NICORETTE QUICKMIST

Indications

• Nicotine dependence
• Smoking cessation support
• Nicotine replacement therapy

Dosage

Children: For children

Adults: Nicotine replacement therapy dosage varies; refer to specific product guidelines for dosing. For bupropion (used in smoking cessation), the usual adult dose is initially 150 mg daily for 6 days, followed by 150 mg daily, with a maximum of 300 mg per day.

Mechanism of action

Nicotine acts as an agonist at nicotinic acetylcholine receptors, which are ionotropic receptors that mediate the release of various neurotransmitters. It binds to these receptors on dopaminergic neurons in the cortico-limbic pathways, leading to depolarization and increased calcium influx. This triggers the release of dopamine in the synapse, which underlies the euphoric and addictive properties of nicotine. Additionally, nicotine stimulates the adrenal medulla, causing the release of epinephrine, which contributes to increased heart rate and blood pressure.

Pharmacodynamics

As a nicotinic cholinergic receptor agonist, nicotine exerts both stimulant and rewarding effects. Its action at the locus ceruleus leads to increased arousal, while its effect within the limbic system is associated with reward and addiction. It also induces peripheral vasoconstriction, tachycardia, and elevated blood pressure, making it a complex pharmacological agent with various physiological effects.

Pharmacokinetics

Nicotine is rapidly absorbed through the lungs, mucous membranes, and skin, with peak plasma concentrations occurring within minutes of smoking. It has a half-life of approximately 2 hours, with a volume of distribution of about 2-3 L/kg. Nicotine is primarily metabolized in the liver by cytochrome P450 enzymes, with its metabolites excreted renally. The pharmacokinetics can be affected by factors such as hepatic impairment and concomitant drug use.

Contra-indications

• Severe cirrhosis
• Hypersensitivity to nicotine or any component of the formulation

Adverse effects

• Abdominal pain
• Anxiety
• Constipation
• Dizziness
• Dry mouth
• Fever
• Gastrointestinal disorder
• Headache
• Hyperhidrosis
• Hypersensitivity reactions
• Insomnia
• Nausea
• Skin reactions
• Taste altered
• Tremor
• Vomiting
• Appetite decreased
• Asthenia
• Chest pain
• Confusion
• Tachycardia
• Tinnitus
• Vasodilation
• Visual disturbances
• Angioedema
• Arthralgia
• Bronchospasm
• Delusions
• Depersonalization
• Dyspnoea
• Hallucinations
• Hepatic disorders
• Irritability
• Memory loss
• Movement disorders
• Muscle complaints
• Palpitations
• Paraesthesias
• Parkinsonism
• Postural hypotension
• Seizures
• Sleep disorders
• Suicidal behaviors

Interactions

• Caution with other serotonergic drugs due to risk of serotonin syndrome
• Increased metabolism of some drugs by inducing hepatic enzymes when combined with polycyclic aromatic hydrocarbons in tobacco smoke

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for adverse effects, particularly in patients with a history of seizures
• Patients should be counseled on the effects of nicotine on driving and skilled tasks due to increased risk of dizziness

Pregnancy

Avoid-no information available on safety during pregnancy.

Breast-feeding

Present in milk-avoid use while breastfeeding.

Storage

Store at room temperature, protected from light and moisture.

Formulations

• Nicotine patches
• Nicotine gum
• Nicotine lozenges
• Nicotine nasal spray
• Nicotine inhalers

Mechanism of action

Nicotine is a stimulant drug that acts as an agonist at nicotinic acetylcholine receptors. These are ionotropic receptors composed up of five homomeric or heteromeric subunits. In the brain, nicotine binds to nicotinic acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways. This causes the channel to open and allow conductance of multiple cations including sodium, calcium, and potassium. This leads to depolarization, which activates voltage-gated calcium channels and allows more calcium to enter the axon terminal. Calcium stimulates vesicle trafficking towards the plasma membrane and the release of dopamine into the synapse. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine. Nicotine also binds to nicotinic acetylcholine receptors on the chromaffin cells in the adrenal medulla. Binding opens the ion channel allowing influx of sodium, causing depolarization of the cell, which activates voltage-gated calcium channels. Calcium triggers the release of epinephrine from intracellular vesicles into the bloodstream, which causes vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar. Nicotine is a ganglionic (nicotinic) cholinergic-receptor agonist. The pharmacologic actions of nicotine are complex and include a variety of effects mediated by stereospecific binding to receptors in autonomic ganglia, the adrenal medulla, the neuromuscular junction, and the brain. The principal pharmacologic effect of small doses of nicotine is initial, transient stimulation of autonomic ganglia; large doses or prolonged neuronal receptor exposure to nicotine results in subsequent persistent depression of receptor activity. Although nicotine has similar dose-related effects at the myoneural (neuromuscular) junction, rapidly developing skeletal muscle paralysis obscures the stimulant phase. The muscle-relaxant properties of nicotine may be mediated through stimulation of Renshaw cells and pulmonary afferent nerves, which results in inhibition of skeletal muscle motor activity; such relaxant effects may contribute to the behavior-reinforcing effects of the drug. Small doses of nicotine directly stimulate sympathetic ganglia and facilitate neurotransmission; however, large doses produce initial ganglionic stimulation, which is quickly followed by inhibition of neurotransmission.

Pharmacodynamics

Nicotine, the primary alkaloid in tobacco products binds stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at the locus ceruleus and a reward effect in the limbic system. Itranvenous administration of nicotine causes release of acetylcholine, norepinephrine, dopamine, serotonine, vasopressin, beta-endorphin and ACTH. Nicotine is a highly addictive substance. Nicotine also induces peripheral vasoconstriction, tachycardia and elevated blood pressure. Nicotine inhalers and patches are used to treat smoking withdrawl syndrome. Nicotine is classified as a stimulant of autonomic ganglia.