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Drugs & Behavior
Antipsychotics (exam 2)
69
Psychology
Graduate
10/16/2010

Additional Psychology Flashcards

 


 

Cards

Term
5 General Principles of Psychiatric Medications
Definition
  1. Drugs are not disease specific, treat symptoms
  2. some patients don't respond to drugs (1/3)
  3. all patients at risk for side effects
  4. can't predict specific effect a drug will have for a patient (can use family history)
  5. don't know how effects of drugs related to their physiological effects (have some theories)
Term
3 core feature criteria for schizophrenia diagnosis
Definition

At least 6 months in which:

 

  • prominent psychotic symptoms present for at least 1 week
  • psychosocial functioning is poor
  • if present, mood disturbance is brief vs psychotic symptoms (not main problem)
Term
5 prominent psychotic symptoms in schizophrenia
Definition
  1. Content of though- delusions (false beliefs, not amenable to change by reason or experience)
  2. form of thought- thought disorder (word salad, loosening of associations among thoughts)
  3. perceptual disturbances- hallucinations- perception occurs in absense of a stimulus usually auditory
  4. negative symptoms
  5. mood or affect- flat or abnormal emotions
Term
3 categories of symptoms in schizophrenia
Definition
  1. Positive symptoms (delusions, hallucinations, thought disorder)-treated by drugs
  2. Negative symptoms (anhedonia, withdrawn, affective blunting)-no drug effect
  3. Cognitive impairment- no drug effect
Term
recent tx vs. earlier era txs for schizophrenia
Definition
-doing better now with long-term outcomes
Term

1st antipsychotic

-how it started

Definition

Chlorpromazine

 

-1856, WWI developemnt of popular purple dye used in genes, variation = methylene blue

Term


Chlorpromazine

WWII

 

Definition

WWI discovered methylene blue could tx symptoms of malaria

 

WWII- allies with same problem synthesized methylene blue analogues including phenothiazine

Term
Phenothiazine
Definition

-discovered in WWII to treat malaria

 

-french scientists interested in phenothiazine because of antihistamine action

Term
Importance of antihistamine discovery
Definition

-dose-response effect of antihistamines: low doses caused tired, large doses caused arousal

-suggested drugs could be more specific than previously though

 

-led to synthesis of chlorpromazine

Term
H. Laborit
Definition

-French Navy anesthesiologists

 

-thought antihistamine could be useful in preventing fatal effects of shock in vietnam

 

-Histamine decreased blood pressure (factor in shock), thought chlorpromazine could stop this

 

-didn't decrease blodo rpessure but observed patients were more mellow after chlorpromazine

Term
Jean Delay
Definition
-gave chlorpromazine to 2 grps of psychiatriac patients, calming effects treated mainia first, but then calmed psychotic symptoms in schizos
Term
Largactil
Definition
-RP (Rhone-Poulenc) marketed chlorpromazine as Largactil (Large CNS effect)
Term
Thorazine
Definition
Smith Kline and French marketed chlorpromazine as Thorazine
Term
neuroleptic
Definition

-refers to effect of chlorpromazine

 

-coined from greek "lepto" to make fine or delicate (makes neurons work fine or better)

Term

News from 50 year search for more drugs to relieve psychotic symptoms

 

Definition

Good

-lots of drugs like chlorpromazine that can reduce some positive symptoms of schizophrenia

-antipsychotics now used for bipolar too

 

Bad

-can't help everyone

-not all symptoms improved

-bad side effects (2nd generation better)

 

Term
what do drugs do to schizophrenic symptoms?
Definition

- 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)

Term

NIH Definitive Collaborative Study

-set up

-groups

-conclusions (4)

Definition

crucial historical results for antipsychotics-showed APs the right med for psychosis

 

-9 hospitals, DSMII diagnosis, 344 subjects

 

-4 groups (3 different APs-chlorpromazine and 2 others, and placebo)

 

Conclusions:

-8% no response, 22% a little better=30% neuroleptic resistant

-higher doses didn't increase response, worsened side effects

-switching APs, usually no better, could help side effects

-negative core symptoms NOT reduced

Term
How do APs work?
Definition
Dopamine Hypothesis
Term
behavioral evidence for the dopamine hypothesis (5)
Definition
  1. drugs activating DA by blocking DA reuptake(amphetamine/cocaine) produce symptoms looking like schizophrenia e.g. stimulants cause paranoia
  2. shizophrenics symptoms got worse when given stimulant (not w/ other diagnosis for if symptoms in remission)
  3. AP could block or reduce psychosis produced by stimulants
  4. L-dopa, DA precursor, worsens schizophrenia
  5. AP side effects look like Parkinsons (due to loss of DA in brain)
Term
D.S. Bell
Definition

-found ppl overdosing with stimulants showed symptoms a lot like schizophrenia

-supported the DA hypothesis

Term
3 main conclusions from behavioral observations
Definition

1. too much DA produces postivie psychotic symptoms

 

2. antagonism or reduction of DA decreases behaviors

 

3. antipsychotics must work because they decrease DA

Term
Clinical prediction for the DA hypthesis
Definition

-if blockade is imp for therapeutic effect then drugs that are more porent in people (clincially work better) should be better at blocking DA receptors, drugs less potent should be weaker

 

-drugs that block more DA should work better if this is why APs work and not simply an explanation for AP side effects

Term

Clinical evidence for DA hypothesis

 

Definition

-better a drug binds to D2 receptor and blocks effect of DA there, better AP it is

 

-Y axis (how much is needed to know off 1/2 of the DA molecules- compared to haloperidol: DA antag)

-X axis (average clinical dose needed for effects)

Term
Depolarization block
Definition

-explains why AP block D2 receptors right away but clinical effects take longer

 

-APs block postsynaptic and presynaptic receptors

-presynaptic (autoreceptors) normally tell neuron to stop sending NT, when blocked it doesn't get this signal so the neuron produces even more of NT, presynaptic block causes an increased release

-neuron eventually burns out and it stops firing DA at high rates, DA is built up in cell so DA firing, and synthesis decrease

Term
Evidence for the depolarization block (3)
Definition
  1. time course
  2. depolarization block seen in animal studies w/ brain imaging
  3. DA metabolites in the urine first go up, then down
Term
Evidence against the DA hypothesis (2)
Definition
  1. nothing wrong with BL DA metabolities in urine
  2. -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
Term
2 results supporting the DA hypothesis
Definition
  • somethings wrong w/ DA function in schizophrenia (more functional analysis then past static view)
    • greater reuptake of L-Dopa in putamen of schizos
    • schizos might synthesize more DA in frontal cortex & striatum
  • DA transmission greater in schizophrenia
    • patients injected w/ amphetamine (DA reuptake blocker) had more DA released than ctrls
    • some had increase in positive symptoms, seen in neuroleptic exposed and naive patients, no increase in stable remitted patients
Term
Evaluation of DA Hypothesis
Definition

-compared schizophrenic patients to ctrl

 

-same amount of D2 receptors, same amount of DA in blood

 

-more amphetamine induced release of DA in schizophrenic patients then in ctrls

Term
Summary of 1st generation APs (5)
Definition
  1. No best AP, choice made on side effects
  2. most imp differences in AP was potencies (divided into 2 grps: low, medium, and high potencies) all are equally effective
  3. AP are physicall safe, overdose death unlikely
  4. AP are not reinforcing, no high, not abused
  5. tolerance may develop to side effects, but there is no/little tolerance to clinical improvements
Term

Neurological side effects of 1st generation AP

(5)

Definition
  1. Dystonia
  2. Pseudoparkinsonism
  3. Tardive dyskinesia (TD)
  4. Akathisia
  5. Neuroleptic Malignant syndrome
Term
Dystonia
Definition

-not that common

-occurs earliest

-abrupt spasms of tongue/face

-frightening; requires immediate attention (lower dose)

-evidence of increaed DA in system

Term
Pseudoparkinsonism (extrapyramidal EPS)
Definition

-Akinesia- proverth of movement

-looks like a "mental patient"

-looks like negative symptoms (no facial emotions)

 

-major class of side effects

Term

Tardive dyskinesia (TD)

-cause

Definition

-late neurological symptoms, 6 months-several years

 

-most feared, could be irreversable, LT outcome variable

-no best tx (increase AP & symptoms could get worse, decrease AP & psychosis could reoccur)

-abnormal motor function, usually face/upper body

 

Cause:

-supersensitivity (upregulation from LT use of meds)

-arguments agiainst supersensitivity, not sure of cause

Term
dyskinesia
Definition
abnormal motor function
Term
Akathisia
Definition

-one of main reasons ppl stop taking AP

-most distressing side effect

 

-restlessness feeling- internal feeling

-can't sit still, often causes pacing to relieve restlesness

Term
Neuroleptic Malignant Syndrome
Definition

-most dangerous side effect

-can occur soon after taking drug

-fever, delirium, death

-very rare

Term
Non-neurological side effects of 1st generation AP (5)
Definition
  1. sedation- some tolerance (antihistamine effect)
  2. postural (orthostatic) hypotension-lowered blodo pressure from standing errect- tolerance (standing too quickly and getting dizzy, due to block of adrenergic receptors)
  3. lowered seizure threshold- carebul w/ drug combos
  4. photosensitivity- blue skin
  5. anticholinergic side effects
Term

Anticholinergic side effects

-receptor

 

Definition

-side effects due to blocking AcH

-constipation, dry mouth, blurry vision, memory problems

 

-common side effect for many drugs (ADs)

 

-anticholinergic is blocking muscarinic

Term

____ block = efficacy

______ block = adverse side effects

Definition

D2 block = efficacy

histamine & adrenergic block = adverse side effects

Term
3 disadvantages of 1st generation antipsychotics
Definition
  1. about 30% of patients don't respond (others only partially respond)
  2. serious, maybe intolerable side effects
  3. negative symptoms not improved
Term
First 2nd generation AP
Definition

Clozapine

 

First atypical antipsychotic

Term
3 reasons atypical antipsychotcs were better then 1st generation
Definition
  1. reduces symptoms in about 30% of nonresponders to 1st generation
  2. practically produces no Parkinsonian side effects or tardive dyskinesia- could help patients who couldn't tolerate side effects
  3. reduced negative symptoms (controversial, might not help, just looks like it from helping parkinsonia side effects)
Term
What we don't know about clozapine
Definition
-we don't know why clozapine can help some patients who have not responded to other drugs
Term

Clozapine's receptor profile

 

Definition

-Histamine antagonism: drowsiness, weight gain

-alpha adrenergic antagonism- dizziness, decreased blood pressure

-anticholinergic (muscarinic) blockade- drowsiness, dry mouth, blurred vision, constipation, cognitive impairment

 

-DA blockade- antipsychotic actions

Term
 4 major DA pathways
Definition
  • Tuberoinfundibular (least sig, small pathway)
    • hypothalamus to anterior pituitary
    • release of hormone prolactin, DA inhibits prolactin (blocking DA=inc prolactin=inc milk)
  • Nigrostriatal pathway
    • substantia nigra to basal ganglia
    • movement control, parkinsons
  • Mesolimbic pathway (AP work here)
    • midbrain VTA (A 10) to nucleus accumbens
    • mediates reward and reinforcement
    • mediates positive symptoms
  • Mesocortical pathway
    • midbrain VTA (A 10) to frontal & cingulate cortex
    • involved in cog impairments & neg symptoms

 

Term

Why are there no Parkinsonian symptoms for 2nd generation antipsychotics (atypicals)?

(3)

 

Definition
  • 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)
  • 5HT2a blockade - 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
Term
2 categories of negative symptoms
Definition
  •  primary negative symptoms (part of disorder)
    • NOT helped by clozapine
  • secondary negative smptoms- side effects
    • Due to EPS, side effect of pos symptoms and meds, depression, no enjoyment
    • Clozapine helps, reducing pos effects and EPS

*Clozapine doens't really reduce neg symptoms, just looks like it cause it helps other symptoms

Term

Other Atypical Antipsychotics

AKA

Definition

- risperidone, risperdal

-olanzapine, zyprexa

-quetiapine, seroquel

-ziprasidone, geodon

-aripiprazole, abilify

 

(all attempts to match clozapine)

-AKA D2/5HT2 blockers

Term

Abilify (general description)

Definition

-AKA Aripiperazole

-First 3rd generation antipsychotic

-incorporates concept of DA modulation or balance rather than blockade

Term
4 receptor actions for Abilify
Definition
  1. presynaptic DA agonist (partial agonist, reduces DA)
  2. postsynaptically a partial DA agonist-produces DA activation to a certain level, w/ lots of DA around you are tuning down full effect
  3. Partial 5HT1a agonist (antidepressant effects)
  4. 5HT2 antagonist

**agonst for DA when concentrations are low, antagonist when DA is high**

Term
Good/Bad News of anitpsychotics (2nd, 3rd generation)
Definition

Good:

-all are effective for pos symptoms

-all produce less neurological sde effects (block 5HT2a)

 

Bad:

-different serious side effects (metabolic syndrome: weight gain, diabetes, blood lipid increase)

 

-abilify could be better

Term
evidence for negative symptoms a result of too little DA (3)
Definition
  1. look like EPS
  2. look like effects of frontal lobotomy (too little DA to frontal lobe)
  3. DA agonist might improve them? difficult cause you'd have to inc DA in frontal while dec in limbic for pos symptoms
Term
Symptoms of frontal lobotomy
Definition
  • emotional dullness
  • impaired judgment
  • poor initiative motivation and drive
  • lack of insight
  • difficulty in planning
  • impaired problem-solving and abstract reasoning
  • decreased concern for personal hygiene
  • social withdrawal
Term

Other transmitter that might be responsible for schizophrenia abnormalities

 

Definition

-Glutamate

 

-NMDA blockade w/ PCP (blocks glutamate to reduce pain and make strong) looks like psychosis

 

-Glutamate interacts w/ DA neurons problem w/ testing cause too much glutamate kills neurons

Term
CATIE Trial (clinical antipsychotic trials of intervention effectiveness) sponsored by National institute of mental health
Definition
[image]
Term
CATIE findings
Definition

-used normal Drs, more realistic

-3 main phases

 

1st phase showed new meds better then old

Term
% of 1st episode patients that have functional recovery after 5 years
Definition
15%
Term
James Devoe
Definition
-wrote personal testimonial about how much drugs helped his schizophrenia
Term
Recent developments in APs
Definition

-revisions of DSM

-2 new antipsychotics approved (Fanapt/Iloperidone, Saphris/Asenapine)

-published recommendations for pharmac and psychosocial treatments from the Schizophrenia Patient Outcomes Research Team (PORT), use related txs: smoking cessation, drug abuse, weight loss

-more LT studies in relapse in better quality of life

-cog and social txs get more attention

-more prescriptions in children

-more reports identifying genetic and neuroanatomical abnormalities

Term
Journal of Pediatrics
Definition

-malicious use of pharmaceuticals: under-recognized form of child abuse

 

-abusing drugs to keep kids under control

Term
% of 1st episode patients having a relapse during a 5 yr follow up
Definition
82%
Term
Patients who stop meds...
Definition
Patients who stop meds are 5xs as likely to relapse
Term
Recovery criteria- schizophrenia
Definition
-2 years in a row of good functioning
Term
How long should an initial AP trial last in a patient w/ little or no response
Definition
4 to 6 weeks
Term
EUFEST
Definition

-study, results showed haloperidol had highest drop outs but no drug showed diff on PANNS scores

 

-should you use primary or secondary measures??

Term
CAFE
Definition
-study on AP, showed no diff b/ drugs but dropout rates were high
Term
8 strategies to address non-responders to AP
Definition
  1. check for compliance
  2. wait for delayed response
  3. increase dose
  4. decrease dose (reduce side effects)
  5. switch drug (same or diff class)
  6. switch to clozapine
  7. augment w/ agents of diff class or other AP
  8. settle for suboptimal level
Term
after 4 wks of tx ____ were in remission, and the rest were _________
Definition
after 4 weeks of tx 33% were in remission, and the rest were non-responders
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