• form of psychosis
• features
  • withdrawal
  • disorder thought processes
  • delusions
  • auditory hallucinations

• hallucinations
• delusions
• behavioral disorganization
• positive formal thought disorder

• alogia (not using words)
• affective blunting
• avolution
• asociality
• anhedonia
• attentional impairment

• amphetamine toxicity produces psychosis
• OD of L-DOPA produce psychosis
  • both of these drugs cause too much dopamine in the synapse
• PET studies of untreated schizophrenics show increased dopamine receptors in brain
• successful treatment with antipsychotics alter DA metabolite levels by increasing turnover
• alternative influences
  • serotonin does play some role (newer drugs block 5 HT₂ R's)
  • Glu plays some role (PCP leads to psychosis via altered NMDA R expression)

• usually takes 4-6 weeks because
  • at first, the neurons will increase firing rate in response to sensing decreased dopamine
  • when you have been chronically tx, you will see neuron go into a state of depolarization inactivation = successful treatment

• G_i- decrease cAMP

• mesocorticolimbic
  • origin- VTA
  • output
    • frontal cortex (too little DA- negative symptoms)
    • NA (limbic limb) (too much DA- positive symptoms)

• mesolimbic corticolimbic (block dopamine influence on NA)
• substantia nigra (cause Parkinson like symptoms)
• tubuloinfundibular system (leads to increase PRL release, causing prolactinemia, gynecomastia)
• medullary periventricular neurons (cell bodies of motor nucleus of vagus targeted, causing weight gain)
• CTZ (antiemetic)

• origin- arcuate nucleus
• terminals- median eminence and pars intermedia of pituitary

• schizophrenia
• acute tx of psychotic episoded

Cause potentiated anesthesia

lower sedation

less alpha block

• lower incidence of EPS compared with typical antipsychotics
• increased ratio of 5 HT₂:D2 R blockade

• advantages
  • no EPS
  • higher potency at 5 HT₂
  • no S2 supersensitivity
  • better against negative symptoms (remember, we dont want to block dopamine in cortex because we will worsen negative symptoms)
• adverse effects
  • agranulocytosis
  • risk of DM

• dose dependent atypical: low risk of EPS
  • if dose too high, increase risk of EPS
• advantage- no risk of agranulocytosis

• advantages
  • smaller increase in PRL than haloperidol
  • no risk of agranulocytosis
• adverse effects
  • weight gain
  • risk for DM

• mechanism of action
  • partial agonist at D2 receptors
  • modest affinity to block 5 HT₂ R's
  • partial agonist at 5 HT_1a R
• advantages
  • decrease DA activity in NA, where its too high
  • increase DA activity in frontal cortex, where it is too low

• chlorpromazine
• risperidone

They have a great affinity to block alpha one, leading to orthostatic hypotension.

• Clozapine
• Risperidone
• Olanzapine
• Ziprasidone
• Aripiprazole

• acute dystonia in 1-5 days (spastic tortocollis)- dx and tx with anticholinergic antiparkinson agents
• akasthisia in 5-60 days- occurs early and tends to persist, but fix by reduce drug, change tx, anticholinergic, propanolol
• Parkinsonism in 5-30 days (rigidity, bradykinesia, mask facies, shuffling gait): anticholinergics
• neuroleptic malignant syndrome
• sedation
• lower seizure threshold (esp. w/clozapine and low potency APS)
  • caution: epilepsy, patient withdrawl from CNS depressant

• symptoms
  • catotonia
  • stupor
  • unstable bp
  • myoglobinemia
• prognosis- may be fatal
• cause- D2 block in hypothalamus
• tx
  • stop drug immediately
  • bromocriptine or dantroline may help
  • DONT give anticholinergics (you will make it worse)

• perioral syndrome after months or yrs of tx (rabbits syndrome)- usually a late variant of parkinson's, so antiparkinson drugs do help
• tardive dyskinesia after months or  years (TEST)- often mistaken for reemergence of psychosis, but prevention is crucial cause tx options arent great

• mechanism- dopamine supersenstivity
  • when you block D2, disrupts normal balance of cholinergic and dopaminergic input
  • eventually, prolonged tx will cause the nerves to produce a bunch of D2 receptors
  • CI: anticholinergics (YOU WILL MAKE THEM WORSE)
• symptoms
  • oral facial dyskinesias
  • widespread chorioathetosis dystonia

• orthostatic hypotension along with a reflex tachycardia (alpha block)
  • CI: elderly
• altered sex function
  • reduce drive in men and increase libido in women
  • prevent ejaculation (alpha block)
• anticholinergic effects- dry mouth, blurred near vision, constipation, urinary retention

• endocrinology- increase PRL leading to galactorrhea and amenorrhea in women
• blood dyscrasias (rare, but usually within first 2 months of therapy)
• metabolic (major with atypicals, esp. Olanzepine and Clozapine)
  • weight gain
  • increased DM risk
  • hyperlipidemia

• dermatology- skin reactions and photosensitivity (esp. with phenothiazines)
• cardiac toxicity
  • thioridazine
    • minor T wave abnormalities
    • OD- vent. arrhythmias, cardiac conduction block, sudden death
  • ziprasidine- prolong QT interval
    • CI: other QT prolongers like thoioridazine, pimozidine, quinidine

• absorption erratic and decreased by
  • food
  • antacids
  • cholinergics
• concentrates in fatty tissues (good sincwe brain is fatty: fathead)
• oxidized by P450
• cojugated by glucuronic acid

• tricyclic structure drugs could block antihypertensive effects of guanithidine
• potentiation of CNS depressants
• qunidine and ziprasidone interfere with digitalis
• antihypertensive agents enhanced by alpha block
• barbituates enhance metabolism
• muscarinic block can exacerbate confusion if on other anticholinergics

organic brain syndrome

acute mania

Tourrettes

bipolar

• example: chlorpromazine
• advantage- low neurological side effects
• disadv.- high ANS side effects

Need high dose to get antipsyc effect

• example- haloperidol
• advantage- fewer ANS side effects
• disadvantage- higher neurological and endocrinological side effects

Low dose to get antipsyc effects