Nicotine

Question 1

Tabacco plant

Answer 1

• Tobacco plant only natural source of nicotine
• Belongs to genus Nicotiana
  
  • ​Rustica: bad taste, planted in Virginia
  • Tabacum: spaniards had monopoly

Question 2

History

Answer 2

• Columbus given tobacco by inhabitants of San Salvador
• British were against it bc it was Spanish
  
  • 1600 got their first shipment of tobacco from Virginia
  • End of Spanish monopoly
• 1700s tobacco was sniffed
• Russia punished smoking with torture exile to Siberia and death (same in Turkey China and Japan) did not stop spread of smoking
• Chewing tobacco was american and patriotic
  
  • Never adapted by british
  • Advantage: free hands
  • Disadvantage: health problems (TB), spit everywhere (even in the courts)

Question 3

20th century

Answer 3

• 1963 peak of sales: 4300 cigarettes/year, half that today
• 1964 First surgeon report that smoking was bad for you
  
  • Decrease in smoking
• 1994: nicotine declared addictive (but the senate still did not think it was addictive)
  
  • FDA could have declared a drug but they didn’t (there’s money in cigarettes)
• 1996 benzopyrene first chemical found w direct link to cancer
• 1998 first Big tobacco settlement 4 billion dollars against the company
  
  • They increased the price of cigarettes and just made people pay for the lawsuit
  • Commericials banned from selling cigarettes to kids

Question 4

What is in tobacco

Answer 4

• 1700 degree farenheit: 4,000 compounds oxidised and released in the smoke
• Two components in smoke
  
  • Particle phase:
    
    • Water
    • Nicotine
    • Tar -> carcinogenic -> taste and smell
  • Gaseous phase
    
    • CO2
    • CO
    • Ammonia
    • Hydrogen Cyanide
    • Acetone

Question 5

Toxic compounds

Answer 5

• CO
  
  • Odorless, colorless & tasteless
  • Extremely toxic
  • Attaches to hemoglobin -> CO has a higher affinity than Oxygen
  • Deprives tissues of oxygen (asphyxiation)
  • Leads to cardiovascular disease
• Tar
  
  • 6-16 mg/cigarette
  • Sticky tar clogs cilia so they can’t filter lungs -> carcinogenic products can settle on tissue
• Nicotine
  
  • 8-10 mg/cigarette (only 20-25% enters bloodstream)
  • Toxic
  • Psychoactive drug and dependence producing
  • Used in insecticides
  • Smokers get 2-8 mg a day (per one pack, LD= 60 mg)
• Ammonia: increases nicotine absorption

Question 6

Route of administration: Orally

Answer 6

• Nicotine absorbed through membranes in mouth
  
  • Chewing: put between cheek and gum
  • Snuff: lower lip and gum

Question 7

Route of administartion: smoked

Answer 7

• Cigarettes: tobacco burned, nicotine vaporizes -> lungs -> heart -> brain in a bolus (intense and all at once)
• Pipes and cigars -> absorbed from the mouth
• E-cigarettes

Question 8

Metabolism and Elimination

Answer 8

• Broken down by liver: cotinine by cytochrome P450 2A6 -> excreted in the urine
• Some have low levels of CYP P450 2A6 -> less likely to become smokers bc negative reaction
• Methoxsalen: prevents the breakdown of nicotine
• Halflife: 2 hours makes you wanna smoke again

Question 9

Mechanism of Action

Answer 9

• Nicotine (agonist) binds to Nicotinic Cholinergic Receptor all over the body (brain and muscle): a subtype of ACh receptor
• Opens Na+ Channels
• Neuron depolarizes: fast excitatory response
• Release of serotonin, endorphin, vasopressin, growth hormone adrenalin and prolactin

Question 10

Physiological effects

Answer 10

• Relaxes smokers, stimulates non-smokers
• Increases blood preassure
• Constricts blood vessels in skin -> cold hands
• Adrenal Glands: E and NE
  
  • Tachycardia (heartbeats way faster)
  • increase in blood pressure
• Medulla -> increase in respiration
• Stimulates vomiting center (first time

Question 11

Behavioral effects

Answer 11

• Mood
  
  • Smokers: Relaxing, reduce tension when needed, stimulates when bored
  • Non-smokers: arousal, more tension
• Cognitive factors: Ach
  
  • increases memory in abstinent smokers (partially relief from withdrawal)
  • Nonsmokers also increase performances
  • Increased attention in EEG

Question 12

Withdrawal and tolerance

Answer 12

• Tolerance to nausea/dizziness
• No tolerance to
  
  • Increase in HR
  • Changes in Skin temp
• Acute tolerance: happens during the day
• Withdrawal
  
  • Within 6 hours of the last cigarette: HR and blood pressure decreases
  • 24 hours
    
    • irritability
    • Fatigue
    • Drowsiness
    • Insomnia
    • Craving for cigarettes

Question 13

Treatments

Answer 13

• 2/3 of smokers say they want to quit
• only 3% successful first attempt
• 50% eventually quit
• 90% who quit do it without help
• Women have a harder time quitting than men (easier when ovulating though)

Question 14

Prescription drugs

Answer 14

• Chantix:
  
  • reduces cravings
  • a partial agonist to nACh: mimics effects of nicotine without hight
• Zyban: reduces withdrawal symptoms (DA and NE reuptake inhibitor, the antagonist of nAChR)
• Methoxalen: inhibits cytochrome P450 2A: makes smoking unpleasant

Question 15

Quitting

Answer 15

• Within 8 hours: CO levels are normal
• 24 hours: risk of heart attack decreases
• 2 weeks to 3 months: circulation improves lung functioning increases by 30%
• 1-9 months:
  
  • Cilia go back to normal: can clean lungs
  • Sinus congestion fatigue and shortness of breath decrease
• 1-year: coronary heart disease risk decreases by half
• 10-years: lung cancer death is half of a smokers
• 15 years: risk of coronary heart disease = same as non smoker

Question 16

CV diseases

Answer 16

• Responsible for 30% CV diseases
  
  • Combination of CO and nicotine
  • Nicotine > release E and NE > increase HR and blood pressure
    
    • Decreases stickiness of platelets can’t clot blood
  • CO > decreases oxygen distribution to organs
    *

Question 17

Digestive diseases

Answer 17

• increases cancer
  
  • Liver
  • Colon
  • Rectum
• Heartburn
• Ulcers
• Crohn’s disease
• Colon polyps

Question 18

lung diseases

Answer 18

• Leaves lungs vulnerable to toxic substances, bacteria and viruses
  
  • Chronic bronchitis
  • Emphysema
• Cancer
  
  • Benzopyrene > lung cancer direct link
  • Increases risk of other cancers too
• In women
  
  • 2x More likely heart attack
  • 3x stroke
  • decreases fertility

Question 19

Why do we still smoke?

Answer 19

• Constant blood theory
  
  • If you give low nicotine cigarettes they inhale deeper to keep constant
  • When stressed kidneys get good at excreting nicotine > person has to smoke more
• Nicotine bolus theory
  
  • Inhale rapidly >> goes to blood >> nicotine bolus >> goes to brain
• Psychological tool theory
  
  • Smokers use nicotine to arouse in boredom and relax in stress

Question 20

Health consequences

Answer 20

• 1.1 billion smokers worldwide
• 6000 billion cig-year
• 2 packs a day for 20 years 13-14 years less of life

Question 21

E cigarettes

Answer 21

• Nicotine delivered without tar
• Other products
  
  • Formaldehyde > carcinogenic
  • Acetaldehyde > possibly carcinogenic
  • Diacetyl > linked to lung disease
  • Acrolin > irritant
• Use increased by 10% in past 4 yeaars

Question 22

EVALI CDC data

Answer 22

• 2172 cases of lung-related injury related to e-cigs or vaping (increases every week)
• 42 deaths

Question 23

EVALI

Answer 23

• Vitamin E Acetate
• Characterized by pneumonitis
  
  • Accumulation of oil or white blood cells in lungs
• Criteria:
  
  • Vaped or dabbed 90 days prior to symptoms
  • Chest image showing substance denser than air in the lungs
  • Absence of lung infection or alternative diagnosis