1. Nicotine, as a Drug Presented by Ishrat Naher Erina, ID: 12346008 Tania Akter Tamanna : 12346010 Shimu Akter:12346007 Sajia Afrin:12346005 Mehmuna Morshed:12346006 Kasfia Tasnim Humaira, ID:12146041 Azamu Shahiullah Prottoy, ID:

2. Introduction to Nicotine Component of Cigarette smoke Poison De-polarisation, Stimulation, paralysis Stimulatory Effects Overall effects Effect of higher dose

3. Therapeutic indication of Nicotine Nicotine has therapeutic potential for a list of common ills. The list includes Alzheimer disease Parkinson disease depression and anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD) pain and obesity.

4. People with depressive-spectrum disorders, schizophrenia, and adult ADHD tend to smoke heavily, which suggested to researchers that nicotine may soothe their symptoms. Common to all these disorders is a failure of attention, an inability to concentrate on particular stimuli.nicotine activates specific brain areas during tasks that demand attention. This may be because of its effects, shared with many other addictive drugs, on the release of the neurotransmitter dopamine. nicotine improves cognitive and motor functioning in people with Alzheimer disease and Parkinson disease. Nicotine itself has provided modest pain relief in animal studies. nicotine is also being investigated as an analgesic in humans. Nicotine may be the most effective drug around for weight control.

5. Pharmacological action of nicotin Within the body, nicotine is quickly distributed to all the organs and crosses into the brain via the blood-brain barrier. Nicotine can reach the brain in as little as 7 seconds after being inhaled. In the body, the half life or nicotine is around 2 hours. Half-life refers to the time taken for a drug to reduce to half its original concentration in the blood. In the body, nicotine is metabolized in the liver by an enzyme system called the cytochrome P450 system, in particular which converts the nicotine to cotinine. Other metabolites of nicotine include N-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide. Once within the blood stream, nicotine travels to the brain where it binds to and activates receptors called cholinergic receptors. These receptors are abundant in the brain as well as in other areas of the body such as the muscles, heart, adrenal glands and other vital organs.

6. Normally, these receptors are activated by the neurotransmitter acetylcholine which is produced at nerve endings in the brain and in the nerves of the peripheral nervous system. Acetylcholine stimulation of the receptors is involved in maintaining healthy respiration, heart function and muscle movement as well as cognitive functions such as memory. Since nicotine has a similar structure to acetylcholine, it can activate the cholinergic receptors. However unlike acetylcholine, nicotine disrupts normal brain function, causing chemical changes and addiction.

7. SAR Combination of structural elements of ACh and nicotine as well as reducing the conformational flexibility by using a cyclopropane ring has led to the discovery of potent and selective nAChR ligands. The modulation of three structural elements, the linker, substitution on the amino group and the pyridine ring can be used to determine the influence on potency and selectivity of the ligands. Factors that decrease the binding are steric hindrance on the amino group and linkers that are saturated/unsaturated carbon chains. Short-chained ether linkers are preferred. Beneficial effects on the binding is seen with substitution on the pyridine ring both mono- and disubstitution with halogens among other groups. Substitution on the amino group with three different amides increased the binding affinity where methylamide had the highest binding. Lower binding in the other substituted amides was explained by steric hindrance or lack of a methyl group resulting in loss of hydrophobic interaction. Stereochemistry of pyridine nitrogen and/or the pyridine ring and its stereoelectronic effects has a subtle beneficial effect on the binding to the α 4 β 2 nAChR. Thus it was shown that a pyridyl ether ligand with bromo substitution on the pyridine and metylatedamide on the amino group had the highest potency.

8. Bioavailability Intrabuccal administration: chewing gum or sucking a lozenge. Readily absorbed Gum: Averages 53–55% with peak concentrations achieved within 25–30 minutes Lozenge: Approximately 25–27% intranasal admnistration absorbed minimally from the GI tract. Approximately 53%, with peak concentrations achieved within 4–15 minutes. Oral inhalation: Approximately 60%, mostly absorbed in the mouth, with peak concentrations achieved within 15–30 minutes. Transdermal administration: topical application. Approximately 68–98%, with peak concentrations achieved within 2–10 hours.

9. Plasma concentrations Gum: Relatively constant blood nicotine concentrations attained following repeated administration are similar to those produced by smoking cigarettes. Transdermal : Plasma nicotine concentrations generally lower and fluctuate less than those produced by smoking cigarettes. Intranasal : Plasma nicotine concentrations similar to those produced by smoking cigarette. Oral inhalation: Lower plasma nicotine concentrations compared with nasal spray.

10. Adverse Effects of Nicotine CNS: Irritability and Tremor Gastrointestinal Effects :Intestinal cramps and diarrhea Cardiovascular Effects: Increased heart rate and blood pressure Curcinogenesis Fetal development disorders

11. Interaction of Nicotine Nicoderm CQ (Comitted Quitter) Interaction 1. Interaction With Drugs (66 brand drugs) Moderate – Aspirin, Acetaminophen. Minor - Phenobarbital, Cafatine. 2. Interaction With Food or Alcohol

12. Interaction of Nicotine Nicorette Gum and Lozenges Nicotrol inhaler (Nicotine and menthol)

13. Withdrawal Syndrome Irritability Anxiety Restlessness Difficulty concentrating Headaches Loss of appetite Insomnia

14. Pharmacologic and Behavioral therapy Nicotine chewing gum. Transdermal Patch. Inhaler. Nasal Spray. Lozenges.

16. Reference. sLippincott’s illustrated reviews. south Asian editioneries Editor : Richard A.Harvey, Pamela C.Champe. sLippincott’s Modern Pharmacology, 8 th Edition, Richar, E. Herpay, Parmela C, Champe.