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Pharmacology 305 > Nicotine 1 > Flashcards

Nicotine 1 Flashcards

0
Q

What are the percentage of men and women that smoke globally?

A

47% men 12% women

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1
Q

Explain the process that occurs when someone smokes

A
  1. Inhale smoke containing nicotine
  2. Carried into lungs
  3. Absorbed into pulmonary venous circulation
  4. Moves to brain
  5. Nicotine binds to and activates nicotinic Ach receptors leading to reward
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2
Q

How many cigarettes are consumed daily?

A

15 billion

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3
Q

How many deaths occur form smoking per year?

A

5.4 million (9% all deaths)

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4
Q

What are the smoking trends in developing vs industrialized nations?

A

Developing is increasing, industrialized is decreasing smoking

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5
Q

By 2020 what percentage of smokers will be in developing countries?

A

85%

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6
Q

What population of Canadians smoke?

A

19%

Numbers are decreasing

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7
Q

What plants can tobacco be obtained from?

A
  • Nicotina rustica and Nicotina tabacum

Most North American products are from tabacum species

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8
Q

What is the nicotine content in a cured leaf of tabacum species?

A

1-3%

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9
Q

What is the tobacco content from the rustica species of tobacco

A

6-9%

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10
Q

How many tons of tobacco are harvested and processed each year globally?

A

7 million tons

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11
Q

Why is Nicotina tobacum predominate in North America?

A

Because it is easier to grow in the climate

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12
Q

What is in tobacco?

A
  • nicotine: neurotoxin and addictive substance
  • carotenoids: gives pigment
  • compounds produced during curing(drying) process
  • up to 599 compounds added during processing
  • 4000 carcinogenic compounds produced during burning
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13
Q

What are some intentional additives in cigarettes, why are they added?

A

Additives added for:

  • flavour
  • modifying burn rates
  • ability to release nicotine
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14
Q

What are some of the consequences of intentional additives?

A
  • can form carcinogenic compounds when burned

- simple sugars can be converted to acetaldehydes when burned

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15
Q

What were the results when young rats specifically self administered nicotine?

A

Rats will triple nico&ne self-administra&on if acetaldehyde is also given at much lower levels than seen with drinkers – only occurs in young rats

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16
Q

What are the effects of acetaldehydes?

A

Thought to perhaps inhibit monoamine oxidases and boost neurotransmiFer levels

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17
Q

How are some unintentional additives incorporated into cigarettes and what are they?

A

 from growing, handling and processing
 conveyor belt fragments, insect parts, pes&cide, herbicide, heavy metals, bacterial toxins, mold toxins, radioac&ve elements from the soil

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18
Q

Apatite is an unintentional additives, why is it present and what are the consequences?

A

 Often fertilized with a mineral called apa&te to starve the plants of nitrogen in order to impart a particular flavour
 However apa&te contains radium and radioactive isotopes of lead and polonium

19
Q

What is curing?

A

 Curing is a drying process that occurs a^er the leaves are harvested and gives the leaves certain flavour characteris&cs
 During the curing process, starches are broken down into more simple sugars which then modify proteins
 This glyca&on of protein adds flavour, but also produces carcinogens

20
Q

What do carotenoids do?

A

carotenoids slowly oxidize and can produce aroma&c chemicals that give the tobacco “smoothness” when smoked

21
Q

What are the different types of curing?

A

There are different types of curing – sun-cured, fire-cured and air-cured (less carcinogenic due to less heat) and each produces different amounts of these products and thus different tobacco characteristics

22
Q

Why does curing take place?

A

There is too much moisture in the tobacco plant to just uproot and smoke thus curing tries to make leaves dry enough to be combustible

23
Q

Explanation some differences between a cigar and cigarette?

A
  • cigarette usually has filter to trap tar and carcinogens
  • premium cigars are very large (8x larger than cigarettes as well as 8x more nicotine produced therefore increased likelihood of inhaling bad things)
24
Q

What is tar?

A

A sticky substance generated from burning organic matter

Non filtered cigarettes produce more tar

25
Q

What is smokeless tobacco?

A

 some claim it to be safer than smoking
 amount of nico&ne absorbed is 3-4 &mes greater than cigareFes, but the process is slow: absorbed into mucous lining of cheek
 At least 28 carcinogens iden&fied in chewing tobacco
 leads to addic&on
 increased risk of oral cancers

26
Q

Explain nicotine s contribution to addiction and cancer

A

 facilitates addiction
 mimics acetylcholine at acetylcholine receptors – agonist
Binds to the same site on the receptor as acetylcholine
 Has potential to cause cancer, but not the main culprit
 Charged at low pHs

tar, carbon monoxide, metals,hydrocarbons are linked to cancer, heart disease etc

27
Q

Explain why there are some doubts on nicotines role in addiction

A

 de-nicotinized cigarettes can be as rewarding and can reduce craving and withdrawal
 humans rarely show preference for nicotine over placebo
 poor results with nicotine replacement therapy
 Pure nicotine given IV has not been convincingly shown
to be reinforcing in human volunteers
 There is no market for pure nicotine

The addiction is said to be more psychological

28
Q

What is the significance of nicotine and changes to PH?

A

 nicotine’s charge depends on pH (weak base)
 diprotonated form does not occur when smoking
 free-base is volatile - more easily released from tobacco and increases ease of absorption
 linked with higher rates of “adoption”(people s,one and keep smoking)

29
Q

What is the significance of freebase nicotine?

A

Produces the “kick” or “impact” also known as “throat catch,” “throat hit” and “throat grip.”
 they increased pH of smoke by introducing ammonia and saw a corresponding increase in sales

30
Q

What are the two components to smoke?

A

The particular phase and the gaseous phase

31
Q

What is the particular phase?

A

 contains volatile and non-volatile nicotine, water, tar (polycyclic aroma&c hydrocarbons (benzo[a]pyrene), metals, radioactive compounds)

32
Q

What’s the gaseous phase?

A

 contains volatile nicotine, carbon monoxide, carbon dioxide, nitrogen oxide, vola&le nitrosamines, ammonia, nitrites, sulfur, alcohols, ketones, aldehydes, volatile hydrocarbons

33
Q

How much pure nicotine is needed to kill a healthy adult

A

60mg: a few drops

34
Q

How much nicotine does a cigarette contain?

A

.5-2g

Note however that smokers only get a fraction of this due to sides stream smoke, pyrolysis (decomposition), filter etc

35
Q

Describe the patterns of smoking

A

most people smoke the same way:
 one or two puffs/minute
 each lasts two seconds
 delivers 1- 2 micrograms per kilogram body weight - seems like the op&mum for s&mula&on of brain
 pack a day - one hundred to two hundred puffs

36
Q

What route of administration is fastest for nicotine?

A

Cigarette smoking: nicotine enters bran within 10s

37
Q

What occurs when there is a mutation in the CYP2A6 enzyme

A

mutation in CYP2A6 that slows metabolism results in lower tobacco use, easier time quitting

38
Q

Want is the half life of nicotine?

A

2hrs

39
Q

Describe the metabolism of nicotine by CYP2A6, CYP2B6 and aldehyde oxidase

A

The transform nicotine not containing which has a half life f 16hrs
80% of nicotine take this route
Corinne is tested as a marker for direct and second hand smoking

40
Q

Describe the metabolism of nicotine by monooxygenase

A

Transforms nicotine into nicotine-1-N-oxide

4-7% of nicotine take this route

41
Q

Why was it difficult to show smoking in animal models

A

 for many years, it was difficult to show self-administra&on in animals
 because they can’t smoke?
 protocol problems? - eg slow infusion of nicotine
 not a robust reinforcer in some animals - argument against addiction?

42
Q

What is the significance of the findings in the 2007 animal self administration study?

A

 2007 - first convincing primate study
 trick was to pair nicotine with another stimuli - exposure to a light for 2 sec - acts as a cue
 in some, seeing the light was a reinforcer long after nico&ne was removed
 argument that things associated with smoking (coffee, donuts, etc) are just as important in reinforcing behaviour

43
Q

Explain the 24hr nicotine level trends

A

 peak at the end of the smoking day
 but adding new drug every hour, get accumulation - new drug added before all of previous drug removed
 receptors resensitize overnight

44
Q

Describe the psychological effects of smoking

A

 many smokers can’t describe why they enjoy it - say they like the taste of the smoke in their mouth and lungs
 In experimental situations, if smokers’ throats are anesthetized, there is a decrease in pleasure from cigarettes
 some report euphoric rush, esp. with first cigarettes of the day - resensitized receptors
 comparable to exposure to morphine, amphetamine
 reduces negative states - boredom, anxiety
 also some say gives stimulatory effect

45
Q

Explain the claim that nicotine is a cognitive enhancer

A

 nicotine causes measurable increases in arousal and cognitive function in animals and humans
 seen as increased cor&cal ac&vity, decreased motor reaction time and improved memory recall
 nicotine and nicotine-like drugs in trials as treatment for Alzheimer’s-induced decreases in cognition

Pharmacology 305 (13 decks)

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