2nd Generation "Atypical" Antipsychotics Flashcards
Atypicals, general
Affect DA and 5-HT
Reduced side-effect profile vs 1st generation
*low risk for EPS, even among high potency atypicals
First drug, clozapine (Clozaril)
Atypicals: Mechanism of Action
Atypicals primarily block D4, occasionally block D2
D4 receptors are rarer than D2
(Typicals primarily block D2)
Atypicals block just enough dopamine reduce positive symptoms
= transient dopamine blockages vs. full antagonists
Atypical Side effects: Metabolic syndrome
Significant weight gain/obesity
Diabetes type 2 onset
Hyperlipidemia
Prolonged Q-T interval
Atypical SFX: Weight Gain
40-60% of SZ patients are overweight or obese (both 1st and 2nd gen AP’s contribute to weight gain)
Increased risk for cardiovascular morbidity and mortality, as well as impairment in:
- psychosocial adjustment
- medication adherence
- ability to participate in rehabilitation efforts
- self-image
Atypical SFX: Diabetes
*more frequently with clozapine and olanzpine
About 7 % of patients receiving atypicals developed new-onset type-2 DM over a one-year period
*fewer case reports on quetiapine and risperidone.
Atypical SFX: Hyperlipidemia
Clozapine and olanzapine associated with greatest increase in cholesterol and triglyceride levels
Atypical SFX: Prolonged QT Interval
Sertindole: largest Q-T effect
Also:
- risk of arrhythmias
- unexpected deaths with
- Not approved in US – but is in Europe
Risperidone (Risperdal)
*Most likely atypical to induce hyperprolactinemia
Weight gain and sedation (dosage dependent)
Functions more like a typical antipsychotic at doses greater than 6mg
*Increased EPS (dose dependent)
Olanzapine (Zyprexa)
Weight gain
As much as 30-50lbs with even short term use
hyperglycemia (even without weight gain)
hypertriglyceridemia
hypercholesterolemia
May cause hyperprolactinemia (< risperidone)
May cause transaminitis (2% of all patients)
Quetiapine (Seroquel)
*Most likely to cause orthostatic hypotension
May cause transaminitis (6% of all patients)
Similar sfx as Zyprexa, but less severe:
hyperglycemia (even without weight gain)
hypertriglyceridemia
hypercholesterolemia
hyperprolactinemia (< risperidone)
Ziprasidone (Geodon)
Absorption is increased (up to 100%) with food
*No associated weight gain
Q-T prolongation
May cause hyperprolactinemia (< risperidone)
Aripiprazole (Abilify)
Unique mechanism of action as a D2 partial agonist
Traditionally used as an adjunct for unipolar depression
Clozapine (Clozaril)
Reserved for treatment resistant patients because of side effect profile:
*Associated with the most sedation, weight gain and transaminitis (liver damage)
**Agranulocytosis!
*Seizures (especially with lithium)
Clozapine: special consideration
**Associated with agranulocytosis (0.5-2%)= severe and dangerous decreased white blood cell count = suppressed immune function
Agranulocytosis Monitoring:
- weekly blood draws x 6 months
- then Q- 2weeks x 6 months
Areas of Cognitive Deficits in Schizophrenia-related Disorders
Attention, memory, language
Cognitive impairment is correlated with poor occupational functioning
Atypicals appear to prevent/treat cognitive decline better than typicals
o But only marginally
Effects of antipsychotics on neurocognition
Risperdal v Haldol
Hypothesis: 5-HT blockade increases DA in mesocortical pathway
Research: Risperdal better than Haldol at improving:
working memory and long-term memory
*Even when SZ symptoms are not reduced
Why Atypicals have lower risk for EPS
Atypicals’ antagonism of 5-HT limits additional reduction of DA and thus the consequent increase of ACH which produces EPS
EPS result in part from increased ACH
Neurocognitive enhancement therapy (NET)
Treat cognitive deficits assoc with SZ
Reminders, artificial support to encourage cognitive skills exercise
Abilify: Pro’s
Not associated with weight gain
Low EPS
No QT prolongation
Low sedation
Abilify: Con’s
Could cause potential intolerability due to akathisia
Drug-drug interactions:
- prozac
- paxil
