nicotine

what are vapes?

Battery-powered devices that heat and aerosolise an 'e-liquid' which is then inhaled

key ingredients of a vape (list 5)

• nicotine

• flavours

• solvents

• propylene glycol

• glycerol

nicotine

• Active ingredient of vapes

• A clear to light brown oily liquid

• Highly toxic in liquid form -> addictive

• Causes a range of physiological effects upon exposure

nicotine (chemistry)

• Alkaloid -> contains N

• Produced in many plants as a poisonous defense mechanism

• Commonly used as a stimulant and an anxiolytic → alleviates nervousness

nicotine is a receptor (a and b)

agonist and antagonist

nicotine is mostly a receptor (?)

agonist

nicotine is a receptor antagonist at what two receptors?

nAChRa9 and nAChRa10

nAChRs

• Receptors that respond to the neurotransmitter acetylcholine (and nicotine)

• Cholinergic receptors

• Located in the central and peripheral nervous system → high affinity

• Transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system

• And in the muscle → low affinity

• Involved in muscle contraction

nAChRs are ligand-gated ion channels, and thus are (?) receptors

ionotropic

ligand-gated ion channels

Transmembrane channels allowing cations through in respond to binding of an agonist/ligand (i.e. nicotine)

what happens after nicotine binds to its receptor?

• Enlarges the pore size of nAChR -> configurational change

• Allows Na+ to flow through down its concentration gradient

• If increasing membrane potential reaches threshold -> inflow of positive charge can cause depolarisation -> action potential formation

nicotine action potential formation

1. Resting state

• Channels are closed

• -ve charge inside the cell

2. Nicotine binding

• Nicotine binds to receptor

• Activates Na channel

• Flow of Na+ into cell

• Depolarisation of postsynaptic membrane

3. Na channels close

• K channels open

• Flow of K+ out of cell

• Repolarisation

4. Refractory period

• Na+ pumped out of cell

• K+ pumped into cell

• Reverts to resting state

nicotine effects (in the brain vs in the autonomic ganglia)

1. In the brain

• Nicotine activates neurons leading to increases in alertness and attention

2. In the autonomic ganglia

• Nicotine stimulates both sympathetic and parasympathetic neurons

• Sympathetic -> increased heart rate, blood pressure, respiration, reduced blood flow

• Parasympathetic -> increased salivation and GI activity

Depolarisation can also trigger the release of substances that act as chemical messengers:

neurotransmitters and hormones

release of neurotransmitters/hormones (in the brain vs in the adrenal medulla)

1. In the brain

• Nicotine stimulates release of dopamine, noradrenalin, serotonin, GABA, and glutamate

• Lead to feelings of pleasure and addiction

2. Adrenal medulla

• Nicotine stimulates release of adrenaline

• Fight or flight response -> increased heart rate, vasoconstriction

nAChRa9 and nAChRa10

• Nicotine is also a receptor antagonist at these two receptors

• Nicotine blocks these receptors -> reduce activation

• Found in the inner ear, immune system, dorsal root ganglia

• Leads to mild analgesia -> pain suppression

• Can potentially interfere with immune responses and hearing

 How much nicotine is in vapes?

• Disposable vapes contain 50mg/mL of nicotine (5%)

• 200 micrograms per puff is absorbed

• A cigarette puff contains 120 micrograms of nicotine per puff

Nicotine poisoning (estimated fatal dose)

• Estimated fatal dose of nicotine -> 6.5 to 13mg/kg

• Cases of people ingesting more than 500mg and surviving

nicotine toxicity mechanisms (low vs high dose)

1. At lower doses

• Nicotine is a receptor agonist

• Mild stimulatory effect on nicotine cholinergic receptors -> sympathetic activation

• Small increases in heart rate, blood pressure, alertness, pleasure

2. At higher doses

• Nicotine acts directly on the peripheral neural system

• Producing excessive ganglionic stimulation and catecholamine release from the adrenal glands

• Causes excessive nerve and muscle activation

• Affects both the sympathetic and parasympathetic nervous system

• Leads to sweating, nausea, high heart rate and blood pressure, anxiety, tremors, seizures, etc

• Vomiting and diarrhea due to GIT stimulation

• CNS overstimulation leads to confusion and convulsions

ganglionic blockade

 

• Caused by high doses of nicotine

• Leads to hypotension and bradycardia

• Respiratory system depression

• Coma and death can result

ganglionic blockade can cause (?) block

depolarisation

depolarisation block

• Ganglionic block can cause prolonged depolarisation by opening channels responsible for depolarisation and not allowing them to close

• Nicotine activates Na channel -> Na+ flows into neuron -> depolarisation

• Channel permanently open due to too much nicotine -> no repolarisation

nicotine addiction

• Compulsive use due to the development of tolerance

• Experiencing withdrawal symptoms

• Addiction is due to both biological and psychological effects

why does nicotine addiction occur? (physiological reasoning)

• Nicotine binds to nAChRs in the brain

• Leads to the release of neurotransmitters such as dopamine, noradrenaline, serotonin, GABA, glutamate

• Leads to feelings of pleasure and motivation towards using more nicotine → particularly dopamine and serotonin

use of nicotine also results in an increase in the number of (?) in the brain

nAChRs

nicotine addiction medications (list 1)

• Varenicline -> nAChR partial agonists

• Binding to nAChRs causes release of same neurotransmitters, reduces cravings for nicotine

• After a period of abstinence the number of nAChRs returns to normal and these symptoms go away

hundred of chemicals have been identified in vapes: hazards (list 5)

• Irritant/ low level toxicity

• Flammable

• Corrosive

• Environmental hazard

• Acute toxicity

common flavours

CYP2A6 → pathway that metabolises nicotine

when glycerol and propylene glycol are heated:

• Breakdown products are released

• Irritants, corrosives, carcinogens

adolescents who vape are more likely to take up:

cigarette smoking (5x more likely compared with non-vapers)

summary

vape → battery powered device that heats and aerosolises an e-liquid which is then inhaled

key ingredients:

• nicotine

• flavour

• solvents

• glycerol

• propyl glycine

• other chemicals

nicotine

• active ingredient of vapes

• clear to light brown oily liquid

• alkaloid → contains N

• associated with addiction

nicotine receptor

• nicotine is both a receptor agonist and an antagonist

• nicotine is a receptor antagonist at nAChRa9 and nAChRa10

• cholinergic receptors

nicotine in the brain

• bind to nicotine receptors on neurons→ secrete dopamine, serotonin, noradrenalin, glutamate, GABA → pleasure and addiction

nicotine in autonomic ganglia

• bind to nicotine receptors within pre and post ganglionic neuron pathways

• sympathetic activation → increase heart rate, increase blood pressure, decrease blood flow

• parasympathetic activation → increase salivation, increase GIT activity

adrenal glands

• nicotine stimulates release of adrenalin from the adrenal medulla

• fight or flight response

at low doses

• binds to central and peripheral chemoreceptors

• stimulates sympathetic activity → small increases in blood pressure and heart rate, alertness

at high doses (nicotine toxicity)

• binds to peripheral nervous system

• produces excessive ganglionic stimulation and catecholamine release from the adrenal glands

• increases sympathetic and parasympathetic activation

• sweating, nausea, tremors, vomiting, confusion

nicotine toxicity mechanisms

ganglionic blockade

• due to high doses of nicotine

• leads to hypotension and bradycardia → respiratory system depression

• can result in coma and death

depolarisation block

• due to high doses of nicotine

• Na+ channels permanently open

• repolarisation cannot occur

nicotine addiction

• due to release of neurotransmitters like dopamine and serotonin which lead to feelings of pleasure, motivation, reward

• leads to increase in the number of nAChRs in the brain

• increase tolerance and increase requirement for higher doses

nicotine medication

• varenicline → nAChR partial agonist

• bind to nicotine receptors to stimulate release of neurotransmitters

• reduce cravings for nicotine

vapes increase the risk of smoking

• adolescents who vape are 5x more likely to smoke compared to adolescents who don’t vape