Nicotine

Nicotine is a stimulant belonging to a ganglionic (nicotinic) cholinergic-receptor agonist.

Nicotine is used in the treatment of Smoking cessation.

Nicotine is readily absorbed through mucous membranes and the skin. It is Widely distributed into most body tissues and fluids, Crosses the blood-brain barrier and placenta; enters breast milk. The Volume of distribution is approx 2-3 L/kg with plasma protein binding: 5-20%. It is metabolized mainly in the liver via CYP2A6 isoenzyme into cotinine and nicotine-N-oxide and undergoes extensive first-pass metabolism. It is excreted Via urine (approx 10-20% as unchanged drug) with elimination half-life: 1-2 hr (intranasal and oral inhalation); approx 4 hr (TTS).

Nicotine shows common side effects like Headache, dizziness, Diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Nicotine is available in Gum, Inhalers, Transdermal kits, Lozenges, and Transdermal Patch, Nasal Solutions.

Nicotine is available in India, Germany, Canada, France, USA

Nicotine, a naturally occurring alkaloid, binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of CNS effects are believed to be the basis of Nicotine's positively reinforcing properties; a stimulating effect is exerted mainly in the cortex via the locus ceruleus, and a reward effect is exerted in the limbic system. At low doses, the stimulant effects predominate, while at high doses, the reward effects predominate.

Nicotine is available in the form of Gum, inhalers, Transdermal kits, Lozenges and Transdermal Patch, and Nasal Solutions.

Gum: Chew slowly until it tingles, then place Gum between cheek and Gum until the tingle is gone; repeat the process until most of the tingle is gone (~30 minutes). Do not eat or drink 15 minutes before using or while the Gum is in your mouth.

Lozenge: Do not chew or swallow; allow to dissolve slowly between cheek and Gum (~20 to 30 minutes); minimize swallowing and occasionally move the lozenge from one side of the mouth to the other until completely dissolved. Do not eat or drink 15 minutes before using or while the lozenge is in your mouth.

Nasal spray: Prime pump prior to first use (pump 6 to 8 times until fine spray appears) or if it has not been used for 24 hours (pump 1 to 2 times); avoid excessive priming. Blow your nose prior to use. Tilt the head back slightly and insert the tip of the bottle into the nostril. Breathe through the mouth and spray once in each nostril. Do not sniff, swallow, or inhale through the nose During administration. After administration, wait 2 to 3 minutes before blowing nose. Avoid contact with skin, eyes, and mouth (nicotine overdose can occur when Nicotine is absorbed through the skin).

Oral Inhalation: Insert cartridge into inhaler and push hard until it pops into place. Replace the mouthpiece and twist the top and bottom so that markings do not line up. Do not inhale into the lungs like a cigarette. Inhale deeply into the back of the throat or puff in short breaths. Nicotine in the cartridge is used up after about 20 minutes of active puffing. Clean mouthpiece regularly with soap and water.

Transdermal patch: Apply new patch to non-hairy, clean, dry skin on the upper body or upper outer arm; each patch should be applied to a different site. Apply immediately after removing the backing from patch; press onto skin for ~10 seconds. Patch may be worn for 16 or 24 hours. If cigarette cravings occur upon awakening, wear for 24 hours; if vivid dreams or other sleep disturbances occur, remove the patch at bedtime and apply a new patch in the morning. Do not cut the patch; it causes rapid evaporation, rendering the patch useless. Do not wear more than 1 patch at a time; do not leave the patch on for more than 24 hours (may irritate skin). Wash hands after applying or removing the patch. Discard patches by folding adhesive ends together, replace in pouch and dispose of properly in trash.

Nicotine is used in the treatment as Smoking cessation

Nicotine, a pyridine alkaloid, is a stereo-selective nicotinic-cholinergic receptor agonist. Low doses cause an initial stimulation of autonomic ganglia, adrenal medulla, neuromuscular junction, and brain. High doses produce initial ganglionic stimulation followed by inhibition of neurotransmission leading to subsequent persistent depression of receptor activity.

Nicotine is approved for use in the following clinical indications

Smoking cessation: Treatment to aid smoking cessation for the relief of nicotine withdrawal symptoms (including nicotine craving)

Nicotine is available in various strengths as 2 mg, 10 mg [contains menthol], 7 mg/24 hr (14s) & 14 mg/24 hr (14s) & 21 mg/24 hr (28s)

Nicotine is available in the form of Gum , Inhaler, Transdermal Kit, Lozenges and Transdermal Patch, Nasal Solution.

• Dosage Adjustment for Pediatric Patients:

Safety and efficacy for Pediatric Patient has not yet established.

Nicotine is contraindicated in patients with

• Recent cerebrovascular accident. Self-medication in patients who will continue to smoke, chew tobacco, or use snuff or other nicotine-containing preparations. Non-smokers and occasional smokers.

Disease-related concerns:

• Cardiovascular disease: Nicotine can increase heart rate and blood pressure. The risk versus the benefits should be weighed in patients with cardiovascular or peripheral vascular diseases, specifically patients with a history of myocardial infarction and/or angina pectoris, serious cardiac arrhythmias, or vasospastic diseases (Buerger disease, Prinzmetal variant angina, Raynaud phenomena); use caution in patients with angina, hypertension, or recent MI. Discontinue use if irregular heartbeat or palpitations occur. Use caution in patients with accelerated hypertension due to the risk of malignant hypertension. Generally, avoid use during the immediate post-myocardial infarction period, in patients with serious arrhythmias, or with severe or worsening angina.

• Gastrointestinal disease: Use with caution in patients with esophagitis or active gastric or peptic ulcer disease; healing may be delayed.

• Hepatic impairment: Nicotine clearance is decreased in patients with moderate to severe hepatic impairment; use with caution. Monitor for adverse effects; consider dose reduction.

• Renal impairment: Nicotine clearance is decreased in patients with moderate to severe renal impairment; use with caution. Monitor for adverse effects; consider dose reduction.

Nicotine may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Nicotine is present in breast milk.

Concentrations of Nicotine in breast milk increase with supplementation. When used as a dietary supplement, the recommended dietary allowance of Nicotine is increased in breastfeeding patients compared to non-breastfeeding patients. Doses of Nicotine for the treatment of dyslipidemias are greater than those used as a dietary supplement. Due to the potential for serious adverse reactions in the breastfed infant (including hepatoxicity), the manufacturer recommends that breastfeeding be discontinued when Nicotine is used for treatment of dyslipidemias

Pregnancy Category C

When used as a dietary supplement, the recommended dietary allowance of Nicotine is increased during pregnancy compared to non-pregnant patients.

It is not known if Nicotine at lipid-lowering doses is harmful to the developing fetus. If a patient becomes pregnant while receiving Nicotine for primary hypercholesterolemia, Nicotine should be discontinued. If a patient becomes pregnant while receiving Nicotine for hypertriglyceridemia, the benefits and risks of continuing Nicotine should be assessed on an individual basis.

Should be taken with meal; low-fat meal if treating dyslipidemia. Avoid alcohol, hot or spicy foods/liquids around the time of Nicotine dose.

• Common Adverse effects

Constipation, faecal impaction, aggravation of haemorrhoids, abdominal discomfort or pain, heartburn, flatulence, nausea, vomiting, diarrhoea

• Less Common Adverse effects:

Increased bleeding tendency (chronic use), steatorrhoea (high doses), skin rashes, pruritus of the tongue, skin and perianal region; hyperchloraemic acidosis

• Rare Adverse effects

Hypophosphataemia, reduced platelet counts, prolonged prothrombin time, arrhythmias, hypersensitivity reactions including angioedema; insomnia, myalgia and hypotension.

• Increased risk of myopathy and rhabdomyolysis w/ concomitant HMG-CoA reductase inhibitors.
• Reduced bioavailability w/ colestyramine or colestipol. Decreased metabolic clearance w/ aspirin.
• May potentiate effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension.

The common side effects of Nicotine include the following

Common

● Constipation, Diarrhea, Heartburn, pain in the back, arm, or legs, Headache, joint pain.

Symptoms: Burning of the mouth and throat, nausea, vomiting, salivation, abdominal pain, diarrhea, sweating, Headache, dizziness, hearing and visual disturbances, weakness, confusion, syncope, prostration, dyspnea, tachycardia, hypotension, rapid or weak or irregular pulse, seizure, resp failure, circulatory collapse, coma.

Pharmacodynamic

Nicotine is a derivative of vitamin B3 and is incorporated into coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in multiple cellular metabolic pathways. Nicotine also reduces total serum cholesterol, LDL, VLDL, apolipoprotein B, and triglycerides, and increases HDL cholesterol.

Pharmacokinetics

• Absorption: Readily absorbed through mucous membranes and the skin. Time to peak plasma concentration: 4-15 min (intranasal); 15-30 min (oral inhalation); 25-30 min (Gum); 2-10 hr (TTS).
• Distribution: Widely distributed into most body tissues and fluids. Crosses blood-brain barrier and placenta; enters breast milk. Volume of distribution: Approx 2-3 L/kg. Plasma protein binding: 5-20%.
• Metabolism: Metabolised mainly in the liver via CYP2A6 isoenzyme into cotinine and nicotine-N-oxide. Undergoes extensive first-pass metabolism.
• Excretion: Via urine (approx 10-20% as unchanged drug). Elimination half-life: 1-2 hr (intranasal and oral inhalation); approx 4 hr (TTS).

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Nicotine -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Nicotine
5. https://europepmc.org/article/med/6988203