Vascular toxicity

Compounds Causing Cardiovascular Toxicity Alcohols are the most important compounds causing vascular toxicity. Ethanol depresses cardiac muscle and attenuates its contractivity when the concentration of ethanol in the blood exceeds 0.75 mg/100 mL. Ethanol also causes arrhythmias, and a metabolite of ethanol, acetaldehyde, also depresses the heart. Furthermore, high concentrations of acetaldehyde cause cardiac arrhythmias. The cardiovascular toxicity of methanol is about the same as that of ethanol, whereas al cohols with longer chains are more toxic than ethanol. 

Mitomycin C-myelosuppression occurs late (approximately 4 weeks) limit cumulative dose to 50 mg/M2 (vascular toxicity)... 

Clinically, this pyrimidine was found to produce prohibitive gastrointestinal and vascular toxic reactions at intravenous doses from 0.3 to 10 mg/kg and total doses of 1.25 to 126 mg/kg for periods up to 60 days. It is not considered to be an agent with significant antitumour effect [333]. 

A number of toxicants have effects on the arteries, veins, and capillaries comprising the vascular system. An important factor in vascular toxicity is that toxic substances are transported by blood, which means that they contact the cells making up the structure of the vascular system, which may be adversely affected as a consequence. It is likely that a significant fraction of organ toxicides are actually the result of damage to blood vessels in the organs. 

Effective DES are able to control drug elution from the polymer, Clinical experience has demonstrated that excessively rapid drug elution often fails to achieve desired clinical efficacy. Rapid drug elution can also produce vascular toxicity by exceeding the safety threshold for the drug, The ideal situation is to have a sustained release of drug for at least 30 days, as this is the critical time window for the resolution of local tissue inflammation and the suppression of neointimal proliferation. 

The primary clinical targets of immunotoxins are tumors, based on the principle that the MAb will target the toxin to the tumor cells and the highly toxic moiety will then kill the cancer cells. Examples of toxins are ricin, diphtheria toxin and abrin, which are all glycoproteins. Their toxicity is based on their ability to block protein synthesis at the ribosomal protein assembly site. They are normally extremely toxic and not suitable for therapeutic purposes because they induce liver and vascular toxicity, even at low dose levels. 

Riviere, J.E., Brooks, J.D., Williams, P.L., Monteiro-Riviere, N.A. (1995). Toxicokinetics of topical sulfur mustard penetration, disposition, and vascular toxicity in isolated perfused porcine skin. Toxicol. Appl. Pharmacol. 135 25-34. 

Ceci G, Bella M, Melissari M, Gabrielli M, Bocchi P, Cocconi G. Fatal hepatic vascular toxicity of DTIC. Is it really a rare event Cancer 1988 61(10) 1988-91. 

Doll DC, Yarbro JW. Vascular toxicity associated with chemotherapy and hormonotherapy. Curr Opin Oncol 1994 6(4) 345-50. 

Samuels BL, Vogelzang NJ, Kennedy BJ. Vascular toxicity following vinblastine, bleomycin, and cisplatin therapy for germ cell tumours. Int J Androl 1987 10(l) 363-9. 

Stefenelli T, Kuzmits R, Ulrich W, Glogar D. Acute vascular toxicity after combination chemotherapy with... 

Selenium appears to accentuate the nephrotoxic effects of cisplatin and its vascular toxicity (SEDA-21, 241). 

There is some evidence that both vincristine and doxorubicin are more often associated with ischemic heart disease than other cancer chemotherapeutic agents. Whether drug-induced platelet activation, altered clotting, or endovascular damage are responsible for vascular toxicity is still unclear. The risk of ischemic heart disease must therefore be kept in mind when patients receive a combination of doxorubicin and vincristine, especially when potential risk factors have been identified. Whether the structural similarity between vinca alkaloids and ergot alkaloids, which are vasospastic, is relevant is highly speculative. 

Cardiotoxicity of primary amines (epinephrine, norepinephrine, isoproterenol) was noted earlier, and has been recognized for nearly 100 years. The vascular toxicity of these and related compounds has also recently been recognized. The effects seem to focus on medial cells of the artery wall, rather than on adventitial or endothelial cells. Early changes include loss of medial cells, mineralization, and loss of elastic fibers. Later there is a compensatory proliferation of intimal cells. The vascular toxicity of two related compounds is particularly striking. One of these compounds, allylamine, will be discussed near the end of this chapter. The second is )S-aminoproprionitrile ()S-APN), which is the active agent in the toxic sweet pea, Lathyrus odoratus. Consumption of flour derived from this plant results in lathyrism, a condition often seen in children and young... 

Chappey O, Wautier MP, Wautier JL (1995) Endothelial cells in culture a model to study in vitro vascular toxicity. Toxicol In Vitro 9(4) 411 19... 

Ballantyne and Salem discuss the experimental and human clinical toxicology of cyanides with particular reference to their potential for apphcation as chemical warfare weapons and use by terrorists. They consider repeated exposure toxicity as well as specific organ, tissue, and functional end-point toxicity. Among the functional end-point toxicities, they review neurotoxicity, cardio-toxicity, vascular toxicity, developmental and reproductive toxicity, and genotoxicity. They conclude this review of the toxicology of cyanide by describing emergency first aid and poison-control... 

Vascular toxicity and influences of cyanide on vascular reflexes... 

Raynaud s phenomenon is common, occurring in one-third to half of those treated with vinblastine and bleomycin or VBP, and there is evidence that blood vessels are pathologically altered. Cisplatin may contribute to the effect. Analysis of late vascular toxicity after chemotherapy for testicular cancer revealed that the use of VBP carried a higher risk of Raynaud s phenomenon than bleomycin with etoposide and cisplatin (BEP). ... 

Samuels BL, Vogelzang NJ, Kennecty BJ. Severe vascular toxicity associated with vinblastine, bleomycin and cisplatin chemotherapy. Cancer Chemother Pharmacol (1987) 19, 253-6. 

Safety/Toxicity Metabobc toxicity neutotoxicity parasite toxicity vascular toxicity ... 

Safety/Toxicity Bacterial toxicity bone marrow tox-icity carcinogenicity cytotoxicity hemato-toxicity hepatotoxicity nephrotoxicity neurotox-icity immunotoxicity cardiovascular toxicity respiratory toxicity vascular toxicity ... 

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