Antipsychotics covers base of midbrain ventral tegmental area (VTA) at floor of midbrain Nucleus Accumbens (NA) mesolimbic pathway dopaminergic cell bodies arising from VTA project to NA regions in cortex Hypothalamus pituitary gland caudate putamen striatum overactive positive features NOT responsible for schizophrenia where schizophrenia arises mesocortical pathway dop. from VTA to cortex negative features Tubuloinfundibular system ↑ Pe ↑ prolactin ↓ dopamine Substantia Nigra (SN) dopaminergic bodies nigrostriatal pathway ↓ responsible for movement coordination basal ganglia when a ptx is managed with anti-psychotics not only the mesolimbic & mesocortical pathways are affected, but also the substantia nigra is ↓ dop ↓ prolactin ? galactoorhea amenorrhea AMENORRHEA (CFN) ↓ dopaminergic ↑ parkinsonism ANTI-PSYCHOTICS mesolimbic ↓ dop → improve +ve symptoms mesocortical ↓↓↓ dop → worsen -ve symptoms nigrostriatal → EPS not always tubuloinfundular → galactorrhea ? ? amenorrhea positive symptoms will go away before negative First Gen. Anti-Psychotics higher incidence of extrapyramidal signs Haloperidol Fluphenazine Chlorpromazine Thioridazine (only HRNV) Histamin - R weight gain & sedation α-1-R orthostasis, HHTN, priapism occasional sexual dysfunction D-2-R M-1-R dry mouth & visual changes receptor profile for both 1st & 2nd gen 1st gen - greatest incidence of EPS & neuroleptic malignant syndrome muscle relaxation ryanodine -R - ↑ intracellular Ca2+ can also happen in 2nd Gen, but 1st gen. more common Dantrolene Mg: promacryptine med emergency life threatening Management = discontinuation of offending med supportive therapy electrolyte correction anti-arrythmias mechanical vent. due to dopamine receptor antagonist use or rapid withdrawal of anti-psychotics Dop. agonist aggressive cooling + correction of volume status may progress to rhabdo mollosis WBC ↑ w/ heart failure death inflammation ↓ myolysis kidney death. Major Criteria all of = exposure to dop. ∅ agents severe m. rigidity fever AMS chest wall rigidity cardiac arrythmias + resp. failure DSM-V minor criteria atleast 2 of = diaphoresis dysphagia tremor incontinence altered level of consciousness mutism + heaving tachycardia ↑ or liable BP leukocytosis ↑ Cr Phosphokinase AS NEEDED e.g. Bromocriptine