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Depressants. Overview • Alcohol • Barbiturates • Benzodiazepines How it works • Depressants go into blood, and cross Blood brain barrier and binds to GABA receptors • GABA receptors signal dopamine receptors, which releases dopamine into the brain (this is what makes you feel “good” or “spacey” on depressants) Alcohol • Stimulant from hormone secretionalcohol stimulates the adrenal glands • Some alcohol is synthesized in stomach, however, if enough is consumed it is: • Absorbed through gastrointestinal tract, however, must be oxidized (cannot be stored) • That happens in the liver • Converted to acetaldehyde, to acetic acid, to CO2 and water • Produces an excess amount of NADH • Ultimately, alcohol and all other depressants inhibit the brain because of their effect on GAVA receptors Side effects-part 1 • Its that acetaldehyde, dude– Extra acetaldehyde goes into bloodstream, inhibits mitochondria, which creates a vicious cycle hepatitis death • Extra NADH is bad– Excess synthesis of glycerol-makes people overweight – Oversynthesize ATP secrete lipids into the bloodstream (to balance it out) heart attacks (those are bad) • Physical dependence-addictions Side effects-why drinking is bad • Malnutrition-the alcohol that most alcoholics drink in a day is enough to provide 50% of energy requirementsdoesn’t contain nutrients (or those carbohydrate, lipid, and essential amino acid things we looked at) • Hangovers-extra acetaldehyde causes a hangover (headaches, nausea, dizziness) because it builds up in the body Alcohol and the law • Urine testing – The least accurate-dependent on climate, metabolic rate, and only accurate for 2 hours after drinking – Tests for alcohol in liver • Blood detection – The MOST accurate – Literally measures alcohol content from blood • Breath detection (only used as proof for arrest) – Oxidizes the alcohol in someone’s breath into acetic acid – The electricity of the reaction is measured and used as a method for determining the BAC Legal Limits • In Colorado – DWAI (less severe penalties)-.5 to .8 BAC – DUI (more severe)- more than .8 BAC – If the subject has a BAC greater than .17, he/she is subject to much more severe penalties and is classified as a severely drunk driver Benzodiazepines (aka Benzos) • Most commonly used since 1960’s • Used instead of barbiturates because they are WAY safer • How it works– Same as the general way – Most benzos undergo oxidative metabolism – All are then conjugated to glucoronic acid – Drugs that DON’T undergo phase 1 metabolism (oxidative) are safer for liver patients http://pharmacy.wingate.edu/faculty/mnelson/PDF/Sedative_Hypnotics.pdf http://pharmacy.wingate.edu/faculty/mnelson/PDF/Sedative_Hypnotics.pdf Benzos-cont. • Short acting, intermediate acting, long term acting determines use. • Based on: – Half life (how long for fifty percent of drug to be eliminated)-longer half life, longer duration – Half life of active metabolite (metabolic fate) the body, Benzos become different benzos with same effects (due to enzyme reactions) [e.g. valium (diazepam) is converted to serax (oxazepam) in the body] Barbiturates • The first depressantswere used as sleeping pills, anesthesia; however, use discontinued due to side effects (death, with high dose) • Synthesized from barbituric acid-aromatic hydrocarbon structure http://www.elmhurst.edu/~chm/vchembook /6673barbit.html Barbiturates-cont. • The duration depends on the number five alkyls-longer chains, shorter effect • Based on the lipid solubility (polarity) of the molecule used Barbiturates-cont. cont. • At low doses, work regularly on the GABA receptor • High doses-antagonize GABA receptors, which causes brain depression (that’s bad, literally means a depression in brain activity) Barbiturates-2cont.+cont. • Used as anti-epileptic medicine • Used as an IV anesthetic • After head injuriesreduce swelling and reduce glutamate • Sedation in therapy Barbiturates-22cont.-Side effects, OR, why we no longer use Barbiturates • THEY KILL YOU • Lethal depression of breathing-easy to overdose (often used in suicides) • Triples birth defects • Decreased REM when used as a sleeping pill (because it is an anesthetic) • Addiction – Rapid tolerance development – Life threatening withdrawal Bibliography • Alcohol Abuse and Dependence: Nutrition on the Rocks. Mary Anne Clairmont, RD. Today’s Dietitian, September 2005 (http://cms.skidmore.edu/health/education/Alcohol_And_Drugs/al cohol-and-nutrition.cfm) • “Pharmacy 725: Sedative and Hypnotic Drugs” http://pharmacy.wingate.edu/faculty/mnelson/PDF/Sedative_Hypn otics.pdf • Elmhurst College, Virtual Chembook “Barbiturate Drugs” http://www.elmhurst.edu/~chm/vchembook/6673barbit.html • Elmhurtst College, Virtual Chembook, “Alcohol Metabolism” http://www.elmhurst.edu/~chm/vchembook/642alcoholmet.html • Office of Legislative Legal Services “Colorado Drunk Driving Laws” http://www.state.co.us/gov_dir/leg_dir/olls/PDF/COLORADO%20D RUNK%20DRIVING%20LAWS.pdf More bibliography • Korschun., H. (2009). Antidepressant directly stimulates brain growth factor receptors. Woodruff Health Sciences Center, Retrieved from http://whsc.emory.edu/home/news/releases/2009/06 /antidepressant-stimulates-brain-growth-factorreceptors.html • Walker, E. (2009). Psychoactive drugs. Weber University, Retrieved from http://faculty.weber.edu/ewalker/Medicinal_Chemistry /topics/Psycho/psycho.htm