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Lecture 5

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PSYC 3403
Tarry Ahuja

Lecture 5 Overview - Barbiturates- specific depressants - Nonbarbiturate sedative-hypnotics • Refers to an agent that has a depressing quality - GHB- general anesthetics - Antiepileptic drugs Barbiturates - Phenobarbital was introduced as a sedative in 1912 • Helps you sleep and helps with anxiety - Originally mechanism of action was unknown • Didn’t know how it actually worked, wasn’t until alter that they figured out how it worked - Classified by chemical structure • Labelled based on interactions rather than structure Barbiturates (structure) *KNOW BASIC STRUCTURE FOR MIDTERM!!* - Phenobarbital: has specific compounds at the binding sites - Barbiturate nucleus: • Neucleus is the core • R , R , R = potential binding sites 1 2 3  Depending on what compound is at the R site determines what compound is created Barbiturates (mechanism) - Nonselective neuronal depression • Decreased activity causes depression - Depress polysynaptic (multiple connections) diffuse brain-stem neuronal pathways in: • The brainstem • Cerebral cortex - Depression was dosage-dependent • Important because you want to know that if you are giving someone ever so much of a barbiturate, what effect is happening? If you give them more, does the depression decrease, or is it an ‘all-or-none’? • As you increase dose, you want an increase in it’s effects - Reduce electrical and metabolic activity - Decreases in while-brain glucose metabolism - Reduction of excitatory activity or increased inhibitory activity • Pulling foot off the gas pedal, or putting our foot on the brake?  Same effect (slow down), but different ways to get there • If reducing excitatory activity, it’s a different set of systems that works Barbiturates (glucose metabolism) - Control shows different activity than experimental • Areas lit up are fuels being burned, glucose showing up (activity) - Experimental • Whole brain shows depression in activity Barbiturates (glutamate) - Research has shown: • Barbiturates act as NMDAR antagonists  Antagonists are blockers  Less excitation because they are being blocked • Amnestic properties due to changes in glutamatergic transmission (taking barbiturates can cause amnesia)  One of the properties is you forget stuff (amnesia)  Blocking at that receptor causes the amnesia • Lower blood flow to brains areas associated with memory  Dealing with part of brain affecting memory, and lower blood flow = decrease in activity = forgetting things Barbiturates (GABA ) A - Current research shows the involvement of GABA recAptors • Multiple binding sites - Enhancement of GABAtransmission • “apply the brake” (increasing activity) - - Increased Cl influx accounts for: • Sedative-hypnotic actions (sleepiness)  Barbiturates effect in the GABAsystem and chloride • Anesthetic properties  From glutamate system at the NMDAreceptor Barbiturates (GABA ) **KNOW THIS FOR MIDTERM!!** A - - Can open Cl channel in the absence of GABA • Barbiturates can open chloride channel in absence of GABA  Dangerous thing, you normally only want channel opened when GABA is present - Increased toxicity of barbiturates • Very quickly can become too powerful  Ex: 1 pill = ok, 2 pills = ok, 3 pills = dead • Barbiturates are not very safe - High doses can produce amnesia and a state of dementia • Amnesia might be desired effect, but dementia is not Dementia - In demented state only if at least 5 of 12 components are altered: • Sensorium (orientation to time and place) • Affect (expression of feelings) • Mental content (fund of knowledge) • Intellectual function (ability to reason) • Insight and judgement Barbiturates (pharmacokinetics) - Wide range of half-lives (3 min to 120h) (6 half-lives to rid body of something) • If half-life is 3 minutes, drug will be out of system in 20 minutes • If half-life is 120 minutes, long time before drug is out of system - Rapidly and completely absorbed - Short-acting barbiturates are very lipid soluble (BBB, induce sleep) • Lipid solubility means easy to get through blood-brain barrier - Long-lasting barbiturates are more water soluble (blood/urine residues) • When more water soluble, can get in more easily in blood and urine, but can’t get into brain as easily Barbiturates (pharmacological effects) **KNOW THIS FOR MIDTERM!!** - Low degree of selectivity • The more specific a drug is, the better it will work and the fewer side effects it will have • Basically, just blankets everything (like alcohol), and causes a lot of side effects - Suppression of REM sleep • When sleeping, 4 stages of sleep + REM (cycles)  Stages 1 & 2: lighter sleep, still aware of things around you  Stages 3 & 4: deeper sleep  REM: when all your dreaming occurs, deepest sleep cycle  Healthy individuals have 3-4 stages of REM cycles during sleep  Earlier stages are “gateway” into sleep, 3 & 4 are “restorative”, and REM is a sort of recall of things from your day  As you get older, don’t remember dreams as well  If you don’t achieve REM, you won’t feel rested  Barbiturates can cause you to not achieve REM  This is why you should not use sleeping aids for long-term solutions to sleep problems affects getting REM sleep  Quality vs. quantity  Long-term drinking can also prevent REM - Cognitive inhibitors • Preventing you from being smart - Combination of barbiturates-alcohol can affect respiration, overdose • Explosive together: barbiturates alone are dangerous, alcohol alone is also dangerous together its really bad  Affects your ability to breathe Barbiturates (psychological effects) - Similar to alcohol-induced inebriation • Generally, someone on barbiturates acts like someone intoxicated on alcohol - Low doses remove anxiety - High doses cause general behavioral depression and sleep - Combination of barbiturates-alcohol can affect respiration, overdose Barbiturates (properties) - Lethal in overdose • OD in general doesn’t always mean death, could cause them to get sick, however, barbiturates are lethal - Narrow therapeutic range • Ex: 10mg-15mg then 15mg-20mg double dose could kill you - Potential for tolerance, dependence, and abuse • Tolerance and dependence common - Possible dangerous interactions • Alcohol is most dangerous - Teratogenic potential?? • Correlation between lower birth weight, lower IQ, but not strong enough to state it will cause it - Truth serum?? • Fake in sense that injecting someone with something so they will only tell the truth • What it does is make you more open to suggestion and more relaxed  Think about alcohol and how people are more willing to share while intoxicated Nonbarbiturates **KNOW GENERAL NAMES (EX: BARBITURATE/NONBARBITURATE) FOR MIDTERM!!** - Soma, Quaalude, Paraldehyde • Can’t be classified as a barbiturate because they lack the central nucleus that all barbiturates share, but they do the same thing - Quaalude was very popular in the 70-80’s • Used as a date rape drug • Sedative that acted as a anaphrodisiac (opposite of aphrodisiac) • Banned in 1984 in the US General anasthetics - Used in medical settings - Potent CNS depressants, unconsciousness (in high doses) - Administration • Inhalation • Intravenous injection - Nitrous oxide, isoflurane, halothane • Halothane used in vet office • Nitrous oxide used in dentist office - Injectable anasthetics **DON’T WORRYABOUT KNOWING THE NAMES** • Pentothal • Brevital • Diprovan • Amidate - Low analgesic or euphoriant activity • Don’t really cause memory loss • Don’t make you feel all giddy and happy in the way cocaine or meth would Gamma Hydroxybutyrate (GHB) - Potent CNS depressant • Used as ‘date rape’drug - Structurally similar to GABA • Interacts with GABAreceptor - Normally found endogenously • We naturally produce GHB - Derived from GABA - Easily crosses the BBB - Used as anesthetic, sleep disorders, EtOH detox • Has good intentions, but abused - High abuse potential (aphrodisiac) - Foreign availability, do-it-yourself - Widely used as a “date rape” drug - Synergistic effects with EtOH • Synergetic means an explosive effect • Alcohol alone has one effect, GHB has another effect, but together are synergetic  ‘date rape’drug generally given with alcohol (slipped in drink), but dosage is hard to control and can be fatal - GHB increases DAlevels in the brain - Activates DAreward system • When activated, makes a drug more prone to becoming a drug of addiction  Not when used as a ‘date rape’drug, but when using for yourself - Used to treat narcolepsy • Narcolepsy is a condition that causes you to pass out when excited • Can be scary and dangerous condition. (ex: passing out at wheel if startled = dangerous) - Both a Schedule I and II drug (FDA) GHB (pharmacokinetics) - Liquid, rapidly absorbed (peak 30-75 min) • Ideal for date rape drug, gives time to get the person out of the bar/club - Rapidly metabolized (30 min half-life) • Leaves the body quickly (within 3 hours essentially out of blood  Can look for other things to see if GHB was given - Low urine detectability Antiepileptic drugs - Help deal epileptic seizures - Treatment of bipolar disorders - Neuromodulators: wide array of applications • Changing activity in the brain - Chemically belong to either: • Barbiturates (Phenobarbital) • Hydan
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