, biotransformation, and excretion.

Cyclosporine is an immunomodulating agent used mainly to inhibit rejection after transplantations and it has a narrow therapeutic interval. Grapefruit juice is a strong inhibitor of the cyclosporine metabolism (CYP 3A4) and increases the blood concentration of cyclosporine. This can lead to toxicity but can also be used to reduce the doses and decrease the costs of the cyclosporine treatment. 

The odor threshold, 0.58 ppm to 5.0 ppm (Amoore and Hautala 1983 Ruth 1986) is low compared with irritant or toxic concentrations. No acute exposures were located resulting in mild effects in humans. Three monitoring studies, involving no symptoms to mild symptoms during chronic occupational exposures of adult males, are relevant to development of AEGL-1 values. The symptoms and blood concentrations of cyanide in the monitoring study of Chandra et al. (1980) indicate that the workers may have been exposed at higher atmospheric concentrations than those reported. 

Because there is usually a critical concentration of a chemical in the blood that is necessary to elicit either a pharmacological or toxic effect, both the rate and extent of input or availability can alter the toxicity of a compound. In the majority of cases, the duration of effects will be a function of the length of time the blood-concentration curve is above the threshold concentration the intensity of the effect for many agents will be a function of the elevation of the blood-concentration curve above the threshold concentration. 

Slow poisoning can occur in several different ways. In some cases, chemicals or their metabolites may slowly accumulate in the body -rates of excretion are lower than rates of absorption - until tissue and blood concentrations become sufficiently high to cause injury. Delayed toxicity can also be brought about by chemicals that do not accumulate in the body, but which act by causing some small amount of damage with each visit. Eventually, these small events, which usually involve... 

Unfortunately, few of the studies that have attempted to relate the blood concentrations of neuroleptics to therapeutic response have fulfilled all these criteria. There is a suggestion that a "thera peutic window" exists for some phenothiazine neuroleptics. A therapeutic window is a range of concentrations of a drug measured in the blood that are associated with a good therapeutic response. Plasma concentrations outside this range are either too low to ensure a therapeutic response or so high that they induce toxic side effects. Despite the numerous studies of the relationship between the plasma concentration and the therapeutic response for a number of "standard" neuroleptics, it would appear that such correlations rarely account for more than 25% of the variance in clinical response to treatment. The existence of a therapeutic window for neuroleptics would therefore appear to be unproven. However, there could be ranges of plasma concentrations associated with optimal antipsychotic action, but these... 

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