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📖PHARM: Psych, RA & Gout > 2-18 Anti-Psychotics > Flashcards

2-18 Anti-Psychotics Flashcards

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1
Q

A: Mesolimbic DA system

B: Which symptoms is this system associated with?



A

A: DA neurons from VTA -> subcortical structures of the brain (NA)
B: Psychotic symptoms

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2
Q

A: Nigrostriatal DA system

B: Which symptoms is this system associated with?

A

A: DA neurons from [Substantia nigra: compacta] -> striatum

B: Extrapyramidal Side Effects (EPS)

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3
Q

A: Mesocortical DA system

B: Which symptoms is this system associated with?

A

A: DA from VTA -> frontal cortex

B: Negative symptoms (and part of positive symptoms)

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4
Q

A: Tuberoinfundibular DA system

B: Which symptoms is this system associated with?

A

A: DA neurons projecting from the hypothalamus to the [ant. Pituitary]

B: Hyperprolactinemia and associated adverse effects

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5
Q

Other names for FGAs (First Generational Antipsychotics) (4)

A
  1. Major tranquilizers,
  2. Neuroleptics,
  3. [conventional antipsychotics],
  4. [Typical antipsychotics]
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6
Q

List the types of FGAs (3)

A
  1. Phenothiazines
  2. Thioxanthines
  3. Butyrophenones
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7
Q

Examples of Phenothiazine FGAs (5)

A

-azine

  1. Chlorpromazine
  2. Thioridazine
  3. Perphenazine
  4. Trifluoperazine
  5. Fluphenazine
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8
Q

Examples of Thioxanthine FGAs

A

Thiothixene

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9
Q

Examples of Butyrophenone FGAs

A

Haloperidol

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10
Q

List the Low Potency FGAs (2)

A

“Cheating Thieves are Low”

  1. Chlorpromazine
  2. Thioridazine
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11
Q

List the Middle Potency FGAs (2)

A
  1. Perphenazine
  2. Thiothixene
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12
Q

A: List the HIGH Potency FGAs (3)

B: Which of these has the highest affinity for D2 receptors?

A

“Try to Fly High”

A:

  1. Trifluperazine
  2. Fluphenazine
  3. Haloperidol = Binding affinity for D2 receptor is 10x greater than any other receptor
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13
Q

Which FGAs can be administered as Long acting injectables (2)

A
  1. Haloperidol
  2. Fluphenazine
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14
Q

Anti-Psychotic Indications (8)

A

OMASTABA!

  1. [Autism in children/adolescents]
  2. Bipolar DO (Acute mania/Maintenance/Depression)
  3. Agitation 2° to Schizophrenia vs. bipolar
  4. Schizophrenia (acute & maintenance)
  5. [Med-induced Psychosis] (Delirium/Dementia/Substance induced Psychosis)
  6. Tourette’s
  7. OCD
  8. Anxiety disorder
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15
Q

[Low Potency FGA] Side Effects (4)

A
  1. [ExtraPyramidalSx] / Tardive Dyskinesia
  2. Hyperprolactinemia
  3. [Muscarinic vs. A1 adrenergic] Effects
  4. Histamine Effects
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16
Q

[HIGH Potency FGA] Side Effects (2)

A
  1. [ExtraPyramidalSx] / Tardive Dyskinesia
  2. Hyperprolactinemia
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17
Q

A: Why is IM route for Anti-Psychotics a more effective route than PO? (2)

B: Describe Anti-Psychotic Protein binding

C: Describe Anti-Psychotic Solubility

A
  1. Poor GI absorption
  2. [Hepatic first-pass effect]

B: 90% Protein bound (the 10% unbound crosses BBB)

C: VERY LIPID SOLUBLE –> STORED IN FAT and slowly removed

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18
Q

Anti-Psychotics Half-Life

A

20 hours (at steady state, half life = 4-7 days)

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19
Q

MOA for FGA Therapeutic Effect

A

occurs [when >65% of [Mesolimbic DA2 receptors] are BLOCKED]

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20
Q

MOA for FGA [ESP Side Effects]

A

occurs [when >80% of [Nigrostriatal DA2 receptors] are BLOCKED]

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21
Q

MOA for FGA [Hyperprolactinemia Side Effects]

A

occurs [when >80% of [Tuberoinfundibular DA2 receptors] are BLOCKED]

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22
Q

A: List components of [Drug induced Parkinsonism] (4)

B: What are the other 2 components of EPS?

A

EPS = DAD

  1. [Drug induced Parkinsonism]
  2. Dystonia
  3. Akathisia

A: [Drug induced Parkinsonism]= PARK = [Pill rolling tremor] / [Areflexia posturally –> Falls] / [Rigidity Cogwheel] / [Kinesia (bradykinesia)]

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23
Q

A: List components of Dystonia (3)

B: What are the other 2 components of EPS? (2)

A

EPS = DAD

  1. [Drug induced Parkinsonism]
  2. Dystonia
  3. Akathisia

A: Dystonia:

  • Sustained muscle spasm–>Abnormal twisted posture
  • Exacerbated with activity
  • Demographic: Young males
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24
Q

A: List components of Akathisia (2)

B: What are the other 2 components of EPS? (2)

A

EPS = DAD

  1. [Drug induced Parkinsonism]
  2. Dystonia
  3. Akathisia

A: Akathisia: Sense of restlessness (typically legs) with need to move. Mistaken for agitation

-Demographic: Women

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25
A: What is **Tardive Dyskinesia** B: What area of the body is most commonly affected?
A: Abnormal involuntary mvmnt that typically does not remit even after drug cessation. B: Facio-Masticatory-Oro-lingual
26
Effects of **Hyperprolactinemia** (4)
* Galactorrhea/lactation * Gynecomastia * DEC **GnRH** --\> [DEC LH & FSH] --\> [Irregular menstruation & infertility] * Osteopenia
27
Effects of Antipsychotics blocking [Muscarinic System] (*Effect of **Anti**cholinergic action*) (5)
*can't **see**, can't **spit**, can't **pee**, can't **shit**, can't **think*** ## Footnote [Blurred vision / Dry Mouth / Urinary Retention / Constipation / Confusion]
28
Effects of Antipsychotics blocking [A1 Adrenergic System]
Orthostatic hypOtension --\> Fall Risk!
29
Effects of Antipsychotics binding to [Histamine Receptors] (2)
Sedation vs. Wt.Gain
30
Describe **Neuroleptic Malignant Syndrome**
**RARE** SE of *Any* Dopamine Blocker (*Antipsychotics vs. GI meds*) that --\> **FEVER** ## Footnote - [**F**ever \> 40C] - **E**ncephalopathy (Confusion) - **V**itals unstable (INC HR / RR / BP from autonomic dysfunction) - **E**nzymes INC (CPK) - **R**igitidy INC (Tremor)
31
Risk Factors for **Sudden Death** when taking Antipsychotics (4)
1. Dementia --\> Death from Stroke when taking Antipsychotics 2. Higher doses 3. Prior CV Dz 4. Black Box Warning
32
List the **Atypical** [**SGA**s - ***S**econd **G**enerational **A**ntipsychotics*] (10)
It's *atypical* for **o**ld **pal**e **cloz**ets to **quiet**ly **risper** from **AA** to **Z** * **O**lanzapine * **Pal**iperidone (*Metabolite of **Risper**idone*​) * **Cloz**apine * **Queti**apine * **Risper**idone * **A**ripiprazole & **A**senapine * **ZiL - Z**iprasidone / **i**Loperidone / **L**urasidone
33
Which **SGA** works as a *partial agonist*
**A**ripiprazole
34
A: Which **SGA** is a [*High Risk / High Reward*] Drug? What is its indication? B: What are the common Side effects of this **SGA** (3) C: Dangerous Side Effects (3) D: Explain the *Reward* component of this **SGA**
A: **Cloz**apine = [_3rd_ Line Schizophrenia tx] B: [Sedation / Anticholinergic / metabolic syndrome] C: - Agranulocytosis (*1-2% of pts*) - Myocarditis - INC Seizures D: Treats negative sx (*tardive dyskinesia / suicide / treatment resistant schizophrenia*)
35
Which **SGAs** can be administered as *Long acting injectables* (4) B: Which of these are excreted via **RENAL**
"**OPRAH**" 1. **Risper**idone 2. **Pal**iperidone (*Metabolite of **Risper**idone*) 3. **Ol**anzapine 4. **A**ripiprazole B: **Pal**iperidone = SHOULD NOT BE USED IN RENAL FAILURE PTS **H**aloperidone = FGA is also long acting injectable
36
Which **SGA**s should be taken with food for better absorption? (3)
"**PLZ** take with food!" 1. **Z**iprasidone 2. **L**urasidone 3. **Pal**iperidone
37
Which **SGA** is sublingual
A*S*enapine
38
A: MOA for **A**ripiprazole (2) B: Explain its binding affinity with [*low vs. High Dopamine*] environments
* Partial agonist tht sits on receptor & blocks the receptor from other stimulation but also partially turns it on * Changes the receptor conformation slightly (G protein organization changes) B: - In low DA receptor stimulation environment, binds DA2 receptor with HIGH AFFINITY & has partial agonist effect - In high DA stimulation environment, exerts antagonist action
39
A: Side Effect for [**A**ripiprazole AND Lurasidone] B: Half life for **A**ripiprazole
"**Ari**elle & **Lura** are *restless* studiers!" A: Akathisia (*restlessness*) B: 3 Days (*longest out of the SGAs*)
40
A: MOA for [**SGA: Serotonin Dopamine Dual Antagnoism**] B: Why does this enhance Cortical Function C: What Radiographic Tool supports this Hypothesis
A: 5HT2A blockade in [Mesolimbic/ Nigrostriatal / Tuberoinfundibular] tract (*blocking yellow piece*) ---\> DA release (*blue* *bullets*) from BG: This DA competes with antipsychotic mediation (*black sphere*) for DA2 receptors --\> DEC EPS B: Mesocortical: 5HT2A blockade may normalize cortical function (possibly by enhancing DA release and ACh release in frontal cortex, thereby reducing negative symptoms/ cognitive deficit C: PET Scan
41
MOA for [**SGA: Hit & Run Concept**]
Lower potency DA2 blockade by atypical antipsychotics --\> ***loose*** receptor blockade with shorter-lasting effect. Effect is present long enough to have antipsychotic therapeutic effect
42
Which two drugs delineate evidence of the [**SGA: Hit & Run Concept**]
[**Cloz**apine & **Queti**apine] have the _lowest incidence of EPS or Tardive Dyskinesia_
43
Relative effects on **nigrostriatal** system by SGAs (5)
Risperidone \> [Ziprasidone = Olanzapine] \> Quetiapine \> Clozapine
44
Relative effects on **tuberoinfundibular** system by SGAs (5)
Risperidone \> [Ziprasidone = Olanzapine] \> Quetiapine \> Clozapine
45
Relative effects on [**A1 adrenergic system**] by SGAs (5)
Clozapine \> [Olanzapine = Quetiapine = Risperidone] \> Ziprasidone
46
A: Relative effects on [**M1 muscarinic system**] by SGAs (4) B: Which SGAs do **NOT** have an affect on this system (5)
A: Clozapine \> Olanzapine \> Quetiapine \> Iloperidone B: NOT: Risperidone, Aripiprazole, Asenapine, Ziprasidone, Lurasidone
47
Relative effects on **H1 system** by SGAs (4)
Clozapine \> Quetiapine \> Olanzapine = Ziprasidone
48
Relative effects on **metabolic syndrome** by SGAs (5)
[Clozapine = Olanzapine] \> [Quetiapine = Risperidone] \> Ziprasidone
49
Which antipsychotics cause **QT elongation** (2)
"Q**_T_** elongated by ****_T_**Z**" **T**hioridazine \> **Z**iprasidone
50
From Greatest to least, list SGAs that cause **sedation** (4)
Clozapine \> Olanzapine \> Quetiapine \> [Risperidone/Paliperidone]
51
3 SGAs that cause the greatest **weight gain**
"**i** _**C**ause_ _**O**besity_" **i**Loperidone / _**C**lozapine_ / _**O**lanzapine_ ***C**lozapine & **O**lanzapine cause [Metabolic Syndrome] as well*
52
Side Effects of [SGA: Asenapine]
High H1 and a1 binding --\> [sedation & orthostasis]
53
Which SGA causes the **most** D2 mediated SEs
Risperidone
54
Which SGA causes the **least** D2 mediated SEs
Clozapine
55
Which SGA causes the **least** [**A1 adrenergic**] mediated SEs
Ziprasidone
56
Which SGA causes the **MOST** [**A1 adrenergic**] mediated SEs
Clozapine
57
Which SGAs cause the **least** M1 mediated SEs (2)
Risperidone and Ziprasidone
58
Which SGAs cause the **MOST** M1 mediated SEs (2)
Clozapine
59
Which SGA causes the **least** H1 mediated SEs
Risperidone
60
Which SGA causes the **MOST** H1 mediated SEs
Clozapine
61
Which SGA causes the **least** metabolic syndrome SEs (3)
Ziprasidone, Molazodone, Ariprazole
62
Which SGA causes the **MOST** metabolic syndrome SEs (2)
Clozapine and Olanzapine
63
A: **High** binding SEs of Risperidone (2) B: Which receptor causes this
A: 1. INC Prolactin 2. EPS B: [A1 adrenergic]
64
**low** binding SEs of Risperidone
NONE
65
A: **High** binding SEs of Clozapine (2) B: Which receptors are blocked (3)
A: 1. Wt Gain 2. Metabolic Syndrome B: [A1 adrenergic] / M1 / H1
66
Which antipsychotic **DOES NOT** cause EPS
Clozapine
67
A: **High** binding SEs of Olanzapine (2) B: Which Receptors are blocked (2)
A: 1. Wt. Gain 2. Metabolic Syndrome B: [A1 adrenergic] / H1
68
**low** binding SEs of Olanzapine
EPS
69
Which receptors does Quetiapine block at **High** concentrations? (2)
[A1 Adrenergic] & H1
70
**low** binding SEs of Quetiapine
EPS (*has very low incidence of EPS or Tardive Dyskinesia 2º to HIt & Run Concept*)
71
Which receptors does Asenapine block at **High** concentrations? (2)
[A1 Adrenergic] & H1
72
**low** binding SEs of Asenapine
[**Metabolic Syndrome** from M1 Blockade]
73
A: **HIGH** binding SEs of iLoperidone B: **M****oderate** binding SEs of iLoperidone (2)
A: None B: [A1 Adrenergic blockade] & [Wt. Gain]
74
**low** binding SEs of iLoperidone (3)
1. EPS 2. H1 blockade 3. Metabolic Syndrome
75
What's the ideal therapeutic window when blocking dopamine receptors? (in terms of % of receptors blocked)
**60-80% blockage of D2 receptors** \> 60% (needed to therapeutically affect mesolimbic tract) \<80% (above which you cause adverse effects)

📖PHARM: Psych, RA & Gout (6 decks)

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