NICOTINE

Baluga, Basa, Casquete, Flaviano, Garcia

2DMT
 HISTORY
Nicotiana tabacum PINNER & WOLFFENSTEIN
Jean Nicot de Villeman First described the structure
1893

POSSELT & REINMANN PICTET & CREPIEUX

First isolated nicotine from tobacco First synthesized nicotine
plant 1904
1812
C H N
10 14 2
Empirical formula
1843
WHAT IS NICOTINE ?
IUPAC NAME
3 - [(2S)-1 - methylpyrrolidin-2-yl] pyridine

C H N
10 14 2

Class of organic compounds called

PYRROLIDINYLPYRIDINES

Colorless, odorless liquid with

oily consistency

Half-life of 1-2 HOURS

WHAT IS NICOTINE ?
PARASYMPATHETIC ALKALOID DRUG
Dramatically stimulates neurons and blocks synaptic
transmission

CHIEF ADDICTING INGREDIENT

Found in TOBACCO and Cigarettes

STIMULANT IN SHORT PUFFS

Excites the brain

PROVIDES RELIEF IN DEEP DRAGS

Can have a tranquilizing effect
Nicotine is a plant alkaloid found in
the tobacco plant, and addictive
central nervous system (CNS)
stimulant that causes either
ganglionic stimulation in low doses
or ganglionic blockage in high
doses
PubChem 2017
PREPARATIONS AVAILABLE

TRANSDERMAL INHALATION
5-21 mg/day 0.5-4 mg/dose
GUM
2-4 mg/dose
absorbed/patch
 USES OF NICOTINE
IMPROVE IMPROVE
PERFORMANCE REACTION
TIME

IMPROVE
MODULATE
CONCENTRATION
S AROUSAL

CONTROL
AID TO MOOD
SMOKING
CESSATION
PHARMACOKINETICS AND METABOLISM
Drug enters circulation rapidly through lungs moves to brain within seconds

Inhaled drugs escape first-pass intestinal and hepatic metabolism.

The more rapid rate of absorption and entry of a drug into the brain, the greater the rush, and the more reinforcing the drug.

The smoking process also allows precise dose titration, so a smoker may obtain desired affects.

Nicotine is rapidly and extensively metabolized by the liver, primarily by the liver enzyme CYP2A6 (lesser content: CYP2B6)

Cotinine is subsequently metabolized to trans-3-hydroxycotinine (3HC) exclusively or nearly exclusively by CYP2A6.

The ratio of 3HC to cotinine can be used as a phenotypic marker for CYP2A6 activity and for the rate of nicotine metabolism. The half-life of
nicotine averages ~2 h, while the half-life of cotinine averages ~16 h. Cotinine levels are fairly stable throughout the day in smokers; because the
levels of 3HC are formation-limited, the ratio of 3HC to cotinine is also fairly stable.

Ratio can be measured in the blood, saliva, or urine of people while they are using tobacco, based on their intake of nicotine from tobacco.

Nicotine and cotinine are also metabolized by glucuronidation, primarily, it is thought, via UGT 1A4, 1A9, and 2B10 .
MECHANISM OF ACTION
Nicotine is a In the brain, nicotine
This leads to
depolarization, which
stimulant drug binds to nicotinic activates voltage-gated
that acts as an acetylcholine calcium channels and
agonist at receptors on allows more calcium to
nicotinic dopaminergic enter the axon terminal
neurons in the and stimulate the
acetylcholine cortico- limbic vesicle trafficking
receptors., which pathways. This towards the plasma
are ionotropic causes the channel membrane and the
to open and allow release of Dopamine
receptors that are into the synapse.
conductance of
composed of five multiple cations Dopamine binding to
homomeric or including sodium, its receptors is
heteromeric calcium, and responsible the
potassium. euphoric and addictive
subunits. properties of nicotine.
MECHANISM OF ACTION
Calcium triggers the
release of
Binding opens
epinephrine from
Nicotine also the ion channel
intracellular vesicles
binds to nicotinic allowing influx of
into the
acetylcholine sodium, causing
bloodstream, which
depolarization
receptors on the causes
of the cell, which vasoconstriction,
chromaffin
activates increased blood
cells in the voltage-gated pressure, increased
adrenal medulla. calcium heart rate, and
channels. increased blood
sugar.
 RECEPTOR

Nicotine binds to NICOTINIC CHOLINERGIC RECEPTOR, facilitating neurotransmitter release and

thereby mediating the complex actions of nicotine in tobacco users.
 SIDE EFFECTS
RESPIRATORY
Bronchoconstriction CENTRAL
Throat Irritation / cough Lightheadedness
Headache
GASTROINTESTINAL Sleep disturbances
Nausea Abnormal dreams
Dry mouth Irritability
Dyspepsia Dizziness
Diarrhea Risk of blood restriction
Heartburn
Peptic Ulcer
Cancer

HORMONAL CARDIOVASCULAR
High insulin Increased / decreased heart rate
Insulin resistance Increased blood pressure
Tachycardia
TO OFFSPRING Arrhythmia
Obesity Coronary artery disease
Type 2 Diabetes Increased clotting tendency
hypertension Atherosclerosis
Respiratory dysfunction Enlargement of aorta
 SIDE EFFECTS
NICOTINE WITHDRAWAL Irritability
Depressed mood
appears to be contributed by
Restlessness
corticotropin-releasing factor
Anxiety
mild compared with opioid
Problems getting along with
withdrawal
friends and family
Difficulty concentrating
Increased hunger and eating
Insomnia
Craving for tobacco
Hedonic Dysregulation
 SIDE EFFECTS
NICOTINE DEPENDENCE
The development of Dopamine, glutamate, and
gamma aminobutyric acid release are particularly
important

- Highly heritable
- most patients who habitually smoke more than
10-15 cigarettes per day (particularly cigarettes
with a nicotine yield of 0.9 mg or more)
develop some degree of dependence.
 MECHANISM OF SIDE EFFECTS
- Affects the cardiovascular system by increasing heart rate and constriction of
peripheral blood vessels via activation of the sympathetic nervous system.

- Stimulates vagal reflex and causes an increased airway resistance by causing

bronchoconstriction.

- Causes smooth muscle relaxation by action of endogenous nitric oxide which

leads to increased incidence of GERD

- Prenatal nicotine exposure alters homeostasis of endocrine control on body

weight resulting to obesity to the child.
 TREATMENT
Nicotine replacement products

INHALER GUM PATCH

Allows smokers to dose Produces sustained nicotine levels
themselves when faced with urges throughout the day
 TREATMENT
BUPROPION
Antidepressant therapy for smoking cessation of nicotine

Fewer mood DOPAMINE AND NOREPINEPHRINE

symptoms simulates the effects of nicotine on these
neurotransmitters

Less weight
gain
 TREATMENT
VARENICLINE
Blocks the effects of nicotine
Added to the system
Partial agonist
Poor
bioavailability Superior to bupropion
in promoting smoking
cessation
Occludes
rewarding effects Second-line
of smoking drugs with
clonidine
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946180/

https://pubchem.ncbi.nlm.nih.gov/compound/nicotine#section=Minimum-Potential-
Fatal-Human-Dose

https://www.medicalnewstoday.com/articles/240820.php

https://www.drugs.com/sfx/nicotine-side-effects.html

http://mentalhealthdaily.com/2015/10/08/how-long-does-nicotine-cotinine-stay-in-y
our-system/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363846/#sec1-15title