1 Nigrostriatal pathway EPSs Stahl S M, Essential 11-4 - PDF document

M1 1 H1 conventional antipsychotic drug D2 Stahl S M, Essential 11-7 Psychopharmacology (2000) pure D2 blocker Stahl S M, Essential 11-2 Psychopharmacology (2000) Mesocortical pathway Increase in negative symptoms Stahl S M, Essential 11-3 Psychopharmacology (2000) 1

Nigrostriatal pathway EPSs Stahl S M, Essential 11-4 Psychopharmacology (2000) Blockade of receptors in the nigrostriatal dopamine pathway causes them to up- regulate This up-regulation may lead to tardive dyskinesia Stahl S M, Essential 11-5 Psychopharmacology (2000) Motor and mental features of neuroleptic- induced extrapyramidal side effects Parkinsonism Tremor (resting), rigidity, bradykinesia, masklike facies Akathisia Restlessness, pacing, fidgeting, shifting from jitteriness, anxiety, irritability, anger, difficulty concentrating Dystonia Muscle contractions, tongue protrusion, torticollis, opisthotonos, fear, distress, paranoia Tardive Buccolingual-masticatory movements of irregular dyskinesia (nonrhythmic) nature; choreiform or athetoid (writhing) movements of fingers, extremities, trunk Adapted from Ayd 1995; Casey 1995 2

D2 antagonist pituitary lactotroph D2 receptor prolactin Stahl S M, Essential 11-32 Psychopharmacology (2000) Typical antipsychotic drugs: potencies and side effect profiles Drug Approximate Sedative Hypotensive Anticholinergic Extrapyramidal dose (mg) effect effect effect effect Phenothiazines Chlorpromazine (Thorazine) 100 H H M L Piperidines Thioridazine (Mellaril) 95 H H H L Piperazines Fluphenazine (Prolixin) 2 M L L H Perphenazine (Trilafon) 8 L L L H Trifluoperazine (Stelazine) 5 M L L H Thioxanthene Thiothixene (Navane) 5 L L L H Butyrophenones Haloperidol (Haldol) 2 L L L H 5HT2A SDA D2 Stahl S M, Essential 11-16 Psychopharmacology (2000) 3

5HT-DA Interactions brake Substantia nigra brake raphe nucleus Stahl S M, Essential 11-17 Psychopharmacology (2000) dopamine neuron dopamine Substantia 5HT2A nigra serotonin receptor 5HT2A receptor serotonin neuron Raphe Stahl S M, Essential 11-18 Psychopharmacology (2000) mesocortical pathway primary dopamine deficiency dopamine release SDA serotonin secondary dopamine deficiency Stahl S M, Essential 11-27 Psychopharmacology (2000) 4

Nigrostriatal pathway 5HT2A receptor Stahl S M, Essential 11-24 Psychopharmacology (2000) 5HT1A 1 M1 H1 5HT2A 2 5HT2C D1 5HT3 clozapine 5HT6 D2 D4 D3 5HT7 Stahl S M, Essential 11-37 Psychopharmacology (2000) 1 5HT2A 2 risperidone D2 5HT7 Stahl S M, Essential 11-39 Psychopharmacology (2000) 5

1 M1 H1 5HT2A 5HT2C D1 5HT3 olanzapine 5HT6 D2 D4 D3 Stahl S M, Essential 11-40 Psychopharmacology (2000) 1 H1 5HT2A 2 quetiapine 5HT6 D2 5HT7 Stahl S M, Essential 11-41 Psychopharmacology (2000) 5HT1A 1 5HT2A 5HT1D SRI 5HT2C NRI ziprasidone D2 D3 5HT7 Stahl S M, Essential 11-43 Psychopharmacology (2000) 6

Side effects of selected atypical agents polypharmacy combos 3rd line treatment clozapine D2 2nd line treatment D2 noncompliant (depot) SDA 1st line treatment D2 BZ in case of emergency POSITIVE SYMPTOM PHARMACY Stahl S M, Essential 11-52 Psychopharmacology (2000) Hierarchy of Treatment Goals in Medical Psychotherapy of Schizophrenia • Acute Phase – Medical/neuropsychiatric assessment – Rapid symptom reduction – Reduce impact of episode on friends, family, housing, activities • Convalescent Phase – Gain trust/alliance with family/caregivers – Assess and mobilize social supports – Ensure human service needs are met (food, clothing, housing) – Ensure safety and predictability of environment • Adaptive Plateau – Establish therapeutic alliance/supportive treatment routine – Achieve effective maintenance medication regime • Stable plateau – Psychoeducation: Promote illness self-management strategies, awareness of relationship between stress and symptoms – Rehabilitation: Teach adaptive competencies 7