antipsychotics (major tranquilizers)

Question 1

Class: typical neuroleptic antipsychotic (aliphatic derivative of phenothiazine)
MOA: strong DA-receptor blockade
-many side effects
Use: schizophrenia, psychotic bipolar disorder, psychotic depression, treatment-resistant depression
Side effects: sedation and weight gain, orthostatic HTN, tachycardia
Interactions: no opioids

Answer 1

chlorpromazine

Thorazine

Question 2

Class: atypical antipsychotic dibenzodiazepine
Produces fewer EPS at equivalent antipsychotic doses in humans and animals
MOA: inverse agonist of 5-HT2c receptor (receptor activation normally leads to inhibition of release of dopamine in cortical & limbic regions)
Use: schizophrenia, psychotic bipolar disorder, psychotic depression, treatment-resistant depression
Side effects: weight gain, hyperglycemia, hyperlipidemia (from insulin resistance), **agranulocytosis in 2%, dose-related lowering of **seizure threshold, myocarditis
Metab: CYP450
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs
Note: abrupt discontinuation of drug results in rapid severe relapse of psychotic symptoms
Check blood counts qweek for agranulcytosis during first 6 months then q3weeks following

Answer 2

Clozapine

Clozaril

Question 3

Class: typical antipsychotic phenothiazine derivative
MOA: strong D2 receptor antagonist (blocker)
Adverse: many side effects due to blocking of alpha-adrenergic, muscarinic, H1 and 5-HT receptors; increased tardive dyskinesia
Interactions: no opioids

Answer 3

fluphenazine

Prolixin

Question 4

Class: typical antipsychotic butyrophenone (potent)
MOA: potent dopamine (D2) receptor antagonist; alpha receptor antagnonist
Side effects: high level of EPS but fewer than some other drugs in its class (doesn’t block as many receptors), increased risk of torsades
Metab: less first-pass metabolism so has 65% systemic availability
Interactions: no opioids

Answer 4

haloperidol

Haldol

Question 5

Class: atypical antipsychotic thienobenzodiazepine
MOA:
Use: effective against negative and positive symptoms with little to no EPS dysfunction in schizophrenia, psychotic & manic bipolar disorder, psychotic depression, treatment-resistant depression, schizoaffective disorders
Metab: CYP450
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs

Answer 5

olanzapine

Zyprexa

Question 6

Class: atypical antipsychotic dibenzothiazepine
MOA: serotonin-dopamine antagonist
Use: schizophrenia, psychotic & manic bipolar disorder, psychotic depression, treatment-resistant depression, schizoaffective disorders
Metab: CYP450
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs

Answer 6

quetiapine

Seroquel

Question 7

Class: Antipsychotic
MOA: antagonist of serotonin 5-HT2A, dopamine D2, alpha1 & alpha2 adrenergic, and histamine H1 receptors
Side Effects: dose-dependent extrapyramidal: dizziness, hyperkinesia, somnolence, nausea. Weight gain, anxiety, nausea/vomiting, rhinitis, erectile dysfunction, orgasmic dysfunction, increased pigmentation
Metab: undergoes first-pass hepatic metabolism to 9-hydroxyrisperidone which has equivalent activity to parent compound (peak for parent 1 hr; peak for metabolite 3 hr); half-life 20 hours - once a day dosing at night (1-4 mg)
Interactions: paroxetine & fluoxetine block formation of active metabolite by inhibiting CYP2D6; combined with other SSRI’s it can cause elevated prolactin (galactorrhea & breast enlargement)

Answer 7

Risperidone

Risperdal

Question 8

Class: typical antipsychotic piperidine derivative
MOA: strong D2 receptor antagonist
Use: schizophrenia, psychotic bipolar disorder, psychotic depression, treatment-resistant depression, schizoaffective disorders
(more potent than aliphatic derivative)
Toxicity: cardiotoxicity; orthostatic HTN & tachycardia torsades
Adverse: retinal deposits (browning of vision)
Metab: CYP450
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs; no opioids

Answer 8

thioridazine

Mellaril

Question 9

Class: typical antipsychotic thioxanthene
MOA: slightly less potent D2 antagonist
Use: schizophrenia, psychotic bipolar disorder, psychotic depression, treatment-resistant depression, schizoaffective disorders
Adverse: blockade of many other receptors causes: dystonia, akathisia, dry mouth, urinary retention orthostatic hypotension, sedation, neuroletpic hyperthermia
Metab: CYP450
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs; opioids

Answer 9

thiothixene

Navane

Question 10

Use: schizophrenia, psychotic depression, treatment-resistant depression, schizoaffective diorder
Metab: CYP450
Adverse: Prolonged QT
Advantage: parenteral form available
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs

Answer 10

ziprasidone

Geodone

Question 11

Class: atypical antipsychotic dyhydrocarbostyril
MOA: partial D2-receptor agonist (in the presence of endogenous DA, it acts as an antagonist) and 5-HT2A antagonist
has very high occupancy of D2 receptors but does not cause EPS, because it is a partial D2-receptor agonist
Use: schizophrenia, psychotic & manic bipolar disorder, psychotic depression, treatment-resistant depression; schizoaffective disorder
Metab: CYP450
Interactions: do not typically interfere with other drugs but use with caution with drugs that inhibit CYPs

Answer 11

aripiprazole
(Abilify)

*the D2 receptor antagonism is a unique feature of this drug

Question 12

side effects limiting use of antipsychotics

Answer 12

tardive dyskinesia from dopamine receptor antagonism
suppression of gonadal hormones
hyperprolactinemia causes absence of menses
BMI, elevated FBS, elevated lipids
clozapine causes agranulocytosis