Drugs toxicity

Stanley LA, Horsburgh BC, Ross J et al (2006) PXR and CAR nuclear receptors which play a pivotal role in drug disposition and chemical toxicity. Drug Metab Rev 38 515-597... 

Fhtients with liver or kidney disease are usually given dragp with caution because a cumulative effect may occur. When the patient is unable to excrete the drug at a normal rate the drug accumulates in the body, causing atoxic reaction. Sometimes, the primary health care provider lowers the dose of the drug to prevent a toxic drug reaction. 

The nurse must carefully monitor fluid intake and output because this drug may be nephrotoxic (harmful to the kidneys). In some instances, the nurse may need to perform hourly measurements of the urinary output. Periodic laboratory tests are usually ordered to monitor the patient s response to therapy and detect toxic drug reactions. 

LEUCOVORIN. When leucovorin is administered after a large dose of methotrexate, the timing of tiie administration is outlined by tiie primary health care provider. It is essential that the leucovorin be given at tiie exact time ordered because tiie purpose of folinic acid rescue is to allow a high dose of a toxic drug to remain in tiie body for only a limited time... 

Baselt RC, Cravey RH The Disposition of Toxic Drugs and Chemicals in Man, 3rd Edition. London, Year Book Medical, 1989 Bordo DJ, Dorfman MA Ecstasy overdose rapid cooling leads to successful outcome. Am] Emerg Med 22 326-327, 2004... 

In comparison with the intravenous route of administration the potential advantages of intraperitoneal therapy are the avoidance of high toxic drug plasma levels and an increased (local) exposure of tumors (cells) to anticancer drugs. Whether this increased exposure... 

Lash LH, Xu Y, Elfarra AA, et al. 1995. Glutathione-dependent metabolism of trichloroethylene in isolated liver and kidney cells of rats and its role in mitochondrial and cellular toxicity. Drug Metabolism and Disposition 23 846-853. 

Baselt, R.C., ed. Phencvclidine-disposition of Toxic Drugs and Chemicals in Man. Davis, California Biomedical Publications, 1982. 785 pp. 

Obtain a complete history of alcohol intake and hepato-toxic drug use, including over-the-counter products and dietary supplements. 

The hydrazine-aldehyde reaction has been used intracellularly to deliver non-toxic drug components, which when linked to form a hydrazone bond in situ, become cytotoxic (Rideout, 1986, 1994 Rideout et al., 1990). This same approach has been used to generate enzyme inhibitors in vivo, wherein the hydrazine and aldehyde precursors are not active, but when coupled together within cells to form a hydrazone linkage, become active site binders (Rotenberg etal, 1991). 

Baselt RC (2004) Disposition of toxic drugs and chemicals in man, 7th edn. Biomedical Publications, Foster City, p 1254... 

It is probably best to avoid p-methoxyamphetamine (PMA) and 2,5-dimethoxy-4-methylamphetamine (STP), the former because it seems to have a high toxicity and the latter because it lasts too long (e.g., 24 hours for a minimum dose). Other 4-alkyl amphetamines also seem to be toxic. A number of apparent fatalities due to MDA have been noted, but the reports usually involve very large amounts, often in combination with other drugs (e.g., 7 g MDA plus barbiturates) and screening for other, more toxic drugs (in particular, PMA) has not been done. 

Nelson SD, Trager WF. The use of deuterium isotope effects to probe the active site properties, mechanism of cytochrome P450-catalyzed reactions, and mechanisms of metabolically dependent toxicity. Drug Metab Dispos 2003 31(12) 1481—1498. 

More precise control of levels of drug than with other routes, especially of toxic drugs, where the levels must be kept within narrow limits. 

With the advent of computer-aided-drug modeling (CADM) the critical, scientific and faster approach to newer drug entities based on the biologically active prototypes, combinatorial chemistry, chiral chemistry and biotechnology has paved the way towards more specific, potent and above all less toxic drugs to improve the ultimate quality of life in humans. 

Acute Nicotine is a very toxic drug in acute high doses (Taylor 1996). The lethal dose in adult humans is approximately 60 mg. Symptoms of acute poisoning include headache, dizziness, salivation, cold sweats, abdominal pain, nausea, vomiting, and diarrhea. Sensory disturbances, confusion, and convulsions also occur. Blood pressure drops, the pulse becomes weak and irregular, and respiration becomes difficult. Death usually results from respiratory failure. 

Halpern JH, Pope HG Jr. (1999). Do hallucinogens cause residual neuropsychological toxicity Drug Alcohol Depend. 53(3) 247-56. 

McGrath P, Li CQ (2008) Zebrafish a predictive model for assessing drug-induced toxicity. Drug Discov Today 13 394-401... 

Note The above formula is obviously a rapid, convenient procedure, and eliminates the need to isolate intermediates and other time consuming operations. The procedure above is described for the p-methoxy derivative, a potent but toxic drug. If you wish to avoid the toxic quality of the p-methoxy derivative the formula may be used to make other phenethyl amines without substantive modification. 

So far, clinical evaluation [396-9] has given hope of a measure of control of Pseudomonas with, for the first time, a non-toxic drug. In view of previous calamities a recent reviewer [400] commented to make the best use of carbenicillin both the minimim inhibitory concentration for each strain of organism and the level of the antibiotic in serum must be established. Unfortunately, the next sentence reads. We fear that in most hospitals this will remain a council of perfection . It is to be hoped that this drug will not be squandered like so many of its predecessors. 

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