What are E-cigs?
Battery-powered devices that heat via a heating cold and aerosolises an e-liquid, which is then inhaled. The primary devices sold currently are known as disposable vapes
What makes up an e-liquid?
E-liquids typically contain propylene glycol and glycerol (also known as vegetable glycerol), other ingredients including flavours, solvents and nicotine
What is nicotine and why is it important?
Nicotine is produced in plants as an alkaloid “antiherbivore defense” chemical. When ingested, it has both a stimulant and anxiolytic effect. Nicotine is the active ingredient not only in e-cigs but originally in traditional cigarettes. Nicotine presents as a light brown, oily liquid, is highly toxic in liquid form due to the high concentration levels, and as it triggers a range of physiological effects, can be highly addictive
Outline what nicotine is and its Receptor actions, cellular and physiological effects
Nicotine is a plant alkaloid. It is an oily liquid that is highly toxic in concentrated form and is the primary addictive active ingredient.
Receptor actions: agonist at most nicotinic acetylcholine receptors (nAChRs), antagonist at some subtypes; nAChRs are ionotropic cholinergic receptors in CNS, PNS and muscle.
Cellular effect: nAChR opening permits Na+ influx, depolarisation and increased neuronal firing, triggering neurotransmitter and hormone release (dopamine, noradrenaline, serotonin, GABA, glutamate, adrenaline).
Physiological effects: increased alertness, heart rate, blood pressure, respiration, vasoconstriction, salivation, GI activity, and release of catecholamines (fight/flight).
What are nicotine’s physiological effects?
Nicotine binds to most nAChR (nicotinic acetylcholine receptors) as an agonist. nAChR are ionotropic receptors or ligand-gated ion channels. These are transmembrane channels allowing the flow of ions such as Na+ and K+ upon the binding of a ligand.
Nicotine also binds to nAChRα9 and nAChRα10 as antagonists.
NAChR are located in CNS, PNS and muscles. They bind to nicotine with higher affinity at the CNS and PNS to transmit signals from presynaptic to postsynaptic signals.
Binding of nicotine to nAChR causes the ionotropic receptor to open 3 fold wide (~ 3 angstroms to ~8 angstroms)
NB Agonists bind and activates a receptor, triggering a response while antagonists bind without triggering a response, therefore acting as a block inhibiting a response.
Compare the effects of nicotine in the brain vs the remainder of the body
In the brain, nicotine increases alertness, attention and response times, while in the autonomic ganglia, it stimultates both SNS and PNS depending on the dose.
At the level of the SNS, it is a stimulus, increasing HR, blood pressure, heightened senses, peripheral vasoconstriction.
At the level of the PNS, it increases salivation, and GIT activity.
What specifically are released as a result of nicotine?
nicotine stimulates release of release of substances like neurotransmitters and hormones. In the brain, neurotransmitter such as dopamine, noradrenalin, serotonin, gamma-aminobutyric acid (GABA) and glutamate are released creating sensations of pleasure, which may lead to addiction in the long term.
At the adrenal medulla, nicotine stimulates release of adrenaline. This causes elevated HR, peripheral vasoconstriction, heighted senses which are related to the flight/fight response.
How does vape nicotine delivery compare with traditional cigarette nicotine delivery?
1 cigarette puff delivers around 120 ug of nicotine whilel 1 vape puff delivers around 200 ug of nicotine.
NB Disposable vapes typically contain 50 mg/ml. TGA permits sale of vapes containing 20 mg/ml or less without prescription. In WA, all vapes require a prescription
How does nicotine become toxic?
Nicotine in small doses result in alertness, increased BP, HR and also pleasure sensations as it stimulates the nicotinic cholinergic receptors of the SNS.
At higher doses, nicotine stimulates the PNS and results in excessive ganglionic stimulation and catecholamine (Adr, NA and dopamine) release from the adrenals:
- excessive nerve and muscle stimulation
- affects BOTH SNS and PNS
- leads to sweating, tremors, high BP, tachycardia, anxiety, seizures, cardiovascular stress
- overstimulation of the GIT which may lead to nausea and vomiting
At very high doses, nicotine can cause ganglionic blockade which results from a lack of repolarisation as excessive levels of nicotine maintains open ionotropic channels and a constant state of depolarisation at the postganglionic neuron.
Describe nicotine toxicity and dependence
Dose and absorption: many vapes contain high concentrations (e.g., 50–100 mg/mL); puff absorption measured in hundreds of micrograms.
Acute toxicity: low‑to‑moderate doses stimulate autonomic responses; higher doses cause excessive ganglionic stimulation (sweating, nausea, tachycardia, tremor, seizures, vomiting, diarrhoea, CNS overstimulation). Very high doses produce ganglionic blockade (hypotension, bradycardia), respiratory paralysis, coma and death. Children represent a major poisoning risk from ingestion.
Dependence: nicotine produces reward via dopamine and other neurotransmitters, increases nAChR numbers (tolerance), and causes withdrawal symptoms when absent; pharmacotherapies (e.g., partial nAChR agonists) reduce cravings.
How does nicotine addiction develop?
Nicotine causes the release of neurotransmitters in the CNS including GABA, dopamine, serotonin, glutamate amont others. These lead to sensations of pleasure and reward, which further motivates the use of nicotine.
NB The primary neurotransmitters leading to these are dopamine and serotonin
Short term use of nicotine desensitizes the nAChR while long erm use results in expression of more nAChR which increases tolerance. When nAChR are not bound to nicotine, they cause withdrawal symptoms.
Are vapes “healthier” than cigarettes?
The primary ingredients in e-liquids are nicotine, propylenes glycol and glycerol. However, there are additional solvents and flavors which are included such as cinnamon, menthol or oils which can be flammable, corrosive and toxic. Furthermore, due to poor manufacturing and quality control, there are many additional chemicals packaged within the e-liquid including industrial chemicals which have yet to be identified.
Vaping in adolescents result in a 5 x increase in addiction to cigarette smoking cf non-vapers
Why do vapes pose a hazard to health?
Major components: solvents/humectants (propylene glycol, glycerol), nicotine (usually), and a large variety of flavouring chemicals and trace contaminants (heavy metals, PAHs, acids, esters).
Flavour chemicals: hundreds identified; many are known irritants, sensitizers, respiratory immune modulators, hepatotoxicants or otherwise harmful when heated and inhaled (examples: cinnamaldehyde, menthol, eugenol, benzaldehyde).
Thermal reactions: heating PG/VG and flavour compounds at high coil temperatures can generate additional irritants, corrosives and potentially carcinogenic byproducts.
Unknowns: many inhalation effects of flavourants and heated byproducts remain uncharacterised; toxicity depends on dose and usage patterns.
