Nicotine

Question 1

Approx. how many adults in the UK smoke cigarettes?

Answer 1

12 million

Question 2

Tobacco smoking is the largest cause of preventable deaths worldwide. How many deaths result from smoking globally per year?

Answer 2

5 million

Question 3

In the UK how many smoking-related deaths are there per year?

Answer 3

120,000

Question 4

What percentage of a) men and b) women smoke in the UK?

Answer 4

a) 28%

b) 26%

Question 5

How many chemicals are there in tobacco smoke?

Answer 5

4000

Question 6

Which is the addictive chemical in tobacco smoke?

Answer 6

Nicotine.

Question 7

How is nicotine absorbed in a) cigarette and b) pipe/cigar smoking?

Answer 7

a) Directly through the lungs into the blood

b) Slowly through the mucosal membranes in the mouth

Question 8

Once inhaled via cigarette smoking, how long does it take for nicotine to reach the brain?

Answer 8

~10 seconds.

Question 9

How does nicotine act in the body?

Answer 9

It acts on nAChRs

Question 10

Where are nAChRs found? List 3 places.

Answer 10

1. At NMJs (neuromuscular junctions)
2. In the autonomic ganglia, both sympathetic and parasympathetic.
3. In the CNS

Question 11

nAChRs are always post-synaptic. True or false?

Answer 11

False: they are post-synaptic but are also found pre-synaptically in the autonomic ganglia and CNS.

Question 12

What kind of receptors are nAChRs?

Answer 12

Excitatory ligand-gated ion channels. They allow Na+ into cells in depolarisation.

Question 13

What 4 NTs does activation of nAChRs release?

Answer 13

1. Dopamine
2. Noradrenaline
3. GABA
4. Endorphins (endogenous opioids)

Question 14

What effect does dopamine release have in cigarette smoking?

Answer 14

nAChRs are present in the VTA, causing dopamine release in the mesolimbic pathway, giving a sense of reward.

Question 15

How does noradrenaline release affect the body? List some effects of noradrenaline release given by smoking.

Answer 15

Via stimulation of the autonomic nervous system: increased heart rate, blood pressure, sweating and decreased gastrointestinal mobility are all sympathetic effects of smoking.

Question 16

Noradrenaline release in smoking causes increased attentiveness due to stimulation of the autonomic nervous system. This has been shown to increase learning and memory. True or false?

Answer 16

True.

Question 17

What effect does increased GABA produce?

Answer 17

Anxiolytic effects due to an increase in inhibitory transmission.

Question 18

What effect does increased endorphin release produce?

Answer 18

Endorphins are endogenous opioids that act on Mu receptors. Opioids reduce GABA transmission in the nucleus accumbens and thus enhance dopamine production, leading to a sense of reward.

Question 19

Describe the metabolism of nicotine.

Answer 19

It occurs in the liver, taking between 30-60mins. It is metabolised to inactive cotinine.

Question 20

List 5 withdrawal symptoms of nicotine.

Answer 20

1. Irritability/agitation
2. Restlessness
3. Attentional deficits
4. Sleep disturbance
5. Hunger

Question 21

Why do heavy smokers show decreased sensitivity to nicotine?

Answer 21

Their blood concentration remains high as they smoke lots of cigarettes. Thus their nAChRs become sensitised to its presence (tolerance).

Question 22

Why do heavy smokers feel compelled to smoke lots of cigarettes?

Answer 22

The acute effects of nicotine disappear within a few minutes, so addicts must maintain the pleasurable effects of smoking by smoking numerous cigarettes to prevent withdrawal.

Question 23

Why is it that withdrawal from nicotine causes irritability and agitation?

Answer 23

Because after cessation the nAChRs regain sensitivity, thus cholinergic transmission is restored and increased. ACh is an excitatory NT.

Question 24

It is hypothesised that another reason behind reward in smoking is that an unidentified compound inhibits the breakdown of MAO-B, thus dopamine is not broken down and remains in the synapse, stimulating the reward centre. True or false?

Answer 24

True.

Question 25

There are low levels of relapse after smoking cessation. True or false?

Answer 25

False: relapse is high.

Question 26

The cravings for nicotine last far longer than the physical withdrawal symptoms of smoking. True or false?

Answer 26

True: they can persist over 6 months after smoking cessation.

Question 27

List some methods of nicotine replacement therapy. What is the point?

Answer 27

Gums, inhalers and patches.

They provide the user with nicotine at a reduced level whilst avoiding the carcinogenic effects of smoking.

Question 28

What is buproprion?

Answer 28

A drug originally used as an AD that appears to help with nicotine withdrawal. The mechanisms behind this are unknown.

Question 29

What is varenicline?

Answer 29

A partial nAChR agonist that target the nAChR sub-types with alpha-4 and beta-2 subunits.

Question 30

How does varenicline work in smoking withdrawal? List 2 ways.

Answer 30

1. It causes a moderate increase in mesolimbic dopamine, which counteracts the low dopamine that results from smoking cessation.
2. It also competitively binds with nicotine. Therefore during a relapse, nicotine does not initiate the same levels of dopamine release and thus reward.