Atypical (2nd generation) antipsychotics Flashcards
Atypical antipsychotics - 10 drugs
Clozapine Olanzapine Molindone Risperidone Ziprasidone Lurasidone Iloperidone Asenapine Aripiprazole Paliperidone
Atypical antipsychotics - MOA
Greater affinity for 5-HT receptors than for D2 receptors. Blockade of 5-HT2 receptors in mesocortical and nigrostriatal pathways cause increased dopamine release. Mesocortical pathway – blockade of negative symptoms.
Atypical antipsychotics - indications
Schizophrenia
Manic episodes in bipolar disorder
Comparison of adverse effects of typical and atypical antipsychotics
Atypical have fewer EPSs and a lower incidence of neuroleptic malignant syndrome.
Potency of the atypical antipsychotics
Low potency: Clozapine
Medium potency: Molindone
High potency: Olanzapine, risperidone, ziprasidone, lurasidone, iloperidone, asenapine.
Clozapine - MOA
5-HT2=D4 > D2.
Antagonism of histamine, muscarinic and alpha 1-adrenoceptors
Clozapine - adverse effects
Significant sedation and autonomic side effects.
Potentially fatal agranulocytosis.
Cardiac arrhythmias
Olanzapine - MOA
5-HT2>D2. Can also block D3 and D4 receptors. Blocks histamine, muscarinic and alpha1-adrenoceptors (less than clozapine)
Olanzapine - indications
Schizophrenia.
Treatment-resistant depression (with fluoxetine)
Olanzapine - adverse effects
Weight gain Sedation. Fewer autonomic side effects than clozapine.
Few EPSs except in high doses.
Molindone - interactions
Additive effects with anticholinergic and CNS depressants. Concurrent use of beta-blocker or antidepressant may increase serum levels of both drugs.
Very short acting atypical antipsychotic
Molindone
Risperidone, ziprasidone, lurasidone, iloperidone, asenapine - MOA
5-HT2>D2
Risperidone, ziprasidone, lurasidone, iloperidone, asenapine - adverse effects
Cardiac arrhythmia (prolonged QT interval – torsade de pointes) and elevated serum prolactin levels. Compared to olanzapine: less sedation, more orthostatic hypotension and EPSs.
Aripiprazole - MOA
Partial agonist at dopamine and 5-HT1A receptors, but 5-HT2A antagonist