001-ANTIPSYCHOTICS-LectureB-2011.key(1)

001-ANTIPSYCHOTICS-LectureB-2011.key(1) -...

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Unformatted text preview: Psychopharmacology Spring 2011 Harvey Alan Berman, PhD [email protected] Antipsychotic agents Part II Schizophrenia Neurotransmitter theories (DA, 5HT, Glutamate) Genetic Disorder of developmental Neurodegenerative disorder Viral Anatomical Findings ↓ Brain size ↑ Ventricle size ↑ Loss of gray matter Loss of brain volume associated with schizophrenia is clearly shown by magnetic resonance imaging (MRI) scans comparing the size of ventricles (butterFy shaped, Fuid-¡lled spaces in the midbrain) of identical twins, one of whom has schizophrenia (right). The ventricles of the twin with schizophrenia are larger. This suggests structural brain changes associated with the illness. Note that such MRI scans cannot be used to diagnose schizophrenia in the general population, due to normal genetic variation in ventricle size -- many unaffected people have large ventricles. Source: Daniel Weinberger, M.D. NIMH Clinical Brain Disorders Branch NIMH scientist shows PET scans from a study of identical (monozygotic) twins, who are discordant for schizophrenia (only one has the disorder) demonstrating that individuals with schizophrenia have reduced brain activity in the frontal lobes (top of scan). Source: William Branson NIH Medical Arts Decreased activity in frontal lobe of schizophrenic brains Average rates of gray matter loss in normal adolescents and in schizophrenia. Thompson P M et al. PNAS 2001;98:11650-11655 Therapeutic uses of antipsychotic medications Schizophrenia Mania in bipolar disorder Tourette’s syndrome Autism Control of emesis Treatment-resistant depression Anxiety disorders: OCD; PTSD (Dementia) 1 2 3 4 Chlorpromazine Low-potency typical • Less likely to cause EPS • More likely to produce other side effects: – Sedation – Orthostatic hypotension D2 D4 α 5HT2 M H1 Chlorpromazine Haloperidol ++- ++ + + + +++- +--- Lower potency Higher potency Chlorpromazine Adverse effects • Anticholinergic effects – Dry mouth, blurred vision, urinary retention, photophobia, constipation, tachycardia • Neuroendocrine effects – Galactorrhea, gynecomastia, menstrual irregularities. • Photosensitivity reactions • Early EPS – Dystonia, akathisia, Parkinsonism • Risk of TD the same among all typical APs • Lowers seizure threshold – Risk greatest in patients with epilepsy and other seizure disorders • Dysrhythmias (i.e., prolongation of QT interval) Haloperidol High-potency typical • Higher affinity for D2 leads to higher incidence of EPS and lesser intrinsic anti- cholinergic properties • High-potency agents cause more early EPS but less sedation, orthostatic hypotension, anticholinergic effects...
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This note was uploaded on 03/06/2011 for the course PMY 406 taught by Professor Berman during the Spring '11 term at SUNY Buffalo.

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001-ANTIPSYCHOTICS-LectureB-2011.key(1) -...

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