Cardiovascular Effects after Inhalation of Large Doses of Albuterol Dry Powder in Rats, Monkeys, and Dogs: A Species Comparison

Petruska, Janet; Beattie, J. Gregory; Stuart, B.O.; Pai, Sudhakar M.; Walters, Karen; Banks, Christopher M.; Lulham, G.; Mirro, Elmer J.

doi:10.1093/toxsci/40.1.52

Cited by 5 publications

(9 citation statements)

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“…Because of such commonalities, monkeys have been used to assess the toxic and therapeutic potential of inhaled substances (e.g., Monticello et al, 1989;Nikula et al, 1997;Petruska et al, 1997;Puri et al, 1987;Zobel et al, 1999) and have been the focus of research on nasal clearance . Macaque monkeys (typically rhesus or cynomolgus) are most commonly used in such research, although an increasing trend in the United Kingdom pharmaceutical industry is to use the common marmoset for preclinical toxicology programs (Smith et al, 2001).…”

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confidence: 99%

Inertial Particle Deposition in a Monkey Nasal Mold Compared with that in Human Nasal Replicas

Kelly

Asgharian

Wong

2005

Inhalation Toxicology

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Information on nasal particle deposition is used in risk assessments for exposure to airborne particulate pollutants and for optimizing the delivery of therapeutic aerosols. Monkeys are commonly used to assess the therapeutic potential of inhaled substances and to a lesser extent the toxicity of inhaled xenobiotics. Yet no reliable measurements of the deposition efficiency of monkey nasal airways for particles >1 microm have been reported to date. The goals of this study were to measure the deposition efficiency (>1 microm) of a replica of monkey nasal airways and to investigate potential differences in nasal deposition between humans and monkeys by comparing results with similar measurements recently reported for human nasal replicas. The monkey nasal replica was an acrylic mold made from a postmortem cast of the nasal airways of a 12-kg, male rhesus monkey. Particle deposition in the monkey nasal mold was measured for monodisperse aerosols between 1 and 10 microm and constant inspiratory flow rates between 2 and 7 lpm. Total deposition efficiency increased from nearly 0 to 100% with increasing particle inertia and was uniquely determined by values of an inertial impaction parameter. The deposition efficiencies of the monkey replica agreed well with those of human nasal replicas when compared according to equivalent Stokes numbers based on minimum cross-sectional area. Results from this study could improve monkey-to-human extrapolation models and interpretations of data from particle toxicity and therapeutic aerosol studies using monkeys.

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mentioning

confidence: 99%

Inertial Particle Deposition in a Monkey Nasal Mold Compared with that in Human Nasal Replicas

Kelly

Asgharian

Wong

2005

Inhalation Toxicology

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“…Naturally, patients with angina pectoris, or with heart failure (where β 2 ‐receptors may become more important due to the downregulation of β 1 ‐receptors) , are particularly sensitive to the cardiac effects of β 2 ‐agonists. Transient hypokalemia may also precipitate the development of dysrhythmias . Pronounced hypotension with myocardial impairment can be achieved in very high doses under experimental conditions .…”

Section: Drugs With Possible Toxic Effects On Both Cardiomyocytes Andmentioning

confidence: 99%

“…Transient hypokalemia may also precipitate the development of dysrhythmias . Pronounced hypotension with myocardial impairment can be achieved in very high doses under experimental conditions . Similarly, elevations in biomarkers of cardiac injury have been observed in humans, but these seem to be transient .…”

Section: Drugs With Possible Toxic Effects On Both Cardiomyocytes Andmentioning

confidence: 99%

Comprehensive review of cardiovascular toxicity of drugs and related agents

Mladěnka

Applová

Patočka

et al. 2018

Medicinal Research Reviews

193

120

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Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta‐blockers, calcium channel blockers, female hormones, nonsteroidal anti‐inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

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“…However, the unique conditions of exposure to the test substance following the inhalation route (e.g., preferential, sustained, and signifi cantly greater exposure of the heart to the test article following administration into the lungs) may not be obtainable by the alternative route [80,81] . The conditions for exposure of animals to the test substance can be the same as those used in the repeat -dose toxicology study, with the monitoring of cardiovascular and electrocardiographic parameters facilitated by radiotelemetry.…”

Section: Route Of Administrationmentioning

confidence: 99%