Unit 8 ~ Nicotine

Dried tobacco leaves contain what percentage of nicotine

5% remember this.

Nicotine is an Alkaloid and the main psychoactive ingredient seen in what

Seen in the tobacco

Why is tobacco smoke a very complex mixture

It contains nicotine & CO2

The Tar will carry nicotine to the lung; furthermore, many of the particles seen here are carcinogenic

What was the dominant form of tobacco consumption in the 20th century

These were seen as Cigarettes and were followed by new curing methods and the invention of the cigarette machine

How is US tobacco use

There is a pattern of decline since the 1960s.

20% of US adults are current users of tobacco products

Furthermore, 30% of high school students are users

Why is E-Cig use among the youth and the young adults increasing

1. The number of flavors is very enticing to the youth

2. E-cigs are not safe, and usage is often correlated to other tobacco products

3. Has a “negative” impact on adolescent brain development

Worldwide Tobacco Use

Nicotine is the 3rd most widely consumed recreational drug, after caffeine & Alcohol

Kills 9 Million a year

Smoking & Vaping of Nicotine

Nicotine will be carried on tar with other particles; this will then be absorbed via the lungs.

Has a much faster onset and shorter duration

provides the highest blood nicotine

By the Mouth (Chew, Dip, Snus) Nicotine

This will be absorbed by the membranes in the mouth

It will not be as effective since nicotine is a weak base, so Strong first pass metabolism

By the nose (Snuff)

This will be absorbed by the membranes in the nose

What do smoking and vaping patterns look like in HS students

Decreased Cigarette use but there is increased vaping

What do smoking and vaping patterns look like in College

Marijuana and cannabis vaping will greatly increase among college students and non-college peers

Nicotine vaping is also increasing in both populations

What are Electric Nicotine Delivery Systems (ENDS)

These are electric devices that will vaporize flavored liquid that often contains nicotine

These will often contain ingredients that are harmful (heavy metals, volatile organic compounds, and other ultra fine particles)

Smoking and Vaping of nicotine, will hit the brain very fast, what is the amount of time

It will usually take 7 seconds.

What is nicotine mostly metabolized into

Cotinine

Nicotine is metabolized into cotinine via what enzyme

Cytochrome p450 Enzyme

People with reduced nicotine metabolism are more or less likely to become smokers

Reduced nicotine metabolism is correlated with a lower likelihood of becoming smokers

Nicotine is directly an agonist of what type of receptors

Nicotinic Acetylcholine Receptors (nAChRs), there are found in the CNS and PNS (controlling the autonomic and somatic nervous systems)

Nicotine Effects on Arousal

Experienced drug users will often misidentify IV Nicotine for Cocaine

There is also drug discrimination where we see cross-substitution with cocaine

Nicotine will enhance the locomotor activity in animals, showing sensitization

Nicotine effects on cognition

ACh is implicated in the cortical function related to sustained attention and memory

A). There is an enhanced performance of attention-demanding tasks

B). Enhanced Performance on cognitive tasks

What does acute tolerance look like in Nicotine

This will develop over the course of the day and later reset.

This is due to the desensitization of nAChRs

What does chronic tolerance look like in Nicotine

This will often last for an extended period following smoking cessation, due to the various aversive effects of smoking

nAChRs will show decreased function

1. There will be a paradoxical increase in the amount due to decreased nAChRs function

How does nicotine effect Mood

Smokers can often not tell the difference between nicotinized and denicotinized cigarettes, furthermore showing that smokers will prefer to smoke denicotinized cigarettes as compared to IV Nicotine.

Showing there is a stronger association with the behavior or habitual nature of smoking

A very high dose of nicotine will cause toxicitity

High doses will produce unpleasant symptoms, such as nausea, sweating, and stomachache

This is largely due to the autonomic actions of nicotine, and there is a strong tolerance to these actions.

A lethal dose of nicotine will kill via the depolarization of the muscles that are involved with respiration.

Chronic use can also show some of these other symptoms

Smoking during pregnancy causes low birth weight

Half of all lifetime smokers will die prematurely

There is also an increased risk for lung diseases, cardiovascular diseases and cognitive deficits

How is ACh synthesized

This occurs via the precursor Choline and the enzyme ChAT (Choline, Acetyl-Transferase)

How is ACh degraded

This will occur via AChE which will turn ACh into Choline and Acetic Acid

ACh is found in many brain systems and has central actions

Striatum shows responses relative to DA

Basal forebrain shows a relation to the cortex and hippocampus, thus involved in Cognition

Dorsolateral Pons in involved in Catecholamine systems, showing involvement with Arousal and sensory stuff

What will package ACh into vesicles

This will occur via VAChT and can later be inactivated by metabolism.

Following conversion to Choline, it will be taken up by a choline transporter and will be reused to make more ACh

What are two common Receptor Agonists of ACh

Muscarine (mAChR) ~ used to treat post-surgery nausea and vomiting, motion sickness, and seasickness

Nicotine (nAChR)

Drugs that will affect ACh Release

Botulinum Toxin ~ This will work by blocking ACh release, so no muscle activation will occur, and will cause muscle paralysis.

Black Widow Spider Venom ~ This will cause a massive influx of ACh Release thus leading to Muscle spasms and cramps.

What are the two Main AChE blockers (blocking re-uptake)

Physostigmine (Reversible) ~ This can be used to treat anticholinergic poisoning (can be used to treat myasthenia gravis, an autoimmune disorder where muscle ACh receptors are attacked)

Nerve Gases (Sarin) ~ Acts on the autonomic nervous system and muscles

Further Characteristics of mAChRs

These are metabotropic and have 5 types of receptors (M1 - M5) that are coupled to either Gq or Gi

Further characteristics of nAChRs

This is ionotropic and is Pentameric in Nature (5 subunits)

It is a ligand gated cation channel that can be found in the Brain and Muscle

Muscle nAChRs (Have two ACh binding sites) usually just NA

Brain nAChRs (have 2a, 3b, or 5a subunits) Will bind nicotine with higher affinity, can be NA or Ca

Nicotine Reinforcement (Self ad)

Yes, this is self-administered in Animals

There is an increase in DA cells of the VTA, which in turn will lead to further DA release in the N.Acc

the a4b2 receptor subtype (nAChR) will show what effects

These will show the rewarding effects of nicotine

the a7 receptor subtype (nAChR) will show what effects

These will show the cognitive (Attention) effects of nicotine

What does Methyllylcaconitine (MLA) do what does it block

This will block A7 receptors, thus blocking the effects of attention

What are the effects of Menthol on Nicotine

Menthol often makes it easier to begin smoking and much harder to quit

1. It will intensify nicotinic withdrawal symptoms

2. It will increase a4b2 nAChRs, even without nicotine, showing an increase in reinforcement or reward feeling

How many say quit, how many attempt, and how many successful

70-75% will say they wish to quit

40-45% will attempt to quit

And only 10% of them are truly successful

What is NRT

This is Nicotine Replacement Therapy. This helps with withdrawal and dependence via gum, patches, lozenges ,and more (however, there are been little advantages seen)

Other options will Target Withdrawal as well as craving

Bupropion

This is a DAT blocker and works as a Weak nAChR antagonist

Varenicline

Partial agonist of a4b2 and the most effective treatment as it works directly towards the rewarding nature of Nicotine