Nicotine

Question 1

tobacco plant

Answer 1

• many species: 60, but only 2 used for cigarettes
• nicotiana tabacum
• nicotiana rustica
• active agent: nicotine

Question 2

Nicotine

Answer 2

• toxic
• used as insecticide before, but turned out to be too harmful
• plant uses it to protect itself from predators
• first smoke: very toxic effects
• attitudes and expectations play an important role in smoking behavior

Question 3

tobacco products

Answer 3

• smoking: cigarettes, cigars, pipes

- smokeless tobacco: snuff, chewing tobacco

Question 4

history of tobacco use

Answer 4

• indigenous to south america
• spain
• flourished in virginia
• popular in europe
• mid-1800’s: medicinal use
• 1964: US public health services warning
• Spanish brought cigarettes to Europe from the indigenous Americans
• English brought it to Europe too
• Panacea = ”cure everything”
• Thought to cure eye or throat problems
• Early 1920’s boom in US: consumer culture, glamorous
• 1930’s first links of smoking to cancer
• 1950’s: evidence that smoking has negative impacts on health
• 1964 increased mortality, causative link to lung cancer
• 1963 peak smoking, then went down

Question 5

prevalence of tobacco use in the US

Answer 5

• 2004 = 25% adult population
• 2011 = 19% of adult population
• males > females
• 25-44 year olds
• white > black > hispanic
• highest rates: unemployment and poor education
• Young people already understood the message that smoking is harmful and therefore smoking went down for young people
• Middle age highest prevalence

Question 6

Pharmacokinetics: Absorption

Answer 6

• small, lipophilic: ready absorption across all body membranes
• lungs
• mouth
• skin
• Very well absorbed
• Some can be later absorbed by the intestines: swallowing some parts of nicotine
• Easy transdermal use since nicotine is very small and hydrophobic, most of the drugs cannot be administered through the skin

Question 7

Smoking Nicotine

Answer 7

• Lungs
• smoke particles, with droplets of nicotine suspended in the smoke
• most rapid and efficient absorption route: huge surface area, thin membranes and rich blood supply of the alveoli
• alveoli has a very thin membrane consisting of one cell only (nicotine can pass through very easily)
• rapid response = more addictive
• no acids, no enzymes, no first pass effect: very efficient
• user has a lot of control over his smoking:
• need to inhale: rate and depth of smoking, length of contact time, brand etc.

Question 8

alveoli

Answer 8

• provide increased surface area, very effective

Question 9

nicotine absorption and pH

Answer 9

• nicotine = basic
• lungs = acidic –> nicotine is charged in the lungs
• cigarettes = nicotine brought to the lungs: charged, but large SA compensated for charge
• Nicotine is charged in the lungs –> actually not so good when its charged: contradiction
• Charged –> polarized –> hidrophilic –> lipophobic
• Surface área makes up for the charge

Question 10

pharmacokinetics: distribution

Answer 10

• rapid distribution to the brain: 5 seconds
• strong reinforcing effect due to rapid distribution
• distributes to other sites too: side effects

Question 11

pharmacokinetics: metabolisation

Answer 11

• rapid metaboliation: about two hours, which is why smokers smoke so many cigarettes

Question 12

pharmacokinetics: elimination

Answer 12

• elimination in kidneys through urine

Question 13

pharmacology of nicotine

Answer 13

• agonist at nicotinic acetylcholhyde (nACh)
• ACh very present in the brain
  nACh binds ar ACh receptors very easily
• has a biphasic effect
• stimulating at low doses
• relaxing at higher doses
• not considered a depressant

Question 14

Nicotine at low doses

Answer 14

• stimulant effect
• agonist at nACh receptors: concentration, memory
• neurotransmitter cascade
  > stimulation of cholinergic neurons = stimulates the release of other neurotransmitters
  > norepinephrine: awake and alert
  > dopamine: pleasure and reward
• cholinergic = ACh

Question 15

Nicotine at higher doses

Answer 15

• block ACh receptors (toxic effect)
• nicotine binds so well, it actually blocks the receptors at high doses
• decreased nerve transmission = less buzz (biphasic)
• neurotransmitter cascade= see more relaxation effects
  > dopamine: pleasure and reward
  > serotonin: mood
  > endorphins: natural painkillers
• also relaxation effects = perception of decreased stress, avoid withdrawal
• Higher doses actually block ACh receptors since nicotine binds so well that it would get stuck at the receptors: PARTIAL AGONIST
• Serotonin reléase: relax
• Expectations: idea that cigarettes reduce stress

Question 16

smoking: can vary the dose

Answer 16

low dose 
- short, quick, puffs 
- long space between puffs 
- less inhaled = low dose = stimulation 
high dose 
- long, slow, drags 
- short space between drags 
- more inhaled = high dose = relaxation

Question 17

Acute effect of nicotine in PNS

Answer 17

• adrenal gland: release of NE and E
• flight or fight effects
• increased heart rate and force of contraction
• vasoconstriction (narrowing of BVs)
• increase blood fats and cholesterol
• increase blood glucose and metabolic rate
• muscle relaxation

Question 18

Tobacco smoke

Answer 18

• nicotine
• enzyme inhibitors in the smoke
• monoamine oxidase degrades NE, Dop, Ser in the synaptic cleft
• mono-amine oxidase inhibitors (MAOIs) in smoke
• hugely potentiates the effects of nicotine
• Tar - carcinogens
• carbon monoxide
• 4000 other chemicals
• light and low-tar myths

Question 19

Chronic effects of nicotine

Answer 19

• yellow teeth, finger
• bleeding gums
• bad breath, smelly clothes and hair
• wrinkles
• digestive effects
• expensive

Question 20

Leading cause of premature death

Answer 20

• die about 10 years earlier than non-smokers
• life-threatening diseases
• cardiovascular disease: heart attack (myocardial infarction), stroke, hypertension
• cancer: lung (85%), throat
• lower respiratory diseases: COPD
• pregnancy
• passive smoking (50,000 deaths/year)

Question 21

Why do people smoke?

Answer 21

• bio-psycho-social
• biology / pharmacology:
• stimulating and/or relaxing effects
• MAOI’s in tobacco smoke: potentiate the effects
• psychology
• smoking = very rapid absorption = Immediate positive re-enforcements
• many positive re-enforcements per day

Question 22

Social / Environment

Answer 22

• believes and attitudes of society
• smoking parents
• advertisement, media, tabaco industry, myths (smoking relaxes me, smoking is cool)
• weight loss: release blood glucose, less appetite
• start with social occasions
  environmental clues
• visual clues especially
• nicotine itself is not that addictive (study with rats)
• one of the hardest drugs to give up

Question 23

Smoking and the adolescent

Answer 23

• earlier start, harder to quit
• self-esteem and self-concept issues: vulnerable to targeted advertising
• adolescent brains = more susceptible to reinforcing effects of nicotine
• trying to find out who one is
• limbic system well developed: emotions and reward
• prefrontal cortex still partly developed: don’t consider the dangers

Question 24

Tolerance and withdrawal

Answer 24

• unpleasant the first time
• CNS stimulation, palpitations, dizziness, sweating, nausea/vomiting,
• tolerance to these effects develops quickly
• psychological and physical dependence
• craving: steady constant background craving (wears off after a few weeks)
• sudden bursts of intense desire: cues (more problematic)
• irritability, anxiety, difficulty concentrating, restlessness (affects neuromuscular functions), increased appetite, insomnia

Question 25

E-cigarettes

Answer 25

• electronic cigarette
• nicotine in vapor: cardiovascular effects (nicotine is still harmful)
• less harm, but still harmful
• does not help quit smoking cigarettes
• gateway drug risk