Nicotine: A Review of Its Role in Atherosclerosis
| Autor: | Omar Araim, Bauer E. Sumpio, Sashi Kilaru, David Gortler, Alan H. Chen, Spiros G. Frangos, Ajay K. Dhadwal |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Nicotine
medicine.medical_specialty Pathology Platelet Aggregation Tertiary amine Arteriosclerosis Coronary Artery Disease Sudden death Muscle Smooth Vascular Tobacco smoke Internal medicine medicine Animals Humans Myocardial infarction Cardiopulmonary disease business.industry Smoking medicine.disease Lipids Intermittent claudication Nicotinic agonist Endocrinology Hypertension Surgery medicine.symptom business medicine.drug |
| Zdroj: | Journal of the American College of Surgeons. 193:538-546 |
| ISSN: | 1072-7515 |
| DOI: | 10.1016/s1072-7515(01)01059-6 |
| Popis: | Overwhelming evidence is available associating cigarette smoking and several pathologic conditions, including cardiopulmonary disease and malignancies (Table 1). In the United States, one in six deaths is related to tobacco smoking. Extensive research has been done over the past few decades aimed at understanding the pathophysiology of tobacco-related disease and elucidating the mechanisms by which tobacco smoke causes disease. The Framingham study is the best-known prospective investigation that established the risk factors for coronary heart disease and peripheral vascular disease. Five factors were shown to be predictors of atherosclerosis: hypertension, serum cholesterol level above 297 mg/ 100mL, glucose intolerance, left ventricular hypertrophy on electrocardiography, and smoking. Of these factors smoking history was the most predictive of the development of intermittent claudication. Cigarette smoking especially accelerates atherosclerosis in the coronary arteries, the aorta, the carotid and cerebral arteries, and the large arteries in the peripheral circulation. Smoking is associated with an increased risk of acute cardiovascular events, including acute myocardial infarction, sudden death, and stroke. Other effects include aggravation of stable angina pectoris, intermittent claudication and vasospastic angina, rethrombosis after thrombolysis, and restenosis after angioplasty. Cigarette smoke is a complex mixture of more than 4,000 chemical constituents distributed in particulate and gaseous phases. The most important constituents includenicotine,aromatichydrocarbons, sterolsandoxygenated isoprenoid compounds, aldehydes, nitriles, cyclic ethers, and sulfur compounds (Table 2). PHARMACOLOGY AND METABOLISM Nicotine is a tertiary amine composed of a pyridine and a pyrrolidine ring (Table 3). Tobacco contains both a levorotatory S-nicotine and an R-isomer in quantities up to 10% of the total nicotine present. Nicotine is a weak base with a pKa of 8.0. At a physiologic pH, approximately 30% of nicotine is nonionized and can readily cross cell membranes. Nicotine binds stereospecifically to acetylcholine receptors at the autonomic junctions and the brain. Nicotine cholinergic receptors have been detected in the brain, autonomic ganglia, and the neuromuscular junction. The diversity of nicotinic cholinergic receptors may explain the varied effects of nicotine in humans. Nicotine is distilled from burning tobacco, carried proximally, and deposited in the small airways and alveoli. On inhalation, nicotine is rapidly absorbed from cigarette smoke, from which it enters the arterial circulation and is rapidly distributed to body tissues. It takes 10 to 20 seconds for nicotine to pass through the brain. Nicotine levels than fall, owing to uptake by peripheral tissues and later to elimination of nicotine from the body. Arteriovenous differences during cigarette smoking are substantial, with arterial levels exceeding venous levels 6to 10-fold. The rapid delivery of nicotine results in an intense pharmacologic response, owing both to higher arterial levels entering the brain and effects occurring rapidly, before there is adequate time for the development of tolerance. Nicotine plasma concentrations in smokers range between 10 mol/L and 10 mol/L.22 The elimination half-life of nicotine during the use of tobacco or nicotine products averages 2 to 3 hours. Nicotine levels accumulate over 6 to 8 hours during regular smoking. But there is a very long terminal half-life, 20 hours or more, reflecting the slow release of nicotine from body tissues. Nicotine crosses the placenta freely and has been found in amniotic fluid and the umbilical cord blood of neonates. Nicotine is metabolized extensively, primarily by the liver, but also to a lesser extent by the lung (Fig. 1). The No competing interests declared. |
| Databáze: | OpenAIRE |
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