Nicotine adverse effects

The gum should be chewed slowly, with intermittent parking of the gum at the side of the mouth, to avoid adverse effects (e.g., hiccups, heartburn, stomach upset). Only 50% of the nicotine in a piece of gum is systemically... 

Patients who use the lozenge for smoking cessation should use one lozenge every 1-2 hours for the first 2— weeks, decreasing the interval to every 2-4 hours thereafter. Adverse effects that are common with the nicotine lozenge include heartburn, hiccups, and nausea (Shiffman et al. 2002). Because the product contains phenylalanine, the lozenge should not be used for smoking cessation by individuals with phenylketonuria. 

Other potential adverse effects include impaired absorption of fat-soluble vitamins A, D, E, and K hypernatremia and hyperchloremia GI obstruction and reduced bioavailability of acidic drugs such as warfarin, nicotinic acid, thyroxine, acetaminophen, hydrocortisone, hydrochlorothiazide, loperamide, and possibly iron. Drug interactions may be avoided by alternating administration times with an interval of 6 hours or greater between the BAR and other drugs. 

The skin absorption of nicotine and subsequent adverse effects make it an effective pesticide. Nicotine poisoning occurs primarily by children coming into contact with nicotine insecticides or tobacco products. 

Nicotine also affects the developing fetus. Adverse effects of chronic nicotine consumption during pregnancy include reduced infant birth weight, attention deficit disorders, and other cognitive problems. Nicotine receptors are expressed early during development, and it is not clear what other effects nicotine exposure during development has on the fetus. 

Clearly, the addictive power of cigarettes is directly related to their nicotine content. It is not known to what extent nicotine per se contributes to the other well-documented adverse effects of chronic tobacco use. It appears highly probable that nicotine contributes to the increased risk of vascular disease and sudden coronary death associated with smoking. Also, nicotine probably contributes to the high incidence of ulcer recurrences in smokers with peptic ulcer. 

Nicotinic acid is also a potent vasodilator, probably by a direct action on smooth muscle cells. It produces cutaneous vasodilatation, itching of the skin, facial flushing, a sensation of feeling hot, pounding in the head, gastric irritation, diarrhea, raised transaminases, hyperglycemia, and hyperuricemia. These unpleasant adverse effects limit its acceptability for many patients. Nicotinic acid as such is not used in the treatment of vascular disorders, but some of its derivatives are, albeit with poor evidence of clinical efficacy. 

Modified-release formulations of nicotinic acid do not appear to be better tolerated than regular formulations, flushing and itching being the most common adverse effects (SEDA-19, 206). There have also been several reports of hepatotoxicity with this form of the drug (SEDA-16,438). Other adverse effects are hepatotoxicity (apparently a dose-related direct toxic effect), hyperglycemia, and hyperuricemia. It has been questioned whether the modified-release formulation, which is available over the counter in some countries, ought to continue to be available for self-medication in view of its serious adverse effects (2,3). 

The beneficial and adverse effects of nicotinic acid (niacin) have been reviewed (12). Standard nicotinic acid from an immediate-release formulation is metabolized primarily by conjugation, which results in a high frequency of flushing. Long-acting nicotinic acid is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Modified-release nicotinic acid, on the other hand, has a more balanced metabolism and causes fewer of both types of adverse effects. 

Nicotinic acid derivatives include acipimox, aluminium nicotinate, nicotinyl alcohol, and xanthinol nicotinate. The adverse effects of these compounds appear to be identical to those of nicotinic acid. 

Severe toxicoderma has been reported with xanthinol nicotinate and confirmed by a provocation test (SEDA-1, 333). Flushing is claimed to be less frequent with xanthinol nicotinate than with nicotinic acid, but has nevertheless been repeatedly observed, and its other adverse effects are likely to be the same as those of nicotinic acid. 

Ocular adverse effects of nicotinic acid include sicca syndrome, blurred vision, and eyelid edema. 

Two patients complained of dental and gingival pain, not previously reported adverse effects of nicotinic acid (29). The pain abated on withdrawal and in one case recurred on rechallenge. 

Of 61 patients with ischemic heart disease and dyslipi-demia treated with nicotinic acid 1.5 and 3.0 g/day, 32 patients were withdrawn, 18 because of adverse effects and 14 for reasons not related to nicotinic acid (32). Of the 29 patients who finished the study, adverse effects included dryness of the skin (14%), acanthosis nigricans (10%), fatigue (6.9%), nausea (6.9%), abdominal pain (3.4%), diarrhea (3.4%), and anorexia (3.4%) the figures in parentheses were the incidences at 33 weeks. Flushing occurred more often at 18 weeks than at 33 weeks (24 versus 6.9%), as did pruritus (35 versus 28%), suggesting tolerance to these effects. 

Late adverse effects include hepatic dysfunction, with altered liver function tests and hyperbilirubinemia. After prolonged use of nicotinic acid and nicotinyl alcohol, histological changes, for example parenchymal cell injury, portal fibrosis, cholangitis, cholestasis, biliary casts, and lymphocytic infiltrations around the bile ducts, have occasionally been seen. 

Nicotinic acid has been associated with the development of myopathy with nocturnal leg aching and cramps, symptoms that can be exacerbated by simultaneous use of other lipid lowering drugs associated with similar adverse effects, or alcohol, which also has myopathic effects (SEDA-15, 413 38). 

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