Antipsychotics, 2nd Generation (Atypical)

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Give eg's of & indications for 2nd generation antipsychotics. eg's: quetiapine, olanzapine, risperidone, clozapine Indications: • Severe psychomotor agitation leading to dangerous or violent behaviour • Schizophrenia particularly when extrapyramidal side effects have complicated the use of first-generation (typical) antipsychotics, or when negative symptoms are prominent • Bipolar disorder particularly in acute episodes of mania or hypomania
MOA of 2nd generation antipsychotics. Antipsychotic drugs block post-synaptic dopamine D2 receptors. There are three main dopaminergic pathways in the CNS. The mesolimbic/mesocortical pathway runs between the midbrain & the limbic system/frontal cortex. D2 blockade in this pathway is probably the main determinant of antipsychotic effect, but this is incompletely understood. The nigrostriatal pathway connects the substantia nigra with the corpus striatum of the basal ganglia. The tuberohypophyseal pathway connects the hypothalamus with the pituitary gland. Features that distinguish 2nd generation antipsychotics from 1st generation agents are improved efficacy in ‘Rx resistant’ schizophrenia (particularly true of clozapine) & against negative Sx, & a lower risk of extrapyramidal Sx. Possible mechanisms for these differences include a higher affinity for other receptors (particularly 5-HT2A receptors), & a characteristic of ‘looser’ binding to the D2 receptors (in the case of clozapine and quetiapine).
SE's of 2nd generation antipsychotics. • Sedation • Extrapyramidal effects • Metabolic disturbance • Prolonged QT interval causing arrhythmias • Risperidone can interfere with secretion of prolactin causing breast Sx (in males & females) & sexual dysfunction • Clozapine can cause agranulocytosis (severe deficiency of neutrophils) and myocarditis - both rare
CI's, cautions, & important interactions of 2nd generation antipsychotics. CI's: • Severe HT DS (clozapine) • Hx of neutropenia (clozapine) Cautions: • CVD Important interactions: Sedation may be more pronounced when used with other sedating drugs. They should not be combined with other dopamine-blocking antiemetics & drugs that prolong the QT interval (e.g. amiodarone, quinine, macrolides, selective serotonin reuptake inhibitors).

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