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Psychopharmacology > Final: Antipsychotics > Flashcards

Final: Antipsychotics Flashcards

1
Q

Features of bipolar disorder

A

1% incidence in all populations

life-long, managed with treatment

Cyclic episodes of mania/depression

2x episodes of severe mania= need for treatment

Treatable, but only ~1/3 seek treatment

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2
Q

Bipolar 1

A

severe mania/severe depression

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3
Q

Bipolar 2

A

Low mania/severe depression

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4
Q

Cyclothymia

A

low mania/low depression

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5
Q

Treatment for bipolar disorder: Lithium

A

lithium- also helps kidneys

first in lethargic guinea pigs

Effect, poor patient compliance (50%)

Narrow Therapeutic range/index, need to be monitored, varies with Na+ levels.

Exerts synaptic effects via GABA, dopamine, glutamate, signal transduction mechanisms.

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6
Q

Treatment for bipolar: Anticonvulsants

A

Valproate

Lamotrigine

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7
Q

Treatment for bipolar: antipsychotics

A

quetiapine, Olanzepine

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8
Q

Treatment for bipolar: Antidepression and more

A

SSRIs

Psychotherapy

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9
Q

Lithium reduces ____ of manic and depressive episodes

A

FREQUENCY

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10
Q

Lithium and carbamazepine reduce ______ of manic episodes

A

SEVERITY

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11
Q

Side-effects of lithium

A

Nausea, Thirst, Polyuria, Tremor, Weakness, Confusion, Seizures, Arrhythmias, Coma, Death

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12
Q

Schizophrenia: gen info

A

1-1.5% world population

similar rates female/males, age onset varies

Onset peak 16-25, later onset possible

complex patterns of symptoms vary across patients

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13
Q

Schizo: Thought disorder

A

Incoherent, delusional, inappropriate associations

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14
Q

Schizo: perceptual disorders

A

Hallucinations in all modalities, most often auditory

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15
Q

Schizo: emotional disorder

A

Inappropriate affect, can be agitated or flat

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16
Q

Schizo: motor disorders

A

○ Repeated purposeless movements (stereotypies)

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17
Q

Schizophrenia diagnosis

A 
2 symptoms for 1 month: 
• Delusions 
• Hallucinations 
• Disorganized Speech 
• Disorganized or Catatonic Behavior 
• Affective Flattening, Alogia, Avolition

Additional Criteria: Dysfunction at Work, Home, or Self-care, Continuous Signs for 6 Months, Not an Affective Disorder, Not Substance Induced

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18
Q

4 types of schizophrenia

A

1) Paranoid: delusions, persecution
2) hebephrenic: immature emotionality
3) catatonic: immobility and agitation
4) undifferentiated: mix of symptoms

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19
Q

Type 1 schizophrenia

A

Positive symptoms
hallucinations
thought disorders
Delusions (persecutions, grandeur, control)

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20
Q

Type 2 schizophrenia

A

Negative symptoms

flattened affect, poverty of speech, lack of initiative, lack of persistence, anhedonia, social withdrawal

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21
Q

Biological correlates:

Genetics

A

mono: 48%, di: 17%

increase risk with relatedness

risk predicted by bio > adoptive parent.

128 gene variants

epigenetics control what genes expressed

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22
Q

Dreadful gene quadruplets

A

identical genes
varied degrees of illness

severity correlated with low birth weight, degree of hypofrontality, and level of stress exposure

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23
Q

Eye tracking (schizo): impaired smooth pursuit tracking

A

control: smooth
Schizo: saccadic

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24
Q

Energy usage (schizo)

A

reduced activity frontal cortex

hypo frontality, low energy use in frontal lobe

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25
Q

Brain Structure in schizophrenia

A

less cortical complexity, enlarged ventricles, small brain volumes, grey matter loss, greater loss in childhood onset.

Disorganized structure: abnormal cytoarchitecture. Prenatal virus: altered development, abnormal cell pattern in hippocampus and cortex.

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26
Q

Brain development in schiophrenia

A

Ventricular Enlargement

Underdeveloped hippocampus

Underdeveloped amygdala

Underdeveloped Cerebral Cortex

Abnormal Cytoarchitecture

Neurochemical imbalance

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27
Q

Neurotransmitter theory of schizophrenia

A

Glutamate interacts with dopamine leading to symptomology consequences

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28
Q

Role of Dopamine in schizophrenia

A

Traditional Antipsychotic Medications Block Dopamine Receptors with High Affinity

Reserpine Depletes Monoamine Levels and Reduces Symptoms of Schizophrenia

Antipsychotics Induce Motor Side-effects Similar to Parkinson’s Disease

Amphetamine-induced Release of Dopamine Exacerbates Symptoms of Schizophrenia

The potencies of traditional antipsychotics are predicted by D2 receptor affinities

Imaging studies in humans demonstrate binding of antipsychotics to D2 receptors

Symptoms of Schizophrenia related to major dopaminergic pathways

29
Q

D2 receptor affinity predicts…

A

clinical potency \

(higher dose = higher Ki)

correlation not seen for 5HT, H1, or alpha-2

30
Q

Antipsychotics compete for _______ labelled by [11C] Raclopride

A

d2 receptors

Haloperiodol, clozapine, risperidone

31
Q

Therapeutic potency graph by…

A

DOSE-RESPONSE CURVE

x-axis: Ki
y-axis: avg. daily clinical dose

32
Q

How do you get Ki?

A

[drug] displaces 50%- COMPETITION

33
Q

Mesocortical pathway

A

Thought/perceptual schizophrenia symptoms

VTA–> Cortex via thalamus

34
Q

Mesolimbic pathway

A

Mediates EMOTIONAL disorders and RESPONSE TO REWARD

VTA–> NA

35
Q

Nigrostriatal Pathway

A

Mediates SENSORY-MOTOR dysfunction

Substantia nigra –> Striatum

36
Q

Schizo: Kraepelin vs. Crow

A

Crow: +/- type 1 and 2 symptoms

Kraepelin: paranoid, catatonic, etc.

37
Q

History of antipsychotics

A

LaBorit first used promethazine as pre-anesthetic in 1950

notes promethazine/chlorpromazine calmed paients. First admin to sedate schizo.

Actions beyond sedation

38
Q

History of antipsychotics:

___ > ____ = ____

A

major tranquilizers > neuroleptics = antipsychotics

39
Q

Rule of thrids in treatment

A

1/3- recover
1/3- chronically ill
1/3- recover by relapse

40
Q

Individual therapy

A

Psychotherapy may help to normalize thought patterns. Also, learning to cope with stress and identify early warning signs of relapse can help people with schizophrenia manage their illness.

41
Q

Social skills training

A

Focuses on improving communication and social interactions and improving the ability to participate in daily activities.

42
Q

Family Therapy

A

Provides support and education to families dealing with schizophrenia.

43
Q

Vocational rehab and supported employment

A

Assists people with schizophrenia to prepare for, maintain jobs.

44
Q

Typical antipsychotics

A

1st gen, traditional

45
Q

Atypical antipsychotics

A

2nd gen

46
Q

Name the Atypical antipsychotics

A 
Clozapine (Clozaril) 
aripiprazole (Abilify)
risperidone (Risperdal) 
quetiapine (Seroquel) 
olanzapine (Zyprexa)

Atypical: CARSZ
CARQO

47
Q

Name the typical antipsychotics

A

Chlorpromazine (Thorazine)
Haloperidol (Haldol)
Reserpine
Thioxanthines (Navane)

48
Q

What are the effects of typical antipsychotics?

A

Block D2 receptors

Require several weeks of treatment

effective on + symptoms

Not effective on negative symptoms

many serious side effects

49
Q

Typical antipsychotics: Extrapyramidal (early developing) motor effects

A

Parkinsonianisms (tremor, rigid, bradykinesia)
Akathisia (restless)
Dystonia (involuntary contraction)

**CAUSED BY D2 RECEPTOR BLOCKING

50
Q

Typical antipsychotics: Tardive Dyskinesia (late developing)

A

abnormal movements of upper body, head (jaw clench, eye blink, jerk torso, twitching)

longterm use in 30-70% patients

can sometimes persist after discontinuation

**POSSIBLY DUE TO SUPERSENSITIVITY OF D2 RECEPTORS

incidence increase w/treatment duration

51
Q

Antipsychotics at D2 receptors causes

Block Dopamine receptors

A

motor: Extrapyramidal/tardive dyskinesia
endocrine: prolactinemeia, glactorrhea

(increase prolactin)

52
Q

antipsychotics at H1 receptors

Block histamine receptors

A

sedation (antihistamine)

53
Q

antipsychotics at M receptors

Block muscarinic receptor

A

Sympathomimetic (Antimuscarinic)

Sympathetic

54
Q

antipsychotics at Alpha 1 receptors

block adrenergic alpha-1 receptors

A

Postural (orthostatic) hypotension

55
Q

antipsychotics at 5HT2 receptors

block serotonin receptor

A

Weight gain

56
Q

Tuberoinfundibular pathways

A

hypothalamic DA inhibits prolactin release

antispychotics block D2 and induce hypersecretion of prolactin

Gynecomastia/galactorrhea, not good

A12 –> Median Eminence –> Anterior pituitary

57
Q

Antipsychotics Block [m] receptors, list of sympathetic side effects

A

Tachycardia, blurred vision (dilate pupils), constipation, urinary retention, dry mouth, erectile dysfunction.

58
Q

Postural (orthostatic) hypotension antipsychotics block alpha-1 receptors

What does this mean

A

alpha 1 receptors constrict vessels

increase blood flow to brain on standing

Antipsychotics block alpha 1 receptors, light headed standing up

59
Q

Difference between 1st and 2nd generation antipsychotics

A

Both: H1, Ach, Alpha-1, D2

Only atypical: 5HT2, 3, 2c, alpha-2, D1, D4

60
Q

Overall: Atypical compared to typical has weaker affinity for ____ and stronger affinity for _____

A

weaker: D2
Stronger: D4 and 5-HT2A

61
Q

Atypical have ___ affinity for D2 and ___ affinity for 5HT

A

lower D2

higher 5HT

62
Q

Are atypical psychotics as effective as typical?

A

Yes! and in patients resisting traditional treatment

fewer extrapyramidal/tardive dyskinesia side effects

63
Q

Side effects of atypical antipsychotics

A

weight gain, diabetes, hyperlipidemia, cardio, urinary, sexual, sedation, agranulocytosis

64
Q

Atypical: Agranulocytosis

A

loss of infection fighting white blood cells (leukocytes)

more infect/death

Clozapine (Clozaril) = highest risk, need to monitor cells regularly

65
Q

Atypical: diabetes

A

alterations in carbo/fat metabolisms

weight gain

diabetes mellitus can develop

66
Q

FDA approved use of antipsychotics

A 
Schizophrenia (adult/adolescent) 
Bipolar affective disorder (mania) 
MDD
agitation
ASD
Tourette
Psychosis
67
Q

Off label use of antipsychotics

A

dementia, substance abuse, anorexia, OCD, PTSD, GAD, ADHD, hiccups, nausea, ICU delirium

68
Q

Block box warnings

A

death with atypical in elderly with dementia

15% increase risk mortality

Psychopharmacology (16 decks)

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