Toxicity drug-induced

The perhaps most important and easily ignored cause of secondary dysmotility is the drug-induced toxic type. Pharmaceuticals are important to consider, in particular those with anticholinergic and/or opioid properties [177]. In individuals with reduced reserve capacity of the gut, either due to concomitant disease or age, such drugs may... 

Various parts of the ophthalmological examination are shown in Table 20.14. The most important common ophthalmological test to evaluate patients for the occurrence of chronic drug-induced toxicity is slit-lamp examination. Specific types of drugs with known potential for ocular toxicity may require that special attention be directed to other evaluations shown in Table 20.14. Most drugs that are to be taken... 

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

The conclusion is inescapable that neither plasma digoxin nor digitoxin levels are infallible guides to drug-induced toxicity, but must be... 

Mercier C, Ciccolini J, Dupuis C et al. Prospective phenotypic screening for DPD deficiency in patients upon fluoropyrimidines administration Impact on the reduction of drug-induced toxicities. Asco Annual Meeting Proceedings. J Clin Oncol. 2007 25. 

However, although the mechanism of hydralazine-induced LE is not yet understood, it is an important example of drug-induced toxicity for two reasons ... 

Mortishire-Smith RJ, Skiles GL, Lawrence JW, Spence S, Nicholls AW, Johnson BA, Nicholson JK. Use of metabonomics to identify impaired fatty acid metabolism as the mechanism of drug-induced toxicity. Chem Res Toxicol 2004 17 165-173. 

The difference in cell sensitivity to cisplatin as a function of the cell cycle can be a useful tool to examine the role played by the inhibition of DNA replication in the drug-induced toxicity. This point was addressed by a study [62] which showed that cells treated with 6 pg/ml in the G1 phase, before the start of DNA replication, exhibited a ten-hour cell-division delay during the first cell cycle after treatment, whereas the delay was only of three hours if the treatment occurred in the late S-phase when most of the DNA replication was terminated. In addition, more chromosomal aberrations were detected following treatment in the G1 phase. The different responses of the cells treated with cisplatin in G1 v.v. cells treated in the late... 

Approximately 3% to 5% of all hospital admissions are directly attributable to drug-induced toxicity, much of which is preventable. 

Park BK,Kitteringham NR, Maggs JL, Pirmohamed M, Williams DP. The role of metabolic activation in drug-induced toxicity. Annu. Rev. Pharmacol. Toxicol. 2005 45 177-202. 

In addition, biliary obstructive jaundice can also be caused by drug-induced toxicity, e.g. with Ciy-substi-tuted steroids, erythromycin estolate, chlorpromazine, chlorpropamide, ajmaline, halothane, methylthiouracil. 

Fig. 29.1 Diagram illustrating potential pathogenetic mechanisms related to drug-induced toxic liver damage...

Obligate, dose-dependent drug-induced toxicity need not be feared, since substances which predictably cause severe toxicity are not usually applied as medical remedies. It is only in cases where the therapeutic effect clearly outweighs the known type of damage that an obligate toxic substance is administered as a therapeutic agent - but in accordance with strict criteria ... 

Liver damage caused by drug-induced toxicity, more specifically the intrahepatic obstructive type of jaundice resulting from the intake of arsphenamine, was first described by EM. Hanger et al. in 1940. (42)... 

Tab. 29.6 Morphological reactions or laboratory findings resulting from hepatic damage caused by drug-induced toxicity (s. tab. 29.10)...

At present, there are no biochemical methods that facilitate early and reliable identification of the drug-induced toxicity which causes the liver damage. 

Kamanabroo D, Schmitz-Landgraf W, Czarnetzki BM. Plasmapheresis in severe drug-induced toxic epidermal necrolysis. Arch Dermatol 1985 121(12) 1548-9. 

Of all the drugs that have been implicated in drug-induced toxic epidermal necrolysis, antimicrobial drugs account for 29-42% (now more than 100 in number) (31,32), and almost all antimicrobial drugs have been implicated, including meropenem (33). 

Paquet P, Jacob E, Damas P, Pierard GE. Recurrent fatal drug-induced toxic epidermal necrolysis (LyeU s syndrome) after putative beta-lactam cross-reactivity case report and scrutiny of antibiotic imputability. Grit Care Med 2002 30(ll) 2580-3. 

Miyauchi H, Hosokawa H, Akaeda T, Iba H, Asada Y. T-cell subsets in drug-induced toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells. Arch Dermatol 1991 127(6) 851-5. 

Eisen ER, Fish J, Shear NH. Management of drug-induced toxic epidermal necrolysis. J Cutan Med Surg 2000 4(2) 96-102. 

Two of nine patients with drug-induced toxic epidermal necrolysis were taking hydrochlorothiazide, one with triamterene and allopurinol, the other with reserpine and hydralazine both died (28). 

Matsueda K, Matsuoka Y, Mizuno M, et al. A case of drug-induced toxic epidermal necrolysis complicated with severe liver injury. Acta Hepatol Jpn 1988 29 949-55. 

By its very nature, the renal system carries a high-risk profile for drug-induced toxicity. Mechanistic and pathophysiologic thinking remains critical for a better understanding of observed harm and prediction of possible future harm. This requires at least vahd data on signals, exposure, denominator and confounders. When ever possible, proactive and prospective design of the data collection is preferable, if not in many cases the only way to get reliable answers. Current... 

Liebler DC, Guengerich FP. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov. 2005 4(5) 410-420. 

---