Nicotine 1 & 2

Question 1

What happens to the body when someone smokes?

Answer 1

Smoke containing nicotine is inhaled and is carried into the lungs, it gets absorbed into pulmonary venous circulation and moves into the brain, and finally is binds to and activates nicotinic acetylcholine receptors

Question 2

Globally, do men or women smoke more?

Answer 2

Men smoke more, with about 47% smoke and only 12% of women smoke

Question 3

What percent of deaths are linked to tobacco?

Answer 3

Almost 10%. ~5.4 million deaths a year

Question 4

By 2020, where will 85% of smokers be coming from which countries?

Answer 4

They will be coming from developing countries

Question 5

What percent of Canadians smoke?

Answer 5

About 19%

Question 6

Which plant does tobacco come from?

Answer 6

Most North American products are from the Nicotiana terbium species. The nicotine comes from the broad leaves of the plant. A curing process occurs where other compounds are produced and added (about 599 are added). When it is smoked, about 4000 new chemicals are produced, and they are linked to cancer

Question 7

What are some of the intentional additives and what do they produce?

Answer 7

They are mostly for flavour, modifying the burn rate and ability to release nicotine. Simple sugars can be converted into Acetaldehyde, and it seems to potentiate how much nicotine you self administer (addictive component). Acetaldehyde is also thought to inhibit monoamine oxidase (which breaks down dopamine in the cleft) which results in a higher reward.

Question 8

What is apatite?

Answer 8

It is an unintentional additive, where the nicotine plants are fertilized with apatite to starve the plant of nitrogen, Apatite contains radium and radioactive isotopes of lead and polonium

Question 9

Does a cigarette or a cigar have more tobacco in it?

Answer 9

Cigars have more tobacco product in them than cigarettes. The more pure tobacco leaves the higher the nicotine (not safer)

Question 10

What is the use of a filter in cigarettes or cigars?

Answer 10

It has been shown that it decreases the amount of tar inhaled

Question 11

What is benzo (a) pyrene? and are they found more in cigars or cigarettes?

Answer 11

It is a known carcinogen and found mostly in the tar of cigars and cigarettes. Cigars have way more BaP, nicotine and tar in them than cigarettes. Equally as bad or even worse than cigarettes

Question 12

Is smokeless tobacco really safer?

Answer 12

You do avoid some of the harsh chemicals from burning it, but there are at least 28 known carcinogens in chewing tobacco and the amount of nicotine absorbed it 3-4 times greater than cigarettes (slower process)

Question 13

Are E-cigs a safer alternative than cigarettes?

Answer 13

There is no tobacco or combustion, but it is nicotine dissolved in propylene glycol. Even though there is no organic material in the e-cig, there is still the nicotine neurotoxin

Question 14

What are come concerns with E-cigs?

Answer 14

• children will ingest the liquid nicotine
• reports finding nitrosamines (known carcinogen)
• do we really want people inhaling pure nicotine?

Question 15

How does Hooka/Shisha work?

Answer 15

Hook is often a tobacco base with added ingredients. It is heated but not burned, smoke is cooled as it passes through water (idea is that the toxins get trapped in the water), and then inhaled.

Question 16

Is Hooka safer than smoking cigarettes?

Answer 16

Not necessarily, one gram is tobacco hooka produces 11 time more CO than 1 gram of cigarette tobacco. The smoke contains carcinogens that can be the same or higher levels of cigarettes. Is increases heart rate and BP

Question 17

How does Nicotine work in the brain?

Answer 17

It mimics acetylcholine and acetylcholine receptors (acts as an agonist). At low pHs, it gets protenated (positive charged H+)

Question 18

How does pH affect the adoption/addiction of nicotine?

Answer 18

check with dr davies

Question 19

Explain the two phases of cigarette smoke:

Answer 19

The Particulate phase: contains volatile and non volatile nicotine, water and tar.
The Gaseous phase: contains volatile nicotine, CO, CO2, volatile nitrosamines, ammonia, nitrites, sulfur, alcohols, ketones, aldehydes, and volatile hydrocarbons

Question 20

What is the lethal amount of pure nicotine?

Answer 20

60 mg would kill any adult. 1 cigarette contains about 0.5 - 2.0 mg of nicotine

Question 21

Explain how the accumulation of nicotine affects the system:

Answer 21

After smoking a few cigarettes and there is accumulation of nicotine in the system, the receptor desensitizes, causing you to need more of the drug to have the same feeling. . If you have a smoke every hour, your metabolism doesn’t have to to break is all down so there is more and more in the system. When they go to sleep, the receptor gets resensitized.

Question 22

Which administration method delivers the highest nicotine rate?

Answer 22

Smoking cigarettes has the highest delivery rate (entering the brain within about 10 seconds).

Question 23

What is the half life of nicotine? And what are its metabolites?

Answer 23

Nicotine has a half life of about 2 hours. Cotinine is a nicotine metabolite that has a half life of about 16 hours, and it is tested as a marker for second hand smoke.

Question 24

A mutation on which receptor slow the metabolism of nicotine and results in lower tobacco use and easier time quitting?

Answer 24

CYP2A6 and CYP2B6. A mutation on this causes less metabolism of nicotine and results in a build up of nicotine in the system, and can cause adverse effects = easier time quitting

Question 25

How many nicotine binding sites are there on the nicotinic acetylcholine receptor? Is it the same site where acetylcholine is binds?

Answer 25

There are two nicotine binding sites and acetylcholine binds to the same sites as nicotine

Question 26

What happens when nicotine activates the acetylcholine receptor?

Answer 26

An integral channel opens and allows sodium and calcium to enter causing depolarization of the membrane

Question 27

Are the nicotinic acetylcholine receptors on the pre or post synaptic membrane?

Answer 27

Both:
Mostly on presynaptic: it will induce the release of NT including: dopamine, glutamate, GABA, noradrenaline, serotonin…
Postsynaptic will cause depolarization of the cell and cause cellular excitation (neuromuscular)

Question 28

Explain desensitization:

Answer 28

Occurs when nicotine or acetylcholine builds up around the receptor for a period of time. The receptor becomes non functional (won’t open when binded with any thing until it becomes resensitized (to be active again). –> this causes a build up of NT the cleft.

Question 29

What happens when an animal has a mutation on alpha4 subunit?

Answer 29

It makes them hypersensitive to nicotine

Question 30

What happens when an animal has had beta2 subunit removed?

Answer 30

Nicotine no longer causes the release of dopamine, and self administration of nicotine stops.

Question 31

Which receptor is likely to be important for dopamine release/rewarding pathway when taking nicotine?

Answer 31

Alpha4 beta 2 receptors

Question 32

Which subunits are responsible for for activating GABA and glutamate?

Answer 32

GABA: A4B2 receptor
Glutamate: A7 receptor

Question 33

Explain how desensitization of GABA and glutamate can explain why nicotine is addictive?

Answer 33

GABA becomes desensitized rather quickly (

Question 34

True or False: nicotine directly and indirectly activates the reward pathway

Answer 34

True. Nicotine directly activates the dopaminergic pathway in the VTA and indirectly by the desensitization of the GABA and glutamate receptor in the VTA as well

Question 35

Explain the study that showed that smokers will consume more alcohol compared to non smokers

Answer 35

Rats were placed in a box where they would self administer ethanol, and would be receiving an IV of either Saline (control), Nicotine (increases stress hormone) or RU486+Nicotine (RU486 is a glucocorticoid antagonist- decrease stress hormones). The rats receiving Nicotine would consume more ethanol.

Question 36

In the study that showed smokers drink more than non smokers, did the nicotine + ethanol show higher dopamine levels?

Answer 36

No, they actually found that when both nicotine and ethanol were present, the glucocorticoids increased GABA release in the VTA–> inhibiting dopamine release and less rewarding. So then why does drinking increase when nicotine is present? Maybe when nicotine is present, you get less of a reward, so you drink more to achieve the same level of reward from ethanol.

Question 37

What effect does cigarette smoke have on monoamine oxidase?

Answer 37

Likely via acetaldehyde may be forming beta carbolines, and those are known to inhibit monoamine oxidase. Without MAO, it results in increased levels of dopamine, adrenaline and noradrenaline. Increased levels of dopamine causes increased reinforcing effects of nicotine

Question 38

Why does tolerance occur with nicotine?

Answer 38

Chronic exposure to nicotine causes nicotinic receptors to increase (mostly A4B2). With more receptors they are activated initially and then rapidly makes them unusable, so the brain compensates and up regulates them even further

Question 39

True or false: lung cancer tops the charts for deaths related to nicotine.

Answer 39

False, its actually heart disease that causes the most deaths linked to nicotine

Question 40

What is benzo[a]pyrene?

Answer 40

It is an aromatic and heterocyclic amine that is produced from incomplete combustion, it gets metabolized into an active form and inserts into DNA and causes breakage, and modification. Results in faulty replication (cancer causing)

Question 41

Does nicotine itself cause cancer?

Answer 41

Not sure if it can initiate cancer, but it can inhibit programmed apoptosis and promote cell proliferation and can perhaps cause mutations

Question 42

How does nicotine prevent cell apoptosis?

Answer 42

Nicotine binds to the A7 receptors on the mitochondria and prevents it from releasing cytochrome C into the cytoplasm. Cytochrome C initiates apoptosis. Inhibiting the release of this causes damaged cells to continue to proliferate and possibly cause cancer

Question 43

What is Zyban (or bupropion)?

Answer 43

It was originally used as an antidepressant, but bupropion seems to lock in nicotinic receptor in a closed state (preventing any ions from entering its channel, even in the presence of nicotine). It prevents activation of this pathway and seems to address some craving issues. With a 30% success rate after 1 year