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by: Spencer Smitham


Spencer Smitham
GPA 3.97


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This 17 page Class Notes was uploaded by Spencer Smitham on Saturday September 12, 2015. The Class Notes belongs to PSYC 5850 at University of Georgia taught by Suplita in Fall. Since its upload, it has received 60 views. For similar materials see /class/202458/psyc-5850-university-of-georgia in Psychlogy at University of Georgia.




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Date Created: 09/12/15
Study Guide for Exam 3 What does psychedelic mean 0 An ability to quotopen the mind hallucinogens Are psychedelics natural synthetic or both 0 Both can come from plants or be made What is the source of mescaline o The peyote cactus o Derived from the quotmagic mushroomquot most popular in America is the mushroom Psylocybin semianceata but can come from various mushrooms in the Psylocybin genus Describe the trip experienced by Wasson in quotSeeking the Magic Mushroomquot Time Magazine 1957 o Felt very awake hallucinations whether eyes were closed or open saw castles gardens art motifs colors ecstasy took a real meaning What does LSD stand for Who created it Was it ever marketed How was it used Why was it suggested that psychotherapists experiment with it o LSD stands for lysergic acid diethylamide 0 Created by Albert Hofmann o It was marketed under the name Delysid used as a psychotherapy medicine to help patients recover repressed thoughts and feelings o Encouraged that psychotherapists experiment with LSD to empathize with their schizophrenic patients psychotic symptoms Describe the anatomy of the typical acid trip four stages 0 Onset I 30 60 min after consumption geometric shapes and colors form spontaneously mild distortions o Plateau I Lasts for 2 hours visual effects intensify more passage of time occurs slowly 0 Peak I Lasts for 3 hours feels as if in another world and time is suspended bizarre and distorted images either beautiful or scary synesthesia o Come down I Lasts about 2 hours perceptual distortions gradually disappear Describe the pharmacological evidence that psilocybin functions as a 5 HT2A agonist I 5 HT2A antagonists eliminate visual illusions and hallucinations What appears to be the relationship between psychedelic effects and regulation of locus coeruleus activity Can someone explain to me the difference between liking and wanting This was in the Valentines Day PPT Thanks I think the point is though it seems like rats like electrical stimulation they are actuallyjust driven want to do so by the reinforcement DA pathway in the nucleus accumbens Yea they get to a point where they dont like it but they want it it says they push the button so much they dont eat or drink and they die 1 What are the characteristics of a drug 0 drug a chemical that is not food that is administered outside of the body in order to alter the physiological functions ofan organism and it s active at minute concentrations 0 Top two drugs used worldwide caffeine to overcome fatigue amp alcohol to relieve stress 1 Requirement for generic drugs I They must be pharmacologically identical to the real thingbrand 1 Drug actions vs drug effects b Drug action The cellularlevel changes that occur when a drug binds to a physiological site of action I Ex when a drug causes a protein to bend a certain way basically if it changes something about the cellular components then it is drug action 0 Drug effects The bigger picture impact andor the large scale changes that occur following the molecularlevel effects I ex If a certain drug affects a man s blood pressure or how sleepy he is this would be a drug Effect 2 What is analgesia and what are three classes ofanalgesic drugs Are there 3 or 44 were listed on the notes Analgesics relieve pain a steroidsantiin ammatory properties eg Hydrocortisone b opiate analgesicsex vicodin c nonsteroidal antiin ammatory drugs NSAle ex aspirin ibuprofen naproxen d cannabinoids effective in treatment of glaucoma pain cancer pain etc Eg THC 3 How are side effects defined a side effect any effect other than the therapeutic effect aka the desired effect I There are NOT any drugs that are absent of side effects I in notes says The de nition of side effects depends on what the therapeutic effect is side effects can be both beneficial and bad things Example amphetamine for ADHD vs weight loss 1 if taken for ADHD and the person experiences weight loss then weight loss is the side effect treatment of ADHD is the therapeutic effect 4 Characterize placebo effects a can regulate physiological processes b can produce side effects c have variable potency injection vs oral asprin placebo vs morpheine placebo d very real and quite common e at least 13 of subjects experience some degree ofthe anticipated effect with psychoactive drugs f This is why for best results it is necessary that tests of drug effects must be placebocontrolled and preferably doubleblind 5 Specific vs nonspeci c effects a Specific depend on the interaction bt drug and its physiological receptor b Nonspeci c do NOT depend on the interaction bt the drug and its physiological receptor c CAN SOMEBODY CLARIFY THIS I is it speci c is a directprimary effect and nonspeci c is secondary indirect Maybe I m way off I think it s like that just think of cocaine or heiron being speicifc because they act on specific receptors etc But maryjaneweed potmarijuanaganja cigarettesgrass doesn t act directly on those NTs or receptors but affects other things like membrane permeability that in turn effect those releases 6 What does pharmacokinetics encompass a absorption how drugs get into bodybrain b distribution how drugs are distributed throughout the body c metabolism in the liver detox center d elimination urinate out most excrete some 7 Common routes of administration in humans and animals Advantages and Disadvantages Route Advantage Disadvantage Oral PO easier for patients to self slow absorptionrecovery admnstr safe economical drugdrug or drug food slower effects ifallergic interactions rst pass effectsconversion by the liver in ineffective typically or even more potentrare metabolite creating stronger effects Inhalation patient admn rapid accurate blood lvls reliable absorption ease of use irritation possible OD damage to respiratory system andor oral mucosa high abuse potential Intravenous IV rapid reliable absorptions accurate blood lvls avoids rst pass effects membrane solubility not an issue needs to be administered by trained professional ie nurse dirty needles in drug abuse can lead to infection some have high abuse potential serious allergic reaction potential Intramuscular IM prolonged slower absor tion eas admin evenlonger absorption when put in oil diffto selfadmin without training drug abuse w dirty needles can lead to infection pain potential allergic reactions Transdermal prolonged reliable absorption easy self admin skin irritationvery difficult to reg blood lvls allergic reactions can t adjust dosage without changing RX Subcutaneous SC Injected under the fatter layer of skin prolonged reliable absorption easy admin easiest injection method selfadmin diff person should be trained infection w dirty needles pain irritation allergic reaction Intraperitoneal IP good when IV not possible small animals organ damage irritation slowerthan IV Epidural great for regional possibility of hitting a nerve anesthesia inject an opioid w needle CNS infection analgesic low Topical ease of use rapid onset high abuse potential readily absorbed through mucous membranes locally or through circulation rapid onset gradual deterioration ofmucosa chronic use 8 How do lipid solubility and ionization in uence pharmacokinetics a The more lipid soluble a drug the easier it is absorbedpasses BBB b Ionization is one form ofinactivation Slows drug distribution Makes drug more watersoluble thus easierto eliminate EX in liver glucuronide can be added to a toxindrug gt drug ionized more watersoluble easierto eliminate i Basically high ionization is less lipid soluble and less likely to be absorbed 9 What is the rstpass effect a basically when the liver converts the drug into ineffective common case or even more potent metabolite rare case b This is a disadvantagedrawback to oral administration 10What is the BBB how is it formed and what are some notable gaps a The bloodbrain barrier BBB is a separation between the blood and brain extracellular fluid The BBB consists of tight junctions formed by astrocytes surrounding capillary endothelial cells Some notable gaps include the Area Postrema aka Chemical Trigger Zone and the Median Eminence 11What is a teratogen a Drugs that produce birth defects at higher rates in babies born to mothers who used them during pregnancy I ex cocaine heart defects SIDS I ethanol FAS I vaprolic acid spinal bi da 12What is pKa and what are its implications for drug ionization a The level at which half ofthe drug becomes ionized b implications if an acidic drug is in an alkaline environment more of it becomes ionized and therefore rendered useless and vice versa 13What is depot binding which tissues are the major contributors and how might this phenomenon affect drug bioavailability 1 Drugs bind to proteins in the plasma The less bound a drug is to a protein the more ef ciently it can traverse cell membranes 2 Depot binding occurs when a drug binds to a physiologically inactive site Major contributors include plasma protein eg albumin The protein acts as a depotreservoir Depot binding reduces immediate effects ofdrug because it lowers the total amount to reach target sites by the protein hanging on to the drug and releasing it slowly but surely 3 Major Contributors Fat and Muscle 14Why is discontinuation of chronic THC marijuana typically NOT associated with signi cant drug withdrawal effects a your body naturally weans itself off of it because THC bound to fat cells is slowly released back into circulation over the course ofdays or even weeks THC has significant depot binding due to high lipid solubility 15What is biotransformation where does it occur for the most part which enzymes speci cally are implicated a biotransformation the main mechanism ofdrug clearance the body alters the chemical structure ofthe drug over time aka drug metabolism b occurs in LIVER c cytochrome P450 enzymes 16Zero vs FirstOrder kinetics which pattern does ethanol follow and what are some implications for ethanol intoxication a Ethanol follows zeroorder kinetics According to this a m linear decrease in conc of a given drug is cleared from bloodstream over a given time period The average clearing time for people is 1015 mLhr I implications since the drug is cleared at a constant rate the men in bluepopo can approximate how recently someone has consumed alcohol THE KIDS JUST WANNA HAVE FUN True b First order kinetics usually assumes that a w a 50 of the free drug is cleared during a stated time interval known as the halflife ie caffeine clearance is exponential 17Contrast Phase I and Phase II biotransformations What is the most common Phase I reaction for psychoactive drugs What is the most common Phase II conjugation a Phase I biotransformations include nonsynthetic modi cations oxidation 1 reduction or hydrolysis b Phase II biotransformations include synthetic reactions aka conjugations ln synthetic reactions the parent drug is combined with another small molecule such as glucuronide 1 sulfate or a methyl rou 18 How does biotransformation affect water solubility a Biotransformation ultimately makes molecules highly water soluble and can therefore be excreted more readily than the parent drug 19 Describe a mechanism of pharmacokinetic tolerance involving liver enzymes a V th frequent use of a drug the liver may upregulate cytochrome P450 levels and metabolize that drug and others metabolized by P450 more readily This increases drug tolerance 20 Describe drugdrug competition as it relates to liver enzymes What is a potential consequence a Drugdrug competition occurs when several drugs are present in the body and each ofthem depends on cytochrome P450 for metabolism A potential consequence is that toxic levels ofone or more ofthe drugs may be reached due to insuf cient processing by the P450 system 21 How might genetic variationpolymorphisms affect drug biotransformation speci cally in the case of ethanol a people differ in how powerfully their particular liver enzymes metabolize drugs about half of all chinese japanese koreans show a reduced ability to metabolize acetaldehyde a metabolite of ethanol this results in the ushed appearance 22 How are pharmacodynamics contrasted with pharmacokinetics a Pharmacokinetics involves how drugs travel through the body absorption distribution metabolism and elimination Pharmacodynamics describes the interactions between drug molecules which act as ligands my 1 21111113141111 and their physiological targets known as receptors 23What is a ligand Are all ligands drugs Are all drugs that are ligands agonists a A ligand is a molecule which binds a certain type ofreceptor with signi cant selectivity Not all ligands are drugs Not all drugs that are ligands are agonists 24What are receptor subtypes and why is it of critical importance to psychopharmacology a most receptors for neurotransmitters come in many different varieties subtypes depending on the goal ofthe transmitterreceptor interaction is in the particular region ofthe brain the outcome ofthe interaction between a neurotransmitter and receptor depends on the receptor NOT on the neurotransmitter 25 Compare and contrast direct vs indirect agonists and antagonists a direct agonists mimic the action ofa particular neurotransmitter examples nicotine barbiturates indirect agonists work through other mechanisms eg inhibition of metabolism inhibition of reuptake to increase the biological activity at a certain ligandreceptor complex antagonists are usually ligands which bind targets and subsequently suppress the activity ofa certain transmitter system 26What is ED50 LD50 Therapeutic lndex T Potency Ef cacy Be able to distinguish these on a doseresponse curve a ED50 50 effective dose is the dose at which the maximal effect is observed in half the people given it LD50 is the dose ofa drug producing toxiclethal effects in 50 ofthe individuals or animals to which it is administered The therapeutic index Tl is the ratio ofa drug s LD50 to its ED50 LD50ED50 I Less toxic safer drugs have Tls that are much highergreater than more toxic drugs ex THC has a much higher Tl compared to that of morphine for cancer pain LD50gtgtED50 1 basically ifthe drug is lethal at a wayyy higher dose than the effective dose its probably safe thus large Tl I Potency is the amountdose ofa drug required to achieve a particular effect deals with concentration NOT power ofthe drug how steep the curve is I Efficacy is the maximum achievable effect with a drug regardless of doseamount given how tall the curve is 27 Compare and contrast pharmacodynamic cellular and pharmacokinetic metabolic tolerance a Pharmacodynamic cellular tolerance refers to adaptive changes in the number of receptors expressed V th chronic administration of an agonist receptors are ooded a removal of some receptors so more drug is needed for same effect downregulation ex adderall amphetamine V th chronic use ofan antagonistic drug a cell expresses more receptors upregulationa more ofantagonist needed to achieve same effect ex caffeine competitive antagonist of adenosine system b Pharmacokinetic metabolic tolerance With the repeated use of many drugs adaptive changes take place in the systems that metabolize biotransform these drugs to enhance drug clearance I ex cytochrome P450 enzyme levels are often increased in the liver allowing drugs to be metabolized more ef cientlyThe initial dose of the drug will now lead to lower levels of bioavailability and will be subject to quicker clearance so more ofthe drug must be used to produce the initial effect 28 Characterize behavioral tolerance a learning how to function proficiently while intoxicated can occur within a single drug use episode eg with ethanol 29What is drug sensitization and with which class ofdrugs and with which effects in particular is it most likely to be observed a Drug sensitization aka reverse tolerance occurs when upon repeated administration of the same dose of a drug a stronger effect is achieved Cocaine and amphetamines have been reported to induce tolerance for certain effects eg euphoria anorexia and sensitization for others eg catalepsy hyperthermia hyperactivity 30 Compare and contrast positive and negative reinforcement a Positive reinforcement involves adding something to the environment to invoke a response Negative reinforcement involves removing something from the environment to invoke a response I Negative Reinforcement strengthens a behavior because a negative condition is stopped or avoided as a consequence of the behavior I Punishment on the other hand weakens a behavior because a negative condition is introduced or experienced as a consequence ofthe behavior 31 Describe the seminal research of Olds amp Milner with the brain s reward areas a Basically discovered the major reward center ofthe brain nucleus accumbens by direct electrical stimulation ofthis area in a rat b Olds and Milner found that rats with metal electrodes implanted into their nucleus accumbens as well as their septal nuclei repeatedly pressed a lever activating this region and did so in preference to eating and drinking eventually dying of exhaustion eso Im IC sys em dopaminergic pathways in the brain The pathway begins in the ventral tegmental area VTA ofthe midbrain and connects to the limbic system via the nucleus accumbens the amygdala and the hippocampus as well as to the medial prefrontal cortex PFC Mesocortical DA system The mesocortical pathway is a neural pathway that connects the ventral tegmentum VTA to the cerebral cortex particularly the frontal lobes It is one ofthe four major dopamine pathways in the brain 1 so is the main difference that mesolimbic goes to preifrontal cortex and meeocortical goes to frontal cortex 33What are the major targets of the VTA a Nucleus accumbens ofthe ventral striatum Amygdala Hippocampus Medial PFC Prefrontal Cortex 34 Does it appear that dopamine is more strongly implicated in liking or wanting Explain a WANTINGll Dopamine is more powerfully associated with motivation cravingobsessive thoughts than with reward b does anyone know why this is true people that are on psychostimulants for long periods oftime no longer like the drug but need it 35What does brain activity look like in people who are in the clutches of deep romantic love Ofthose who have just been dumped a Clutches of deep romantic love People who have been in relationships for 2530 years who have reported that they are in love as compared with couples who say that they have recently fallen in love both have the same areas of the brain being activated b Ofthose that have just been dumped I VTA the more you want to forget the more you crave I Nucleus accumbens PFC seeks to determine what went wrong assesses gainslosses willing to assume huge risks associated with deep emotional attachment Anterior Cingulate Cortex considered to be a limbic part ofthe PFC 36 Describe the history ofthe Harrison Act the 18th Amendment the Marijuana Tax Act and the CSA of 1970 Harrison Act of 1914 0 first major US antinarcotic Law 0 regulated the dispensing and use of opiates and cocaine nonmedical use prohibited records from drs needed taxes imposed OTC low concentrations still okay gtracism against Chinese The 18th amendment 19201933Prohibition o banned distribution ofany beverage with an alcohol content greater than 05 except for medical purposes 0 consequences speakeasies organized crime Marijuana Tax Act 1937 0 Harrison Act ignored marijuana o banned nonmedical uses of cannabis and heavily taxed importers sellers distributors gtracism against Mexicans o Reefer Madness Smoke pot amp become psychotic males and sexcrazed females Controlled Substances Act CSA of 1970 0 Comprehensive Drug Abuse Prevention and Control Act 0 updated and replaced all prior legislation concerning narcotics and other drugs believed to have abuse or addiction potential exceptions alcohol nicotine and caffeine even though they are addicting tool 37What is the DEA When was it formed 0 stands for Drug Enforcement Administration 0 are the police force ofthe CSA 0 created in 1973 38 Describe the CSADEA Schedules for controlled substances Where is marijuana and why might this be an inappropriate categorization a The CSA Controlled Substances Act established 5 categories or schedules of controlled substances I Schedule 1 Heroin Marijuana No proven therapeutic indication signi cant abuse potential No FDA approval Usually used for research purposes only I Schedule 2 Narcotics Percocet Oxycodone Acetaminophen and AmphetaminesLimited therapeutic indications High abuse potential FDAapproved clinical indications Records receipt and dispensing at Pharmacy and Physician s of ce Need special order forms Need DEA number to prescribe No re lls Emergency telephone orders prescriptions only I Schedule 3 and 4 Opiatelike drugs Vicodin Propoxyphene Acetaminophen Tylenol 3 Tylenol Codeine drug combinations Limited therapeutic applications Lower but real abuse potential FDAapproved indications Records Need DEA numberto prescribe Maximum of ve refills in 6 months I Schedule 5 Formerly exempt narcotics Codeinecontaining cough preparations Limited abuse potential Records Need DEA number Maximum of five re lls in 6 months Laws and regulations vary by state b Marijuana is located on schedule 1 which is the worst category of controlled substances as these drugs are the worst and have no medicinal value 0 Two ofthe top 4 highest abuse potential drugs are legal but Marijuana is on Schedule 1 Public perception of the drug 39 Describe the Henningfield and Benowitz ratings a The Henning eld and Benowitz ratings compare some drugs for I The severity ofwithdrawl from the drug painful symptoms when you stop using How reinforcing they are one use makes you want to do it again How much tolerance they create you need to use more and more each time I How much dependence they create or how quickly they create it you need to keep using the drug or you39ll feel withdrawl symptoms I How intoxicating they are you feel very different when you take the dru b The drugs compared were nicotine heroin cocaine caffeine alcohol and marijuana Both ratings agree that alcohol causes the worst withdrawal Both agree that cocaine is most reinforcing Heroin then cocaine then nicotine are the highest for tolerance when you combine the ratings Nicotine and then heroin rate highest for dependence Alcohol and then heroin rate highest for intoxication c Keep in mind that methamphetamine would probably rate nearthe top for the rst four ratings especially reinforcement if it was included Also keep in mind that other opiates like morphine and oxycodone Oxycontin have nearly the exact same effects as heroin especially if one is snorting or injecting them HENNINGFIELD RA TINGS Substance Withdrawal Reinforcement Tolerance Dependence lntoxicant Nicotine 3 4 2 1 5 Heroin 2 2 1 2 2 Cocaine 4 1 4 3 3 Alcohol 1 3 3 4 1 Caffeine 5 6 5 5 6 Marijuana 6 5 6 6 4 BENOWITZ RATINGS Substance Withdrawal Reinforcement Tolerance Dependence lntoxicant Nicotine 3 4 4 1 6 Heroin 2 2 2 2 2 Cocaine 3 1 1 3 3 Alcohol 1 3 4 4 1 Caffeine 4 5 3 5 5 Marijuana 5 6 5 6 4 1 Most serious 6 Least serious equal ratings 40 Compare and contrast drug dependence and drug abuse How do the phenomena oftolerance and withdrawal relate a Per DSM drug dependence is worse than drug abuse b Abuse Negligence Danger Continued use despite arrests and social interpersonal problems c Dependence Tolerance and withdrawal lack of control drugseeking obsessions and compulsions risk taking a p196 198 b drug addiction is a result of lasting neural adaptations that alter the brain s response to DA I candidates for these adaptations druginduced changes to gene expression in DA neurons in mesolimbcort parthways I cFOS and CREB proteins are essential for construction ofthe cellular adaptations resulting from drug use I rapid rate ofdrug delivery and availability to the brain enhances CREB and cFOS upregulationgtincreased dendritic branching gtincreased D1 receptorsgtincreased sensitivity to DA 42 Characterize lEGs cF OS and how this cascade of intracellular signals may come to produce neural adaptations a Immediate Early Genes lEGs are activated by stimulationinduced intracellular signaling cFOS is an IEG that is powerfully activated by addictive drugs eg cocaine AMPH nicotine morphine etc b cFOS cascade 1 D1 receptor activation 2 Increased cAMP 3 Activation of PKA PKA enters nucleus 4 PKA activates CREB cAMP response elementbinding 5 Synthesis of cFOS protein 6 cFOS promotes synthesis of mRNA 7 Protein synthesis supports adaptations Result of cFOS Cascade i increased density of dendritic branches expressing D1 receptors ii sensitization of existing D1 receptors iii both factors contribute to overall sensitization positive feedback loop 43 Compare and contrast positive reinforcement models negative reinforcement ie dependence models and incentivesensitization models ofdrug addiction a Positive reinforcement model ofdrug addiction Focus of Hedonic impact People use drugs to feel euphoria ie high positively reinforcing their expenence b Negative reinforcement model physical dependence model emphasize withdrawal symptoms person already in badpooranxious state and they perform a behavior take the drug and the stimulusbeing miserable is removed Incentivesensitization model Wanting incentivedrivecraving does NOT equate to liking enjoyment high etc Stimuli associated with drug use become more attention grabbing and cause increasingly intense cravings 44 Characterize the Medical Model ofdrug addiction What are some of its assumptions a The perspective ofAA NA etc b Addicts are born not made They have the psyche and predisposition takes away personal responsibility C O Key Terms and Concepts for Exam One 1 Equot Equot 5 Equot 9 1 9 H C H H H N H M H A We must stipulate that drugs must be able to alter their physiology in minute concentrations because even water can kill you at high concentrations Drug A chemical administered from outside of the body which selectively alters cellular physiology at relatively low doses Psychotropic drug Any drug capable of affecting the mind emotions and behavior crosses bloodbrain barrier and primarily acts upon CNS Drug Action The cellularlevel changes that occur when a drug binds to a physiological site of action often a membranebound receptor ExCocaine binds to catecholamine and serotonin transporters preventing the reuptake of these transmitters Drug Effect The bigger picture impact and or largescale changes that occur following the molecularlevel effects ExCocaine is a potent psychomotor stimulant Therapeutic Effect The desired cognitive affectiveemotional or behavioral changes anticipated with drug use Side Effect Any effect other than the therapeutic effect Speci c Effect Physical or behavioral changes 39 39 with 39 39 39 39 39 39 quot of a drug with the target site Non Speci c Effect Instead of being based on physical or behavioral changes on the chemical activity of a drugreceptor interaction based on certain unique characteristics of the individual Explains why the same individual responds to a treatment with lightheartedness one day and with depression another day Placebo Effect A perceived or actual improvement in a medical condition with the use of an inert drug or deceptive treatment sometimes still causing real therapeutic changes to the body Double Blind Placebo Controlled Studies Neither the participant nor the administrator of a drug knows if a drug is the active or inert form Sequence of Pharmacokinetic Events from Drug Admin through Excretion a Route of Administration b Absorption c Distribution d Binding 6 M I I39 Y P39 iuatiuu f Elimination The route of administration is important when considering the effects of psychotropic drugs because it determines how much drug reaches its site of action and how quickly the drug effect occurs Oral Administration PO a Advantages Selfadministration economical relatively safe slow onset of effects decreased abuse potential and comfort Disadvantages Poor absorptionrecovery rates drugdrug or drugfood interactions firstpass effect when the liver processes the drug into typically ineffective or rarely even more potent metabolite so if a drug shows extensive firstpass effects it must be administered in higher doses or in an alternative manner b 15 IV Administration a Advantages Very high absorptionrecovery rates avoids the firstpass effect membrane solubility is not an issue and very rapid onset of action Disadvantages Potentially bad with allergic reactions higher abuse potential with recreational use and disease risks with recreational use Ex HIV Hepatitis etc 16 Inhalant Administration a Advantages Similar to IV also great for general anesthesia b Disadvantages Potential damages to the respiratory system high abuse potential for recreational drugs compared to oral administration Ex Smoking methamphetamine vs oral Adderall XR 17 How do lipid solubility and ionization affect drug absorption and distribution WhyLipid solubility is positively correlated with drug absorption Lipid soluble drugs readily cross the bloodbrain barrier Ionization is inversely related to drug absorption directly associated to excretion Most drugs become ionized when dissolved in water and this greatly limits absorption 18 The blood brain barrier a Selectively permeable does not impede lipid soluble molecules b Principal component distinct morphology of brain capillaries i Tight Junctions intercellular cleft are closed because adjoining edges of the endothelial cells are fused to form tight junctions ii Fenestrations are absent Pinocytotic vesicles are rare c Gaps in BBB are found at the area postrema CTZ of the medulla and the median eminence of the hypothalamus 19 Chemical Trigger Zone CTZ Area postrema located in the medulla of the brainstem a The vomiting center causes vomiting when toxic substances are detected in the blood 20 Teratogens Any drug of substance capable of interfering with the development of an embryo a Environmental factors including drugs that have a negative impact on the development in the uterus inducing birth defects or even death Radiation Cocaine Heart defects stroke SIDS Ethanol Fetal Alcohol Syndrome Addicted to alcohol at birth Lithium Heart defects Phenytoin Dilantin an antiepileptic FASlike suppresses neuronal ability Valproic Acid Depakote used in epilepsy bipolar disorder schizophrenia and to treat migraines Spina bifida microencephaly 21 Depot binding Binding to anything in the body other than the receptor target reducing the immediate effect of drugs and the 1 site is a plasma protein albumin major contributions to fat and muscle a Most likely to contribute to drug overdose when the drugs saturate depot sites at some point Elderly patients are on a multitude of drugs depot sites are saturated so you have to titrate the dose accordingly since a larger amount of the drug is available to patient must scale back dose of drug to avoid overdose 5quot EFL59919quot 22 What s the difference between rst order and zero order kinetics Firstorder is when there is an exponential reduction decay or a halflife decay while a Zeroorder is when a constant amount of a drug is cleared from the bloodstream of a given time Ethanol Drug half lifeThe time required for half the drug dose to be eliminated from the body 24 How most psychotropic drugs undergo biotransformation a Type I Phase I Nonsythetic through oxidation reduction hydrolysis could be active inactive equally active b Type II Phase II Synthetic reactions conjugations with glucuronide group highly ionized and lipophobic becomes inactive 25 What are P450 enzymes A class of liver enzymes in the microsomal enzyme group responsible for both phase 1 and phase 2 biotransformation of psychoactive drugs a Liver enzymes responsible for metabolizing the widest variety of psychoactive dru s b Also metabolize environmental pollutants and toxins in food c Your body treats drugs as toxins which they all are in high enough doses How might expression of the P450 enzymes relate to drug disposition tolerance Upregulatation of CYP enzymes cytochrome P450 levels that metabolize that drug and others metabolized by P450 more readily More abundance leads to better efficiency to metabolize 27 What s the difference between pharmacokinetics and pharmacodynamicsPharmacodynamics describes the interactions between drug molecules which act as ligands and their physiological targets known as receptors while pharmacokinetics is concerned with movement of drugs within the body factors of how drug gets to its target Ligands Any molecule that binds to a receptor with some selectivity Receptors The initial site of action of biologically active agents such as neurotransmitters hormones and drugs Receptor Subtypes Agonists a Direct Agonist Mimics the action of a particular neurotransmitter b Indirect Agonist Works by various other mechanism such as inhibition of metabolism to increase the biological activity at a certain ligandreceptor complex 32 Antagonists Ligands which bind targets and subsequently suppresses the activity of a particular transmitter system A competitive antagonist is a ligand True of false Dose response curves Graphs of the relationship between drug concentration or dose and the physiological or psychological effect 35 ED50 Dose at which 50 of the population shows a response the dose at which half the maximal effect is observed 36 LD50 Dose at which 50 ofthe population dies the dose ofa drug producing toxic effects in 50 of the individuals or animals to which it is administered 37 Therapeutic Index TI LG50ED50 as an indication of the safety of a drug The higher the better 38 Drug potency Minimum amount of drug needed to produce a given effect N M N O NN W00 MM HG uh uh 5 4 l Drug ef cacy Maximum effect that a drug can produce Drug tolerance Decreased response t oa drug of the same dosage as a direct result of repeated drug exposure Sensitization Increase effect of the drug following repeated doses opposite of tolerance Pharmacodynamic cellular toleranceAs receptors are ooded with chronic administration of agonists the cell removes some of the receptors so that more drug is needed to achieve the same effect Drug disposition tolerance With the repeated use of many drugs adaptive changes take place in the systems that metabolize these drugs to enhance drug clearance The same dose of the drug now leads to lower levels of bioavailability and subject to quicker clearance so more of the drug is needed for the same initial effect a ExCytochrome P450 enzyme levels are often increased in the liver allowing drugs to be metabolized more efficiently Behavioral tolerance Seen when tolerance occurs in the same environment was administered but tolerance is not apparent or is much reduced in a novel environment a ExA heroin user usually uses in his own apartment everyday but overdoses with the same dosage at a friend s house the next day Characterize the basic features of a multipolar central nervous system neuron a Dendrites Projections from the soma that receive signals and information from other cells large surface area to increase the amount of absorption is possible S0maCell body of a neuron containing all of the organelles needed to maintain the cell Axon Hillock Connects the neuron to the axon Nodes of Ranvier Gaps in the myelin sheath that expose the axon to the extracellular uid Myelinated Segments Fatty insulating sheath that surrounds axons and increases the speed of nerve conduction It is produced by oligodendrocytes in the CNS and by Schwann cells in the peripheral nervous system Axon Collaterals Branches formed when an axon splits giving the neuron the ability to signal more cells Axon Terminals End of the axon where the signal may be passed to the dendrites of the next cell Synapses Structural unit of information transmission between two nerve cells the gap in between them 5quot as 5 Lquot g h In what way is neural communication electrochemicalThe axon that extends from the soma carries an electrical signal all the way to the axon terminals The axon terminals contain synaptic vesicles filled with neurotransmitter molecules that are released into the synapse between cells when the action potential arrives Basically it sends an electric signal which releases chemicals Resting Potential 70 mV More negative in the cell than out due to the negatively charged molecules such as proteins in the cell 48 Graded Potential AKA Local Potentials a EPSP More positive than 70 mV causes depolarization Excitatory 5 UI UIUI Ul Ul l UI b IPSP More negative than 70 mV causes hyperpolarization Inhibitory If EPSPs outweigh IPSPs once it gets to the threshold of 55 mV an action potential will occur Action Potentials Rapid change in the membrane potential that is propagated down the length of the axon Must reach the threshold of 50 mV At 50 mV the voltage gated Na channels open generating a rapid change in membrane potential Saltatory conduction The mode of action potential conduction along a myelinated neuron characterized by jumps from one node of Ranvier to the next action potential is only regenerated at the nodes Why does there need to be periodic nodes of Ranvier along a myelinated axonNodes of Ranvier are the sites at which the action potential is regenerated during conduction of the electrical signal along the length of the axon Ifthe nodes of Ranvier were not present the action potential would just dissipate before it reaches the nerve terminal What are voltage gated calcium channels Where are they located What is their role in initiating exocytosisThey initiatedocking where the vesicle and the pre synaptic membrane line up ready to fuse and are found in the membrane of excitable cells As CA2 levels increase there is an increase in protein interaction vesicles dock at membrane vesicles fuse and release NT so as calcium levels increase docking occurs followed by fusion and then exocytosis What is enzymatic deactivationdegradation Enzymes either break down neurotransmitters or convert them into inactive forms Reuptake The neurotransmitters are taken back into their original neuron Which specific presynaptic proteins accomplish reuptake The 5HT transporter and the NE transporter What happens to synaptic levels of a neurotransmitter in the presence of a reuptake inhibitor They increase over time because they cannot be taken back into the neuron so they keep piling up Is this an agonist 0r antagonist effect Explain An antagonist effect because while while agonists cause an action an antagonist blocks an agonist or prevents an action from taking place How is the nervous system subdivided Describe the major roles of the autonomic branch including the sympathetic and parasympathetic nervous systems What is meant by afferent and efferent a Central Nervous System b Peripheral Nervous System i Somatic Innervation of skeletal muscle 1 Afferent Conduct signals into CNS 2 Efferent Conduct signals away from CNS ii Autonomic Energy expenditure Sympathetic System or energy conservation Parasympathetic System 59 What are the major components of the telencephalon a Cerebral Cortex Neocortex b Limbic Cortex Allo amp Paleo includes the Hippocampus Amygdala and Cingulate Gyrus c SubCortex includes the Basal Ganglia


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