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Neuro-Psych Exam II > Antipsychotic Drugs > Flashcards

Antipsychotic Drugs Flashcards

1
Q

Describe the Dopamine Hypothesis of Psychotic Disease:

Evidence supporting? Evidence against?

A

Abnormal DA transmission within the mesolimbic and mesocortical pathways cause psychosis sx.

Support: Antipsychotics block D2 receptors and improve sx.

Against: Antipsychotics take pharm effect immediately, but psychosis takes time to disappear (synaptic remodeling)

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2
Q

How is the nigrostriatal DA pathway implicated in the treatment of psychosis?

A

Extrapyramidal (parkinson like syndrome) effects due to drugs that block DA receptors in this tract

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3
Q

Describe the changes in mesolimbic DA associated with psychosis:

What kind of sx do they cause?
How are they treated?

A

Elevated DA signaling/ neuronal activity
Hyperactive/ positive sx.
Tx: Neuroleptics/Typical antipsychotics

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4
Q

Describe the changes in mesocortical DA associated with psychosis:

What kind of sx do they cause?
How are they treated?

A
  • Decreased DA signaling/ neuronal activity
  • Hypoactive/ negative sx.
  • Tx: Atypical antipsychotics > Neuroleptics/ Typicals
  • Negative sx are harder to treat than positive sx.
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5
Q

What kind of hallucinations are associated with drug abuse/ withdrawal?

A

Visual

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6
Q

What kind of hallucinations are associated with innate psychosis?

A

Auditory

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7
Q

List three toxic agents that can cause psychosis

A
  1. Heavy metals (Hg)
  2. Digitalis
  3. L-Dopa
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8
Q

List 5 metabolic syndromes that can cause psychosis

A
  1. Hypoglycemia
  2. Acute intermittent porphyria
  3. Cushings***
  4. hypo/hyper Ca++
  5. hypo/hyperthyroid
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9
Q

List 3 nutritional deficiencies that can cause psychosis

A
  1. Thiamine
  2. Niacin
  3. B12
    (All of the Bs)
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10
Q

List 4 neurological illnesses that can cause psychosis

A
  1. stroke
  2. tumor (brain)
  3. neurodegenerative disease
  4. hypoxic encephalopathy
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11
Q

List 6 Examples of positive psychotic sx.

A
  1. Agitation
  2. Delusion
  3. Hallucination
  4. Disorganized speech
  5. Disorganized thought
  6. Insomnia
    (Addition of a quality that was not originally there/ altertness, increased activity)
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12
Q

List 6 Examples of negative psychotic sx.

A
  1. Apathy
  2. Flat Affect
  3. Lack of motivation
  4. Lack of pleasure
  5. Poverty of speech
  6. Social isolation
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13
Q

How does treatment of psychosis differ in an inpatient vs. outpatient setting? What are the goals like in each situation?

A
  • Inpatient–treat active psychosis, get patient home/ prevent violence
  • Outpatient–prevent relapse, maintain social adjustment
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14
Q

What is the MOA for ALL Antipsychotic Drugs?

How does this differ between typicals and atypicals?

A

Competitive block–> DA + 5HT Receptors

Typicals: Affinity D2 > 5HT2
Atypical: Affinity 5HT2 >D2

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15
Q

Which part of the DA pway is primarily targeted by the atypicals?

How is this possible?
Which patients are these drugs exceptionally good for?
Do they treat + or - sx?

A

Mesolimbic > Nigrostriatal

  • 5HT2 regulates release of DA in mesolimbic away
  • Atypicals are more selective for 5HT2R’s

Good for drug refractory pts
Treat + and - sx.

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16
Q

Where are antipsychotics metabolized? Excreted?

A

Met: liver, active and inactive metabolites
Excreted: Renal, glucuronide conjugates

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17
Q

What is the half life like for antipsychotic drugs?

A

Broad range: 20-40hrs.

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18
Q

How are antipsychotic drugs absorbed? excreted?

A

Erratically in GI tract; renally excreted

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19
Q

What are three effects of D2 blockade that initially activate pre-synaptic D2 receptors?

A
  1. ^ DA synth and release
  2. ^ cAMP
  3. LOWER K+ currents
    * Will eventually be reversed
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20
Q

Describe the short and long term effects of antipsychotics at the D2 pre-synaptic cleft

A

short term: activate neurons

long term: inactivate neurons

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21
Q

Describe the short and long term effects of antipsychotics at the D2 post-synaptic cleft

A

short term: receptor blockade

long term: receptor hypersensitivity (due to low DA levels)

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22
Q

Describe the symptomatic changes with 1-3 days of antipsychotic treatment (4)

A
  1. Decrease agitation/hostility
  2. Decrease combativeness/ aggression
  3. Decrease anxiety
  4. Normalization of eating and sleeping patterns
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23
Q

Describe the symptomatic changes with 1-2 weeks of antipsychotic treatment (3)

A
  1. Increase socialization
  2. Improve self care
  3. Improve mood
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24
Q

Describe the symptomatic changes with 3-6weeks of antipsychotic treatment

A
  1. Improve disorders thought
  2. Decrease delusion and hallucination
  3. Patients can have appropriate conversation and participate in psychotherapy***
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25
Q

How long does it typically take the for antipsychotics to alleviate positive sx. ?

A

1-3 weeks

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26
Q

Haloperidol:
Drug Class
Therapeutic uses (3)
Notable ADRs

A

Typical Antipsychotic–Butyrophenone

Tx: Psychosis, Gilles de la Tourette’s, Huntington’s

ADRs: Severe extrapyramidal effects

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27
Q 
Chlorpromazine: 
Drug Class 
Therapeutic uses (2) 
ADRs (2)
CI
A

Typical Antipsychotic–Phenothiazine (prototype)

Tx: Psychosis, intractable hiccups

ADRs: *Fewer extrapyramidal effects due to simultaneous anticholinergic effects (maintain balance), deposits in lens and cornea

CIs: seizure disorders (lowers threshold)

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28
Q

All antipsychotics with the exception of these two can be used as antiemetics

A
  1. aripiprazole

2. thioridazine

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29
Q

Why are antipsychotics effective antiemetics?

A

Block D2 at in the area postrema CTZ–do not need to cross BBB

30
Q

Prochlorperazine
MOA
Therapeutic Use
Broad drug class

A

Treatment of nausea asstd with chemotherapy
(blocks D2Rs in CTZ)
Typical

31
Q

Scopolamine
MOA
Therapeutic Use

A

Treatment of motion sickness (blocks D2Rs in CTZ)

32
Q

Antagonism of 5 receptor types causing ADRs to antipsychotics

A
  1. Muscarinic
  2. Alpha Adrenergics (esp A1)
  3. D2 (excess)
  4. 5HT (excess)
  5. H1
  • Drugs affect different receptors in different proportions
  • Choose drug based on pt needs
33
Q

3 Extrapyramidal Effects of Antipsychotic Drugs
Which Drugs are worst for this?
How do we treat the ADR?

A
  1. Restless/Akathisia
  2. Pseudoparkinsonism
  3. Dystonia/ Facial grimace

WORST in D2 Specifics:
Haloperidol***
Fluphenazine
Thiothixene

Tx: Withdraw neuroleptic + Admin centrally active anticholinergic–> start on atypical or drug with more anticholinergic effects when clear

34
Q

Which drugs cause the least extrapyramidal effects?

A

Atypical antipsychotics + typicals with more anticholinergic effects (Thioridazine, Chlorpromazine)

35
Q

What is tardive dyskinesia and how does it develop?
Which antipsychotics are the worst for this?
How is it treated?

A

Mos/ yrs of antipsychotic tx–> abnormal facial and oral movements due to hypersensitivity of DA receptors
WORST: Typicals
Tx: None for advanced cases, must be recognized early, may worsen with withdrawal

36
Q

Which drug has a low incidence of tardive dyskinesia?

A

Clozapine (Atypical)

37
Q

Neuroleptic Malignant Syndrome:
Describe disease
Which drug class causes this ADR?
How is it treated?

A

Like malignant hyperpyrexia
WORST: Typicals
TX: Bromocriptine, Dantrolene–> Switch to atypical upon recovery

38
Q 
How do antipsychotics elevate prolactin? 
What kind of side effects may this cause, and why is this a problem? 
Which drug class is exceptionally bad for this ADR?
A

-Inhibition of D2R’s in Tubuloinfundibular Pway
-Menstrual irregularity/Low libido/Galactorrhea/osteoperosis
POOR COMPLIANCE
-WORST: Phenothiazines

39
Q
  • What are the effects of cholinergic blockade by antipsychotic drugs?
  • Which drugs cause these effects? (4)
  • How are these ADRs managed?
A

Opposite of SLUDE BBB;

  1. Thioridazine
  2. Chlorpromazine
  3. Olanzapine
  4. Clozapine (except increases salivation*)
    - Change to drug with lower M1 activity
40
Q

Which antipsychotics have a lot of A-Adrenergic activity? (2)

Which patient populations should avoid treatment with these drugs?

A
  1. Chlorpromazine
  2. Mesoridazine

CI: CVD, HTN (due to ^TPR, BP, Cardiac vasocnstrxn)

41
Q

Describe three metabolic side effects of antipsychotic drugs

A
  1. New onset/ exacerbation of DM II
  2. HTN
  3. Hyperlipidemia
42
Q

Clozapine, Olanzapine

Relative weight gain, lipids, glucose effects

A

Weight gain ++++
Lipids +++
Glucose +++

43
Q

Chlorpromazine

Relative weight gain, lipids, glucose effects

A

Weight gain +++
Lipids +++
Glucose ++

44
Q

Risperidone

Relative weight gain, lipids, glucose effects

A

Weight gain +
Lipids +/-
Glucose +/-

45
Q

Haloperidol

Relative weight gain, lipids, glucose effects

A

Weight gain +/-
Lipids -
Glucose -

46
Q

What are important monitoring tests to be done on patients taking antipsychotics? (3)

A
  1. BMI/ waist circ.
  2. Serum lipids
  3. Fasting glucose or A1C
47
Q

Which antipsychotic causes a Leukopenia and Agranulocytosis?

A

Clozapine (1-2% pts)

48
Q

Describe “Perioral Rabbit Syndrome”

How is it treated

A

Perioral tremors caused by years of antipsychotic use

Treat with anticholinergic antiparkinson drugs

49
Q

Which two antipsychotic drugs have cardiac effects?
What are the effects they cause?
Typical or atypical?

A

Thioridazine: minor T wave abnormalities (OD = ventricular arrhythmia); typical

Ziprasidone: QT prolongation; Atypical

50
Q

WHICH PATIENT POPULATION NEVER GETS ANTIPSYCHOTICS?

A

PREGGOS/ BREASTFEEDING

51
Q

What is one very important comorbid drug of abuse in psychotic patients? Why is it important?

A

Cigarettes/ nicotine–alter CYP activity

Can cause overdose or ineffectiveness of prescribed antipsychotic

52
Q

List 5 drugs that should not be taken in tandem with antipsychotics

A
  1. Central depressants–> DEATH
  2. Amphetamines–> negate effects
  3. Centrally acting anticholinergics–> worsen tardive dys.
  4. SSRI–> serotonin storm
  5. Antihypertensives–> excessive HypoTN
53
Q 
Phenothiazines: 
Typical or Atypical?
How to identify them 
Important drug in this class 
Important ADR assc with this entire class
A

Typical
All end in “azine”
*Chlorpromazine
Prolactin secretion

54
Q

Thioxanthenes:
Typical or Atypical?
How to Identify them

A

Typical

All end in “ene”

55
Q

Haloperidol, Spiperone- broad drug class

atypical vs typical

56
Q

Typical antipsychotic in the Azepine drug class

57
Q

Molindone- broad drug class

58
Q

Two important Atypical Azepines

A

Clozapine

Olanzapine

59
Q

Common ending for all Azepines

A

*All drugs in this class end in “ine”, whether

60
Q

Risperidone- broad drug class

A

Atypical antipsychotic

61
Q

Ziprasidone- typical or atypical?

62
Q

Most anti-psychotics have what effect on the circulatory system?

A

hypotension; perpetuate the effect of anti-hypertensive agents

63
Q

Both cocaine and amphetamines may mimic?

64
Q

Cocaine/ amphetamine MOA

A

Cocaine- blocks DA/NE reuptake

Amphetamine- ^DA

65
Q

Anti-cholinergics commonly used to reduce extra-pyramidal sx assc with anti-psychotics

A 
Trihexylphenidine 
Benztropine 
(1936 mercedes benz)
BIperidine 
ProCYCladine 
(bicycle)
66
Q

MOA and use for Bromocriptine

A

D2 agonist

reverses neuroleptic syndrome along with dantrolene

67
Q

In addition to D2 and 5HT2 block, what are the three other receptors that are blocked by anti-psychotics and responsible for many ADRs?

A

H1, a1/2, m

68
Q

Mesoridazine- broad class; 1 assc ADR

A

typical; a adrenergic activity (hypotension)

69
Q

Chloropromazine has a TON of ADRs/CI; List (6):

A 
prolactin
weight gain/metabolic syndrome 
anti-muscarinic 
anti-histamine
anti-adrengeric 
CI in seizures
70
Q

Ariprazole- broad class and one fact that distinguishes is from other anti-psychotics?

A

atypical; cannot be used as an anti-emetic

Neuro-Psych Exam II (11 decks)

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