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week 7

by: Emma Notetaker

week 7 NSCI 4530

Emma Notetaker
GPA 3.975

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week 7 of notes
Dr. Donhanich
Class Notes
25 ?




Popular in Psychopharmacology

Popular in NSCI

This 5 page Class Notes was uploaded by Emma Notetaker on Tuesday October 11, 2016. The Class Notes belongs to NSCI 4530 at Tulane University taught by Dr. Donhanich in Fall 2016. Since its upload, it has received 14 views. For similar materials see Psychopharmacology in NSCI at Tulane University.


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Date Created: 10/11/16
Sunday, October 9, 2016 Week 7 Amphetamines • **keeping nt inside vesicles is similar to ion trapping - pH used) • drug names: • 1. chemical : (S)-1-phenylpropan-2-amine 2. generic: dextroamphetamine • • 3. trade: dexedrine • amphetamines: very similar in structure to norepinephrine • amphetamine-like compounds • ephedrine (ma huang) - natural plant • stimulant, anti-asthma dilates bronchial tubes • • stimulate respiratory centers in medulla • first general stimulant • not for severe asthma, but for bronchial congestion • meth made from these • fenfluramine (serotonin releaser) - weight control phenylephrine (alpha 1 agonist) - decongestant • • formulations of amphetamine: • dextrolevoamphetamine (Benzedrine) • racemic (both isomers) • least potent • dextroamphetamine (Dexedrine) active isomer (only one of the two) • • dextromethamphetamine (Desoxyn) • most potent form in CNS • likely because it enters the brain more easily • added methyl group to amphetamine • isoproterenol stimulates beta-adrenergic receptors, which are only on some sympathetic tarter organs • (including bronchial muscle) • doesn’t cross BBB, so doesn’t have much CNS stimulation (makes it good for medication) • does have adverse heart effects bc beta adrenergic receptors are there too • bath salts • cathinone (khat extract), synthetic cathinones, mephedrone intranasal, oral, IV, IM • • amphetamine-like effects • administrations: • all forms: oral • methamphetamine powder: intranasal and IV • burned methamphetamine crystals: inhalation absorption: • • weak base: • increasing pH increases GI absorption rate (orally) • very rapid absorption via inhalation • onset/duration of action 1 Sunday, October 9, 2016 • oral: onset in 30 min, variable duration • inhalation: onset in seconds, duration of 15 min • distribution: crosses BBB • metabolism • via liver • first order • elimination • increased excretion at lower renal pH (very susceptible to the effects here) • due to basicity • half-life • 6-36 hours depending on renal pH (wide range) • metabolites persist up to 3-5 days after last administration, much longer in heavy users • mechanisms • subvert reuptake mechanisms for NE and E • attachment causes transporter to release NE • amphetamine recognized as NE, so actually enters the cell (via reuptake) • leakage of DA/NE because such a large concentration already inside cell • increased pH inside vesicle due to amphetamine • this causes unionization of NE/DA and they start leaking through membrane • inhibits MAO to reduce DA/NE breakdown (MAO goes after amphetamine, so there is less to break down dopamine and norepinephrine) • reverse transport of DA/NE into synapse (nt leave through same transporter) • —> increases catecholamine release! • mimic activation of the sympathetic nervous system - increases function of norepinephrine/ epinephrine • acute effects: VERY similar to cocaine • cognitive and behavioral • arousal, alertness, wakefulness, energy • increased concentration, decrease in distraction • confidence, euphoria, sense of well-being • euphoria caused by dopamine in VTA • increased activity, improved physical performance • body weight • increases general activity, suppresses appetite, decreases digestion • reduces weight • peripheral side-effects (sympathomimetic) • increased heart rate, blood pressure, respiration • dilation or airways and pupils • inhibited digestion • decreased salivation • urinary retention • increased metabolism and body temp • toxic effects: • headache, dizziness, confusion, agitation, fatigue, insomnia • seizures, cardiac arrest • dental disease - “meth mouth” • dry mouth (sympathetic activation - thickened saliva) • clenching (Bruxism) • poor hygiene 2 Sunday, October 9, 2016 • stimulant psychosis - possibly due to dopamine dysfunction • paranoia • delusions • hallucinations • stereotypy - highly repetitive motor patterns • neurotoxicity: not associated with cocaine, just amphetamines • measures of dopamine transporter via PET scan • fewer axons in dopaminergic neurons due to amphetamine (looks similar to those with Parkinson’s) • —> loss of striatal DA in stimulant abusers • therapeutic uses: • legal uses: • narcolepsy • ADHD - helps them increase concentration (not necessarily calm down) • most common condition treated by amphetamines • paradoxical effect: amphetamines used to treat both narcolepsy and ADHD • off-label therapeutic uses • obesity • very ineffective, due to quick tolerance build-up • depression - very low doses, not a typical treatment • ADHD subtypes: • predominantly inattentive • hyperactive/impulsive • combined • is ADHD a dysfunction of the PFC? • executive function (right PFC) • attention • planning • impulse control • mental flexibility • monitoring actions • PFC lesions (right) • distractibility • disorganization • impulsivity • perseveration • forgetfulness • PFC confers inhibition on other brain regions • basal ganglia • cerebellum (via pons) • motor and premotor cortices • dopamine modulates neuronal excitability in frontal cortex and limbic • microdialysis in vivo measurement of transmitters • methylphenidate (MPH) increases NE and DA release in PFC • ADHD treatment formulations • dexedrine - dextroamphetamine (1-3) • adderall - amphetamine salts (1-3) • ritalin - methylphenidate (2) • concerta - methylphenidate ER (1) 3 Sunday, October 9, 2016 • daytrana - methylphenidate ER (1) • strattera - atomoxetine (1-2) • non stimulant • noradrenergic reuptake blocker • less effective than psychostimulants • lower risk of abuse • vyvanse - lisdexamfetamine (1) • prodrug • converted to D-amphetamine • longer duration of action • lower risk of abuse • therapeutic effects of psychostimulants for ADHD • improve attention span and focus • increase ability to follow directions • decrease distractibility • decrease impulsivity, stubbornness, aggression • ADHD psychostimulants side effects • increased heart rate and blood pressure • nausea, dizziness, headache • insomnia • poor appetite, weight loss • suppressed growth • cardiovascular issues • abuse potential • • drug tolerance • reduced effect after repeated administration • increased dose restores original effect • tolerance varies wth drug and drug effect • psychostimulant tolerance • rapidly forming • appetite suppression • euphoria • cardiovascular effects • slowly or non forming • effect on narcolepsy • effects on ADHD • reverse tolerance (sensitization) • seizures • locomotion • physical dependence • withdrawal • opposite of acute effects • psychological dependence • reinforcing effect of drug • psychostimulant dependence • physical • fatigue/exhaustion • prolonged sleep 4 Sunday, October 9, 2016 • depression/crash • intense hunger • psychological • extremely powerful, intense craving • anhedonia • self-administration • physical dependence model (Wikler) • initial drug use —> repeated use —> physical dependence —> attempts at abstinence —> withdrawal symptoms —> relapse —> attempts at abstinence —>…. • Koob: same model but brain experiences reinforcing effect of drug (positive reinforcement) • physical vs psychological dependence • positive reinforcement • self-administration • conditioned place preference • determine pre-drug compartment preference • condition non-preferred side to drug • condition side to vehicle • test post-conditioning preference without drug • mesolimbic pathway (DA) • VTA —> nucleus accumbens • cocaine blocks DA reuptake • prevents dopamine transporter from working, which allows DA to accumulate • amphetamine stimulates DA release • amphetamines bind to transporter and are carried into the neuron • promote the leakage of DA from vesicles • intracellular DA transported outwards • incentive-sensitization model (Robinson): brain becomes sensitized to effects of drug • this increases DA activity and alters brain structure • dendritic remodeling in nucleus accumbens • axons from VTA release dopamine • increased spines • dopamine in NA is key factor in drug addiction • xanthine: purine related to uric acid • caffeine, theophylline • caffeine inhibits phosphodiesterase, which metabolizes cAMP • blocks adenosine (depressant) 5


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