Transcript Nicotine
Nicotine Troy 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. Image from: agecon.vt.edu 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 • Nicotine containing insecticides have largely been replaced by safer alternatives. Image from: marketeo.com 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. Textbook Image p. 313 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. Textbook Image p.304 Pharmacokinetics • Activates nicotinic cholinergic receptors. – nAChRs found in the cerebral cortex, thalamus, striatum, hippocampus, autonomic ganglia, and monoaminecontaining 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. Textbook Image p.306 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. Image from: treatobacco.net 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. Image from: myquit.net 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 Image from: decodeme.com “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 References Meyer, J. S., & Quenzer, L. F. (2005). Psychopharmacology, drugs, the brain, and behavior. (pp. 304-318). Sunderland, MA: Sinauer Associates Inc.