Drugs and Behavior Exam 2 Flashcards

Terms Definitions
dyskinesia
abnormal motor function
Nefazodone
-generic
-blocks
Serzone
 
-blocks 5HT2a
-possible solution to SSRIs side effects
Dopamine
Mostly inhibitoryMetabotropicInvolved with movement control, attention, and learningImplicated in Parkinson's, schizophreniaMost importantly: reward system of brain
Agonist
Activates receptor fully
Phosphate
HydrophilicPart of membranes
RIMAs

eg.
Reversible Inhibitors of MAO
-eliminates problem of dietary/med restrictions
 
-tyramine or other amine would push RIMA off MAO
 
eg. Moclobemide
Befloxatone
Teloxantrone
Brofaromine
Glutamate
"workhorse"Most prevalent excitatory NTAmino acid transmitterIonotropic and MetabotropicFormation of memoriesHighly toxic when out of control
Khat
Cathinone = active ingredientChewedSynthetic Version = meth-cathinone
CATIE Trial (clinical antipsychotic trials of intervention effectiveness) sponsored by National institute of mental health
Tachykinins receptors
NK1- SP
NK2- Neurokinin A
NK3-neurokinin B
 
-SP receptors are used in stress (pain, vomiting, asthma, migraing, inflammatory bowel)
Ionotropic Receptors
Fast receptorsClose/open ion channelsAlters charge of cell
Schedule II
Morphine, Cocaine, Ritalin, Amphetamine, Methamphetamine, Oxycontin
Absorption: Affected By
Route of administrationLipid-solubilityForm of drug (solution vs. suspension; pH)
Opioids
Compounds with opiate-like actions (synthetic endogenous opioids)
Rectal
EnteralHas enormous variability of absorption.
Abilify (general description)
-AKA Aripiperazole
-First 3rd generation antipsychotic
-incorporates concept of DA modulation or balance rather than blockade
neurogenic Theory

evidence
-suggests that altered neurogenesis (birth and survival of new neurons) relates to depression, Depression kills brain
 
Evidence: smaller hippocampus in depressed patients
Bupropion
-generic
-blocks
Wellbutrin or Zyban
 
DA & NE reuptake blocker
- no sexual dysfunction side effect (possible solution to SSRIs side effects)
Adrenergic functions
Frontal Cortex (mood, attention, cognition)
Limbic cortex (temporal, emotion, energy)
psychomotor agitation- retardation

Cerebellum- Tremor
Brainstem- cardiovascular (blood pressure)
sympathetic NS (leaving spine)
heart rate, bladder emptying
NT most commonly associated with schizophrenia
DA
Inhalants exert their primary effects by inhibiting...
CNS
Metabolic Receptors
Slow receptorsAct through 2nd messenger chemicals
Opiates
Increases activity in the opiate system leading to pain suppression, euphoria, well-being, and respiratory depressionEx. Heroin, Codeine, Morphine, Vicodin
Depressants
Depress CNS activity leading to decreased physiological activity and sedation Ex. alcohol, barbituates, benzodiazepines
Cigarettes
Not popular in US unitl cigarette-making machine producedNicotine in 1 cig = 8-10mgSmoking delivers 1-3mg of nicotine (depends on technique of user)
Amethst Initiative
Movement calling for reconsideration of US drinking age lawsWanted to increase drinking age up from 21
Pulmonary
Inhaling a drug (another parenteral route) NOT SNORTING Absorption is rapidShortest route to brain
Intranasal
TOPICALIntense inhalation of a drug, usually in powdered form, through the nostril. Does not reach the lungs but lays on the olfactory mucousal membranes of the nose.
Neuroleptic Malignant Syndrome
-most dangerous side effect
-can occur soon after taking drug
-fever, delirium, death
-very rare
Depletion studies
-decreased 5HT and NE in brains
 
-caused relapse of recoverd depressed ppl
-didn't make dep worse if already depressed
-didnt make ctrl group depressed
 
Supports monoamine hyp of depression (relation b/ depr and level of MA in brain)
Iproniazid
-1952, iproniazid used for tx of TB
-saw it improved mood in patients
-studies showed iproniazid inhibited MAO
 
-1st MAOI
Buspirone
Antianxiety drug with effects equal to Valium but w/o cross tolerance/dependence or withdrawal symptoms when discontinued after chronic use. Lab animals do not self-administer and humans indicate an absence of euphoria and do not have impaired motor skills. Takes very long to take effect, and works on 5HT, not GABA.
Acetylcholine
Found in both CNS and PNSNicotinic receptors - ionotropicMuscarinic receptors - metabotropicReleased at synapses on skeletal muscles and cell bodies of PNSLearning/memory, attention, sleeping, dreamingImplicated in Alzheimers
Clinical Trials
Phase 1: Safety - normal volunteersPhase 2: Efficacy - Patients (50-200) highly controlledPhase 3: Efficiency - Patients, large scaleAfter 3a: FDA approval (5-18 years from discovery)Phase 3b/4: Post-marketing safety is monitoredPatent only lasts 20 years
Positron Emission Tomography
Measures positron emission tracers, radiation
Alcohol Distribution
BAC: measured in g/100 mlDistributed throughout body fluidsLess distributed in fatty tissues
Central Nervous System
INJECTIONFor pain management, drugs are injected directly onto the spinal cord. Keeps drug confined to very small area.Two types: epidural (just outside the protective layers surrounding the spinal cord); spinal anesthetics (directly onto the spinal cord)
% of 1st episode patients having a relapse during a 5 yr follow up
82%
___ of population has a mood disorder
over 10%
According to lecture, for every $___ invested in drug abuse treatment, we see a $___ savings/return
$1; $7
3 subtypes of GABA receptors
cortex (sedative), amygdala/limbic (anti-anxiety), hippocampus(anti-convulsant)
REM sleep rebound
When taking barbiturates for insomnia, it suppresses REM sleep. When you stop taking barbiturates, your body tries to compensate for the loss of REM so you have longer REM periods, which leads to vivid and unpleasant dreams and a barb. hangover (groggy)
Benzodiazepine withdrawal
Physical: anxiety might be worse than before, possible insomnia, restlessness and agitation (but symptoms are much better than barbiturate withdrawal)
Opium Wars
1839 - Chinese destroy shipments of English opium1842 - Treaty of Nanking = England gets Hong Kong1856 - 2nd opium war begins1858 - Treaty of Tientsin
Cocaine in 1900s
Prescribed to morphine addicts1906 - 1/2 as many users in US as in '761906 - Food and Drug Act1914 - Harrison Narcotics Act1930 - Cocaine disappeared1985 - Crack uses exploded
Medical Use of Opiates
AnalgesiaSedation - poor in generalAnti-diarrheal agents
Alcohol Sites of Action
CNS depressantEnhances GABA effectHigh doses blocks effects of glutamateAffects DA,5HT, ACh neurons
Therapeutic Index
LD-50/ED-50 The larger the number, the less likely you are to die, the safer the drug dosage.Measures how close you are to the LD (small number = close)
Enzymes
Some _____ can bind drug molecules and have their energy changed as a result. Sometimes the normal activity is blocked.
CAFE
-study on AP, showed no diff b/ drugs but dropout rates were high
5 eg of other indications antidepressants should be used
1. organic disorders (postpartum, grief, dementia)
2. anxiety - SSRIs
3. sleep-drousy w/out addiction
4. eating disorders (bulimia, not anorexia)
5. ADHD
Hypothesis for antidepressant mechanisms
-2 possible mechanisms for drugs
Biogenic Amine Hypothesis of Affective Disorders
 
-Depression related to a deficit of monoamines at critical synapses where mania is associated with an excess
 
1. MAOIs let monamines accumulate and more release (back to normal state)
2. reuptake blockers let MA accumulate in synapse (back to normal state)
This is the idea that smokers adjust their smoking behavior to obtain a stable dose of nicotine
Titration hypothesis
This term refers to a set of considerations specific to a particular ethnic group or community in order to enhance the effective of a substance abuse intervention
Sociocultural filter
These are the 3 principal medical properties of aspirin
Analgesic, anti-inflammatory, antipyretic (fever reducing)
ED50
Dose of a drug required to produce a 1/2 maximal effectDose of a drug required to produce a given effect in 50% of individuals tested
Crystal Meth (d-amp)
Smoked b/c of purityStarted in West and moved EastDangerous to make
History of Cocaine
5000 years in Bolivia and PeruCoca leaves chewed by IncasAlfred Nieman extracted active ingredients (1850s)Sigmund Freud popularized cocaine
Tobacco Use in 20th Century
Favored cigarettes over other usagePublic health issues of infectious diseaseCigarettes in WWI
Dependence on Alcohol
Phase 1: few hours afer stopped drinkingPhase 2: 24 hours - severe seizuresPhase 3: 30 hours can last 3-4 days - DTs, high body temp., hallucinations, high HR
3 Ways for Excretion
1. Lungs2. Liver (accumulate in bile)3. Fluid (sweat, mom's milk)
Evidence for the depolarization block (3)
time course
depolarization block seen in animal studies w/ brain imaging
DA metabolites in the urine first go up, then down
Why are there no Parkinsonian symptoms for 2nd generation antipsychotics (atypicals)?
(3)
 

Weak DA blockade-striatum/basal gangla (where parkinsons happens) has a lot more DA then the limbic system (where schizophrenia happens)
lower potency and can get kicked off of receptors easier
gets kicked off in striatum (no side effects) stays on limbic (helps schizophrenia)


5HT2ablockade - 5HT reduces DA release in striatum (PD)
 activates a heteroceptor on DA neuron in basal ganglia (nigrostriatal pathway) blocking 5HT lets the DA get here


Strong anticholinergic blockade- clozapine blocks muscarinic
counteracts effects of DA block, DA & AcH act in opposite direction (inc DA= dec AcH, vv)
drugs blocking DA inc AcH, blocking AcH balances effect
PD patients have drugs that block AcH receptors
Hippocampus is implicated in .. (3)

-evidence for
-hippocampus implicated in cognition, HPA control, and anxiety
 
Evidence for neurogenic theory:
-50% of depressed patients have dysfunctional HPA (cortisol) regulation
-activation of HPA axis w/ too much glucocorticoid for too long inhibits adult neurogenesis in hippocampus
5 new directions for AD medication
1. serotonin Transporter (SERT)
2. glutamate
3. Peptides
4. 2nd messengers
5. Neurogenic theory of depression
FDA categories for OTC drugs
1: safe, effective, not mislabeled
2: unsafe, ineffective, possibly mislabeled (must be removed w/in 6 months)
3: not enough data to determine
Most chronic of life-long smokers begin smoking around this age/grade
6th-7th grade; 11-12 years old
San Francisco Ordinance (1875)
Banned opium dens, set precedence for other drug laws
Side Effects of Major Stimulants
Stimulant psychosis, euphoria turns to paranoid delusion, tactile and auditory hallucinations, disrupted associative thinking, aggressive, formication (bugs crawling on skin)
Combat Meth Epidemic Act (2006)
All products containing ephedrine and pseudophedrine sold OTCMust sign log, be over 18, limited quantity
What does a drug do?
1. Enters the body2. Distributes through the body3. Excreted in a changed or unchanged form4. All the while, interacting with receptors
How long should an initial AP trial last in a patient w/ little or no response
4 to 6 weeks
blood levels with AD
-used with..
-important bc (4)
- Used w/ TCAs, antipsychotics, lithium, anticonvulsants
 
imp bc.
1. index of metabolism (30x diff b/ ppl for the same dose, blood level tells how quickly ind is getting rid of drug
2. shows therapeutic windown when drug is working
3. can tell if patient is taking meds
-determine right dose for therapy vs side effects
2 components of affective disorders
1. mood and emotional disturbances are primary problems
2. may lead to distortions in thought process (thinking organs are shutting down- psychoses)
These processes in the brain produces the stimulant effects of caffeine
Blocks the inhibitory NT, adenosine
In the US each year ___% smokers try to quit and about ___% are successful the first time
33% (1/3); 3%
Describe the typical "Type 2" alcoholic
Male, started drinking before 25, fights and gets arrested a lot, dependence on alcohol, drinks to achieve positive mood, has 5HT abnormalities in the brain
Evidence against the DA hypothesis (2)
nothing wrong with BL DA metabolities in urine
-Post-morten binding assays- showed supersensitivity of D2 receptors (critics say this coudl be due to neuroleptic tx, upregulation of DA receptors due to blocking receptors for a long time) -Pet scans in living brains conflicting
Overall findings of Star D study (4)
67% cumulative remission rate after all 4 levels
relapse rates higher and time to relapse shorter for those entering more tx steps
Lots of patients left at each step
Remission had better prognosis then only responders
 
These are all negative side effects of caffeine consumption
Increased heart rate, nervousness, twitching, GI upset, diarrhea, cardiovascular effects, bone fractures, breast disease, effects during pregnancy and breast feeding, panic attacks
what do drugs do to schizophrenic symptoms?
- first dose makes patient sleepy (antihistamines are 1st generation), this wears off in a few week due to tolerance, not the reason they work
 
-symptoms improve in a few weeks (sto hearing voices, paranoia and suspiciousness less, speech connected/coherent, more self-care, more emotionally responsive)
2 ways to increase amount of transmitter in cleft
1. block enzymes that break down NT
2. block reuptake
Participant and results of Level 1- Star D
-mod to severe depression
- over 75% had recurrent/chronic dep
mean length of illness=15.5 yrs
 
Results
-started w/ citalopram (celexa) (avg 41.8 mg/day)
-about 30% remission
-about 47% responded
-about 6.7 weeks until remission
Fetal Alcohol Syndrome can lead to the following deformities
Smaller than normal head, small wide-set eyes, drooping smile, short upturned nose
Duration of Action of Cocaine/Amp
Cocaine - oral = 2-3 min., peak in 15-20; duration = less than an hourAmphetamine = oral = 30 min, peak in 2-3 hours, duration - 10-12 hours
Rational for SP as depression target (5)
1. located in CNS site for stress
2. acute & chronic stressors increase SP
3. chronic AD tx reduce SP
4. depressed patients have higher levels of SP in plasma and CSF
5. Saredutant (antagonist) now in clinical trials
 
These are the significant problems for safety associated with using dietary supplements as mentioned in lecture
Not approved by the FDA, studies of safety or efficacy for dietary supplements is not required, any new ingredients added to existing supplement do not need to be tested
What do all of the body compartments have in common?
They must make contact with the blood. The blood reaches every compartment in the body.
__ recover w/ no tx, ___ will stay depressed, __ with recover to dysthymia
40% recover w/ no tx, 40% stay depressed, 20% recover to dysthymia
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