Question

Variants of a gene called CYP2A6 are associated with the speed at which a person metabolizes nicotine. A "fast-metabolizer" smokes more cigarettes than a "slow-metabolizer". Design a clinical trial using this information to test whether the CYP2A6 genotype can be used to predict which individuals will respond to specific smoking cessation medications.

Answer 1

This gene, CYP2A6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids

These genes and enzymes help determine our individual rate of metabolism, which varies from person to person. Depending on your genetic profile, you may process some medications too quickly, or others, too slowly, which can both cause complications.

The Four Metabolizer Types

1. Poor metabolizer: Patients who are poor metabolizers experience a very slow breakdown of medications, making side effects more pronounced. That means standard doses of certain medications may not work as intended.
2. Intermediate metabolizer: A slowed metabolism may impact breakdown of medications, causing effects similar to poor metabolizers, but not as pronounced.
3. Extensive metabolizer: Considered a “normal” rate of metabolism. Patients are likely to metabolize medication normally and medication is likely to work as intended.
4. Ultrarapid metabolizer: Patients in this group metabolize medications too quickly to experience relief from symptoms of depression or other disorders.
5. `AS WE ALREADY KNOW THAT CYP2A6 is a member of the cytochrome P450 superfamily and is expressed predominantly in hepatic cells, with some expression in specialized extrahepatic cell types. Compared with CYP2D6 and CYP3A4, relatively few clinically used drugs are metabolized to a significant point by CYP2A6.

6. Genes Impact Metabolism

   Our unique genetic profile contains six enzymes that metabolize 90 percent of all medications patients are given.

   These genes and enzymes help determine our individual rate of metabolism, which varies from person to person. Depending on your genetic profile, you may process some medications too quickly, or others, too slowly, which can both cause complications

7. CYP2A6 polymorphisms, rather than age, are thought to play the most important role in determining individual clearance of cotinine (the primary metabolite of nicotine), as children with reduced function alleles had longer cotinine half-lives than those with wild-type CYP2A6
8. APART FROM THAT Cigarette smoking persists in part because long-term smoking cessation rates are modest on existing treatments. Smoking cessation outcomes are influenced by genetic factors, including genetic variation in enzymes that metabolize nicotine and smoking cessation medications, as well as in receptor targets for nicotine and treatment medications
9. smoking cessation medications.in which nicotine replacement therapy (NRT), bupropion, and varenicline, which bind selected subtypes of nicotinic acetylcholine receptors (nAChRs) to exert their varying effects [1–3]. Bupropion can additionally bind to the dopamine transporter which is thought to also contribute to its pharmacological action [4]. A large proportion of the ability to quit smoking is heritable

10. Nicotine’s metabolic ways

    Nicotine is the major psychoactive compound in cigarette smokeThe rate at which nicotine is metabolically inactivated, or cleared, from the body has important implications for nicotine dependence and the ability to quit smoking. Up to 80% of a nicotine dose is metabolically inactivated to cotinine,undergoes further metabolism

11. CYP2B6 slow metabolizers (516 G>T). In this study, NVP coadministration did not show decreased lumefantrine levels, which may reflect its milder effect on CYP3A4 induction.

12. AND the reason for smokers with genetically slow nicotine metabolism have higher cessation success on behavioural counseling and nicotine patch compared to smokers with genetically fast nicotine metabolism. AND WE ALL ARE FAMILIER WITH THIS FACT i.e jus tBecause nicotine it is addictive, it is normal to have withdrawal symptoms when you quit. The good news is these symptoms are temporary and there are safe medication Nicotine Replacement Therapy (NRTs). NRT replaces the nicotine you were getting from tobacco with a pure form of medical nicotine that is much safer than tobacco product

13. Medications that contain nicotine enable health care providers to increase markedly the ability of their patients to achieve and sustain tobacco abstinence.