Nicotine

Nicotine

Naturally occuring alkaloid found in wide variety of plants

What plants can nicotine be found in?

Potatoes, tomatoes, green peppers, eggplants, cauliflower, celery

Pure nicotine

Typically clear and odorless, when exposed to air/light turns brown and stinky

Why do plants produce nicotine?

Defense mechanism to pests and pathogens.

Nicotine disrupts neurotransmisson in small herbivores

Attracts pollinators, creates scents to draw in predators of herbivores

History of nicotine

Relatively new

Stone drawings from Mayans may be the earliest depiction - 600 AD

Introdcued to Europe by Christopher Colombus - 1500s

Recieved its name from the island Tobago

In the early ages tobacco was initially..

thought to have unlimited benefits

-helping with toothaches, gum disease, mental depressions, belly aches, urinary obstructions, warts, anxiety, and improved deafness

-1601 an anonymous pamphlet was released about the real conseuquences

-1604 King James provided further warnings (but did not stop himself)
-1760s Dr. John Hill provided cancerous growth research associated with tobacco use

Types of nicotine products

Cigarettes, cigars, smokeless tobacco, e-cigarettes, heat not burn devices, dissolvable tobacco, nicotine gels

Cigarettes

dried tobacco leaves, usually filtered

Cigars

Dried tobacco leaves, unfiltered, 5-17x more tobacco than a cig

Smokeless tobacco

snuff, chew, snus/absorped orally

E-cigarettes

battery-powered device heating liquid / alternative nicotine product

Heat not burn devices

heat real tobacco but does not burn it

Dissolvable tobacco

lozenges, orbs that dissolve in mouth / slow nicotine delivery

Nicotine gels

patches / absorbed through skin

Absorption

Oral, pulmonary, surface absorption

Cigarettes have ~4-8 mg nicotine

Chew (around 30 minutes) has ~4 mg nicotine

Vaping (approx. per puff) has ~1 mg

Distribution

Vd = 2-3 L/kg

- Easy membrane passage

Absorption through mucosa is relatively slow

Inhalation allows for a fast spike within seconds in the CNS

Metabolism

Around 85% of nicotine is metabolized -mainly liver, but also in the kidneys and lungs

• An isozyme (group of enzymes that have different forms and efficiency) break down nicotine into Cotinine (among other metabolites)

• ~5-10% is unchanged, ~50% into cotinine types, and the rest is a mixed bag of metabolites

Half lives

Nicotine- 1-3 hours

Cotinine - 15-20 hours

Elimination

Mainly excreted in urine

• Can be excreted in milk of a lactating mother

• Clearance = 1.2 L/min (if healthy)

What is nicotine classified as

stiumlant/depressant of the autonomic NS

acts as an agonist on nicotine acetylcholine receptors (ionotropic)

Neurospecfic MOA

Targets (depolarizes) dopaminergic cells in the cortico-limbic pathway; inducing dopamine release

• Targets (depolarizes) cells in the adrenal medulla; inducing release of epinephrine

Overall MOA

Depolarizes cells in the adrenal medulla inducing release of epinephrine producing a sympathetic response

Nicotinic receptors are found at neuromuscular junctions and the immune system

Targets addiction pathways and regions critically associated with addiction

Targets limbic regions areas that are critical for learning/memory

Hippocampus, substantia nigra ventral tegmental area

What systems do nicotine target

Immune system and NMJ

NMJ

Neuromuscular junction, where nerve cells connect to muscles. Help process nerve action and activation of muscles

Nicotine effect on the immune system

Regulate inflammatory response

Psychoactive effects

Induces pleasure

• Reduces stress

• Regulates mood / arousal

• Improves concentration

• Improves reaction time

Tolerance and Dependence

Chemical dependence occurs in around 1/3 smokers

Tolerance will develop in consistent users •

The variance for chemical dependence can lead to instances of addicts (that aren’t actually addicted) that can “cold-turkey” stop

Even though nicotine doesn’t produce the same euphoric effects as other drugs its one of the most addictive, why?

Ionotropic receptors directly act on dopamine pathways

Medicinal Uses

Studies being done to help memory

Nicotine Replacement Therapy

Cardiovascular targets - increases blood pressure

Reducing infections - reducing cytokine respons

Medicinal Consequences

Increases chances of heart and lung disease, cancer and othe infections

Access and harm every tissue in the body

Developmental Consequences

Nicotine Poisioning

Nicotine Poisioning

Fatal dose of nicotine is 40-60 mg pure nicotine (combustion of a cigarette = ~1.2mg)

Rapid onset, nausea, abdominal pain, salivation, vomiting, tiredness, reduced BP & RR – followed by convulsions and death

Smoking during pregnancy leads to..

-Spontaneous abortion

- Placenta previa

- Placental abruption

- Preterm birth

- Reduced growth size

- Reduced birth weight

Neuroteratogen

A substance that compromises fetal development

Nicotine is one!!!

Nicotine on child development

Learning disabilities, increased rates of ADHD and addiction disorders

Acetylcholine receptors and ACh act as a morphogen

Influences differentiation and neuronal connectivity / pruning