Tobacco Nicotine Escandell Mc Kim Hancock CDC Prus
Tobacco & Nicotine Escandell Mc. Kim, Hancock, CDC, Prus escandell nicotine 1
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Figure 1: Areas in the brain involved in nicotine addiction. Nicotine stimulates nicotinic acetylcholine receptors located in the ventral tegmental area, which leads to the release of dopamine in the nucleus accumbens, an important step in the process of nicotine addiction. Neurons projecting from the prefrontal cortex and amygdala modulate the release of dopamine in the nucleus accumbens, which allows for control of these addictive behaviours. These regulatory pathways are comprised of glutamate and gamma-aminobutyric acid (GABA) neurons. Image by: Lianne Friesen and Nicholas Woolridge escandell nicotine 4
• Tobacco is the only natural source of nicotine • Tobacco is of nightshade family (solanacea) • Rustica and tobacum are used for nicotine • Tobacum is the easiest to cultivate and most used source • Rustica is generally used by native peoples and in shaman rituals as it carries hallucinogens (harmine) and nicotine escandell nicotine 5
Background & History (cont’d) • Origin is exclusively American • Spanish indicated the Indians perfumed themselves and drank smoke • Tobacco was thought to prevent the plague as it gave reduction of apprehension • Healing was accepted until Victorian period escandell nicotine 6
Preparation • Flute cured or bright tobacco discovered in America had low nicotine, sweet mild smoke, suited to a cigarette became popular with ladies and men. escandell nicotine 7
Legal Status • Regulated by the FDA • An estimated 45. 3 million people, or 19. 3% of all adults (aged 18 years or older), in the United States smoke cigarettes. 1 Cigarette smoking is more common among men (21. 5%) than women (17. 3%). • Cigarette smoking is the leading cause of preventable death in the United States, 2 accounting for approximately 443, 000 deaths, or 1 of every 5 deaths, in the United States each year. 3, 4 escandell nicotine 8
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By Gender • 21. 5% of adult men • 17. 3% of adult women escandell nicotine 10
By Age • 20. 1% of adults aged 18– 24 years • 22. 0% of adults aged 25– 44 years • 21. 1% of adults aged 45– 64 years • 9. 5% of adults aged 65 years and older escandell nicotine 11
By Race/Ethnicity • 31. 4% of American Indians/Alaska Natives (non-Hispanic) • 9. 2% of Asians (non-Hispanic; excludes Native Hawaiians and Pacific Islanders) • 20. 6% of blacks (non-Hispanic) • 12. 5% of Hispanics • 21. 0% of whites (non-Hispanic) escandell nicotine 12
By Education 45. 2% of adults with a GED diploma 33. 8% of adults with 9– 11 years of education 23. 8% of adults with a high school diploma 9. 9% of adults with an undergraduate college degree • 6. 3% of adults with a postgraduate college degree • • escandell nicotine 13
By Poverty Status • 28. 9% of adults who live below the poverty level • 18. 3% of adults who live at or above the poverty level escandell nicotine 14
State Estimates • By state, in 2010, smoking prevalence ranged from 9. 1% in Utah to 26. 8% in West Virginia. 1 • By region, in 2010, smoking prevalence was highest in the Midwest (21. 8%) and South (21. 0%) and lowest in the West (15. 9%). 1 • Overall, in 2010, states with the highest prevalence of adult smoking were clustered in the Midwest and Southeast (see CDC Vital Signs map for more information). 1 escandell nicotine 15
Family Smoking Prevention and Tobacco Control Act • Tobacco is under FDA control • FDA regulates marketing and sets performance standards including nicotine content escandell nicotine 16
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Route of Administration • Nicotine is a highly toxic poison • Nicotine is most controlled in its natural form as well as by patch, gum to avoid toxic doses • Consumed in three ways: burned/inhaled, snuff and chewing escandell nicotine 18
Inhalation • Burning tobacco vaporizes nicotine and becomes dissolved in the mucus membranes of the lungs • 90% of inhaled nicotine is absorbed in the blood in this manner • The amount of nicotine delivered is determined more by the way the cigarette is smoked than the nicotine content of the cigarette (content between 0. 3 and 3. 2 per cigarette) • The major determinant of nicotine absorption is volume of smoke inhaled per puff escandell nicotine 19
Nicotine Bolus Theory • Not validated • Non-dependent smokers absorb nicotine faster than dependent smokers • Nicotine concentrations in the blood continue to accumulate and do not fall back as would be expected by a bolus theory escandell nicotine 20
Absorption • Nicotine is a weak base • Few lipid soluble molecules • Large number of poisonings occur each year among children • Nicotine induces vomiting and most frequently and are expelled before toxic levels are reached escandell nicotine 21
Newer Forms • • Patch Gum Nasal spray E-cigarettes escandell nicotine 22
Oral routes of administration (enteral) Solids Pill · Tablet · Capsule · Time release technology · Osmotic delivery system (OROS) Liquids Elixir · Emulsion · Herbal tea · Hydrogel · Molecular encapsulation · Softgel · Solution · Suspension · Syrup · Tincture Buccal (Sublabial) Sublingual Solids Orally disintegrating tablet (ODT) · Film · Lollipop · Lozenges · Chewing gum Liquids Mouthwash · Toothpaste · Ointment · Oral spray Respiratory tract Solids Smoking device · Dry powder inhaler (DPI) Liquids Anaesthetic vaporizer · Vaporizer · Nebulizer · metered-dose inhaler (MDI) Gas Oxygen mask · Oxygen concentrator · Anaesthetic machine · Relative analgesia machine escandell nicotine 23
Routes of administration Ophthalmic / Otologic / Nasal spray · Ear drops · Eye drops · Ointment · Hydrogel · Nanosphere suspension · Mucoadhesive microdisc (microsphere tablet) Urogenital Ointment · Pessary (vaginal suppository) · Vaginal ring · Vaginal douche · Intrauterine device (IUD) · Extra-amniotic infusion · Intravesical infusion Rectal (enteral) Ointment · Suppository · Enema (Solution · Hydrogel) · Murphy drip · Nutrient enema Dermal Ointment · Liniment · Paste · Film · Hydrogel · Liposomes · Transfersome vesicles · Cream · Lotion · Lip balm · Medicated shampoo · Dermal patch · Transdermal spray · Jet injector escandell nicotine 24
Route of administration Injection / Infusion (into tissue/blood) Skin Intradermal · Subcutaneous · Transdermal implant Organs Intracavernous · Intravitreal · Intra-articular injection · Transscleral Central nervous system Intracerebral · Intrathecal · Epidural Circulatory / Musculoskeletal Intravenous · Intracardiac · Intramuscular · Intraosseous · Intraperitoneal · Nanocell injection escandell nicotine 25
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Distribution • Depends on the route of administration and time after the administration • After 30 minutes, nicotine leaves the brain and are concentrated in the liver, kidneys, salivary glands and stomach • Nicotine crosses body barriers including placenta escandell nicotine 27
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Excretion Smokers metabolize faster than non-smokers Females metabolize faster than males Eating speeds up metabolism Menthol slows metabolism 25% of the population has a genetic defect in ability to metabolize nicotine. This is a protective effect. • 30 -40% eliminated by urine • Reduced ionization alkaline p. H and loads to the liver • Nicotine accumulates in the course of the day and also day-to-day • • • escandell nicotine 29
Neurophysiology • ACh has two receptors: muscarinic and nicotinic • Nicotinic act at neuromuscular junctions of striated muscles and control voluntary muscle action • Nicotinic receptors are ionotropic, have five subunits each coded by a specific gene • Excitatory post-synaptic potential • Pre-synaptic synapses are neuromodulators stimulating transmitter release escandell nicotine 30
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Nicotinic Receptors • Homomeric • Heteromeric • Basal state • Active state • Desensitized state • The return of the receptor to the normal sensitized state may take hours. The desensitized state accounts for acute tolerance to nicotine. escandell nicotine 32
Effects of Nicotine • Nicotine stimulates and then inhibits transmission of autonomic ganglia as nicotinic receptors enter desensitized state • Other transmitters are released such as epinephrine • Neuromuscular and parasympathetic stimulation and blocking makes complicated array escandell nicotine 33
Effects on the Body • Increases heart rate • Increases blood pressure • Constricts blood vessels in the skin • Drops skin temperature • Reduces blood flow to the skin • Inhibits stomach secretions • Stimulates bowel movement escandell nicotine 34
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he twin on the left has smoked 17 years longer than the twin on the right. Note the differences in lower lid bags and upper and lower lip wrinkles. escandell nicotine 37
CNS Releases epinephrine Stimulates reticular activating system Increases respiration Muscular tremors Decreases patellar reflex Lowers tone of voluntary muscles Stimulates vomiting center (tolerance increases) Increases glutamatergic release by presynaptic receptors and increasing depolarization of postsynaptic neuron • Surge in dopamine at nucleus accumbens with ventral tegmental area • • escandell nicotine 38
Behavior • Improves cognition • Increases exploratory behavior • Acute effect: pleasure related to blood nicotine level • Chronic effects: smokers have lower levels of psychological well being; mood worsens, but returns to normal when smoking stops. When discontinued, person’s mood is better than it was before smoking escandell nicotine 39
Effects on Performance • Fine motor improves • Accuracy and speed of alerting attention improves • Accuracy and speed of orientation to a particular targeted object improves speed • Accuracy of short and long-term episodic memory. Nicotine improves short-term episodic memory, but has no effect on long-term memory • Working memory: negative effect on accuracy, response time improves • Positive influence of fine motor and attention as well as working memory but not accuracy and orienting • Nicotine improves cognitive functioning in Alzheimer’s patients escandell nicotine 40
Conditioned Behavior • Effect is dependent on control rate; high rates depressed, low rates increase • Nicotine disrupts withholding response to differential reinforcement of low response rate (DRL). escandell nicotine 41
Drug State Discrimination • Intravenous nicotine is similar to cocaine Like acetylcholine, nicotine leads to a burst of receptor activity. However, unlike acetylcholine, nicotine is not regulated by your body. While neurons typically release small amounts of acetylcholine in a regulated manner, nicotine activates cholinergic neurons (which mainly use acetylcholine to communicate to other neurons) in many different regions throughout your brain simultaneously. Nicotine and dopamine Nicotine activates the same reward pathways in the brain that other drugs of abuse such as cocaine or amphetamines do, although to a lesser degree. Research has shown that nicotine increases the level of dopamine in the brain, a neurotransmitter that is responsible for feelings of pleasure and well-being. The acute effects of nicotine wear off within minutes, so people must continue dosing themselves frequently throughout the day to maintain the pleasurable effects of nicotine and to prevent withdrawal symptoms. escandell nicotine 42
Withdrawal • Nicotine is harder to give up than heroin • After chronic exposure, all systems show adaptation • Smoking cessation disrupts new equilibrium and produces physiological and psychological changes • Withdrawal: decreases heart rate; increases weight gain, inability to concentrate, increases awakenings and craving for cigarettes, anxiety, anger, aggression and depression, nervousness, drowsiness, light headedness, headaches, dizziness, tremor and nausea • Brain waves are slowed to levels seen in light sleep escandell nicotine 43
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Non-nicotine Factors • Cues associated with nicotine infusion acquire reinforcing properties and maintain selfadministration (smell, taste and motor activity of smoking) • Components of smoking other than nicotine play a significant role in cigarette addiction escandell nicotine 45
Dual Reinforcement Models • Primary reinforcement by nicotine in Mesolimbic dopamine system • Non-nicotine repeated stimuli become conditioned • Nicotine has reinforcement enhancing properties, that is ability to make a weak reinforcer stronger and enhance the effect of non-nicotine stimuli escandell nicotine 46
Harmful Effects • • Heart disease COPD Cancer Reproduction (infant death rate is increased by 10% by smoking) escandell nicotine 47
Environmental Tobacco Smoke • Living with a smoker increases lung cancer chances by 30% • Breast cancer, nasal cancer, nasopharyngeal cancer, leukemia, lymphoma and brain tumors increase • Heart disease is increased by 30% • Second-hand smoke – Mainstream – 300 degrees hotter than sidestream – Sidestream escandell nicotine 48
Treatment • 2/3 of adults smokers would like to quit • 17 million adults try to quit, but less than 10% succeed • Between 67% and 75% of ex-smokers were able to stop without benefit of any treatment escandell nicotine 49
Nicotine Replacement Therapy • Better than placebo escandell nicotine 50
Bupropion • Anti-depressant • Zyban • As effective as NRT escandell nicotine 51
Varenicline • Twice as effective as a placebo • Side effect: erratic behavior and suicidal behavior escandell nicotine 52
Other Interventions • Vaccine • In metanalysis, group behavior is the most effective form of therapy • Group 2. 17 • Bupropion 2. 0 • NRT 1. 77 escandell nicotine 53
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