2-18 Anti-Psychotics Flashcards
A: Mesolimbic DA system
B: Which symptoms is this system associated with?
A: DA neurons from VTA -> subcortical structures of the brain (NA)
B: Psychotic symptoms

A: Nigrostriatal DA system
B: Which symptoms is this system associated with?
A: DA neurons from [Substantia nigra: compacta] -> striatum
B: Extrapyramidal Side Effects (EPS)

A: Mesocortical DA system
B: Which symptoms is this system associated with?
A: DA from VTA -> frontal cortex
B: Negative symptoms (and part of positive symptoms)

A: Tuberoinfundibular DA system
B: Which symptoms is this system associated with?
A: DA neurons projecting from the hypothalamus to the [ant. Pituitary]
B: Hyperprolactinemia and associated adverse effects

Other names for FGAs (First Generational Antipsychotics) (4)
- Major tranquilizers,
- Neuroleptics,
- [conventional antipsychotics],
- [Typical antipsychotics]
List the types of FGAs (3)
- Phenothiazines
- Thioxanthines
- Butyrophenones
Examples of Phenothiazine FGAs (5)
-azine
- Chlorpromazine
- Thioridazine
- Perphenazine
- Trifluoperazine
- Fluphenazine
Examples of Thioxanthine FGAs
Thiothixene
Examples of Butyrophenone FGAs
Haloperidol
List the Low Potency FGAs (2)
“Cheating Thieves are Low”
- Chlorpromazine
- Thioridazine

List the Middle Potency FGAs (2)
- Perphenazine
- Thiothixene

A: List the HIGH Potency FGAs (3)
B: Which of these has the highest affinity for D2 receptors?
“Try to Fly High”

A:
- Trifluperazine
- Fluphenazine
- Haloperidol = Binding affinity for D2 receptor is 10x greater than any other receptor
Which FGAs can be administered as Long acting injectables (2)
- Haloperidol
- Fluphenazine

Anti-Psychotic Indications (8)
OMASTABA!
- [Autism in children/adolescents]
- Bipolar DO (Acute mania/Maintenance/Depression)
- Agitation 2° to Schizophrenia vs. bipolar
- Schizophrenia (acute & maintenance)
- [Med-induced Psychosis] (Delirium/Dementia/Substance induced Psychosis)
- Tourette’s
- OCD
- Anxiety disorder
[Low Potency FGA] Side Effects (4)
- [ExtraPyramidalSx] / Tardive Dyskinesia
- Hyperprolactinemia
- [Muscarinic vs. A1 adrenergic] Effects
- Histamine Effects
[HIGH Potency FGA] Side Effects (2)
- [ExtraPyramidalSx] / Tardive Dyskinesia
- Hyperprolactinemia
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
- Poor GI absorption
- [Hepatic first-pass effect]
B: 90% Protein bound (the 10% unbound crosses BBB)
C: VERY LIPID SOLUBLE –> STORED IN FAT and slowly removed
Anti-Psychotics Half-Life
20 hours (at steady state, half life = 4-7 days)
MOA for FGA Therapeutic Effect
occurs [when >65% of [Mesolimbic DA2 receptors] are BLOCKED]

MOA for FGA [ESP Side Effects]
occurs [when >80% of [Nigrostriatal DA2 receptors] are BLOCKED]

MOA for FGA [Hyperprolactinemia Side Effects]
occurs [when >80% of [Tuberoinfundibular DA2 receptors] are BLOCKED]

A: List components of [Drug induced Parkinsonism] (4)
B: What are the other 2 components of EPS?
EPS = DAD
- [Drug induced Parkinsonism]
- Dystonia
- Akathisia
A: [Drug induced Parkinsonism]= PARK = [Pill rolling tremor] / [Areflexia posturally –> Falls] / [Rigidity Cogwheel] / [Kinesia (bradykinesia)]
A: List components of Dystonia (3)
B: What are the other 2 components of EPS? (2)
EPS = DAD
- [Drug induced Parkinsonism]
- Dystonia
- Akathisia
A: Dystonia:
- Sustained muscle spasm–>Abnormal twisted posture
- Exacerbated with activity
- Demographic: Young males
A: List components of Akathisia (2)
B: What are the other 2 components of EPS? (2)
EPS = DAD
- [Drug induced Parkinsonism]
- Dystonia
- Akathisia
A: Akathisia: Sense of restlessness (typically legs) with need to move. Mistaken for agitation
-Demographic: Women
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
Effects of Hyperprolactinemia (4)
- Galactorrhea/lactation
- Gynecomastia
- DEC GnRH –> [DEC LH & FSH] –> [Irregular menstruation & infertility]
- Osteopenia
Effects of Antipsychotics blocking [Muscarinic System] (Effect of Anticholinergic action) (5)
can’t see, can’t spit, can’t pee, can’t shit, can’t think
[Blurred vision / Dry Mouth / Urinary Retention / Constipation / Confusion]
Effects of Antipsychotics blocking [A1 Adrenergic System]
Orthostatic hypOtension –> Fall Risk!
Effects of Antipsychotics binding to [Histamine Receptors] (2)
Sedation vs. Wt.Gain
Describe Neuroleptic Malignant Syndrome
RARE SE of Any Dopamine Blocker (Antipsychotics vs. GI meds) that –> FEVER
- [Fever > 40C]
- Encephalopathy (Confusion)
- Vitals unstable (INC HR / RR / BP from autonomic dysfunction)
- Enzymes INC (CPK)
- Rigitidy INC (Tremor)
Risk Factors for Sudden Death when taking Antipsychotics (4)
- Dementia –> Death from Stroke when taking Antipsychotics
- Higher doses
- Prior CV Dz
- Black Box Warning
List the Atypical [SGAs - Second Generational Antipsychotics] (10)
It’s atypical for old pale clozets to quietly risper from AA to Z
- Olanzapine
- Paliperidone (Metabolite of Risperidone)
- Clozapine
- Quetiapine
- Risperidone
- Aripiprazole & Asenapine
- ZiL - Ziprasidone / iLoperidone / Lurasidone
Which SGA works as a partial agonist
Aripiprazole
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: Clozapine = [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)
Which SGAs can be administered as Long acting injectables (4)
B: Which of these are excreted via RENAL
“OPRAH”
- Risperidone
- Paliperidone (Metabolite of Risperidone)
- Olanzapine
- Aripiprazole
B: Paliperidone = SHOULD NOT BE USED IN RENAL FAILURE PTS
Haloperidone = FGA is also long acting injectable
Which SGAs should be taken with food for better absorption? (3)
“PLZ take with food!”
- Ziprasidone
- Lurasidone
- Paliperidone
Which SGA is sublingual
ASenapine
A: MOA for Aripiprazole (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
A: Side Effect for [Aripiprazole AND Lurasidone]
B: Half life for Aripiprazole
“Arielle & Lura are restless studiers!”
A: Akathisia (restlessness)
B: 3 Days (longest out of the SGAs)
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
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
Which two drugs delineate evidence of the [SGA: Hit & Run Concept]
[Clozapine & Quetiapine] have the lowest incidence of EPS or Tardive Dyskinesia
Relative effects on nigrostriatal system by SGAs (5)
Risperidone > [Ziprasidone = Olanzapine] > Quetiapine > Clozapine
Relative effects on tuberoinfundibular system by SGAs (5)
Risperidone > [Ziprasidone = Olanzapine] > Quetiapine > Clozapine
Relative effects on [A1 adrenergic system] by SGAs (5)
Clozapine > [Olanzapine = Quetiapine = Risperidone] > Ziprasidone
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
Relative effects on H1 system by SGAs (4)
Clozapine > Quetiapine > Olanzapine = Ziprasidone
Relative effects on metabolic syndrome by SGAs (5)
[Clozapine = Olanzapine] > [Quetiapine = Risperidone] > Ziprasidone
Which antipsychotics cause QT elongation (2)
“QT elongated by TZ”
Thioridazine > Ziprasidone
From Greatest to least, list SGAs that cause sedation (4)
Clozapine > Olanzapine > Quetiapine > [Risperidone/Paliperidone]
3 SGAs that cause the greatest weight gain
“i Cause Obesity”
iLoperidone / Clozapine / Olanzapine
Clozapine & Olanzapine cause [Metabolic Syndrome] as well
Side Effects of [SGA: Asenapine]
High H1 and a1 binding –> [sedation & orthostasis]
Which SGA causes the most D2 mediated SEs
Risperidone
Which SGA causes the least D2 mediated SEs
Clozapine
Which SGA causes the least [A1 adrenergic] mediated SEs
Ziprasidone
Which SGA causes the MOST [A1 adrenergic] mediated SEs
Clozapine
Which SGAs cause the least M1 mediated SEs (2)
Risperidone and Ziprasidone
Which SGAs cause the MOST M1 mediated SEs (2)
Clozapine
Which SGA causes the least H1 mediated SEs
Risperidone
Which SGA causes the MOST H1 mediated SEs
Clozapine
Which SGA causes the least metabolic syndrome SEs (3)
Ziprasidone, Molazodone, Ariprazole
Which SGA causes the MOST metabolic syndrome SEs (2)
Clozapine and Olanzapine
A: High binding SEs of Risperidone (2)
B: Which receptor causes this
A:
- INC Prolactin
- EPS
B: [A1 adrenergic]
low binding SEs of Risperidone
NONE
A: High binding SEs of Clozapine (2)
B: Which receptors are blocked (3)
A:
- Wt Gain
- Metabolic Syndrome
B: [A1 adrenergic] / M1 / H1
Which antipsychotic DOES NOT cause EPS
Clozapine
A: High binding SEs of Olanzapine (2)
B: Which Receptors are blocked (2)
A:
- Wt. Gain
- Metabolic Syndrome
B: [A1 adrenergic] / H1
low binding SEs of Olanzapine
EPS
Which receptors does Quetiapine block at High concentrations? (2)
[A1 Adrenergic] & H1
low binding SEs of Quetiapine
EPS (has very low incidence of EPS or Tardive Dyskinesia 2º to HIt & Run Concept)
Which receptors does Asenapine block at High concentrations? (2)
[A1 Adrenergic] & H1
low binding SEs of Asenapine
[Metabolic Syndrome from M1 Blockade]
A: HIGH binding SEs of iLoperidone
B: Moderate binding SEs of iLoperidone (2)
A: None
B: [A1 Adrenergic blockade] & [Wt. Gain]
low binding SEs of iLoperidone (3)
- EPS
- H1 blockade
- Metabolic Syndrome
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)