Pharm for Psychotic disorders

disturbances lasts for atleast 6 months including atleast 1 mont of 2 or more of the following:

• Delusions
• Hallucinations
• Disorganized speech
• Grossly disorganized or catatonic behavior
• Negative symptoms

schizophrenia but less than 6 months duration

schizoprhenia lasting only 1 day to 1 month

Mood disturbances and schizophrenia

• Hallucinations
• Delusions
• Disorganized thought
• Behavioral disturbances
• Combativeness
• Disorganized speech
• Tension

• Blunted emotions
• Psychomotor retardation
• Avolition - no drive
• Alogia - poverty of speech
• Anhedonia - no pleasure
• Social withdrawal
• Loss of executive functions

Persecution: paranoia (they are out to get me)

Grandeur: megalomania (God Complex)

Being Controlled: (the CIA is controlling my brain with a radio signal

Prodromal Phase:  gradual development of symptoms... (negative predominate)

• Active Phase:  onset of positive symptoms
• Acute Phase - impairment often severe... positive symptoms predominate and are responsive to treatment
• Stable Phase - negative symptoms predominate... impairment can be moderate

increased dopaminergic activity in the MESOLIMBIC pathway

all antipsychotics block D2 receptors

amphetamines and cocaine can cause psychosis that resembles positive symptoms

Most antipsychotics can produce acute EPS's reflecting a decrease in central dopaminergic activity... with continued use tardive dyskinesia can occur

• Phenothiazines (potency low to high)
• Chloropromazine (aliphatic)
• Thioridazine (Piperidine)
• Fluphenazine (Piperazine)
• *All have equal Efficacy

Butyrophenones (Haloperidol)

• Clozapine
• Risperidone
• Olanzapine

DA System Stabilizers (aripiprazole)

all antipsychotics have an R2 group containing a 3 carbon spacer

Phenothiazines with a 2 carbon spacer have clinically effective antiemetic/antihistaminic activity but no antipsychotic (promethazine)

Mesolimbic - arousal, memory, behavior - treats positive and negative symptoms

Nigrostriatal - motor activity - EPS

Tubero-infundibular - inhibits prolactin release - increased prolactin release

• D2 - dopamine
• M1-3 Muscarinic
• H1 - Histamine
• a1 - adrenergic

side effects of typical antipsychotics depend on their potency at D2 receptors...

Higher potency drugs (piperazines) have fewer side effects due to blockade of the other receptors

• Sedation - H1 receptor blockade 
• low potency more problematic

• Lowered Seizure threshold
• low potency more problematic

• EPS - blocking nigrostriatal pathway
• ♦ occur early in treatment
• ♦ eventually disappear but must be treated
• ♦ higher potency more problematic
• ♦ Thioridazine has the lowest incidence since its also a strong antimuscarinic

Dystonia - onset 1-5 days... more common in young

• Muscle Spasms
• spasm of the neck (torticollis)
• upward deviation of the eyes (oculogyric crisis)
• spasms of the jaw and tongue (oromandibular dystonia)
• Parkinsonism - onset 2 wks to 2 months

• Akathisia - onset 1-3 months
• extreme motor restlessness
• should be discerned from agitation
• most common acute EPS

• Neuroleptic Malignant Syndrome
• medical emergency - potentially fatal
• hyperthermia, muscle rigidity, autonomic instabilitiy

• Tardive Dyskinesia
• repetitive, involuntary, movements of the facial musculature, arms and trunk

not predictable from chemistry

DISUSE supersensitivity

• Treatment: NONE
• discontinue antimuscarinic
• switch to clozapine or other atypical
• BDZ, Propranolol, Lecithin/ Choline

Hyperprolactinema b/c of inhibition of the tubero-infundibular pathway... stops the dopamine projection from the arcuate nucleus

all potency's equally problematic here

• In Women
• amenorrhea, Galactorrhea, False positive pregnancy tests

• In Men
• gynecomastia

• a1 blockade (low potency more problematic)
• Nasal Stuffiness
• Orthostatic Hypotension
• Ejaculatory Disturbances

• Muscarinic Blockade (Dine > aliphatic > zine)
• dry mouth
• blurred vision
• constipation
• urinary retention
• mydriasis
• decreased sweating
• male impotence

• ECG changes
• QTc interval - time for ventricular depolarization and repolarization

Thioridazine blocks potassium channels to prolong QTc interval

• Temperature Dysregulation
• Hyperpyrexia - avoid heat and sun (heat stroke)
• Hypopyrexia

Obstructive jaundice (low potency more problematic)

• Skin
• Photosensitivity
• Hyperpigmentation

• Eyes
• Pigmentary Retinopathy (potential blindness)
• discontinue APD

• L-Dopa and Bromocriptine
• antagonized by phenothiazines

• CNS depressants
• additive effect with other depressants
• opiods
• ethanol
• antihistamines

Haloperidol - most commonly used

• Droperidol
• Antiemetic
• Neurolept Analgesia (+ fentanyl)
• Neurolept Anesthesia (+ fentanyl and N2O)

Side Effects - Like a high potency Phenothiazine (Piperazine)

Greater efficacy for negative symptoms

Lower incidence of Acute EPS's

Lower incidence of Tardive Dyskinesia

Can produce Hyperglycemia and Type 2 Diabetes

atypicals block D₂ receptors and 5-HT_2A receptors

Serotonin inhibits DA activity in certain pathways

Negative symptoms are caused by decreased DA activity in mesocortical pathway

mesolimbic - decrease positive and negative symptoms by decreasing DA

mesocortical - decrease negative symptoms by increasing DA

Nigrostriatal - few EPS's

Tubero-infundibular - little effect on prolactin release

• similar to low potency PTZ...
• Especially sedation, seizures, ortho hypo
• Lack of EPS's
• Little prolactin elevation

• Agranulocytosis - potentially fatal
• baseline WBC followed by weekly WBC

• Sialorrhea - excessive drooling
• factor in noncompliance

Weight Gain - average 10 lbs at 10 weeks

Treatment-resistant Schizophrenics

• Treatment-intolerant Schizophrenics
•       Tardive Dyskinesia
•       Psychotic disorder with Parkinson's

Parkinson's Disease - Iatrogenic Psychosis

• Risperidone
• weight gain

• Olanzapine
• weight gain, type 2 diabetes

• Quetiapine
• weight gain, cataracts

• Ziprasidone
• QTc prolongation, no weight gain

All have similar side effects to high potency PTZ's except few acute EPS's and lower than typicals in Tardive

Dopamine system stabilizer

no weight gain, no QTc prolongation

partial agonist at D₂ receptors and antagonist at 5HT_2A receptors

• Bipolar I disorder
• Mania (Acute Phase)
• haloperidol until lithium takes effect
• atypical antipsychotics (not Clozapine)
• aripiprazole

• Maintenance Phase
• Olanzapine, Quetiapine, Ziprasidone, Aripiprazole

• Major Depressive Disorder
• Adjunctive treatment of depression
• Aripiprazole, Olanzapine

• Hyperkinetic Extrapyramidal Disorders
• Huntington's Disease
• loss of cholinergic neurons in striatum... Haloperidol

• Tourette's Disorder
• Haloperidol / Pimozide
• treats tics but not Coprolalia

• acute intoxication with CNS stimulants
• Cocaine, Amphetamine
• haloperidol for acute psychosis

• Post Hallucinogen Perception Disorder
• PCP / Hallucinogens (LSD)
• Treat with Haloperidol if frequent

• Phenothiazines
• Prochlorperazine
• Perphenazine
• NOT thioridazine

• Butyrophenones
• Droperidol

• Benztropine
• Diphenhydramine
• Amantadine
• Lower dose

• Propranolol 
• Lorazepam
• Benztropine or Diphenhydramine
• lower dose or different one

• Dantrolene
• Bromocriptine
• Diazepam
• discontinue antipsychotic agent