NicotineTroy Hanson, Betsy Casey, Levi Kellogg

Topics Covered• Background and History• Pharmacology• Route of Administration • Biotransformation• Pharmacological and Physiological Effects• Addiction and Kicking the Habit

Background and History• Two major sources of nicotine

– Large leaf tobacco plants (Nicotiana tabacum)– Small leaf tobacco plants (Nicotiana rustica)

• Initially administered through chewing and the smoking of pipes and cigars.– Finely powdered tobacco leaves (snuff) were also snorted.

• 1610- first attempts to commercialize tobacco in Virginia by the English.• Cigarettes were first used around 1850 in England and over the next 30

years in America.

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Why Do Plants Make Nicotine?

• No role in pollination, storage, or photosynthesis.• Toxic to vertebrates and insects.

– Causes paralysis in insects.– Believed to be an evolutionary response to insect predation.

• Nicotine containing insecticides have largely been replaced by safer alternatives.

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Basic Pharmacology and Smoking• Nicotine was isolated in 1828 by Posselt and Reimann.• Typical cigarette- 6 to 11 mg of nicotine.• Vaporized at 800⁰ Celsius in cigarettes.

– Attaches to tar molecules which contribute to the unique smell and taste of cigarettes.

• Average smoker takes 10 total puffs from a cigarette at intervals of 30-60 seconds.– Nicotine reaches brain in only 7 seconds.

Smoking Facts

• Most common mode of transport for nicotine.

• Yearly consumption is highly variable.

• 2002- 70 million Americans used tobacco.

• Consumption is related to many social factors.

• Cigarettes cause a large reduction in the activities of MAO-A and MAO-B. – Not caused by nicotine.– Slows the breakdown of DA.

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Biotransformation

• 70-80% is transformed to cotinine by cytochrome P450 2A6.– Amount of CYP2A6 activity

varies from person to person.– Cotinine and other

metabolites are mainly secreted in urine.

• Half-Life of about two hours.

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Pharmacokinetics

• Activates nicotinic cholinergic receptors.– nAChRs found in the cerebral

cortex, thalamus, striatum, hippocampus, autonomic ganglia, and monoamine-containing nuclei.

• Produces a sodium influx creating an excitatory response.– Some nAChRs also open calcium

channels and act on presynaptic nerve terminals.

• High doses produce continuous depolarization leading to nicotine poisoning.

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Nicotine and the Mesolimbic System

• Reinforcing affects mediated by the mesolimbic dopamine pathway from the VTA to the NA.

• Animals and humans will self-administer nicotine.– Not as reinforcing as cocaine, amphetamine, or opioids.

• Adolescents who use the drug have an increased chance of addiction.

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Pharmacological Effects• Different effects in smokers and nonsmokers.

– Smokers- increases calmness and relaxation.– Nonsmokers- increases attention, tension, produces nausea, dizziness.

• Has been shown to increase cognitive function in both smokers and nonsmokers.– Possibly affects the α4ß2 receptor.

– Supported by studies of ß2 knockout mice.

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Nicotine’s Physiological Effects

• Activates the sympathetic and parasympathetic nervous systems.– Release of adrenaline and noradrenaline.– Release of HCl in the stomach.– Increases metabolic rate and decreases appetite.

• Produces an increased risk of cardiovascular disease and strokes.

• Fatal at doses as low as 60 mg.– Causes respiratory failure due to depolarization block of the breathing

muscles.

Nicotine Poisoning• Can occur through accidental swallowing and absorption

through the skin.– Usually the result of exposure to insecticides or contact with wet

tobacco leaves.

• Symptoms– Nausea, salivation, stomach pain, vomiting, diarrhea, cold sweat,

headache, dizziness, confusion, and weakness.

• Treatment– Induce vomiting (if swallowed)– artificial respiration– shock treatment.

Tolerance and Dependence• Short Term Tolerance

– Tolerance can occur over the course of one day.– Dissipates over night. Smokers wake up in the morning craving a cigarette.

• Long Term Tolerance– First indicated by green-tobacco illness.– Large doses of nicotine produce no symptoms in long time smokers and

produce toxic effects in nonsmokers.

• Dependence– Withdrawal is characterized in rats by gasps, shakes, tremors, and reduced

locomotor activity. – Decreased ability to experience reward.– Role of DA release in the NA.

Formation of Nicotine Dependence

• 5 Step Process described by Mayhew et al.– 1A: Nonsmoking– 1B: Nonsmoking-contemplation and preparation.– 2: Initiation– 3:Experimentation– 4:Regular smoker– 5:Established smoker

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“Kicking the Habit”• Nicotine replacement

– Focuses on: Nicotine withdrawal symptoms, maintaining a level of nicotine circulating in the blood, utilizing safer ways to administer nicotine.

• First accomplished in 1984.– Gum, patch, nasal spray, inhaler, lozenges.– Combinations with supportive therapy are most successful.

Images from: medicineworld.org; bupropion-150mg.com; and mayoclinic.com

ReferencesMeyer, J. S., & Quenzer, L. F. (2005). Psychopharmacology, drugs,

the brain, and behavior. (pp. 304-318). Sunderland, MA: Sinauer Associates Inc.