Anti-Psychotic & Anti-Manic Drugs Part 1

Question 1

What are the 4 main symptoms of Psychosis?

Answer 1

• Derangement of personality
• Loss of contact w/ reality
• Delusions
• Hallucinations

Question 2

All disorders in this class (Schizophrenia) share some form of the syndrome psychosis w/ abnormalities in one or more domains.

What are these 4 domains?

Answer 2

• Delusions
• Hallucinations
• Disorganized thinking
• Abnormal motor behavior & negative symptoms

Question 3

What is the criteria for Schizophrenia?

Core positive symptoms?

Answer 3

• Central Criteria: 2 or more symptoms during a 1 mo period
  
  • At least 1 must be a core positive symptom; no subtypes
• Core Positive
  
  • Delusions
  • Hallucinations
  • Disorganized speech

Question 4

What are the other symptoms of Schizophrenia aside from positive? Negative symptoms?

Answer 4

Grossly disorganized or catatonic behavior

• Negative symptoms
  
  • Blunted affect
  • Lack of spontaneity
  • Poor abstract thinking
  • Poverty of thought
  • Social withdrawal

Question 5

What is the Dopamine Hypothesis?

Answer 5

Schizophrenia results from hyperactivity of dopaminergic neurons or their receptors, particularly those w/ terminals in limbic areas of the brain

Question 6

What are the 4 Dopaminergic Pathways?

Answer 6

• Mesolimbic tract
• Mesocortical tract
• Nigrostriatal pathway
• Tuberoinfundibular tract

Question 7

Originates in A10
Arousal, memory, stimulus processing, locomotor activity, motivational behavior
Dopamine hyperactivity = positive symptoms

Which tract?

Answer 7

Mesolimbic tract

Question 8

Originates in A10
Cognition, communication, social activity
Diminished dopaminergic activity = negative symptoms

Which tract?

Answer 8

Mesocortical tract

Question 9

Originates in A9
Dopamine blockade = increased EPS
Blockade of 5-HT_2a = decreased EPS, Parkinsonism

Which tract?

Answer 9

Nigrostriatal Pathway

Question 10

Dopamine blockade = increased prolactin release

**Which tract? **

Answer 10

Tuberinfundibular tract

Question 11

Dopamine Synapse

What are the pre-synaptic receptors? post-synaptic?

Which receptors are D₁-like?

Which receptors are D₂-like?

Answer 11

• Pre-synaptic: D₂/D₃R
• Post-synaptic: D₂R, D₁R
• D₁-like: D₁, D₅
  
  • • AC, increased cAMP
• D₂-like: D₂, D₃, D₄
  
  • – AC, decreased cAMP

Question 12

The better a drug can effectively _____ the dopamine receptor, the better it acts as an anti-psychotic.

Answer 12

block

Question 13

Anti-schizophrenic effects take time because….

Answer 13

the neuron senses less dopamine & wants to compensate to an extent

Question 14

What is the mechanism of Atypical Antipsychotic drugs?

Answer 14

• Most of the newer drugs have an additional neurochemical effect in addition to DA receptor blockade
• Block 5-HT2 receptors in the forebrain (often w/ greater potency than for DA receptors)

Question 15

What are the pharmacokinetics of Atypical Antipsychotics?

Answer 15

• Oral absorption (variable)
• Lipid soluble (absorbed in the brain better/faster)
• Protein binding (longer t1/2 – medicate less often)
• Large volumes of distribution
• Complex metabolism

Question 16

What are the 3 main actions of Antipsychotic Drugs?

Answer 16

• Decrease in psychotic behavior
• Sedation
• Extrapyramidal effects

Question 17

Atypical drugs, in addition to treating _______ symptoms, may be more effective in treating ________ symptoms

Answer 17

positive

negative

Question 18

What are the 4 main extrapyramidal effects of Antipsychotics?

Answer 18

• Dystonias
• Parkinsonism (early rxns – more w/ typicals)
• Akathisia
• Tardive dyskinesia (late rxn – may be less frequent w/ atypicals)

Question 19

What are some other side effects of Antipsychotics? (7)

Answer 19

• Anticholinergic
  
  • Dry mouth, blurred vision, urinary retention
• Orthostatic hypotension
  
  • Blockage of alpha receptors on blood vessels
• Neuroendocrine effects
  
  • Result of dopamine receptor blockade
  • Galactorrhea, gynecomastia
• Allergic & idiosyncratic effects
  
  • Liver, blood, cutaneous
• Cardiac effects
  
  • Thioridazine is the worst (limited daily dose)
• Decreased seizure threshold (phenothiazines)
• Weight gain
  
  • Diabetes related events more common w/ atypicals (olanzapine, risperidone, clozapine, quetiapine)

Question 20

What is the difference btwn early & late reactions of Antipsychotic drugs?

Answer 20

Question 21

Neuroleptic Malignant Syndrome

Definition

Symptoms

Treatment

Answer 21

• Potentially lethal hypodopaminergic side effect of antipsychotic drugs
• Symptoms
  
  • Hyperthermia
  • Parkinson-like symptoms (muscular rigidity & tremor)
  • Mutism
  • Possible death
• Treatment
  
  • Cooling & hydration
  • Bromocriptine
  • Dantrolene (skeletal muscle relaxation; blocks Ca2+ channels)

Question 22

What are the advantages of atypical antipsychotics over typical? (6)

Answer 22

• Lower incidence of extrapyramidal symptoms (better compliance)
• Possible lower incidence of tardive dyskinesia (TD)
• Improve negative symptoms
• Improve positive symptoms in many anti-psychotic-resistant or refractory patients
• Less impact on cognitive functioning
• More cost effective ?

Question 23

What are the uses for antipsychotic drugs? (7)

Answer 23

• Acute psychotic episodes
• Chronic Schizophrenia
• Manic episodes, bipolar disorder
  
  • Aripiprazole, olanzapine, quetiapine, Ziprasidone, risperidone, Asenapine, Lurasidone
• Schizoaffective disorder – Paliperidone
• Augmentation in depression – aripiprazole, olanzapine, quetiapine
• Tourette’s syndrome – haloperidol, pimozide
• Anti-emesis – NOT Thioridazine

Question 24

What are the criteria for Bipolar Disorder? (DSM IV)

Answer 24

• Inflated self-esteem/grandiosity
• Decreased need for sleep
• Talkativeness
• Flight of ideas/racing thoughts
• Distractibility
• Increased goal-directed activity/psychomotor agitation
• Excessive involvement in pleasurable activities w/ potential for adverse consequences