Antipsychotics, 1st Generation (Typical)

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Give eg's of & indications for 1st generation antipsychotics. eg's: haloperidol, chlorpromazine, prochlorperazine Indications: • Severe psychomotor agitation leading to dangerous or violent behaviour • Schizophrenia particularly when the metabolic side effects of second-generation (atypical) antipsychotics are likely to be problematic • Bipolar disorder particularly in acute episodes of mania or hypomania • N & V particularly in the palliative care setting
MOA of 1st 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. D2 receptors are also found in the chemoreceptor trigger zone, where blockade accounts for their use in N & V. All antipsychotics, but particularly chlorpromazine, have some sedative effect. This may be beneficial in the context of acute psychomotor agitation.
SE's of 1st generation antipsychotics. • D2 blockade in the nigrostriatal pathway can lead to extrapyramidal effects. These can include: acute dystonic reactions (parkinsonian movements/muscle spasms), akathisia (state of inner restlessness), & neuroleptic malignant syndrome (rare life threatening SE: rigidity, confusion, autonomic dysregulation, & pyrexia). Tardive dyskinesia is a late SE occurring after months/years of Rx (pointless, repetitive, involuntary movements eg lip smacking). • Drowsiness • Hypotension • QT-interval prolongation leading to arrhythmias • Erectile dysfunction • Tuberohypophyseal D2 blockade may lead to hyperprolactinaemia (Sx may inc: menstrual disturbance, galactorrhoea, & breast P)
CI's, cautions, & important interactions of 1st generation antipsychotics. CI's: • None Cautions: • Elderly (lower dose) • Dementia • Parkinson's DS due to extrapyramidal effects Important interactions: Consult the BNF when prescribing for a pt taking antipsychotics as there is an extensive list of interactions. Prominent among these are drugs that prolong the QT interval (e.g. amiodarone, macrolides).
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