Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHAR 300 > L7: Nicotine > Flashcards

L7: Nicotine Flashcards

1
Q

How does a cigarette have a highly perfected drug delivery system?

A

The lungs have an enormous surface area designed for gas exchange as well as the absorption of chemicals that you breathe in. This causes rapid absorption of nicotine and the chemicals into the blood. The blood then goes from the lungs back to the heart and the heart pumps the oxygenated blood to the rest of the body and nicotine gets into the brain right away (7 seconds).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is smoking cigarettes so addictive?

A

The nicotine gets to the brain very quickly (7 sec) which causes a very rapid effect to the nicotine. The faster the drug gets to the brain the more addicting it is.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does the cigarette filter not successfully filter?

A

Chemicals, many of which are carcinogens.
Enzyme inhibitors.
Ciliotoxins, impair the ability of the lung to get rid of all of the particles and pollutants inhaled.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the mucociliary system? What happens to the mucociliary system when you smoke?

A
  1. The cilia in the lungs are always beating and propelling particles and mucus out of the lungs. How the lungs clean themselves.
  2. When you smoke, your cilia get paralyzed and damaged which compromises the mucociliary clearance rate.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens when you smoke and are exposed to asbestos at the same time?

A

Your chance of getting lung cancer is 50 to 90 times more than normal. On its own, smoking is 10x more and asbestos is 5x more.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What medical problems does smoking cause?

A
  1. Cancer
  2. Coronary heart disease
  3. Strokes
  4. Peripheral vascular disease: decreased blood flow to legs = hard to walk
  5. Lung diseases
  6. Increased risk of diabetes, pneumonia, tuberculosis, and influenza
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does nicotine do to veins and blood flow? Explain the effect.

A

Vasoconstriction. Constricts blood flow to all of the fine vessels in the periphery. Causes major wrinkles and cataracts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is second hand smoke and what is it composed of?

A

Second hand smoke is what the person exhales and mainly what is coming off the burning end of the cigarette. It has a different chemical composition than what the smoker is inhaling because when a smoker inhales, more oxygen moves through the cigarrette which increases the temperature and changes the chemical composition.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What can happen to children as a result of second hand smoke?

A

Sudden infant death, brain cancer, other cancers, asthma, infections.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the different ways to administer nicotine? What is it soluble in?

A

Chewing tobacco, swallowing pills, sublingual, transdermal patches. Nicotine is lipid soluble.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What kind of base is nicotine? And in what environment will it be more soluble?

A

Weak base. Most soluble form at a high pH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the consequences of smoking bypassing the first pass effect?

A
  1. Absorption through the lungs is as fast as IV injection.
  2. Chemicals in cigarettes aren’t partially metabolized by the liver before going to the systemic circulation so there is a larger quantity of chemicals in the blood to affect the body.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What allows nicotine to diffuse into the capillaries so easily?

A

Thin walls between the alveoli and capillaries maximizes gas exchange.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why doesn’t lowering nicotine cigarettes make the cigarette safer?

A

The smoker will adjust the drug delivery in order to get the required level of nicotine they are addicted to; the smoker will control their bioavailability of nicotine. When given lower level nicotine cigarette, they take more puffs and hold it in their lungs for longer. If given higher nicotine cigarettes, they will take less puffs so the nicotine level wont be much higher than usual.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is swallowing nicotine very dangerous? For children?

A

Because it is absorbed from the intestine. If children eat it they will die if they don’t vomit quickly enough.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why shouldn’t pregnant woman and breastfeeding women smoke?

A
  1. Nicotine will reach the fetus

2. Nicotine is present in breast milk (lipid soluble)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Why can nicotine cross the blood brain barrier?

A

It is lipid soluble

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What will save a child from nicotine?

A

The fact that nicotine stimulates the “chemoreceptor trigger zone” (CTZ) which does not contain a blood brain barrier. This is important because it will be quickly affected by nicotine and will send a signal to the vomiting center.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why don’t smokers throw up every time they smoke?

A

The CTZ becomes desensitized to nicotine after chronic use.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What mainly metabolizes nicotine?

A

The CYP450 system in the liver. The predominant CYP enzyme for nicotine is CYP2A6.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does CYP2A6 metabolize nicotine into?

A

The less active metabolite, cotinine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the plasma concentration of nicotine in a smoker throughout the day.

A
  1. In the morning they are in the “abstinence zone” before having their first cig.
  2. The first few cigarettes of the day bring the smoker to their normal nicotine levels.
  3. When they sleep, their nicotine levels decrease.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why is having a deficient (under-active) CYP2A6 enzyme an advantage for smokers?

A

It does not metabolize nicotine as quickly so they don’t have to smoke as frequently and as much to maintain blood nicotine. This means they get less exposed to the other harmful chemicals. Also, CYP2A6 activates some procarcinogens which makes toxic metabolites. So someone with a CYP2A6 deficiency will make less of the toxic metabolites.

24
Q

Where are nicotine, cotinine and carcinogens mainly excreted?

A

From the kidney. The urine of a cigarette smoker is carcinogenic.

25
Q

How does alkaline urine affect nicotine excretion?

A

It will decrease nicotine excretion because nicotine will be in its unionized lipid soluble form due to the alkaline environment. This will cause it to get reabsorbed in the tubules of the kidney and go back into the circulation.

26
Q

What receptors does nicotine act on, and in what way?

A

Nicotine acts on nicotinic receptors as an antagonist and as an agonist.

27
Q

Where are nicotinic receptors found?

A

The ganglia of the sympathetic and parasympathetic nervous systems, at innervation of skeletal muscle, and in the brain.

28
Q

Are muscarinic acetylcholine receptors in the parasympathetic nerve terminals affected by nicotine?

A

No because they are not nicotinic.

29
Q

What is the nicotinic cholinergic receptor and what happens when it is activated?

A

It is an ion channel selective to sodium and calcium. The cell depolarizes when it is stimulated.

30
Q

What type of receptor is a muscarinic cholinergic receptor and what acts on it?

A

A GPCR. Acetylcholine. NOT NICOTINE.

31
Q

Describe the composition of the nicotinic cholinergic receptor.

A

Made of 5 subunits. Can either be homomeric with all alpha subunits or heteromeric with a mix of alpha and beta subunits. However, there are always at least 2 alpha subunits because that is where acetylcholine binds. There are 9 variations of the alpha subunit.

32
Q

What is the most common nicotinic receptor in the brain?

A

alpha-4-beta-2 (heteromeric) and alpha-7 (homomeric).

33
Q

Where and how does nicotine bind on the nicotinic cholinergic receptor?

A

On the same site acetylcholine binds. It binds to the alpha subunit and 2 molecules must bind to the receptor to activate it. (same as acetylcholine)

34
Q

What is the difference in affect between acetylcholine binding or nicotine binding to the nicotinic cholinergic receptor?

A

When acetylcholine binds, the channel is activated, sodium flows into the cell, the channel becomes desensitized and the agonist cannot bind but the channel eventually goes back to standby (ready to be activated again).
When nicotine binds, the desensitization phase and binding of nicotine lasts longer than acetylcholine. The desensitization phase is longer because nicotine disrupts the process that desensitized channels use to go back to standby. This contributes to tolerance.

35
Q

What happens when a smoker becomes tolerant to nicotine?

A

Cells synthesize more nicotinic receptors.

36
Q

What is nicotine’s effect on the periphery?

A

It blocks and stimulates the autonomic ganglia which contributes to side effects.

37
Q

What is a side effect nicotine has on the heart and why?

A

Nicotine leads to the release of norepinephrine from sympathetic nerve endings and releases adrenaline from the medulla. This leads to different heart rate, increased blood pressure, and vessel damages caused by other toxic compounds.

38
Q

What is nicotine poisoning and what are the symptoms?

A

Poisoning = excitation followed by inhibition. This leads to tremors, convulsions, paralysis, and death from respiratory failure.

39
Q

How does nicotine affect norepinephrine, memory, and cognition?

A

Via modulation of glutamate and GABA (gives one the sense of relaxation).

40
Q

Does nicotine only affect the reward pathway?

A

No, there are nicotinic receptors found on presynaptic nerve endings of many types of neurons throughout the brain, not just in the reward pathway.

41
Q

What happens to a mouse that has a beta-2 subunit removed from the nicotinic cholinergic receptor? What is important about the alpha-4 nicotinic receptor?

A

The mouse will not get an increase in dopamine when exposed to nicotine. Therefore, the mouse will not get addicted to nicotine and will not press a lever for more nicotine.
The alpha-4 nicotinic receptor is essential for dopamine release.

42
Q

What is a monoamine oxidase inhibitor?

A

It is a chemical found in cigarettes that inhibits the enzyme “monoamine oxidase”. Monoamine oxidase breaks down NE and dopamine in the presynaptic terminal after their reuptake. Smokers will therefore have a decreased level of monoamine oxidase in the brain and periphery because they inhale monoamine oxidase inhibitor. This affects other transmission systems in the brain.

43
Q

What is added to give cigarettes a minty flavour? What does it do?

A

Menthol is added. It makes cigarettes much more addictive because it is a cholinergic receptor modulator.

44
Q

What is the success rate of quitting smoking compared to other drugs?

A

It has one of the lowest success rates of quitting in all of the addictions even compared to highly addictive drugs such as alcohol and heroine.

45
Q

On average, how many times do smokers try to quit before they’re successful? What eventually leads them to success?

A

11 times. A health scare like a heart attack or cancer eventually leads them to success.

46
Q

What is the affect of nicotine on the GABA neuron and ultimately the dopaminergic neuron?

A
  1. The dopaminergic neuron is stimulated by glutaminergic neurons and inhibited by GABA neurons.
  2. GABA neurons have cholinergic inputs. Nicotine can act on the alpha-4-beta-2 receptors on the GABA neuron to inhibit the dopaminergic pathway. However, these nicotinic receptors desensitize rapidly and for a long time which causes less inhibition of dopaminergic neurons by GABA, which leads to less inhibition of the dopaminergic pathway, therefore dopamine is released.
47
Q

What is the affect of nicotine on the glutaminergic neuron and ultimately the dopaminergic neuron?

A
  1. The dopaminergic neuron is stimulated by glutaminergic neurons and inhibited by GABA neurons.
  2. Nicotine stimulates alpha-7 nicotinic repectors on glutaminergic neurons which release the neurotransmitter glutamate. This stimulates dopaminergic neurons to release more dopamine.
48
Q

What is the total effect of activation and inhibition of the dopaminergic neuron by the GABA and glutaminergic neurons stimulated by nicotine?

A

There is more stimulation fo the dopaminergic neuron due to nicotines desensitization of alpha-4-beta-2 receptors on GABA neurons (less inhibition of dopaminergic neuron) in addition to stimulation of alpha-7 receptors on glutaminergic neurons (activation of dopaminergic neuron).
In sum, increased excitation and decreased inhibition leads to an increase in dopamine release.

49
Q

What are the acute nicotine withdrawal symptoms?

A
  1. Depression
  2. Irritability
  3. Trouble concentrating
  4. Trouble sleeping
  5. Increased appetite
  6. Constipation
50
Q

How long does it take before all the receptors bound by nicotine are turned over and replaced by normal receptors? How long does it take to get rid of the excess receptors from upregulation?

A

6 weeks. Also 6 weeks.

51
Q

What are the treatments for nicotine addiction?

A
  1. Replacement therapy
  2. Bupropion
  3. Varenicline
  4. Block CYP2A6
  5. Topiramate
52
Q

How does replacement therapy treat nicotine addiction?

A

It substitutes nicotine to only get nicotine and not all of the bad chemicals in cigarettes. Example: patch, spray, chewing tobacco, or sniff it. Helps with withdrawal but wont get you the high due to a slow release.

53
Q

How does Bupropion treat nicotine addiction?

A

Blocks nicotinic receptors on dopaminergic neurons in the ventral tegmented area.

54
Q

How does Varenicline treat nicotine addiction?

A

Partial agonist at the alpha-4-beta-2 nicotinic receptors in the ventral tegmented area. Allows for moderate dopamine release to prevent withdrawal symptoms without giving a high.

55
Q

How does blocking CYP2A6 treat nicotine addiction?

A

Decreases the metabolism of nicotine which causes people to smoke fewer cigarettes and decreases toxicity of cigarettes.

56
Q

How does Topiramate treat nicotine addiction?

A

Blocks the ability of nicotine to give you a high because of decreased dopamine release in response to nicotine.

57
Q

Why are e-cigarettes worse than cigs?

A
  1. the flavourants are burned and create new chemicals that are harmful and that we don’t know the effect of.
  2. E-cigarettes have smaller particles which can get deeper into your lungs and cause more damage.

PHAR 300 (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions