Class 11/10/2010

StudyBlue printing of Class 11/10/2010 html, body, div, span, applet, object, iframe, h1, h2, h3, h4, h5, h6, p, blockquote, pre, a, abbr, acronym, address, big, cite, code, del, dfn, em, font, img, ins, kbd, q, s, samp, small, strike, strong, sub, sup, tt, var, b, u, i, center, fieldset, form, label, legend, table, caption, tbody, tfoot, thead, tr, th, td { margin: 0; padding: 0; border: 0; outline: 0; font-size: 100%; background: transparent; } body { line-height: 1; } blockquote, q { quotes: none; } blockquote:before, blockquote:after, q:before, q:after { content: ''; content: none; } /* remember to define focus styles! */ :focus { outline: 0; } /* remember to highlight inserts somehow! */ ins { text-decoration: none; } del { text-decoration: line-through; } /* tables still need 'cellspacing="0"' in the markup */ table { border-collapse: collapse; border-spacing: 0; } /* end RESET */ .header { min-width:800px; } .logo { padding:6px 20px 2px 20px; margin:0; font-size:25px; font-weight:bold; color:#808285; position:relative; border-bottom: 1px solid #c5c5c5; } .logo-blue { color:#70adc4; } .logo-desc { font-weight:normal; font-size:19px; color:#cccccc; margin-top:50px; position:absolute; display: none; } .back-button { position:absolute; top:20px; right:20px; font-size:13px; line-height:25px; color:rgb(0,175,225); font-weight:normal; } .back-button a { color:rgb(0,175,225); } .instructions { padding:0; margin:0; width:100%; position:relative; color:rgb(100,100,100); } .step-holder { border-left:1px solid #ededed; margin-left:20px; } .steps { padding:15px 0; float:left; width:24%; border-right:1px solid #ededed; text-align:center; } .steps-01 { } .steps-02 { } .steps-03 { } .steps-04 { } .label { padding:5px 10px; } .print-button { } .print-button a { background-color:rgb(0,175,225); color:white; line-height: 19px; padding:9px 8px 5px 30px; font-size:14px; text-decoration:none; background-image: url(images/printer.png); background-repeat: no-repeat; background-position: 7px 50%; -moz-border-radius: 5px; -webkit-border-radius: 5px; } .print-button a:hover { background-color:black; } .theNote .content { width: 8.0in !important; margin: 5px auto; padding:20px; background-color:white; } .theNote .header { border-bottom: 1px dashed #C8C8C8; font-size: 17px; padding: 0 0 10px; line-height: 19px; color: #00ADE1; min-width:500px; } .theNote .body { font-size: 14px; line-height: 19px; padding: 10px 0; } .theNote{ padding:6px 0; clear:both; background-color: rgb(200,200,200); } .theNote h3{ color: rgb(100,100,100); } .theNote h1, .theNote h3{ background-color:white; padding:2px 20px; width:8.0in !important; margin: 0 auto; font-size: 15px; } .theNote h1{ padding-top: 10px; font-size: 15px; } .theNote h1:first-child{ font-size: 20px; } .theNote h3 { font-size: 14px; font-weight: normal; } #options { border: 3px double #ccc; padding: 5px 12px; margin: 10px 50px 10px 20px; float: left; } #info { border-top: 1px solid #ccc; padding-top: 5px; font-style: italic; } li { margin: 5px 10px 5px 25px; } ul li { list-style: disc; } ol li { list-style: decimal; } img { border: 0; } table { clear: both; width: 100%; border: 1px solid #c5c5c5; border-width: 1px 0; margin: 0; page-break-after: always; } table#page { page-break-after: auto; } td { text-align: center; font-size: 12px; border-bottom: 1px dashed #c5c5c5; height: 1.75in; width: 50%; padding-left: 15px; } .leftside { border-right: 1px solid #cccccc; padding: 0 15px 0 0; } .bottom td { border-bottom: none; } .clearfix { clear:both; line-height:1px; height:1px; } img { max-width:80%; max-height:150px; margin:20px; } @media print {.header { display: none; } .content .header{ display:inherit; } table { border: 1px dashed #bbb; border-width: 1px 0; } .theNote{ background-color:white; } } Nicotine History Brought here by Columbus, brought to Spain by Ovieda (named Tobacco and brought "wrong" small leaf seeds) Name nicotine for Jean Nicot de Villemain who was a proponent of smoking 1600's spread use of Tobacco with large leaf variety from South America in 1800s one worker could make 3000 cigarettes in a day, invention of the cigarette machine allowed for 120000 made per day...now significantly increased Pharmacology Nicotine is in the plant because it was adapted as toxin to prevent insects from eating the plant Tar is the carrier which is the carcinogenic aspect of cigarettes Typical cigarettes 10 puffs per cigarette and smokes 1.5 packs a day - 300 hits where you are reinforcing behavior, making associations with places, people, and situations Gets to brain faster than even IV, 7 seconds with rapid action. This all enhances the reinforcing effects. Metabolism Enters into oxygenated blood, and is very quickly broken down in a single step in to cotinine If you have fewer enzymes, there is reduced smoking Methoxsalen inhibits metabolism which is studied for use as a pharmacological treatment Nicotinic cholinergic receptors nAChR Ionotrip* with 5 subunits (2 alpha and 3 beta) Nicotine binds to this receptor and opens Na+ (some allow Ca2+) Channel and polarizes cell and the cell fires Presynaptically enhances NT release and therefore increase effects of cell High doses creates a depolarization block, leading to respiratory suppressant effects Acute Effects Mood changes different for experienced smokers or nonsmokers Smokers feel calm and relaxed, withdrawal relief Nonsmokers feel anxious, nauseous, dizziness and arousal Enhances cognition because it acts on the cholinergic system and enhances working memory (including in rats) Radial arm maze - looks like a star, bait food in arms. Put rat in the middle and observe working memory. Every now and again they will make an error and go down a previous path and these errors are tracked. "where have I been before?" With nicotine, rats will perform significantly better and remember where they have been Also enhances inhibitory avoidance, dark and light side of box. Rats naturally prefer dark, but when they receive a shock they will learn avoidance more quickly and lasts longer before they re-enter the box (more than double the amount of time) If we KO the receptor, with lower affinity for nicotine all animals will perform the same Nicotine and reinforcement Smokers will self-admin pure nicotine (low doses) Animals self-admin in low doses as well (like how a smoker does) and more likely to take if they are adolescent!! (same with humans) Affects Mesolimbic DA system VTA -> NA With in 7 seconds get to VTA, binds to receptors and signals to fire DA neurons (more than doubled) to the NA 6-hydroxydopamine (lesion DA neurons) eliminates self-admin Additional Effects Autonomic Nervous System Effects Increase Norepi and Epi by stimulating adrenal glands Increases hydrochloric acid in stomach which leads to ulcers Increased bowel contraction leading to diarrhea Increased metabolic rate and reduced appetite Nicotine poisoning Toxic at 60 mg, several lethal doses in one pack swallowing, skin contact and contact with insecticides Low exposure causes nausea, etc a lot of unpleasant things but not death Medium exposure can cause fainting and respiratory problems high exposure causes respiratory failure, convulsions and death Tolerance and dependence Acute Tolerance Pretreatment reduces response to subsequent exposure nAchR become desensitized and will return after overnight abstinence, most sensitive right away after waking up Chronic tolerance - become tolerant to adverse effects of drug (nausea, etc) Dependence Insert minipump under skin in rats (like the patch), slow leakage. Once pump is removed, they develop an abstinence syndrome displaying that they are in withdrawal, all of which are mediated by the nicotinic receptors Tobacco Use Every time we have a war, there is an increase in nicotine use/ Lack of money means less smokers (e.g. Great Depression) After the Surgeon General reported cancer as a result of smoking use decreased, although temporarily increased after tobacco companies put filters on the cigarettes indicating that this should stop cancerous effects' Anti-smoking ads impact, but taxes had the most significant decrease in nicotine use It is now disfavored by society to be a smoker, we now feel being exposed to nicotine is a violation of rights. Needs to be done away from non-smokers and children. Approx 30% of population over 12 in US (as of 2002) Women smoke less, but typically start a little earlier Education and ethnicity also affect use Men smoke cigarettes only for the nicotine, give them a patch and they will not want the cigarette as much Women are not as addicted to nicotine as much as men, but they are smoking more for the social factors. Treatments need to be modeled differently for individuals. Why do people "abuse" nicotine (chronic users)? Use Factors -> Stress relief, avoiding abstinence syndrome (the more you smoker, the more severe the withdrawal), LEARNED ASSOCIATIONS (fantastic at learned exposures and we are able to associate smoking during MANY different exposure to drugs), enhanced DA action (allows for prolonged effects, not necessarily increased release) by reducing monoamine axidase activity Health risks 33-50% of smokers die prematurely #1 preventable cause of death Very expensive for medical costs Leads to low birth weight of children from pregnant women smokers We are taking in heaps of toxins - tar, Carbon monoxide (starving brain of oxygen), carcinogens Treatment 70-75% want to quit, 40-45% TRY every year, but there is extreme amount relapse Behavioral intervention, need to stop in youth BEFORE they start Can use pharmacological interventions -> Nicotine replacement drugs (one thing that replacement therapies do not help is HUNGER); Buproprion decreases cravings (DA and Norepi reuptake blocker. NEW vaccine for nicotine; antibodies should bind to the alcohol and never reach the receptors. Can be developed for systems that we do not produce endogenously.