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
