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Physiological Effects of Nicotine and Ethanol Rebecca B R Milholland Tobacco Plant • Grown for its nicotine containing leaves which are smoked, chewed, or sniffed Nicotiana tobacum Nicotine • Nicotine is an alkaloid found naturally in tobacco plants, tomatoes, potatoes, eggplant and green peppers Nicotine • Nicotine is an alkaloid found naturally in tobacco plants, tomatoes, potatoes, eggplant and green peppers Neuromuscular System Motorneuron Neuromuscular Junction Muscle Fiber Neuromuscular System Signal from the Brain Motorneuron Nerve Terminal Muscle Fiber Neuromuscular System Signal from the Brain Motorneuron Acetylcholine (ACh) Muscle Fiber Neuromuscular System Signal from the Brain Motorneuron Acetylcholine (ACh) Muscle Fiber Neuromuscular System Signal from the Brain Motorneuron Nicotine Muscle Fiber Nicotinic Syndrome •Nicotine produces tachycardia and blood pressure through its action in the sympathetic nervous system or the “Fight or Flight” system. Nicotine decreases appetite. Nicotine’s action on skeletal muscles and the diaphragm to produce paralysis and asphyxiation Chronic Effects of Nicotine •Chronic administration leads to coronary artery disease and hypertension Nicotine produces peptic ulcer disease,and esophageal reflux through its influences on the Gastrointestinal tract. •Nicotine enhances learning and memory •Nicotine enhances learning and memory •Nicotine’s influences in the brain also produces its addictive properties Most Likely Avenues for Exposure • • Tobacco Products Insecticides – Anti-AChE (Acetylcholine Esterase) – nAChR activators (like nicotine) Alcohol H OH C H H C H H Factors which Influence Ethanol Movement Though the Body • Absorption Factors which Influence Ethanol Movement Though the Body • • Absorption Distribution and Solubility – Body Fat Percentage Dose-Response Curve for Acute CNS Response to Ethanol Response Death Labored breathing Unconscious Deep sleep Sleep Giddy No effect Dose Chronic CNS Effects of Ethanol • Korsacoff’s Syndrome – Loss of short term memory – Due to a Thyamine Defficiency Ethanol Alcohol Dehydrogenase NAD NADH Acetaldehyde Ethanol Alcohol Dehydrogenase NAD NADH Acetaldehyde Aldehyde NAD Dehydrogenase NADH Acetate Ethanol Alcohol Dehydrogenase NAD NADH Acetaldehyde Aldehyde NAD Dehydrogenase NADH Acetate Citric Acid Cycle Energy Ethanol Alcohol Dehydrogenase NAD NADH Acetaldehyde Aldehyde NAD Dehydrogenase NADH Acetate Citric Acid Cycle Energy Fatty Liver Fibrosis Cirrosis Ethanol Alcohol P450 Dehydrogenase NAD NADH Acetaldehyde Aldehyde NAD Dehydrogenase NADH Acetate Citric Acid Cycle Energy Fatty Liver Fibrosis Cirrosis Ethanol Interaction with P 450 • • Acute Administration - P 450 Chronic Administration - P 450 Acetominophen Detoxication Sulfation Glucuronidation Safe Excretion by Kidney and in Bile Acetominophen Detoxication Activation to a Toxic Metabolite Sulfation Glucuronidation Quinoneimine Free Radical Safe Excretion by Kidney and in Bile Liver and Kidney Damage Acetominophen Detoxication Activation to a Toxic Metabolite P450 Sulfation Glucuronidation Quinoneimine Free Radical Safe Excretion by Kidney and in Bile Liver and Kidney Damage Acetominophen Detoxication Activation to a Toxic Metabolite P450 Sulfation Glucuronidation Quinoneimine Free Radical Safe Excretion by Kidney and in Bile Liver and Kidney Damage Ethanol Induction Of P450 Expression Other Alcohols • Methanol Other Alcohols • Methanol – Induces blindness and death due to formic acid production Other Alcohols • Methanol – Induces blindness and death due to formic acid production • Ethylene Glycol Other Alcohols • Methanol – Induces blindness and death due to formic acid production • Ethylene Glycol – Kidney damage due to oxalic acid production and crystal formation in the renal tubules Other Alcohols • Methanol – Induces blindness and death due to formic acid production • Ethylene Glycol – Kidney damage due to oxalic acid production and crystal formation in the renal tubules Treat Exposures to Both Alcohols with Ethanol!! Conclusions: Nicotine • Acute Conclusions: Nicotine • Acute – Acts at acetylcholine receptor in muscle – Produces asphyxiation and paralysis Conclusions: Nicotine • Acute – Acts at acetylcholine receptor in muscle – Produces asphyxiation and paralysis • Chronic Conclusions: Nicotine • Acute – Acts at acetylcholine receptor in muscle – Produces asphyxiation and paralysis • Chronic – Acts at acetylcholine receptors in the sympathetic nervous system to coronaroy artery disease and high blood pressure – Acts at acetylcholine receptors in the brain to induce physical addiction. Conclusions: Ethanol • Acute Conclusions: Ethanol • Acute – Fatty Liver – CNS Depression Conclusions: Ethanol • Acute – Fatty Liver – CNS Depression • Chronic Conclusions: Ethanol • Acute – Fatty Liver – CNS Depression • Chronic – Korsacoff’s Syndrome – Cirrosis of the Liver