Drug Exam 3 Prep PDF

caffeine, morphine, tobacco, thc are all made from plants temperance movemnent that lead to 18th admendment (prohibition) which equated drug use to criminal behavior, repealed in 1933 disease model of drug addiction continues to be strongly promoted by the treatment community government b...

caffeine, morphine, tobacco, thc are all made from plants temperance movemnent that lead to 18th admendment (prohibition) which equated drug use to criminal behavior, repealed in 1933 disease model of drug addiction continues to be strongly promoted by the treatment community government began cointrolling commercialization of drugs with pure food and drug act of 1906 harrison act of 1914 controlled use of opiates and cocaine heroiin began as a drug marketed for coughs marijuana tax act of 1937 banned nonmedical use of cannabis, overtruned by supreme court in 1969 controlled substance acts of 1970 lead to the creation DEA and schedule of conmtrolled substance (5 schedules) consequences of prohibition in 1920 - speakeasies - organized crime rate increased 21st admendment in 1933 ended prohibition 19th admendment - womens suffarage laws have limioted ability to prevent drug use and are sometimes not consistent with science i.e nicotine is mor addictive than thc Schedule of controlled substances 1 - Have 0 medical use and high abuse rates (heroin, LSD, THC, MDMA) 2 - Have high abuse rates with severe psychic or physical dependance (opium, morphine, amph., PCP) 3 - Less abuse potential than 1&2, certain narcotic compounds and nonnarcotics (Barbituates, paregoric) 4 - Abuse potential less than schedule 3 (Xanax, valium, phenobarbital) 5 - less abuse potential than 4, containing limited amounts of narcotics (cough suppresant/antidiarrheal) (alcohol and tabacco are excluded) Addiction is complex but most definitions includ: - Physical dependence, this includes highly unpleasant withdraw symptoms during abstinence - Behavior, this includes compulsive drug seeking habits thatre driven by cravings stages of addiction include REMISSION (drug-free periods) and RELAPSE (drug use reoccurs despite negatiuve consequences) Features of substance use disorder (addiction): - chronic relapsing that includes compoulsion to seek/take, loss of intake control, neg. emotional state when no access - Substance use disorder: cluster of cognitive, behavioral, and physiological symptons indicating continued use despite neg. consequences DSM diagnostic criteria for alchol use disorder: 1 - often taken in larger amounts/for longer periods than intended 2 - persistent unsuccessful efforts to quit 3 - great deal of time spent doing associated activities (buying, drinking, recovering) 4 - strong craving 5 - Failing major obligations due to use 6 - reccurrent use despite social or interpersonal problems persisting 7 - other important activities given up in exchange 8 - repeated use in hazardous situations 9 - continued use despite obvious psychological or physiological ailments 10 - aquired tolerance (increased amounts needed for high, diminished results from using same amount) 11 - withdraw (withdraw syndrome and alleviating withdraw symptoms with substance) use of drug does not equate disorder, its the marked decline by impairment or distress due to use severity component to drug use disorder diagnosis: Mild - two to three criteria met Moderate - four or five criteria met Severe - six or more criteria behavioral addictions include compulsive gambling, excesive internet use, binge eating DSM5 includes gambling addiction with chemical addictions Gambling disorder criteria: 1 - needs to gamlbe with increasing amounts to feel pleasure 2 - restless or irritable when not gambling or cutting back 3 - repeated unsuccessful efforts to control gambling behaviors 4 - often preoccupied with gambling (compulsive thoughts, thinking of how to afford more gambling) 5 - often gambles when feeliung distressed(helpless, guilty, anxious) 6 - Chasing ones losses to get even 7 - lies to conceal gambling involvement 8 - jepordizes or loses significant relationships, job, or educational oppurtunities due to gambling 9 - relies on others for financial relief due to situations caused by gambling Cycle of pathological drug use includes: 1 - periods of preoccupation with drugs and anticipation of upcoming use 2 - periods of drug intoxication, possibly bingeing 3 - periods following drug use characterized by neg. effects and withdrawl symptoms Gateway theory implies that illegal drug use begins with legal drug use addiction potential is influenced by route of administration - oral and transdermal are slowest - IV and inhalation are rapid, therefore produce strogest euphoric effects - long term neurological changes occur from repeated rapid delivery Positive reinforcer effect, invloves preceding behaviors being strengthened by drug consumption Drug reward, refers to the positive drug experience - self administer animal studies allow us to study drug reinforcement profgressive-ratio procedure, involves animals being trained to press lever on a continuous reinforcvement schedule - responding ceases at the BREAKING POINT, which generally occurs at high doses Reinstatement of drug-seeking behaviors describes the renewed responsding to stimuli Three most effective stimuli to reinstate behavior 1 - delivering a small dose (drug priming) 2 subject animal to stress 3 - environmental cues paired with drug delivery two procedures to study drug reward: - Place conditioning, which involves animals associating one compartmetn with rewarding effect of drug - Electrical self stimulation of the brains reward circuit when performing an operant response. threshold for stimulaotion decreases when animals are treated acutely Factors that influence developement and maintance of drug addictiion: - Drug induced euphoria occurs immediately following administration but negativ eeffects develop over longer periods - Most individuals stop before developing disorder, even heroin & cocaine - Adverse effects may not be sufficient to cease use - physical dependence develops - Withdrawl symptoms are very unpleasant Koob and Le Moal proposed that drug taking behavior occurs in progressivce stages: Impulsive & compulsive - Impulsive stage involves the primary motivation being substances reinforcing effects - compulsive stage involves primary motivation being the negative reinforcement caused by relieving withdrawl symptoms with continued drug use developement stages: - repeated drug use - physical dependence - reduce levels of drug in system due to delay in obtaining - Unconditionded withdrawl symptoms (UR) - environmental stimuli associated with prior withdrawl symptoms (CS) - conditioned withdrawal symptoms, including cravings (CR) fMRI showing brains of methamphetamine men shows increased physiological response related to increased drug craving - areas include the ventral striatum, including nucleus accumbens, and the medial frontal cortex - genetic variations may also contribute to addiction (adoption&twin studies show.3-.8 fro heritability/ rest is detemrined by environment) Two genetic hypothesis': Common disease-Common variant hypothesis & Common disease-Rare variant hypothesis - CD-CV states the whole p[opulation has a pool of risk-conferring alleles - CD-RV states genetic risk for disorder stems from rare mutations and other genetic anomalies risk of developing a disorder may depend on a combination of common and rare risk alleles Approaches to studying genetics of neuropsychiatric disorders: - canidate gene anaalysis focuses on genes involved in disorder - linkage analysis - identify chromosomal regions often associated with the disorder - Genome- wide association studies investigate the entire genome to search for associated alleles There are also psychosocial variables that contribute to addiction risk: - one study found increased risk to be asociated with young age, low education, nonwhite, lack of employtment - exhibiting conduct problems during childhood and having substance using friends - stress and coping mechanisms useds - Anxiety, mood disorders, personality disorders (comorbidities) Seld medication hypothesis: stressful life events can trigger anxienty and mood disorders, such as depression, which could lead to substance use disorder in an attempt to self medicate Shared etiology hypothesis: certain factors (genetic/environment) contribute to eleveated risk of both addiction and other psychiatric disorders Personality variable that influence include: 1 - Behavioral disinhibition: links substance use to traits like impulsivity, antisociality, unconventionality, aggressiveness, and low levels of constraint and harm avoidance 2 - Stress reduction: high scores on stress traits like reactivity, anxiety and neuroticism and indicaztive of increased vulnerabilty to stress (think self medication hypothesis) 3 - Reward sensitivity: drug abuse is related to sensation seeking, reward seeking, extraversion, and gregariousness (Think drug seeking because of its positive qualities) Familial factors that have an influence include - childhood maltreatment - presence of violence - low parental monitoring What have socialcultural studies showN? - Cwhen drugs are consumed in group setting they may enhance social bonds - escapism from normal roles/responsibilities - drug can enhance solidaitry with ethnic group - distinct drug subcultures involve users embracing rituals surround drug and rejecting conventional norms and lifestyles protective factors include the abscence of the aformentioned Natural recovery (spontaneous recovery) involves long term abstinence with little or no treatment factors the contribute to drug cesation vary widely and can include positve or negative experiences - Positive includes marriage, pregnancy, spiritual experience - Negative includes health problems, financial problems, imprisonment, death of other users Risk of relapse is reduced by moving to new area, new relatiuonships with non users, employment, substitute activities like gym or meditation BIOPSYCHOSOCIAL MODEL of addiction includes all pharmalogical, biological and psycho/social factors that influence addiction risk ______________________________________________________________________________________________________________ Neuroimaging confirms that humans have a REWARD CIRCUIT, the neural circuit responsible for acute rewarding and reinforcing effects of abused drugs, that can be activated by drug and non-drug rewards (money) - different drugs affect different parts of circuit ACCTIVATION OF THE [MESOLIBIC DA PATHWAY (VTA -> NAcc)] PLAYS A CENTRAL ROLE IN DRUG REWARD AND REINFORCEMENT - drug reward often diminshes with tolerance ___________________________________________________________________________________________________________ Incentive sensitization or salience reffers to the growing difference between drug euphoria (liking) and drug craving (wanting). As addiction develops the want increases but not the euphoria - thought to occur because different brain areas are associated with these two compnents - liking may include hotspots whereas craving may include much of the circuitry Neuroadaptations in response to drug addiction: - decrease in drug reward due to within-system adaptations in reward circuitry, resulting in progressive down regulation of activity - between system adaptations involves the gradual recruitment of the antireward system - antireward system is marked by increase in release of NE and neuropeptides corticotropin releasingfactor (CRF) and dynophrin System acts to limit rewardss and mediate some of averse affects - activated during drug withdrawl and plays major role in it and negative reinforcement Koob & Le Moal model propose the neural mechs responsible for affect (mood & emotion) provoke an intitial strong reaction (pleasure & discomfort) and automatically set in motion an opposing response that occurs after initial stimulus ends. - also proposed that allostasis gradually changes the baseline hedonic state (i.e. mood) of thew drug user ALLOSTASIS: a physiological, behavioral, or psychological variable that if repeatedly challenged (e.g. by drug exposure) mantains stability by changing its set-point Brain imaging shows that abnormalities in structure/function of PFC are common among addicts PFC plays central role in executive function and contributes to regulation of emotional and motivational processes - dysfunction in PFC and associated areas hypothesized to play key role in preoccupation/anticipation stages of addiction - stage characterizwed by intrusive thinking, drug craving, and lack of impulse control intrusive thinking linked to abnormal pathways from PFC, hippocampus, and amygdala to the ventral striatum - cue induced craving correlates with activation of the dorsal lateral prefrontal cortec (DLPFC), Orbital frontal cortex (OFC), Anterior cingulate cortex (ACC), dorsal and ventral striata, and insula - insula has been implacted in motivational regulation, including drug craving and control over drug use ___________________________________________________________________________________________________________ Intrusive thinking: AMYGDALA, HIPPOCAMPUS, PFC, AND VENTRAL STRIATUM PATHWAY ABNORMALITIES Cue induced cravings: ACC, DORSALATERAL PFC, DORSAL&VENTRAL STRIATUM, INSULA, AND ORBITAL FRONTAL CORTEX Moticational regulation (craving & control): Insula ____________________________________________________________________________________________________________ drugs of abuse affect expression genes and thus proteins they encode for - neuronal proteins can increase or decrease due to drug use - three categories of proteins: a, b, c - Category A proteins may help mediate drug-induced behavioral and physiological reponses that undergo tolerance - Category B proteins may play a role in the transition from recreational use to addiction - transcription factor FosB rapidly induced in the NAcc and dorsal striatum, last several weeks in NAcc - mice that overexpress have enhance sensitivity - proteins regulated by this factor are involved in glutamate transmission and structure plasticity - Category C proteins might be important for maintaining the "addicted" state - FosB transcription factor modulates gene expression by epigenetic mechs: - DNA methylization represses transcription (down-regulation of proteins) - Histone acetylation promoting transcription (up-regulation of other proteins) Epigenetic regulation is seen as an important factor in substance use and addiction vulnerability Depending on drug and gene of interest, chronic exposure to drugs can: - prime gene to be more strongly expressed in response to later drug use - desensitize gene, repressing expression during later drug use Epigenetic mechs include inherited predispositions (genes and epialleles) and environmental stimuli (life stressors) - these plus acute drug exposure can lead to epigenetic changes (think DNA methylation (down-reg) and histone modification (up-regulation)) - suseptibility to addictive disorders are influenced Epigenetic changes in gene expression have been implicated in greater risk of substance use disorder and early childhood maltreatment - can occur in germ line, so parental experiences play a role Disease/medical model of addiction is based on evidence of neuroadaptations cause by repeated edrug use - arose from work on alcholism - used by most 12step programs - impacts societal perception of addiction, with earlier views being addiction/drug use as moral/personal weakness - reduces sense of guilt in redcovering addicts Criticisms of disease model include: - whether brain changes in addicted ppl are pathological, causing a disease state, is questioned because all experiences influence afferct structure/function of brain - addiction can only be diagnosed on basis of behavioral symptoms (no lab test), all dependent on mental/berhavioral symptoms observed by physician - people recover without treatment, and users exhibit cognitive control of cravings and associated regional brain activations - nondisease theories argue addiction rises out of the drug serving a purpose - Brain centric view pays too little attention the the whole person, and few drugs aid in treatmen - lack of progress in research based off this model, suggest psychosocial roots run deeper than expected how does disease model affect empowerment/self-efficacy, both of which are great recovery resources? contigency management is the idea that you incentivise someone to come into treatment with compensation ---------------------------------------------------------------------------------------- THERAPEUTICS FOR SUBSTANCE USE DISORDERS: Pharmacotherapy 1. cigarettes and vaping - Treatments include behavioral interventions (antismoking media, surgeons warning, high taxes) - counselling programs that provide social support and traning in coping skills - Pharmacological intervention: Nicotine replacement therapy and bupropin/zyban - NRT involves nicotine being delivered in safer ways to relieve withdrawl symptoms (gum, patches, nasal spray). Often available without prescription. still concerns about CV toxicity. little info on effectiveness. - Bupropin, initially an antidepressant, has antismoking properties related to its role as a reuptake inhibitor of DA and NE and as a weak nAChR antagonist. - Varenicline (CHantix) is a partial agonist at high-affinity for nAChRs expressed in VTA and other brain areas. elicits a moderate amount of receptor activation, rather than full full activation like nicotine. reduces cravings and withdrawl effects Advantages and Disadvantages of NRT: Gum - advatge is ease of use, availability, flexibility - disadvantage is need frequent dose, mouth soreness Lozenge - advatge is ease of use, availability, flexibility - disadvantage is need frequent dose, heartburn, idigestion Transdermal - advantage is ease of use, availability, few side effects - disadvantage is less flexible dosing times, possible insomnia with overnight use Nasal spray - advantage is flexible dosing, rapid delivery, reduced craving - disadvantage is need for frequent dosing, nose+eye+throat irritation Inhaler - Flexible dosing, similar to smoking act, few side effects besides throat irritation - disadvantage is need for frequent doses 2. Alochol use disorder -Treatments include detoxification, psycho social rehabilitation programs, CBT, community reinforcement approach, and pharmacotherapeutics - Detoxification comes with withdrawl symptoms, which are strong motivators but also psychologically dangerous - Benzos such as librium or valium are given to prefvent severe withdrawl symptoms -Psychosocial programs help to prevent relapse - may provide residential alcohol-free treatmnet settings - individual (CBT) or group therapy (AA, CRA) -Pharmacotherapeutic treatment work to make drinking unpleasant or reduce alcohols reinforcing qualities\ - Antabuse inhibits ALDH, which works in the metabolism of alchol by converting acetaldehyde to acetic acid. Drinking alcohol results in flushing, nausea, vomitting, increased HR - Naltrexone is an opiod recptor antagonist; reduces consumption and craving, improving abstinence - assumed to reduce subjective high feeling by blocking effect of endorphin release fropm alcohol - genetic factors seem to influence effectiveness, as well as accompaning treatments (counselling) - Nalmefene is an opiod recptor modulator that is more effective in animal models - Acamprosate acts as a partial antagonist at the glutamate NMDA receptor, significantly blocking the glutamate increase that occurs during alcohol withdrawl in rats. possible positive allosteric modulator of GABBA receptor effdects - New treatments may involve CRF antagonist. Patterns of addiction have lead to increwased CRF gene expression in amygdala, sensitization of reasctivity to stimuli, and sig. elevated consumption Glucocorticoid receptor (GR) signalling may have a role in compulsive alcohol consumption - admistration of GR antagonist in rats reduced alcohol self administration Another target for stress modulation is the neuropeptide substance P and its receptor, NEUROKININ 1 RECEPTOR (NK1R) - blocking NK1R reduces anxiety, alcohol consumption, and relapse - individuals with AUD who had NK1R antagonist increase saw reduced cravings when exposed to cues COMBINE: Combining medication and Behavioral intervention - most effective treatment was naltrexone or cognitive behavioral intervention NO specific treastment for inhalants; stadard approaches such as CBT, 12step programs, and other social therapies NO specific treatment for GHB - However high doses of benzos can help with withdrawl side effects - high relapse in protocol using Xyrem NO specific treatment for cannabis - most users do not become dependent or seek treatment - standard approaches such as CBT, relapse prevention, etc. but pts. are very susecptable to relapse - some meds releive withdrawl symptoms but not long lasting realiablity - Nabiximols, cannabinoid agonist, reduce withdrawl effects but no effect on abstinence rate\ Opiod use disorders often use a biopsychosocial model due to the multidimensional nature of chroinic drug us - includes physiological effects, psychological state, and environmental factors - detoxification is the first step and can be assisted by longer lasting opiods such as methadone - Clonidine is an a2-adrenergic agonist, acts upon noradrenergic autoreceptors to reduce NE activity in the locus coeruleus (NE neurons are inhinbited by opiods, and cells increase in firing during withdrawl) - Withdrawl has also been treated with electroacupuncture (EA). EA restyored low levels of prodynophrin mRNA to normal levels in spinal cord, hypothalamus and Periaqueductal gray (PAG) in rats - suggest withdrawl suppression is assisted by increased dynophrin synthesis Methadone Maintanence Program (most common treatment) - long term substitution of methadone reduces cravings and allows addicts to redirect energy away from drug attainment - significant risk for accidfental overdose at start due to difficulties in determining individuals tolerance - cross dependence with heroioin due to it being an opiod, this helps with preventing symptoms, this also reduces euphoric effects of heroin helping to prevent relapse - can produce a high if injected, risk of illegal diversion of intended drug use. programs require supervision - oral administration of methadone also eliminates cues associated with heroin, such as needle use - long-acting effects creat stable plasma levels and helps to normalize function, such as hormone secretion - daily contact with program staff also provides behavioral therapies Buprenorphine (Buprenex) is a partial opiod agonist used in same way as methadone, with weaker effects and longer half life - doses r 1-3/wk, allowing more freedom for afflicted - Available as Suboxone, which contains antagonist naloxone. Taken sublingually, Buprenorphine is absorbed but naloxone is not. If injected, the naloxone with block buprenorphine euphoric effects. Suboxone can be abused if snorted. - ED visits due to buprenorphine have increased fivefold from 2006 to 2011 - New option, Probuphine, offers an implantable option, which could enhance compliance and prevent diversion - Associated with lower risk of birth complication when comparedf to methadone in trateing withdrawl symptoms in pregnant women Some treatment programs use narcotic antagonist such as Naltrexone or Nalmefene - Naltrexone (trexan) is commonly used for its longer duration of action vs naloxone, effective orally and has few side effects - Nalmefene 9revex) is a newer opiod antagonist and is similar to naltrexone but more potent and longer lasting An opiod vaccine is being devloped to produce antibodies that would bind to the drug molecules in the blood circulation and prevent them from entering the brain - been tested in rats for heroin Multidimensional approach includes detoxification, pharmacological support and individual or group therapy counselling helps individuals identify environmental cues and design behavioral response for them Narcotics Anonymous NO treatment for benzos -Flumazenil, a benzo antagonist, has high affinity binding to GABAa complex, but shows no activity - Blocks access of active benzos, effectively reversing effects - used for its role as an antidote to benzo overdose, has advantage of short half life NO currently licensed treatments for cocaine and other psychostimulants - psychostimulants that increase DA transmission at lesser levels are being explored, similarly to how methadone is used - neurotransmitter systems such as noradrenergic, serotonergic, glutamatergic and GABAergic systems are being explored - antibody treatment is explored buyt its easy top overcome with increased amounts of drug BEHAVIORAAND PSYCHOSOCIAL THERAPIES: -Psychosocial treatment programs taht involves individual, group, family counselling to educate user and promote behavioral change and alleviate harmful symptoms - CBT aims to restructure thought processes and training users to avoid high risk situation or apply positive coping mechanisms (aka relapse prevention therapy) 12 step programs such as NA, AA, CA Contigency management plan is based on premise that drug taking is an operant response that persist because of reinforcing drug properties. assumes you can replace with another reward, or alternat reinforcer, thatd help reduce druh use. Community reinforcers that enhance relationships or oppurtunities are also useful Substance dependance is a chronic illness. No treatment fits all. continued care maybe required throughout life. worth treating because it saves lives, reduce crimes, and increases employmenty rates. SAVE LIVES ------------------------------------------------------------------------------ CAFFEINE Major source of coffee is the coffee beans, the seeds of the plant coffea aarabica tea leaves have caffeine and a similar compound called THEOPHYLLINE CaFFein and thephylline are members of a group of plant derived chemicals called METHYLXANTHINES 165mg/day avg consumption for US adults completely absorbed in 30-60min, 4hr half liofe stimulating and fatigue reducing affects, but tension and anxiety may occur at high doses. subjective reports of enhanced concentreation and viogor intake/tolerance can affect sleep, cardiovascular and respiuratory function withdrawl includes headache, fatrigue, impaired concentration, mild anxiety or depression caffeine doesnt meetr5 criteria for being considered adictive because generally it does not interfere with dail living acute intake leads to an increrase in BP, HR, Diuresis, and stimulation of catecholomine release from adrerenal medulla nicotine decreases caffeine metabolism. pregnant women metabolize more slowly Caffeine intoxication is associated with recent 1000+mg dose. Restlessness, insomnia, tachycardia, nervousness, muscle twitching, GI upset Caffeine dependence syyndrome/use disorder is controversial THERAPEUTIC USES: - Potentiates analgesics - Effectine in treatment of apnea in premi's, regulize breathing - could assist in asthma and cough (theophylline and theobromine (part of methylxanthines)) - possible ADHD treatment - reduce parkinsons risk - athletic performance CAFFEINES ACTION ON THE BODY - Blockade of GABAa receptors - Stimulation of CA2+ release WITHIN cell - Blocking of A1 & A2 adenosine receptors A few cups of coffee will only initiate blocking of adenosine receptors Blockade of A2 receptor may be the cause caffeines induced behavioral stimulation (a subtype of purinergic P1 receptor) ADENOSINE has a neurotransmitter like function in the brain. ONLY EXTRACELLULAR adenosine has access to tthe adenosine receptors - most of the adenosine here comes from the breakdown of ATP, which is released from other cells and transported through channels called PANNEXINS outside the cell, ATP acts on PURINERGIC recptors P2X & P2Y. ATP can also be broken down by enzymes into adenosine FOUR adenosine recptor subtypes - A1 & A2a mediate most of adenosine effects in brain and ar emajor caffeine targets - primary location of A2a receptors is on the GABA a output neurons in the DORSAL STRIATUM (caudate-putamen)and VENTRAL STRIATUM (NAcc), rich in DA receptors A2a receptors may form heteromers (join) with D2 receptors In these heteromes, when the A2 receptor is occupied by adenosine there will be a lower affinmity (allosteric influence) for DA on the D2 receptors. This causes a decrease in the arousing and behavioral activating effects of DA Caffeine blocks the adenosine receptors, enhancing D2 signalling, leading to mild arousal and psychomotor activation MONSTER AND PEPSI IS SHANES FAV DRINKS KOLA NUT BIGGEST SOURCE OF CAFFEINE