PYB260 Psychopharmacology of Addictive Behaviour - Week 6 Nicotine PDF

PYB260 PSYCHOPHARMACOLOGY OF ADDICTIVE BEHAVIOUR Week 6: Action & Effects of Nicotine Melanie White, QUT 1  Lecture Outline What is nicotine? History Administration, distribution & excretion Effects of nicotine – physiological & performanc...

PYB260 PSYCHOPHARMACOLOGY OF ADDICTIVE BEHAVIOUR Week 6: Action & Effects of Nicotine Melanie White, QUT 1  Lecture Outline What is nicotine? History Administration, distribution & excretion Effects of nicotine – physiological & performance Conditioning, tolerance & withdrawal Harmful effects Pharmacological treatments for smoking cessation  Reflection Questions (egs, not exhaustive) Reflecting on today’s lecture material & your own consumption of caffeine: Compare the absorption, distribution and excretion profiles of nicotine administered via different routes (e.g., smoking vs. vaping vs. NRT routes) which of these is likely to be the most reinforcing and why? Apply one of the theories of nicotine addiction to this explanation Explain a possible mechanism of acute tolerance to nicotine Could nicotine be considered a performance enhancing drug? In what way or domains of measurement?  What is nicotine? & The history of nicotine  What is nicotine? Tobacco - only natural source of nicotine Nicotiana rustica; Nicotiana tabacum Leaves from the plants are harvested & dried Leaves are prepared differently for different uses Smoking tobacco Chewing tobacco – processed & flavoured Tobacco snuff – dried, powdered leaves Smokeless tobacco  History of nicotine & tobacco North & South American indigenous people first to discover & use tobacco 1492: Columbus offered dried tobacco leaves by native Americans 1560 Jean Nicot sent tobacco to Paris Tobacco seen as a cure for many diseases 1604: King James I prepared an antismoking campaign John Rolfe – grew tobacco in Virginia & established the English as a forceful colony  History of nicotine & tobacco 1828: nicotine extracted from the tobacco plants 1840’s: Smoking cigarettes popular in France, esp. women WWI: cigarette use exploded; many tobacco companies marketing cigs WWII: peak cigarette use 1950’s: companies start to become more aware of the health risks & starting marketing lowered tar & filtered cigarettes 1964: U.S. Surgeon General’s Report – smoking & cancer  History of nicotine & tobacco 1966: health warnings on packets 1971: Royal College of Physicians of London report 1971: cigarette ads removed from TV in the US 1982: Surgeon General’s report on passive smoking 1985: lung cancer is the greatest killer of women 1980’s-1990’s: Marlboro & Coca-Cola battle for #1 brand in the world 2020s: ENDS products (E-Cigarettes, Vapes, and Other Electronic Nicotine Delivery System Products) https://www.abs.gov.au/statistics/health/health-conditions-and- risks/smoking-and-vaping/2022) https://www.abs.gov.au/statistics/health/health-conditions-and-risks/smoking- and-vaping/2022) Administration, absorption, distribution & excretion of nicotine  Routes of administration, absorption & distribution Oral administration – chewing tobacco & moist snuff Chewing tobacco: nicotine absorbed through mouth membranes (cheek & tongue) Rarely swallowed (spat out) Not quickly absorbed via digestive system (not v. lipid soluble in acidic solutions) Nicotine metabolism in the liver v.fast → most swallowed is metabolised during first-pass metabolism Usually induces vomiting → guards against poisoning Oral administration – nicotine gum Nicotine level rises & falls with chewing → closer to smoking Peak levels of nicotine released ≈ 1/3 that released by smoking  Routes of administration, absorption & distribution Inhalation - smoking Nicotine vapours are in smoke & ash particles Particles dissolve in mucous membranes of the lungs (~90% absorbed this way) → directly to heart & then brain ( ~ 15-30 mins & concentrates in liver, kidneys, salivary glands & stomach Nicotine crosses most barriers & is found in sweat, saliva, breast milk & placenta  Excretion Kidneys Amount nicotine excreted through urine depends on pH Up to ~30-40% excreted through acidic urine (if pH 1 month; cravings may persist & triggered by cue exposure Severity not related to dose, length of smoking, previous attempts to quit, age, gender, alcohol or caffeine Fast metabolisers: more severe withdrawal Harmful effects of nicotine  Harmful effects of nicotine Heart disease Combined action of nicotine & carbon monoxide Nicotine – ↑ workload of heart Carbon monoxide –  ability of blood to carry oxygen Other agents  ability of lungs to absorb oxygen –> heart needs to work harder Atherosclerosis  Harmful effects of nicotine Lung disease Smoking ability of cilia & phagocytes to clear particles such as ash & tar from the lungs Compromised action of cilia & phagocytes results in ↑ susceptibility to: Bronchitis Emphysema Lung damage due to other bacteria & viruses  Harmful effects of nicotine Cancer Smoking ↑ risk of cancer of mouth, nasal & sinus cavities, lungs, kidney, bladder, stomach & ↑ risk of cancer caused by other carcinogens (e.g., asbestos, alcohol) Mechanism not fully understood Risk  with length of time post-cessation Reproduction ↑ infertility in women & men Birth defects; low birth weight (~150-200g; dose-dependent); spontaneous abortion; premature; babies more likely to die Cognitive damage?  Harmful effects of nicotine Passive Smoke 2 sources of secondhand/passive smoke: 1. Mainstream smoke 2. Sidestream smoke Concentration of carcinogens is higher in sidestream smoke Responsible for lung cancer (↑ 20-30%), breast cancer, nasal sinus cancers, bronchitis, pneumonia, asthma, SIDS & brain tumours in children  Treatment 2/3 adult smokers want to quit; only 1/10 attempters succeed Nicotine replacement therapy Patches Gum Nasal spray Pharmacotherapies Buproprion (Zyban) Varenicline (Champix) The future: nicotine vaccination? TA-NIC & NicVAX clinical trials Figure 8.5 Efficacy comparison of select smoking cessation treatments, expressed as relative risk (RR) of quitting.  Conclusion At the end of this lecture you should: Know what nicotine is & what it is contained in Have an understanding of the history of nicotine use Be familiar with administration, distribution & excretion of nicotine Understand the effects of nicotine (physiological & behavioural & variables that mediate these effects) Know about nicotine conditioning, tolerance & withdrawal Understand different theories of nicotine addiction Understand the harmful effects of nicotine Understand pharmacological treatments for tobacco cessation  Reflection Questions (egs, not exhaustive) Reflecting on today’s lecture material: Compare the absorption, distribution and excretion profiles of nicotine administered via different routes (e.g., smoking vs. vaping vs. NRT routes) which of these is likely to be the most reinforcing and why? Apply one of the theories of nicotine addiction to this explanation Explain a possible mechanism of acute tolerance to nicotine Could nicotine be considered a performance enhancing drug? In what way or domains of measurement? Compare NRTs with common pharmacotherapies for treatment for cessation of smoking/nicotine addiction  Reminder & further information Tutorials This week- workshops in computer lab running the lab report’s caffeine experiment Next week – navigating the data analysis output for your lab report’s Results section Lecture Next week – Caffeine Experiment Briefing/Protocol Debrief (will be prerecorded and posted earlier to allow review prior to next week’s tutorials)