Research Paper on the Drug Varenicline

Background/History

Varenicline, also known as Chantix, is a drug prescribed by doctors for nicotine addiction. The drug is a partial agonist which blocks nicotine receptors reducing its impact on the body. As a result it reduces cravings and takes the pleasure out of smoking. The person taking the drug will eventually put down cigarettes as their need for nicotine begins to reduce. The drug is taken orally and can be prescribed in 0.5mg, 1mg, and 0.5-1mg (Eisenberg et al., 2015). Chantix is designed to bind nicotine receptors in the brain (Eisenberg et al., 2015). The drug is designed to take over a 12 week period. The user of the prescription drug continues to smoke while taking the drug (Eisenberg et al., 2015). An additional 12 weeks is recommended to support continued cessation. For people who have success with a drug, there will be a gradual reduction in tobacco use until the desire for tobacco is gone. 

Varenicline was first introduced to the market in 2006 but approved by the FDA in 2005. The drug was marketed globally. The drug Varenicline is a nicotinic receptor partial agonist. It is from the drug class of antismoking products. Nicotine receptor agonist were identified based on activity and structure of the natural compound cytosine (Eisenberg et al., 2015). The new drug formula was used to promote quitting of tobacco use and was marketed as a tool to help smokers cease their tobacco use. Studies showed people who take Chantix should be closely monitored in the event it creates emerging mental health issues. The drug also has other known side effects. 

Despite its popularity, in 2007 the drug captured the attention of the media when a number of suicidality-related adverse events occurred in Europe and were associated to Chantix (Eisenberg et al., 2015). As a result of psychotic mental events from taking Varenicline, the FDA conducted an in-depth study into the drug. The study found the drug caused significance changes in mood and negatively impacted cognitive functioning for some takers of the drug. As a result, the FDA required changes to the labelling of the drug and a warning of its side effects.

Chemistry

The chemical names of Varenicline (INN); 6,10-Methano-6H-pyrazino[2,3-h][3]benzazepine,7,8,9,10-tetrahydr (NIH, 2016). Chemical properties of Varenicline includes a molecular weight of 211.268 g/mol and a molecular formula of C13H13N3 (NIH, 2016). The exact mass is 211.111 g/mol with the same monoisotopic mass (NIH, 2016). The heavy atom count is 16 and the compound is canonicalized (NIH, 2016). The hydrogen bond donor count is one and the hydrogen bond acceptor count is three. The undefined atom stereocenter count is two while the covalently-bonded unit count is one. 

The drug Varenicline is soluble in water, 5.15X10+4 mg/L at 25 deg C (est) and has a vapor pressure of 4.65X10-6 mm Hg at 25 deg C (NIH, 2016). The log Kow is 1.03 and the drug is stable under right conditions. Decomposition of the drug Chantix is hazardous. Varenicline is hazardous when burned, resulting in toxins in the air. Fire releases Carbon oxides, nitrogen oxides (NOx) (NIH, 2016). The Dissociation Constants of the drug is pKa1 = 1.82 (amine); pKa2 = 9.73 (secondary amine) (NIH, 2016). 

Pharmacology

Nicotine is smoked in order “to satisfy a brain dopamine pathway "wanting" disorder or nicotine dependency” (Benowitz, 2010). When a person is addicted to nicotine, the substance activates pleasure centers in the brain. The brain is made up of neurotransmitters which fit into a specific receptor. Once the neurotransmitter reaches its receptor, it activates the nerve cell in the receptor. Acetylcholine is a neurotransmitter with receptors involved with nicotine addiction. This receptor is involved in many important functions of the body, but it also play a role in receptors involved with mood, pleasure, etc. 

Once nicotine enters the persons system it flows to the brain. Upon entering the brain, the nicotine will attach to the acetylcholine receptor (Benowitz, 2010). The nicotine will mimic the actions of the receptor. Nicotine then activates pleasure centers in the brain. This creates pleasure and alert rewards systems. People continue to smoke as a result of the pleasure it brings to the brain. To activate the feeling of pleasure and reward, nicotine raises the levels of dopamine in the brain (Benowitz, 2010). Dopamine is a neurotransmitter. Dopamine has been linked to addiction in the brain. Decreasing levels of dopamine can reduce feelings of pleasure. 

Varenicline is a nicotinic agonists. It binds to nicotinic cholinergic receptors in the peripheral and central nervous system (NIH, 2016). The chemical polarizing agent in the drug acts as blocking agents. When the drug is taken it is used y to block nicotinic transmission to their Acetylcholine neurotransmitter. Varenicline is designed to binds with high affinity and selectivity to the acetylcholine receptor. The activity to identify the right receptor consists α4β2 sub-type of the nicotinic receptor (NIH, 2016). Research shows the drug binds to the α4β2 sub-type which is the nicotine receptor. When it binds to the nicotine receptor, it stimulates receptor-mediated but not to the same degree as the actual nicotine. 

Varenicline blocks the drugs ability to alert pleasure centers and the level of reward ((NIH, 2016). Overtime, taking the prescribed drug results in nicotine failing to effect the dopamine systems in the brain (NIH, 2016). If the person does not feel pleasure from smoking nicotine, they will begin to slowly drop their addition to the substance. Once the drug is first taken, it begins to work after about three to four hours. For consistent results, the drug will need to be taken for four to five days. After this time frame, the user should be experiencing a reduction in their desire for nicotine. The drug is taken orally with dosages differing for adults. 

Chantix is only recommended for adults not adolescents under the age of 18. In some rare cases, the drug is prescribed to adolescents who weigh over one hundred pounds (NIH, 2016). Steady-state systemic exposure is essential to the proper working of the drug (NIH, 2016). When Chantix enters the body it does not only send the necessary receptor block to the brain, the drug also processes through the organs in the body. The drug enters the livers and kidneys and is secreted out of the body though urine. 

Side Effects/Adverse Effects/Toxicology

The drug Varenicline is also known as Chantix. The drug has many benefits to the user. Its blocks nicotine receptors and helps the person overcome their addiction to nicotine. This can save their lives and prevent all types of adverse health impacts. Despite the benefits, Chantix has some serious side effects. Research conducted by the FDA (2011) identified a potential risk for liver damage. The risk is small but the damage can be irreparable. The greater risk is to the person’s mental health and for potential renal failure. The toxicity of the drug can damage the kidneys resulting the failure of the organ. 

Research indicates people with normal renal function can experience impairments after taking Varenicline. For many subjects in the study with normal renal function (Bird & Vesta, 2008). There was little impairment but for people with renal function problems, the damage from taking the drug was far more extensive and in some case severe (Bird & Vesta, 2008). In one case a 52 year old man had moderate renal failure (Bird & Vesta, 2008). After one week of taking Chantix, the patient was rushed to the hospital with full renal failure (Bird & Vesta, 2008). 

Adverse effects of Chantix are generally mild or not existent in over 40% of people who take the drug (Bird & Vesta, 2008). For others the side effects are more extreme. For some users of Chantix, they will experience mild feelings of depression while for others it can have a more drastic impact on mental health. Taking of the drug can result in changes in mood and physical behavior. People taking the drug experienced depression from mild to extreme. The extreme case involved suicidal ideation and actual cases of suicide (Moore et al., 2011). As a result, the FD required the pharmaceutical company’s marketing the drug to place a black box label on the boxes to warn consumers of its potential negative impact to mental health. 

In some case, the drug has been connected to acts of violence and severe mood swings (Moore et al., 2011). Some people taking the drug react violently. In a study involving 13,243 cases of adverse events, 25% of cases resulted in depression and less than two percent resulted in violence (Moore et al., 2011). In 15% of cases, suicidal thoughts will appear and in 6.5% harmful behaviors occurred (Moore et al., 2011). The research showed 8% of people who took the drug experienced headaches. The headaches could be the result of the drug or a result of the withdrawals from nicotine. Some users of Chantix have reported pain. 

Taking Varenicline is also known to cause mild gastro-intestinal effects and has been known to cause seizures. Drinking alcohol with Chantix can be dangerous and increase the side effects. Some people reported feeling drunk even though they had not drank any alcohol. Varenicline can also cause side effects, such as nausea, stomach pain, indigestion, constipation, dry mouth, and trouble sleeping (Moore et al., 2011). The drug is not addictive but for some it can be dangerous to their health. Chantix can cause pain in the legs and burning in the toes. The effects of Chantix on the fetus is not known so it is not recommended to prescribe the drug to pregnant women.

Therapeutic Applications

Varenicline, better known as Chantix, is a prescription tools used to aid smokers in quitting as well as to assist in reducing the levels of addiction. Within the first week of taking the drug, the smoker will begin to feel a reduce desire for nicotine. Despite the potential side effects, Varenicline can be beneficial to stopping smoking. Duration for taking the drug is 12 weeks, but to support the persons desire not to smoke, the drug can be taken for an additional 12 weeks. The drug will enter the brain in just a few hours but the cessation of smoking occurs in a week. By week two most people who have not experienced severe side effects, will have totally quit smoking. Despite the success of the drug, smokers also need psychological and social support in quitting smoking. 

Chantix has the potential of causing depression and the acts of smoking has psychological undertones. It is recommended to pair Chantix with therapy to assist the person in changing their thoughts and behaviors involved with quitting smoking. Smoking can be more than an addiction. For people just quitting using Chantix, there is a high risk they will return to smoking. Pairing Chantix with therapy will provide better results for long-term smoking cessation. When a person experiences adverse side effects, they should stop taking the drug. Therapy can assist them in quitting smoking. In fact, research has shown taking Chantix alone does not guarantee long-term smoking cessation (FDA, 2011). The research showed quitting cold turkey shows the greatest signs of success. To improve the outcome of taking Chantix, the smoker should also seek out psychological support. 

References

Benowitz, N. (2010). Nicotine Addiction. New England Journal of Medicine, 362(24), 2295–2303.

Bird, M. & Vesta, K. (2008). Varenicline-associated acute renal failure. Annuals of Pharmacology, 42(12), 1908-11

Eisenberg, M. et al. (2015). Varenicline for Smoking Cessation in Hospitalized Patients with Acute Coronary Syndrome. Circulation, 135(13), 

Food and Drug Administration. (2011). FDA Drug Safety Communication: FDA updates label for stop smoking drug Chantix (varenicline) to include potential alcohol interaction, rare risk of seizures, and studies of side effects on mood, behavior, or thinking. Retrieved March 28, 2017 from https://www.fda.gov/Drugs/DrugSafety/ucm436494.htm

Moore, T. et al. (2011). Suicidal Behavior and Depression in Smoking Cessation Treatments. PLoS One, 16(11)

National Institute of Health. (2016). Varenicline. Retrieved March 28, 2017 from https://pubchem.ncbi.nlm.nih.gov/compound/170361#section=Top