Toxicity pulmonary

PULMONARY TOXICITY Drug-Induced Pyrimethamine- Hypersensitivity pneumonitis 

Amiodarone Acute pneumonitis, fibrosis, Pyrimethamine- Hypersensitivity pneumonitis 

Azathioprine Hypersensitivity pneumonitis Sulfasalazine Hypersensitivity pneumonitis. 

Beta-adrenergic blockers Bronchospasm bronchiolitis obliterans, fibrosis 

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Chronic Pulmonary Toxicity Chronic damage to the lungs may be due to several subsequent exposures or due to one large dose that markedly exceeds the capacity of pulmonary defense, clearance, and repair mechanisms. Chronic pulmonary toxicity includes emphysema, chronic bronchitis, asthma, lung fibrosis, and lung cancer. The single most important reason for chronic pulmonary toxicity is tobacco smoke, which induces all types of chronic pulmonary toxicity, with the exception of fibrosis. 

Plasma digoxin levels may decrease when the drug is administered with bleomycin. When bleomycin is used witii cisplatin, there is an increased risk of bleomycin toxicity Pulmonary toxicity may occur when bleomycin is administered with other antineoplastic drugs. Plicamycin, mitomycin, mitoxantrone, and dactino-mycin have an additive bone marrow depressant effect when administered with other antineoplastic drugs. In addition, mitomycin, mitoxantrone, and dactinomycin decrease antibody response to live virus vaccines. Dactinomycin potentiates or reactivates skin or gastrointestinal reactions of radiation therapy There is an increased risk of bleeding when plicamycin is administered witii aspirin, warfarin, heparin, and the NSAIDs. 

Minchin, R.F. and Boyd, M.R. (1983). Localization of metabolic activation and deactivation systems in the lung. Significance to the pulmonary toxicity of xenobiotics. Ann. Rev. Pharmacol. Toxicol. 23, 217-238. 

Kehrer, J. P Witschi, H. Effects of drug metabolism inhibitors on butylated hydroxyto-luene-induced pulmonary toxicity in mice. Toxicol. Appl. Pharmacol 1980,53,333-342. 

Mizutani, T. Yamamoto, K. Tajima, K. Isotope effects on the metabolism and pulmonary toxicity of butylated hydroxytoluene in mice by deuteration of the 4-methyl group. Toxicol. Appl. Pharm. 1983, 69, 283-290. 

Phenols are carcinogenic [39-42] and mutagenic thus affect the central nervous system. Long term contact to phenol may even paralyze the body and damage liver, kidneys [41] and heart [43]. Phenol and its vapour are corrosive to the eyes, skin and respiratory tract [44], Renal failure and pulmonary toxicity has been reported with overdose of 89% injectable phenol solution [45]. According to Central Pollution Control Board (CPCB) the discharge limit of phenol in inland water should be lower than 1 mg/1 [46],... 

Warheit, D.B., Brock, W.J., Lee, K.P., Webb, T.R., and Reed, K.L. (2005) Comparative pulmonary toxicity inhalation and instillation studies with different Ti02 particle formulations impact of surface treatments on partide toxicity. Toxicological Sciences, 88 (2), 514-524. 

Little progress was made after these preliminary findings until 2004, when Lam et al. investigated the pulmonary toxicity of three types of SWNTs (raw HiPCO SWNTs, purified HiPCO SWNTs, and Ni-catalyzed arc discharge SWNTs) instilled in mice [58]. It was found that all three SWNT samples induced dose-dependent lung lesions and interstitial inflammation after 7 days. These lesions persisted and worsened after 90 days. 

Controversial results were reported by Warheit et al. in two studies [57, 65] in which rats were exposed to raw SWNTs. Cell proliferation and cytotoxicity indices indicated that exposure to SWNTs produced only transient inflammation. Histological examination of exposed animals, however, identified the development of granulomas, which were non-dose dependent, nonuniform in distribution and not progressive after 1 month. The presence of granulomas was considered inconsistent with the lack of severe lung inflammation. These two reports highlighted the need for more research on the potential pulmonary toxicity of CNTs, shifting the scientific focus towards this aim. 

In summary, intratracheal instillation of CNTs has shown that their potential in eliciting adverse pulmonary effects is influenced by exposure time, CNT dose, CNT biopersistence, surface defects, and metal contamination [71, 72]. Despite the use of surfactants, all studies showed that intratracheal instillation caused major difficulties due to the agglomerative nature of CNTs in a biological environment. More realistic exposure methods, namely inhalation rather than intratracheal administration, are therefore needed for determining the pulmonary toxicity [59, 65, 73]. Several investigations have been performed by using administration different from intra-... 

SWNTs Pulmonary toxicity HiPCO (30wt% Fe) Mice Topical exposure 5d Oxidative stress Skin thickening Inflammation [46]... 

Intratracheal instillation Inhalation 24 d Pulmonary toxicity induced only by intratracheal instillation [75]... 

Aerosol 14d No pulmonary toxicity Suppression of systemic immunity [82, 83]... 

Mutlu, G.M. et al. (2010) Biocompatible nanoscale dispersion of single-walled carbon nanotubes minimizes in vivo pulmonary toxicity. Nano Letters, 10 (5), 1664-1670. 

Huczko, A. et al. (2005) Pulmonary toxicity of 1-D nanocarbon materials. Fullerenes, Nanotubes, and Carbon Nanostructures, 13 (2), 141—145. Grubek-Jaworska, H. et al. (2006) Preliminary results on the pathogenic effects of intratracheal exposure to onedimensional nanocarbons. Carbon,... 

Shvedova, A.A. et al. (2009) Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes two faces of Janus Pharmacology Therapeutics, 121 (2), 192-204. 

Bleomycin—give test dose of 1 -2 units because of possible acute pulmonary, anaphylactoid, or severe febrile reactions must dose adjust for renal insufficiency total lifetime dose should not exceed 400 units avoid high Fi02 as it can exacerbate pulmonary toxicity... 

Warheit, D.B., B.R. Laurence, K.L. Reed, D.H. Roach, G.A. Reynolds, T.R. Webb, Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol. Sci. 77(1), 117-125, 2004. 

Benson, J.M., Y.S. Cheng, A.F. Eidson, F.H. Hahn, R.H. Henderson, and J.A. Pickrell. 1995. Pulmonary toxicity of nickel subsulfide in F344/N rats exposed for 1-22 days. Toxicology 103 9-22. 

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