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90 Cards in this Set
- Front
- Back
changes in the brain due to addiction
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tolerance, sensitization(cravings), dependence, withdrawal
Mesolimbic DA: VTA to NA |
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too much vs too little
DA 5HT NE ACh |
DA: XS -- Schizophrenia, Neuroleptic malignant syndrome, Addiction (mesolimbic)
DA: deficit -- Parkinson's, EPS, ADHD? 5HT: XS -- 5HT: deficit -- depression NE/Ach deficit - ADHD?? |
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what does the addicted rat want to inject where?
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DA/Amphetamine/Cocaine into NA
opiates into VTA (disinhibition causes DA release in the NA) DA as final common pathway Ethanol, Nicotine, Cannabis cause increased DA into the NAcc |
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relapse triggers
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low dose drug exposure(priming)
drug associated cues Stress |
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cross priming
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person addicted to cocaine should not start with alcohol because that will cause them to relapse with the cocaine
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alcoholism stats
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50% have comorbidity
women: anxiety and mood DO men: substances, conduct DO, antisocial PD Bipolar and secondary alcoholism 25-55% of alcoholics develop a secondary depression alcoholism = depression as suicide risk! |
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questions for alcohol addiction
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CAGE
Cut down? Annoyed? Guilty? Eye opener? |
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NT affects of Alcohol
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potentiates GABAa
inhibits NMDA 5HT3 R potentiation mu opioid receptor alcohol promotes agonist binding mesolimbic DA Ssystem - reinforcing |
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GABA binding
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Alcohol
Benzodiazepines Barbituates all help with seizures - withdrawal from these substances causes seizures |
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management of alcohol intoxication
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nutritional support
IV thiamine then alcohol |
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amnestic disorders that are alcohol induced
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Wernicke's encephalopathy
-thiamine deficiency -abrupt onset of encephalopathy -truncal ataxia -opthalmoplegia Korsakoff's psychosis - chronic -severe anterograde amnesia -confabulation -thalamic nuclei and mamallary bodies frontal lobes |
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Alcohol withdrawal
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autonomic hyperactivity (increased HR, BP, RR, T, sweat)
anxiety Insomnia Psychomotor agitation N/V tremor rare: auditory, visual, tactile hallusc/illsn, grand mal seizure peak at 3 days (lasts 7-10) |
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delirium tremes
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1/3 of pt with seizures go on to develop DT's with more medically compromised populations
confusion disorientation fluctuating/clouded consciousness perceptual disturbance mortality 1-2@ (emboli, arrhythmias, metabolic disturbances, ifxn, hyperkalemia, hyperpyrexia, dehydration |
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management of Alcohol withdrawa;
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Benzodiazepines (silver bulled to Alco withdrawal) Lorazepan
... |
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after detox - now treat the addiction
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denial is major defense mechanism
family help with intervention - might occur over time. |
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first step in AA
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we admit that we are powerless over alcohol and that our lives have become unmanageable (to overcome the denial)
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two approaches with alcoholics
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1) make sure the depression/bipolar are treated
2) Naltrexone(opioid antagonist), Acamprosate, Disulfram |
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naltrexone
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opioid antagonist
reduces craving easier to say no |
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acamprosate
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GABA ergic -
reduces cravings easier to say no |
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whats better than treatment with either naltrexone or acamprosate??
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treatment with both!
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disulfiram
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alcohol sensitizing agent
inhibits Alcohol dehydrogenase buildup of acetaldehyde --> disulfiram - ethanol reaction complication - quite ill if they do binge on alcohol bad: doesn't help with cravings some patients take all three togehteR: naltrexone, acaprosate, disulfiram |
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alcohol physical sx
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increased MCV (vit 12 deficiency)
B1 - thyamine deficiency |
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opioid - opiates
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opiates: opium and naturally occurring derived drugs = morphine and codeine
opioid: synthetic, different chemically, but acting at the same receptors: hydrocodone (vicodin) all euphorogenic capacity to reinforce avoidance of averse feelings will reinforce (withdrawal is so bad) |
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opioid intoxication
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sedation
euphoric, constricted pupils- the PS is activated - patients are relaxed, slurred speech |
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opioid withdrawal
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agitated, anxious, DIALATED PUPIL, dysphoric mood +
flu-like: nausea, vomiting, muscle aches, diarhea lacrimation, insomina |
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OD opiate
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reverse the opium intoxication: opium antagonism via:
NALOXONE (20 min half life - very short) |
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opioid detoxification
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methadone (mu receptor agonist)
clonidine is an antihypertnesive used to make the withdrawal more barable Buprenorpine - partial agonist on mu |
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opioid dependence
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after detoxification - now treat the addiction
maintenance therapy: mu replacement: methadone (also detox agent) LAAM buprenorphine (parital ago - can't die from the OD of this) naltrexone (reduce cravings - helps that heroin doesn't give them the high anymore) |
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careful with ??? after OD heroin
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naloxone will wear off fast - 20min - don't let the OP pt go - we should treat them - prognosis is bad for the long term -
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benzodiazepines with half life differences
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help with sleep, anxiety, panic, anti-seizure,
the lower the half-life, the more dangerous for addiction - ex: Xanax is most addicting, then valium (diazepam) also: they cause dependence and abuse, paradoxical agitation, disinhibition, |
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prescription sleep
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Benzodiazepine-like:
Zolpidem (Ambien) Zaleplon (Sonata) Eszopiclone (Lunesta) |
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when do we do maintenance treatment?
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if the condition has progressed to for example severe heroin addiction, the patient should be kept on maintenance treatment - however, if the patient is not that addicted, we want to get them clean of the substances - and not use the maintenance = just more mu ago: methadone/buprenorphine
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cannabis intoxication
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>4000 years old
gateway hashish - resin intoxication: dry mouth, tachycardia, red eyes, appetite changes |
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cannabis withdrawal
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mild flu-like:
irritable, tremor, diaphoresis, nausea, appetite changes, sleep disturbance, similar to opioid withdrawal in animal studies with synthetic cannabinoid antagonist |
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cannabis chronic abuse sx
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cognitive difficulties
impaired motor function depression paranoia psychosis feminization amotivational syndrome |
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cocaine speed of reactions with different modes of acqusition
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intranasal: 2-3min
injection dissolved cocaine (IV): 15-30s smoking "crack" cocaine ": 6-8s crack: It is a freebase form of cocaine that can be made using baking soda (sodium bicarbonate) or sodium hydroxide,[1] in a process to convert cocaine hydrochloride (powder cocaine) into methylbenzoylecgonine (freebase cocaine). |
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cocaine mechanism of euphoria
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increased DA/NE/5HT
simulant essentially ! inhibition of reuptale mesolimbic DA system |
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pupils with cocaine
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DIALATED (vs opiates)
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treatment for cocaine dependence
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12 step, behavioral
wellbutrin? cocaine vaccine! ! |
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personality =
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character+temperament
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devoted becomes what pathologically?
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dependent
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self confident pathologically?
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narcisstic
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vigilant pathologically
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paranoid
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mercurial (loves relationships, energetic, shows how they feel, creative, explorative, skilled at distracting from reality when it's painful)
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borderline
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adventerous pathological
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antisocial
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aggressive pathological
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sadistic
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serious pathologicallt
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depressed
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conscientious pathological
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obsessive compulsive
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dramatic pathological
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histrionic
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solitary pathological
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schizoid
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sensitive pathologically
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avoidant
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leisurely style pathologically
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passive-aggressive
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borderline and treatment
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they get more anti-depressants than MDD! hard to control -
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treatment of PD
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1) heterogenous group, treatment not "one fits all"
2) tx plan should address axis II plus co-morbid Axis I conditions 3) both psychohterapy and pharmacotherapy should always be considered 4) motivation for tx varies greatly among PD 5) Cluster A are very mistrustful 6) Cluster B can seek tx (BPD, HPD) deny the need for tx (ASPD, NPD) be untreatable (ASPD) 7) cluster c will seek tx, 8) have to be flexible |
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schizotypal
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common markers with schizophrenia
and they have + sx |
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schizotypal
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hallucinations,
once a week was enough very violent scary dreams derealization feelings anxiety overwhelmed spending sprees- impulsivity self-destructive chaotic mental states after 4 yrs he realized that medication might work - TCA and then MOA - carbamate she had to be on meds |
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stimulant danger
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cerebrovascular vascoconstriction
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what outdoes food and even sex with respect to DA stimulation?
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Amphetamines!! ! and also cocaine and even nicotine and morphine(slower onset)
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DA inactivation? and then cocaine?
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reuptake
binds to the reuptake inhibitor!! (amino acid transporter- 2 states of helix springs - actin like) |
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in nl state of DA vs stimulators
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with chronic use of amphetamines -- the DA transporter is upregulated;
the receptors on post symaptic are also downregualted because they have been bombarded with DA for so long Also MAO - bkdn DA - the metabolate forms 6hydroxine overactive neurons are killed too much knowledge can give you seizure/stroke! |
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brain scans of PD vs Cocaine/Amphetamine addicts
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due to cytotoxicity of the metabolite of MAO with too much DA - the striatum looks equally affected
the D2 receptors are degenerated |
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life just sux
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they need a supercharge od DA to stimulate the reward sx
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3 ways to diminish DA In the synapse
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transporter is upregulated, cells that make the DA are killed, receptor function is reduced - don't recover even after 4month abstinence
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learn
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glutamate to learn, GABA to stay seated
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D2 receptor
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decreases correlated with decreases in orbitofrontal and cingulate brain metablism in stimulant abusers
frontal ctx needed for getting in / staying in med school |
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stimulant abusers perfusion
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adherent platlets, vasoconstriction
occipital brain perfusion defect occipital bad perfusion - made last as with fontal ctx blood supply serves the other areas well |
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depending on the stickyness of your platelets
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right insula (reptitive)
cingulate (decision) temporal (auditory) occipital )calcarine cortex 2nd dorsal stream frontal eye fields |
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cocaine abusers and the sad videotape
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they are not emotionally affected, - they are only activated by people takinf cocaine - cocaine clues
they are inhibiting themselves not to go and steel... automatic - there is no real thinking involved - they see it they act |
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GABA and cocaine
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GABA deficit after chronic cocaine
cortical CBF reflects mostly GABA inter-neuronal activity GABA activity reduced during visual activaton to usual cues like sadness compared to normals cocaine cues lead to over- arousal in users but are irrelevant to normals, so little visual cortex activity in normals. they don't understant complex emotional events that they are seeing cocaine abusers can not decide quickly stimulat abusers--> DA deficiency like PD vasoconsticaion - corical affective sensory stimuli |
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beta endorphine and naltrexone
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block the feedback - presynaptic blockade
post synaptic are also blocked by the naltrexone - but there are many more receptors in the presyatpticl cell the b-endorphins don't rise with sb with no addiciton |
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naltrexone works best if
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you're worse off
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genetic responsitivity to naltrexone
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G-protein coupling is intense
naltrexone works much better with sons of alcoholics |
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prone to alcohlism
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low lvs of beta-endorphines
of you give them ONE drink - they get a very big charge out if it |
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mu opiate receptor knockout
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don't like alcohol
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the farthery you go north there is
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more and more this polymorphism
high genetic risk of alcoholism |
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polymorphism with altitude
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the beta endorphine helps you withstand pain
3 fold greater affinity with beta-endorphines they have low levels of beta- endorphine bc they have a sensitive receptor then when they are stimulated they have a 3x increase of halliness |
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nicotine drugs
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Nicotine patch, gum, lozenge, inhaler, spray
Bupropion Varenicline: Partial nicotinic receptor agonist |
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personality disorders A-C
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A: schizoid, schizotypal, paranoid
B: nihilistic, histrionic, borderline, antisocial C: avoidant, dependent, OCPD |
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treatments for stage fright
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beta blockers - -olols
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treatment for hypochondriac
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imipramine, fluoxetine, paroxetine
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only SSRI approved for only OCD
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furoxetine
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drug for GAD
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SSRI / SNRI / TCA
or transient: Benzodiazepines specifically: fluoxetine, paroxetine, escitalopram, citalopram, sertraline |
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difficulr DD-ineractions antidepresant
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nefazodone 3A4 enzyme
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buproprion
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seizure counterindicated, not for anxiety disorders
no serotonin activity no sexual side effects |
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antipsychotics
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typical: D2 antagonism: haldoperidol (high potency - you don't need alot, so there is little Ach SE) vs Clopromazine(trazodone) which is low potency (less risk of Neuroleptic malicnancy disorder, and less EPS)
Atypical - shorter D2, 5HT2 compoent: Quetiapine, Olazepine (wieght gain) Clozapine (weight gain) Abilify - aripirazole Ziprasidone (no weight gain) Risperidone (peds, dose dependent - can become typical AP) perospirone Paliperidone |
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varenicline
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as the dose increases, slowly produce a blocker - they won't feel good
must start with slow dose - CHANTIX partial BLOCKER at the NA |
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selegiline
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MOA-I inside tabacco smoke!!
so, when you stop smoking - thy get sad - and to replace the smoke antidepressant - we use segiline |
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SERT
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ss prone to depression after repeated stress
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NE and DA in the prefrontal cortex
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attnetion and positive moor goal directed behavior
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2D6 inhbition
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some SSRI block this - and this one might be needed for the breakdown by this ezye - and the other drug will go up to toxic lvl 3A4 inhibition is worse
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