Behavioral Med Drugs Flashcards
What is the prototypical low-potency first gen antipsychotic?
Chlorpromazine (Thorazine)
What is the prototypical high-potency first gen antipsychotic?
Haloperidol (Haldol)
What are 5 examples of second gen antipsychotics?
Clozapine Quetiapine (Seroquel) Risperidone Ziprasidone (Geodon) Aripirazole (Abilify) - this has a unique MOA
(Olanzapine is used frequently in Rosh questions)
What is the therapeutic MOA of first gen antipsychotics?
Antagonize D2 receptors in the mesolimbic dopamine pathway
(Keep in mind this is non-selective, so antagonism of D2 receptors in other pathways also occurs – but is not therapeutic)
What are other receptor (non-therapeutic targets) effects of first generation antipsychotics?
Anti-H.A.M. (antagonize the following:)
H1 receptors: sedation; weight gain (may be related to 5HT2A block, along with glucose intolerance)
Alpha-1 receptors: orthostatic/hypotension, sexual dysfunction, cardiac problems (think arrhythmias), and seizures
Muscarinic receptors: dries everything up
First gen antipsychotics are indicated for what in schizophrenia? Why?
Positive symptoms only:
- hallucinations
- delusions
- paranoia
Does not address negative symptoms; can potentially exacerbate negative symptoms.
This is because the first gen meds are non-specific in their dopamine antagonism activity. Decreasing dopamine activity in the mesolimbic system decreases positive symptoms; decreasing dopamine activity in the mesocortical system can INCREASE negative symptoms.
What is the pathophys/etiology of positive symptoms in schizophrenia?
Excess of dopamine in the mesolimbic system
What is the pathophys/etiology of negative symptoms in schizophrenia?
Deficiency of dopamine in the mesocortical system, secondary to excess serotonin
(or secondary to dopamine blocking caused by 1st gen antispsychotics/other drugs)
When an first gen antipsychotic drug acts on the nigrostriatal dopamine pathway, what occurs?
Dopamine suppresses ACh activity (via GABA), so blocking dopamine –> increased ACh activity –> adverse effects of the extrapyramidal system (EPS)
Dysfunction of the EPS = movement disorders
Deficiency of dopamine = Parkinson’s syndrome
Hyperactivity of dopamine = chorea, tics
Dopamine inhibition = akathisia (tense restlessness), dystonia (uncontrollable contractions/spasms -> repetitive movements), tardive dyskiniesia (similar, often involves face/head - smacking lips, sticking out tongue, etc)
When an first gen antipsychotic drug acts on the tuberoinfundibular dopamine pathway, what occurs?
The tuberoinfundibular pathway mediates dopamine from arcuate nucleus to the hypothalmus.
Dopamine release from the hypothalmus inhibits prolactin release from the pituitary gland.
Thus, dopamine blockade in the tuberoinfundibular pathway –> increased prolactin release.
Adverse effects include:
Women: breast engorgement; galactorrhea, amenorrhea
Women and men: sexual dysfunction, infertility
What is the therapeutic MOA of second-gen antipsychotics?
Weakly antagonize D2 receptors in the mesolimbic dopamine pathway (or weakly agonize)
Antagonize serotonin receptors in mesocortical system
Other than mesolimbic and mesocortical effects, what are some actions of second gen antipsychotics?
Nigrostriatal pathway:
Promotes dopamine release to compete with D2 block
Tuberoinfundibular pathway:
5Ht-stimulated prolactin release is blocked
Which antipsychotic class is likely to cause the MOST sedation?
Low-potency first generation (chlorpromazine)
All antipsychotics have the potential to cause some sedation
Which antipsychotic class is most likely to cause seizures?
First gen (haldol and chlorpromazine) AND clozapine (2nd gen)
What antipsychotic class is most likely to cause EPS symptoms?
First generation (especially high potency)
Also, risperidone (dose-dependent)
If a patient, who is otherwise stable on their antipsychotic medication, exhibits laryngospasm, what should be done?
Laryngospasm (as well as torticollis and oculogyric crisis) are forms of dystonia, which is an EPS side effect caused by increased ACh activity due to reduced dopamine levels.
Dystonia responds to anticholinergics.
If a patient, who is otherwise stable on their antipsychotic medication, exhibits repetitive lip smacking, what should be done?
This is a form of tardive dyskinesia, which is an EPS side effect caused by hypersensitivity of dopamine receptors after long-term suppression of dopamine release.
Change this patient’s antipsychotic to a second gen, as these symptoms can become permanent.
Which antipsychotic has the highest risk of prolonged QT interval?
*ZZ:
Ziprasidone and cloZapine
You have a patient with obesity who requires an antipsychotic. She reports no cardiac history. Which might be a good choice?
Aripiprazole has less potential for weight gain and less sedation.
Ziprasidone also has less potential for weight gain.
Which second gen antipsychotics are most associated with weight gain?
Clozapine
Risperdone, but this is a dose-dependent effect
Your patient tells you she has a history of “heart problems”. When considering an antipsychotic for her, what would be some considerations?
Ziprasidone and iloperidone have highest risk of QT prolongation.
Your patient has diabes and requires an antipsychotic medication. What are some considerations?
Many second gen antipsychotics cause hyperlipidemia, weight gain, and hyperglycemia.
- Olanzipine has a high risk of metabolic effects
- Arpiprazole and ziprasidone have the lowest risk of these side effects among the second gen (but do carry some risk of QT prolongation)
- Or, maybe consider a first gen
Which antipsychotic agents are most likely to cause EPS symptoms?
High-potency first gen (haloperidol)
Which antipsychotic agents are most likely to cause anti-HAM effects?
Low potency first generation (chlorpromazine)
anti-HAM = histamine, a1, and muscarinic antagonism-related side effects + seizures
