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 secretion-alcohol

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 requirements-doesn’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

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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 depressants-were 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 injuries-

reduce 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/alcohol-and-nutrition.cfm)

• “Pharmacy 725: Sedative and Hypnotic Drugs” http://pharmacy.wingate.edu/faculty/mnelson/PDF/Sedative_Hypnotics.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%20DRUNK%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-factor-receptors.html

• Walker, E. (2009). Psychoactive drugs. Weber University, Retrieved from http://faculty.weber.edu/ewalker/Medicinal_Chemistry/topics/Psycho/psycho.htm