Nicotine

Nicotine [NIC o teen) is the active ingredient in tobacco. Although this drug is not currently used therapeutically (except in smoking cessation therapy, see p. 117), nicotine remains important., because it is second only to caffeine as the most widely used CNS stimulant and second only to alcohol as the most abused drug. In combination with the tars and carbon monoxide found in cigarette smoke, nico­tine represents a serious risk factor for lung and cardiovascular dis­ease, various cancers, as well as other illnesses. Dependency on the drug is not easily overcome.
1. Mechanism of action: In low doses, nicotine causes ganglionic stimulation by depolarization. At high doses, nicotine causes gan­glionic blockade. Nicotine receptors exist in the CNS, where simi­lar actions occur.
2. Actions:
a. CNS: Nicotine is highly soluble in lipid and readily crosses the blood-brain barrier. Cigarette smoking or administration of low doses of nicotine produces some degree of euphoria. and arousal as well as relaxation. It improves attention, learging. problem' solving, and reaction time. High doses of nicotine result in centra' respiratory paralysis and severe hypotension caused by medullary paralysis (Figure 10.3).

b. Peripheral effects: The peripheral effects of nicotine are com­plex. Stimulation of.sympathetic ganglia as well as the adrenal medulla increases blood pressure and heart rate. Thus, use of tobacco is particularly harmful in hypertensive patients. Many patients with peripheral vascular disease experience an exacerbation of symptoms with smoking. For example, nicotine-induced vasoconstriction can decrease ccronary blood flow, adversely affecting a patient with angina. Stimulation of parasympathetic ganglia also increases motor activity of the bowel At higher doses, .blood pressure falls, and activity ceases in both the gastrointestinal tract and blad­der musculature as a result of a nicotine-induced block of parasympathetic ganglia.

3. Pharmacokinetics: Nicotine is highly lip;a-soluble. Thus, absorp­tion readily occurs via the oral mucosa, lungs, gastrointestinal mucosa, and skin Nicotine crosses the placental membrane and is secreted in the milk of lactating women. Most cigarettes contain 6–8 mg of nicotine; the acute lethal is 60 mg. More than ninety percent of nicotine inhaled in smoke is absorbed Clearance of nicotine involves metabolism in Ine lung and the liver, and urinary excretion. Tolerance to the toxic effects of nico­tine develops rapidly, often within. days after beginning usage..
4. Adverse effects; The ONS effects cf nicetirle include irritability and tremors. IV/coffee may also cause intestinal cramps: diarrhea, and increased heart rate and blood pressure. In addition, cigarette smoking increases the rate of metabolism for a number of drugs. [Note: It is not known which of the more than 3000 com­ponents of cigarette smoke are responsible for this phenomenon, although the benzopyrenes have been implicated.]