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Behavioural Pharmacology > Chapter 12: Antipsychotic Drugs > Flashcards

Chapter 12: Antipsychotic Drugs Flashcards

1
Q

What are the symptoms of Schizophrenia?

A
  • Positive: hallucinations, delusions of grandeur and persecution, disordered cognition etc
  • Negative: social withdrawal, flat affect, anhedonia, alogia, catatonia, reduced motivation and poor focus
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2
Q

Antipsychotics only work on one type of symptoms, which one?

A
  • Positive

- it can actually enhance negative ones

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3
Q

With positive symptoms there is hyperactivity in what System?

A
  • Mesolimbic DA synapses
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4
Q

With negative and cognitive issues there is hypoactivity at was synapses?

A
  • Mesocortical DA synapses
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5
Q

Explain why DA blockers work with Positive symptoms and not negative ones!

A
  • with positive symptoms you have hyperactivity so DA blockers will reduce that! But with negative symptoms you have HYPOACTIVITY so you will actually be making it worse
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6
Q

What are the three brain abnormalities in schizophrenia ?

A
  • enlargement of Cerebral ventricles
  • shrinkage of brain tissue
  • disorganized cellular development
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7
Q

Is the DA Hypothesis relevant?

A
  • no its been dismissed !
  • meaning: schizophrenia and other psychoses result from excessive DA activity
    L> Support: drugs that increase dopamine function produce almost indistinguishable positive symptoms seen in schizophrenia
    L> Antipsychotics at the time were all DA blockers
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8
Q

Glutamate Hypothesis?

A
  • lack of glutamate activity
    L> due to genetics…and NMDA receptor
    L> many genes involved with schizophrenia are involved with development of glutamate connectivity, synaptogenesis and neurotransmission at NMDA.
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9
Q

Dopamine and Glutamate interactions?

  • Normal
  • Abnormal
A

-Stimulation of GA neurons in the prefrontal cortex result in the inhibition of DA neurons of the mesolimbic pathway
L> Normally cortical GA stimulates Mesocortical DA
-cortical GA activity is diminished resulting in loss of NMDA receptors, ventral tegmental area DA neurons become understimulated. The mesocortical pathway becomes hypoactive and the mesolimbic DA pathway becomes hyperactive

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10
Q

In 1951 what antipsychotic was discovered?

A
  • Chlorpromazine (largactil and Thorazine)

- Antimedic effect— helps with nausea

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11
Q

Alternative terms for these types of drugs?(3)

A
  • Antipsychotics
  • Neuroleptics - causes rigidity and difficulty of movement seen in Parkinson’s
  • Major Tranquilizers -sedating effect
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12
Q

Typical Antipsychotics?

  • developed?
  • blocks?
  • effective in treating?
  • side effects?
  • ineffective in ?
A
  1. developed before 1975
  2. D2 blockers
  3. effective for positive symptoms
  4. produce diff degrees of EPS (extra pyramidal side effects)
  5. Ineffective in 1/3 of patients…no placebo effect as seen in depression
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13
Q

Atypical Antipsychotics?

  1. weak affinity for?
  2. low risk of ?
  3. high affinity for ? catch?
  5. Bind to what other receptor?
  6. first atypical?
  7. New atypical?
A
  1. weak affinity for D2 receptors
  2. low risk for EPS due to weak affinity in nigrostriatal system
  3. high affinity for D3 and D4 receptors in the motor system
  4. very few D3 and D4 in motor system
  5. Bind to 5-HT receptors (serotonin )
  6. First: Clozapine ( Clozapril)
    L> 2% patients died = wiped out WBC
  7. Aripiprazole ( Abilify)
    L>3rd gen, take with antidepressants that are not working to enhance effect
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14
Q

Third gen antipsychotics ( Atypical)

  • partial agonist to?
  • how does it act in areas where DA is low /high
  • What does this solve?
  • partial agonist /antagonist to what other receptor?
A
  • partial agonist to D2 D3 and D4
  • high affinity for its receptors but activates the receptor to a lesser degree vs natural ligand
  • where DA is decreased acts an agonist ( prefrontal cortex)
  • Where DA is increased it acts as an antagonist by blocking DA and activating receptors to a lesser degree (nucleus accumbans)
  • partial agonist or antagonist at 5-HT receptor subtypes.
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15
Q

How are they usually taken?

A
  • orally but it can be given intramuscular or intravenous injections
    L> rarely injected when needed for antipsychotic (usually only when needed as a tranq )
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16
Q

What does intravenous injection avoid?

A
  • any irregularities or delways in effect arising from erratic absorption from the digestive system.
17
Q

Are the antipsychotic effects speed up when given parenterally?

A
  • no it takes several days or weeks to develop
18
Q

When are they given depot injections?

A
  • Typical drugs dissolve in any oily base

for chronic patients, avoids reliability issue of them taking it on their own

19
Q

Newer Atypical antipsychotics are taken how?

ex?

A
  • depot injection via salt
  • risperidone
  • Olanzapine
  • Paliperidone
20
Q

Are they readily absorbed from the digestive system?

A

yes

  • once absorbed they can easily pass the placental and blood brain barriers
  • tend to slowly absorb into body fat
  • blood protein binding is considerable
21
Q

Of the two types which have the longer half life?

A
  • Typical antipsychotics due to their strong protein binding and tendency to stay in body fat
22
Q

They typicals and atypicals undergo ___ metabolism prior to excretion in urine and feces.

A

extensive

23
Q

In relation with excretion of antipsychotics how does being on other medications cause difficulties?

A
  • mood stabilizers, anxiolytics, antidepressants etc rely on cytochrome P450 enzymes as do antipsychotics …therefore competition occurs and it is slowed down
24
Q

People on antipsychotics are at an increased risk of __ failure.

A
  • renal
25
Q

Explain the following effects antipsychotics have on the body:

  1. Tardive dyskinesia
  2. Agranulocytosis
  3. Atypical specific effects
  4. akathisia
  5. temperature?
  6. Cardiac ?
A
  • they all vary from person to person!
    1. lack of control of muscles
    2. lack of white blood cells (specific to Clozapine)
    3. disturbances in glucose metabolism, fat regulation, weight gain, increased risk of diabetes
    4. uncontrolled restlessness, constant compulsive movement and protruding tongue and facia grimacing
    5. issues with temperature regulation ..easily influenced by environment now …hot environments= risk of heat stroke, cold= hypothermia, oversensitivity to sun via skin
    6. Cardiac dysfunction…and blood pressure
26
Q

Why does Aripiprazole have a high compliancy?

A
  • absence of most SE

- SE: nausea and dizziness

27
Q

Low down on the effects of sleep?

A
  • very little effect! some is due to the sedating effects
28
Q

Atypicals may do what to sleep?

A
  • increase the risk of obstructive sleep apnea
29
Q

Do antipsychotics effect REM or sleep cycles ?

A

NO

30
Q

Subjective Effects:

  1. Chloropromazine
  2. Halopreidol
  3. Atypical?
A
  1. tiredness in healthy patients, slower and confusing thinking, diff concentrating, clumsiness, need for sleep, dejection, anxiety, and irritability.
  2. like other atypical drugs it makes subjects feel internally aroused and externally sedated
  3. antipsychotic subjective effects in general are never described as pleasant….Atypicals though seem to have higher compliancy
31
Q

Performance effects?
- Typical
- Atypical
L> Clozapine and Remoxipride

A
  • typical antipsychotics have been examined for cognitive and attention performance but results vary… might be due to sedative effects (tolerance occurs)
  • effect performance…but mized
32
Q

Tolerance?

A
  • no tolerance to therapeutic effects

- tolerance to sedating effects and eps (eps not always fully)

33
Q

Withdrawal?

A
  • physical dependence is rare or mild
  • muscular discomfort, exaggeration of psychotic symptoms and movement disorders, and diff sleeping …some effects are not seen until years later!
34
Q

Self Administration in Humans?

A
  • never abused !
  • lots of compliance issues
  • typical = high issues with compliance
  • atypical= less of an issue
  • it is avoided by monkeys..they press bar to avoid infusions
35
Q

Reproduction?

A
  • reduces sexual interest and performance in males (failure to ejaculate, erection and orgasm are unaffected)
36
Q 
Other uses? 
A.  Antiemetic
B. Treatment of?
C. Treatment of?
D. Laborit used them as?
A
  • prevention of vomiting and nausea (useful in treating motion sickness)
  • movement disorders (Huntington’s Chorea, Tourettes)
  • psychotic behaviours induced by other drugs
  • presurgical and preanesthetic medications

Behavioural Pharmacology (52 decks)

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