Fatal toxicity

Deficiency of thiopurine S-methyl transferase (TPMT) is another phenotype that exhibits inter-ethnic differences in frequency. TPMT is an enzyme that catalyzes methylation of therapeutic agents used in the treatment of acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune/inflammatory diseases, as well as in organ transplantation. Patients who have TPMT deficiency experience less efficient methylation and are at greater risk of fatal toxicity when treated with standard doses of fhiopurines. TPMT phenotype is defined by erythrocyte 6-mercapto-purine methylation. African American populations exhibit a 20% lower erythrocyte TPMT than Caucasian Americans, and persons of Chinese descent tend to exhibit greater activity than either of these other American subpopulations. 

The answer is c. (Hardman, pp 1134-1135.) Hematologic toxicity is by far the most important adverse effect of chloramphenicol The toxicity consists of two types (1) bone marrow depression (common) and (2) aplastic anemia (rare) Chloramphenicol can produce a potentially fatal toxic reaction, the gray baby syndrome, caused by diminished ability of neonates to conjugate chloramphenicol with resultant high serum concentrations. Tetracyclines produce staining of the teeth and phototoxicity... 

Potentially fatal toxicities Potentially fatal toxicities with pulmonary toxicity have occurred with ventricular arrhythmias (at approximately 400 mg/day), and... 

Concurrent leucovorin Trimetrexate must be used with concurrent leucovorin to avoid potentially serious or life-threatening complications, including bone marrow suppression, oral and Gl mucosal ulceration, and renal and hepatic dysfunction. Leucovorin therapy must extend for 72 hours past the last dose of trimetrexate. Inform patients that failure to take the recommended dose and duration of leucovorin can lead to fatal toxicity. Closely monitor patients for the development of serious hematologic adverse reactions. 

Weekly dose Physicians and pharmacists should emphasize that the dose is taken weekly. Mistaken daily use has led to fatal toxicity. Encourage patients to read the Patient Instructions in the Dose Pack. Do not write or refill prescriptions on a PRN basis. 

Idiosyncratic dmg reactions (IDRs) are most commonly characterized by a reaction involving fever or rash, with or without internal organ involvement. The spectrum of responses ranges from a minor rash, to potentially fatal toxic epidermal necrosis and Stevens-Johnson syndrome. Immunoglobulin E (IgE)-mediated anaphylactic shock, occasional joint pain, hepatotoxicity or nephrotoxicity are also well documented [24]. The frequency of such reactions are unknown but estimated to be between 1 1000 and 1 10000 exposures and may be enhanced on re-challenging susceptible individuals with the same dmg. 

Buckley NA, McManus PR (2002) Fatal toxicity of serotoninergic and other antidepressant drugs analysis of United Kingdom mortality data. BMJ 325 1332-1333 Buckley NA, Dawson AH, Whyte IM, O Connell DL (1995) Relative toxicity of benzodiazepines in overdose. BMJ 310 219-221... 

Mason J, Freemantle N, Eccles M (2000) Fatal toxicity associated with antidepressant use in primary care. Br J Gen Pract 50 366-370... 

One of the major reasons for the popularity of the benzodiazepines is their relative safety. Overdoses with the benzodiazepines occur commonly, but fatal toxic occurrences are rare. Fatal intoxications are more likely in children, in individuals with respiratory difficulties, and in individuals who have consumed another central nervous system depressant, such as alcohol. After an overdose, the patient begins a deep sleep that may last for 24 to 48 hours, depending on the dose. However, even with large overdoses, the patient can usually still be aroused. 

Benign leukocytosis Weight gain Narrow therapeutic index Tremor Potentially fatal toxicity Alopecia Risk of Ebstein s anomaly with first-trimester exposure... 

Avitaminosis A results in the loss of night vision nyctalopia). Furthermore, the removal of vitamin A from the diet causes the cornea of the eye to dry out xerophthalmia). However, excessive intake of vitamin A can result in severe and even fatal toxicity. 

Fischer M, Bhatnagar J, Guarner J, Reagan S, Hacker JK, Van Meter SH, Poukens V, Whiteman DB, Iton A, Cheung M, Dassey DE, Shieh WJ, Zaki SR. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005 353(22) 2352-60. 

Krivoy N, Zaher A, Yaacov B, Alroy G. Fatal toxic intrahepatic cholestasis secondary to glibenclamide. Diabetes Care 1996 19(4) 385-6. 

The toxic effects of digitalis are frequent and may be fatal. Toxicity may result from overdosage, decreased metabolism and excretion, and hypokalemia stemming from the use of thiazide diuretics, diarrhea, and vomiting. Digitalis toxicity has several manifestations ... 

Toxicity to Fish(14). As to the relationship between surface activity and fish toxicity of surfactants, it is said that at a surface tension of water below 48 dynes/cm fish cannot breathe through their gills, resulting in fatal toxicity due to the changes in physical properties. 

However, the use of antidepressants in completed suicide showed an upward trend, while the use of more violent methods (gassing, hanging) fell During this time prescription of moclobemide and two SSRIs (citalopram and fluoxetine) increased, while that of tricyclics (mainly doxepin and amitriptyline) remained steady. The mean annual fatal toxicity index was highest for tricyclics, such as doxepin, trimipramine, and amitripyline, and lowest for SSRIs. 

Cassidy S, Henry J. Fatal toxicity of antidepressant drugs in overdose. BMJ (Clin Res Ed) 1987 295(6605) 1021M. 

Schreinzer D, Frey R, Stimpfl T, Vycudilik W, Berzlanovich A, Kasper S. Different fatal toxicity of neuroleptics identified by autopsy. Eur Neuropsychopharmacol 2001 ll(2) 117-24. 

Buckley N, McManus P. Fatal toxicity of drugs used in the treatment of psychotic illnesses. Br J Psychiatry 1998 172 461 1. 

Ryan A, Molloy FM, Farrell MA, Hutchinson M. Fatal toxic leukoencephalopathy clinical, radiological, and necropsy findings in two patients. J Neurol Neurosurg Psychiatry 2005 76(7) 1014-6. 

Hazards Handle 99% anhydrous hydrazine with care. Never distill it in the presence of air, and keep it out of contact with strong oxidizers. Wear gloves, and use proper ventilation when handling cyanogen bromide. Cyanogen bromide is highly poisonous, and inhalation of vapors, or skin absorption can be fatal toxic effects are similar to hydrogen cyanide. 

Later on in the war the middle-class (2) gases gradually dropfied out and the Ormans came to recognise only two great classes (1) the iionfaial Irritants, and (2) the fatal toxic gases. 

Imipenem, which is related to meropenem, has also been reported to cause toxic epidermal necrolysis (34). The authors stated that to the best of their knowledge, this was the first report of a possible cross-reaction between two classes of antibiotics in causing toxic epidermal necrolysis. The time between first administration and the occurrence of epidermal necrolysis is considerably shorter in recurrence or provocation testing (35,36). They also claimed that it is likely that the beta-lactam ring is responsible for this hypersensitivity reaction, citing the evidence that the patient had been given amoxicillin 15 days before the cephalosporin, and that could have served as the sensitizing event. They did not discuss whether aztreonam, a monobactam, also could have caused a cross-reaction however, it has been involved in two cases of fatal toxic epidermal necrolysis (37). 

Digoxin crosses the placenta and enters the neonatal circulation (130). It has therefore been used, for example, to improve fetal cardiac function (131). In normal circumstances there seem to be no adverse effects on the neonate, and neonatal plasma concentrations are below those generally considered to be therapeutic. There has been one report of fatal toxicity in the fetus of a woman who took an overdose of digitoxin (132). 

Fatal toxic epidermal necrolysis has been associated with hydroxychloroquine (28). 

Murphy M, Carmichael AJ. Fatal toxic epidermal necrolysis associated with hydroxychloroquine. Chn Exp Dermatol... 

Fatal toxic epidermal necrolysis and fulminant hepatitis occurred shortly after the start of treatment with clarithromycin in a 47-year-old man who was taking disulfiram (60). 

Masia M, Gutierrez F, Jimeno A, Navarro A, Borras J, Matarredona J, Martin-Hidalgo A. Fulminant hepatitis and fatal toxic epidermal necrolysis (Lyell disease) coincident with clarithromycin administration in an alcoholic patient receiving distrlfiram therapy. Arch Intern Med 2002 I62(4) 474-6. 

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