The P-I-E-N-O Parkinsn's List Drug Database
nicotine,NicoretteTM ,HabitrolTM ,NicodermTM ,ProStepTM
STIMULANT:
Deter smoking
Description: Nicotine is a naturally occurring alkaloid, long used by pharmacologists to investigate the autonomic nervous system. It is now used clinically as a drug to help smokers quit smoking. Nicotine by itself is not considered a health threat. Commercially, nicotine is marketed as a chewing gum, complexed with polacrilin, a cationic resin, and as a transdermal patch. Dosage forms that deliver nicotine more rapidly, such as inhalers and sprays, are currently in development. Nicotine chewing gum was approved by the FDA in January 1984, and transdermal patches were approved in November 1991. In 1994, a meta-analysis of 17 double-blind, placebo-controlled studies demonstrated the benefit of nicotine patches in helping smokers quit smoking. The patent for NicoretteTM gum expired in 1994. A less potent analog of nicotine, lobeline sulfate, is currently undergoing investigation as a smoking deterrent.
Mechanism of Action: Nicotine's pharmacological actions are complex and include effects on both the central and peripheral nervous systems. Nicotine is classified as a stimulant of autonomic ganglia, although it possesses both stimulant and depressant actions. The end result of stimulation at what are now referred to as nicotinic receptors is a variety of cholinergic and adrenergic effects. These include: tachycardia or bradycardia mediated by either stimulation or interference with sympathetic or parasympathetic pathways, stimulation of receptors in the carotic and aortic bodies, release of epinephrine from the adrenal medulla, and stimulation of the chemoreceptor-trigger zone. At the neuromuscular junction, nicotine is an agonist, but paralysis ensues due to receptor desensitization. The effects on the GI tract are secondary to parasympathetic stimulation.
Pharmacokinetics: Nicotine is readily absorbed through the buccal mucosa when the gum is chewed, although the absorption is slower than that from cigarette smoke. The rate and extent of absorption during 20-30 minutes of rhythmic chewing vary from 50-90% of the content of the gum. The amount absorbed depends on the time the saliva is held in the mouth as opposed to being swallowed or expectorated. Very little nicotine is absorbed from the GI tract due to extensive first-pass metabolism through the liver. While regular use of the gum provides steady-state blood levels of nicotine similar to those achieved by smokers, neither the gum nor the patch can provide peak levels as rapidly as occur after inhaling tobacco smoke. Nicotine levels reach the brain within 7 seconds after a single puff on a cigarette, but peak concentrations can require as long as 4 hours after application of a patch. Chewing gum produces peak plasma concentrations within 15-20 minutes. Peak plasma concentrations from the various transdermal preparations are as follows: Habitrol: 5-6 hours; Nicoderm: 4 hours; and ProStep: 9 hours after application.
Nicotine is widely distributed in the body tissues, particularly the CNS. It crosses the placenta and is secreted in milk. The concentrations of nicotine in amniotic fluid and fetal serum exceed those in maternal serum. Detectable amounts also appear in the serum and urine of infants of smoking, nursing mothers.
Plasma concentrations decline in a biphasic manner. The initial half-life is 2-3 minutes and the terminal half-life is 30-120 minutes, with considerable variation among individuals. Most of the drug is metabolized in the liver by oxidation to cotinine and nicotine-1'-oxide. Cotinine has a plasma half-life of about 10-40 hours. Nicotine and its metabolites are excreted by the kidneys; about 10-20% of nicotine is eliminated unchanged in the urine.
CONTRAINDICATIONS/PRECAUTIONS: Nicotine is contraindicated in patients with severe angina pectoris or cardiac arrhythmias, and in patients with a history of myocardial infarction because coronary ischemia can occur. This may be the result of nicotine's action on the sympathetic nervous system or secondary to release of catecholamines from the adrenal medulla. Tolerance to this effect does not develop.
Nicotine use should be discouraged during pregnancy because spontaneous abortions have been reported. Nicotine is classified as FDA category D for the transdermal systems and category X for the gum. Nicotine should not be used during breast-feeding.
Nicotine is relatively contraindicated in patients with insulin-dependent diabetes mellitus, hypertension, hyperthyroidism, pheochromocytoma, vasoplastic diseases (e.g., Buerger's disease, Prinzmetal's angina) because increases in blood pressure, heart rate, and plasma glucose can follow the effects of nicotine-induced catecholamine release.
Nicotine is relatively contraindicated in patients with a history of peptic ulcer disease because the ulcer can be exacerbated.
Additional contraindications and/or precautions for chewing gum only: Nicotine is relatively contraindicated in patients with dental disease and in patients with temporomandibular joint (TMJ) disorder because injury to teeth or aggravation of TMJ can result from chewing.
Nicotine is relatively contraindicated in patients with a history of esophagitis or mouth or throat inflammation because these conditions can be exacerbated.
Additional contraindications and/or precautions for transdermal systems only: Nicotine should not be applied to areas of skin disease.
DRUG INTERACTIONS: Smoking cessation and therapy with a nicotine preparation can increase the effect of insulin. Insulin dose reduction may be necessary if an insulin-dependent patient suddenly stops smoking.
Smoking cessation can increase the therapeutic effects of propoxyphene, propranolol (and possibly other œ-adrenergic blockers), theophylline, warfarin, and other drugs that are metabolized by the hepatic P-450 enzyme system. Substances in tobacco smoke can induce these hepatic enzymes. Smoking cessation may allow for a correction in the activity of these enzymes, necessitating a dose reduction of drugs metabolized via this pathway.
ADVERSE REACTIONS: Nicotine rarely causes atrial fibrillation, ventricular tachycardia, premature ventricular contractions (PVCs), myocardial ischemia, myocardial infarction, hypertension, erythema, pruritus, rash, or urticaria that need medical attention.
Symptoms of overdose include nausea/vomiting, severe abdominal pain, diarrhea, severe headache, and/or severe weakness. More severe symptoms of overdose include fainting or syncope, hypotension, weak pulse, and seizures.
Minor side effects that occur during use of nicotine products include sinus tachycardia, mild headache, appetite stimulation, constipation, diarrhea, dizziness, dysmenorrhea, flushing, insomnia, and irritability. Other reported side effects include hiccups, jaw ache, and sore throat.
Nicotine chewing gum is stickier and heavier than regular gum and can affect artificial teeth or other dental work.
PATIENT INFORMATION:
What does nicotine chewing gum do?
Nicotine (NicoretteTM ) helps people stop smoking. By replacing nicotine found in cigarettes, physical withdrawal effects are less severe. Using nicotine chewing gum in combination with a supervised stop-smoking program is essential. It is important to learn how to cope with psychological dependency on cigarettes as part of quitting the habit. Nicotine gum is for use over short periods of time (not more than 6 months). Generic nicotine chewing gum is not yet available.
What should my doctor, dentist, or pharmacist know before I use nicotine? They need to know if you have any of these conditions:
How should I use this medicine?
Chew nicotine gum in the mouth. Do not swallow the gum. Follow carefully the directions that come with the chewing gum. Use exactly as directed. When you feel an urgent desire for a cigarette, chew one piece of gum slowly. Slow chewing reduces belching problems. Continue chewing until you taste the gum or feel a slight tingling in your mouth. Then, stop chewing and place the gum between your cheek and gum. Wait until the taste or tingling is almost gone then start chewing again. Continue chewing in this manner for about 30 minutes. Do not use more than 30 pieces of gum a day. Too much gum can increase the risk of an overdose. As the urge to smoke gets less, gradually reduce the number of pieces each day over a period of 2 to 3 months. When you are only using 1 or 2 pieces a day stop using the nicotine gum.
Special precautions for use in children:
This medicine is not for children.
What if I miss a dose?
This does not apply. Only use the chewing gum when you have a strong desire to smoke. Do not use more than one piece of gum at a time.
What other medicines can interact with nicotine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from using nicotine?
Serious side effects with nicotine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with nicotine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I use nicotine? Always carry the gum with you. Do not smoke while you are using nicotine chewing gum to reduce the chance of a nicotine overdose.
If your mouth gets sore from chewing the gum, suck hard sugarless candy between pieces of gum to help relieve the soreness. Brush your teeth regularly to reduce mouth irritation. If you wear dentures, contact your doctor if the gum sticks to your dental work.
If you are diabetic be prepared that stopping smoking can increase the effects of insulin, and you may need to reduce your insulin.
Where can I keep my medicine?
Keep out of the reach of children. Store nicotine in a safe place where children and pets cannot reach it, and be careful about throwing gum away. If a child chews or swallows nicotine gum, call your doctor or a poison control center at once.
Store below 30C (86F). All nicotine products are sensitive to heat. Store in manufacturers packaging until ready to use. Protect from light. Throw away unused medicine after the expiration date.
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