Cardiovascular system nicotine effects

Murexine and related compounds have marked actions on the nicotine receptor as expected from choline esters (87-89). Toxins from the digestive glands of nudi-branchs have marked effects on the cardiovascular system of the rat (23). Antiviral and antibacterial substances have been obtained from molluscs (90,91). 

Although nicotinic acid and nicotinamide function identically as vitamins, their pharmacologic effects differ. In large doses (up to 6 g/day), nicotinic acid is effective in reducing serum lipids (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides, and lipoprotein A. Nicotinic acid produces vasodilation and increased blood flow due to histamine release. Nicotinamide does not affect blood lipid levels or the cardiovascular system. 

The effects of nicotine on the cardiovascular system mimic those seen after activation of the sympathoadrenal system, and they are principally the result of a release of epinephrine and norepinephrine from the adrenal medulla and adrenergic nerve terminals. These effects include a positive inotropic and chronotropic effect on the myocardium as well as an increase in cardiac output. In addition, both systohc and diastolic blood pressures are increased secondary to stimulation of the sympathoadrenal system. These effects are the end result of a summation of adrenergic and chohnergic stimulation. 

The actions of nicotine on the central nervous system are the result of a composite of stimulatory and depressant effects. These can include tremors, convulsions, respiratory stimulation or depression, and release of antidiuretic hormone from the pituitary. Nausea and emesis are frequently observed after the initial use of nicotine in the form of tobacco smoke. However, tolerance to these effects rapidly develops. This is in contrast to the effects of nicotine on the cardiovascular system, where tolerance develops much more slowly. 

Actions Carbachol has profound effects on both the cardiovascular system and the gastrointestinal system because of its ganglion-stimulating activity and may first stimulate and then depress these systems. It can cause release of epinephrine from the adrenal medulla by its nicotinic action. Locally instilled into the eye, it mimics the effects of acetylcholine, causing miosis. 

The heart may be affected by both muscarinic and nicotinic effects. In the former, stimulation of the parasympathetic nerve endings, while in the latter, excess ACh on the nicotinic receptors, is of importance. The cardiovascular effects are tachycardia caused by the overstimulation of the sympathetic system, bradyarrhythmias, atrioventricular block, hypotension and QT prolongation, VF, and TdP (Grmec et al, 2004). 

Tolerance develops to some of the effects of nicotine, taken repeatedly over a few hours a first experience commonly causes nausea and vomiting, which quickly ceases with repetition of smoking. Tolerance is usually rapidly lost the first cigarette of the day has a greater effect on the cardiovascular system than do subsequent cigarettes. 

Another point to notice in Table 7.5 is nicotine s autonomic effects, particularly on the cardiovascular system. The stimulation of the heart and its resultant increased demands for oxygen underlie the association of nicotine and heart disease. In this regard, a less than adequate supply of oxygen to the heart may result in chest pain (angina) or a heart attack (Julien, 2005). 

Tobacco smoke includes 4000 chemical species with varying potential which cause adverse effects. Nicotine is stimulating to the autonomic nervous system ganglia and neuromuscular junction. The most prominent effects relate to stimulation of the adrenal medulla, central nervous system (CNS), cardiovascular system (release of catecholamines), gastrointestinal tract (parasympathetic stimulation), salivary and bronchial glands, and the medullary vomiting center. There is subsequent blockade of autonomic ganglia and the neuromuscular junction transmission, inhibition of catecholamine release from the adrenal medulla, and CNS depression. 

Peripheral Pharmacological Actions of Nicotine. Nicotine effects on the cardiovascular system include tachycardia and peripheral vasoconstriction, which leads to elevated blood pressure. Because the cardiovascular effects are mainly caused by elevated levels of catecholamines and cortisol, tolerance to these effects does not occur. Other pharmacological actions of nicotine include increased gastrointestinal motility caused by parasympathetic ganglionic stimulation and skeletal muscle contraction caused by the effect on nicotinic receptors in the neuromuscular junction (184). 

The side effects and toxicity of local anesthetics seem to be related to their actions on other excitable membrane proteins, such as in the sodium and potassium channels in the heart, the nicotinic acetylcholine receptors in the neuromuscular junctions, and the nerve cells in the CNS. In general, neuromuscular junctions and the CNS are more susceptible than the cardiovascular system to the toxic effects of local anesthetics. 

This drug is both sympathoplegic and parasympathoplegic, due to blockade of nicotinic ganglia in both parasympathetic and sympathetic pathways. Thus, effects on both systems are seen. Effects due to sympathetic blockade include sedation, hypotension, and cardiovascular abnormalities, whereas those due to parasympathetic blockade include dyspepsia and constipation. 

Bupropion appears to reduce nicotine withdrawal symptoms and may simulate the actions of nicotine on the brain reward system. The most common side-effects related to bupropion are insomnia (30-45% at a dose of 300 mg/day) and dry mouth. Other commonly reported adverse events include hypertension, headache, and nausea. Seizures are a known risk associated with the use of somewhat higher doses compared with other antidepressants (0.1-0.4%), especially for the immediate-release form of the drug and when given at dosages of 450 mg/day or higher. Bupropion, unlike the TCAs, is virtually free of adverse cardiovascular effects, which makes it quite attractive for specific populations. 

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