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M2 Neuro/Psych > Antipsychotics - Bloom > Flashcards

Antipsychotics - Bloom Flashcards

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1
Q

Give 4 major behavioral features of psychosis

A
  • Derangement of personality
  • Loss of contact with reality
  • Delusions
  • Hallucinations
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2
Q

Give 3 possible core positive symptoms of schizophrenia

Give 5 negative symptoms

A

Positive

  • Delusions
  • Hallucinations
  • Disorganized speech

Negative

  • Blunted affect
  • Lack of spontaneity
  • Poor abstract thinking
  • Poverty of thought
  • Social withdrawal
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3
Q

What is the dopamine hypothesis?

A

Schizophrenia is the results of hyperactivity of dopaminergic neurons or their receptors, particularly those with terminals in the limbic areas of the brain

Evidence: all effective antipsychotics interact with dopaminergic systems

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4
Q

Mesolimbic tract

  • Origin?
  • Function?
  • Result of dopamine hyperactivity?
A
  • A10
  • Arousal, memory, stimulus processing, locomotor activity, motivational behavior
  • Dopamine hyperactivity results in positive schizophrenic symptoms
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5
Q

Mesocortical tract

  • Origin?
  • Function?
  • Result of diminished dopaminergic activity?
A
  • A10
  • Cognition, communication, social activity
  • Diminished dopaminergic activity leads to negative schizophrenic symptoms
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6
Q

Nigrostriatal pathway

  • Origin?
  • Course?
  • Does dopamine blockade increase or decrease extrapyramidal symptoms (EPS)?
  • What happens if 5-HT_2alpha is blockaded here?
A
  • A9
  • Substantia nigra to basal ganglia
  • Increased EPS
  • Decreased EPS, parkinsonism (possibly)
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7
Q

What is the effect of dopamine blockade in the tuberoinfundibular tract?

A

Increased prolactin release

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8
Q

Gs or Gi?

  • D1
  • D2
  • D3
  • D4
  • D5
A
  • G2
  • Gi
  • Gi
  • Gi
  • Gs
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9
Q

What trend among the neuroleptic drugs supports the dopamine hypothesis of schizophrenia?

A

Increased potency among these drugs is linearly related to affinity for D2 receptors.

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10
Q

What is the major mechanism difference between typical antipsychotics and newer atypical antipsychotics?

A

Newer atypicals also block 5-HT2 receptors (sometimes with potency greater than that of dopamine receptors)

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11
Q

Typical antipsychotics… name:

  • (1) with an aliphatic side chain
  • (2) with a piperazine side chain
  • (1) with a piperidine side chain
  • (1) thioxanthene
  • (1) butyrophenone
A
  • chlorpromazine
  • fuluphenazine, trifluoperazine
  • thioridazine
  • thiothixene
  • haloperidol
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12
Q

Name (3) atypical antipsychotics

A
  • risperidone
  • clozapine
  • olanzepine
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13
Q

Are typical antipsychotic agents better at treating positive symptoms or negative symptoms?

A

Positive

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14
Q

Describe the major features of the extrapyramidal effects of antipsychotic drugs

Among these reactions, which presents the earliest? The latest?

A
  • Dystonias
  • Parkinsonism (moreso with typical antipsychotics)
  • Akathisia (restlessness, difficulty holding still)
  • Tardive dyskinesia (more frequent with typicals)

Acute dystonia develops first (1-5 days), followed by parkinsonism (5-30 days) and akathisia (5-60 days).

Tardive dyskinesia develops last, often over a period of months to years

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15
Q

Which typical antipsychotic may produce severe cardiac side effects?

A

thioridazine

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16
Q

Which side effect is more common with atypical antipsychotics than typicals? Which one in particular?

A

Weight gain

Olanzapine in particular

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17
Q

Which class of typical antipsychotic is particularly prone to lowering seizure threshold?

A

phenothiazines

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18
Q

What is a potentially lethal hypodopaminergic side effect of antipsychotic drugs?

Describe its symptoms

How do you treat it?

A

Neuroleptic Malignant Syndrome

Sx: hyperthermia, parkinson-like symptoms, mutism, death

Rx: cooling and hydration, bromocriptine (dopamine agonist), and dantrolene (muscle relaxant that abolishes excitation-contraction coupling in muscles, reducing hyperthermia)

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19
Q

Name seven drugs (excluding lithium) useful in the treatment of mania, including the manic episodes of bipolar disorder.

A
  1. aripiprazole
  2. olanzapine
  3. quetiapine
  4. ziprasidone
  5. risperidone
  6. asenapine
  7. lurasidone

Agitated ornery queens zooming rapidly around lodgings

[best I could do on short notice.]

20
Q

Name a drug useful in the treatment of schizoaffective disorder.

A

Paliperidone

21
Q

Name three drugs used as augmentation therapy in the treatment of depression.

A
  1. quetiapine
  2. aripiprazole
  3. olanzapine

Quick Add-Ons

22
Q

Name two drugs useful for treating Tourette’s Syndrome.

A
  1. Haloperidol
  2. Pimozide
23
Q

Which antipsychotic drugs are noted to have high antipyramidal side effects?

A
  1. Piperazine phenothiazines (e.g. fluphenazine)
  2. Butyrophenone
24
Q

Which type of antipsychotic drugs are noted to have high sedative side effects? Name a drug of this type.

A
  • Aliphatic phenothiazines
    • e.g. Chlorpromazine
25
Q

Which type of antipsychotic drug would you want to avoid giving to a patient prone to hypotension?

A
  • Aliphatic phenothiazines (e.g. chlorpromazine)
    • High hypotensive side effects
26
Q
  1. What is the 12-month prevalence of bipolar disorder?
  2. What percentage of cases are classified as severe?
  3. What is the average age of onset of bipolar disorder?
A
  1. 2.6% of adult US population
  2. The majority (83%) are classified as severe
  3. 25 years old
27
Q

What are the seven DSM-IV criteria for a manic episoide?

A

DIG FAST

  1. Distractibility
  2. Indiscretion (excessive involvement in pleasurable activities with little thought for consequences)
  3. Grandiosity (inflated self-esteem)
  4. Flight of ideas (racing thoughts)
  5. Activity level increase (often goal-directed)
  6. Sleep deficit (decreased need for sleep)
  7. Talkativeness
28
Q

Define 1) bipolar I disorder, 2) bipolar II disorder, and 3) cyclothymic disorder.

A
  1. At least 1 episode of mania is sufficient for diagnosis. Pt often also cycles manic and depressive episodes but hx of depressive episodes is not needed for dx.
  2. At least 1 episode of major depression and 1 episode of hypomania. Characterized by hypomania (less severe mania) with more frequent cycling and shorter intervals of well-being between hypomania and depressive episodes.
  3. Milder form of bipolar disorder. Frequent “mood swings” characterized by hypomanic states (do not meet criteria for full mania) and **mild/moderate depressive states **(do not meet criteria for major depression).
29
Q

What is a “mixed episode”?

Although it was said we wouldn’t be grilled on the differences between DSM-IV and V, what major change to this designation occured with the new edition?

A

In DSM-IV, a mixed episode “ required an individual to simultaneously meet all criteria for an episode of major depression and an episode of mania.”

This was eventually seen to be very rare, thus:

In DSM-V, the diagnosis of “mixed episode” was replaced “with a mixed-features specifier that can be applied to episodes of major depression, hypomania or mania”

Source: http://tinyurl.com/kcz5cns

30
Q

What is a potential mechanism of action of lithium?

Aside from that mechanism, what enzyme is litium also known to affect?

A
  • Lithium appears to inhibit the recycling of inositol substrates, which may decrease PIP2 and therefore reduce the release of IP3 and DAG.
  • Also affects glycogen synthase kinase (GSK)
31
Q

What group of the periodic table is lithium part of?

A

Group 1 (first column), aka alkali metals

32
Q

What is unique about the effects of lithium among antipsychotic drugs?

A

One of few psychotherapeutic drugs that (at therapeutic dosage) has no behavioral effects in “normal” individuals

33
Q

Lithium - Pharmacokinetics

  1. When are peak serum levels seen?
  2. What is lithium’s half-life?
A
  1. Peak serum levels in 2-4 hours
  2. Serum t1/2: 18-24hrs in young adults, 30-36hrs elderly pts
34
Q

Lithium - Pharmacokinetcs

  1. Is lithium bound to plasma proteins? If so, which ones?
  2. What is lithium’s volume of distribution?
A
  1. Not bound to plasma proteins
  2. VoD = Total Body Water
35
Q

Lithium - Pharmacokinetics

  1. How much of lithium makes it to the CNS?
  2. How is lithium eliminated?
A
  1. CSF concentration is 40-50% of plasma concentration
  2. 95% eliminated in urine
36
Q

How do sodium levels affect lithium levels?

Knowing this, how would thiazide diuretics, ACE inhibitors, ARBs, or general fluid loss affect lithium levels?

A

Increased Na excretion causes clinically significant increases in Li levels.

Thiazide diuretics, ACE inhibitors, ARBs, or general fluid loss would cause increased Li levels.

(This is important to monitor, as lithium has a narrow therapeutic window.)

37
Q

What are the more common side effects of lithium?

What toxic reactions can occur at excessive Li levels.

How much is an “excessive” level?

A
  • S/Es:
    • Fatigue & muscular weakness
    • Tremor (can be treated with beta-blockers)
    • GI symptoms
    • Slurred speech
    • Ataxia
    • N.B. Use w/ caution in pregnant women
  • Serious toxicity at 2-3x normal plasma levels (narrow therapeutic window!)
    • Imparied consciousness
    • Rigidity & hyperactive deep reflexes
    • Coma
38
Q

What are the clinical uses of lithium?

Are there any off label uses of lithium?

A
  • Mania
  • Bipolar Disease
  • In some pts, may be useful in preventing recurrences of unipolar depression
  • Off-label
    • Schizoaffective disorder
    • Cluster headaches
39
Q

What are some alternatives to lithium for the treatment of bipolar disorder?

A
  • Carbamazepine
  • Valproic Acid
    • first line treatment for bipolar
  • Lamotrigene (off-label)
  • Topiramate (off-label)
  • Haloperidol or clonazepam (off-label)
    • Initial control of manic sxs
  • Olanzapine + Fluoxetine combination (Symbyax)
40
Q

What are the three different types of phenothiazines?

Which type has the most potency?

Which type has the fewest sedative effects?

Which type has the least extrapyramidal and anticholinergic side effects?

A
  1. Phenothiazines with aliphatic side chains
  2. Phenothiazines with piperidine side chains
  3. Phenothiazines with piperazine side chains

Piperazines are the most potent

Piperazines have the fewest sedative effects

Piperadines have the least extrapyramidal, anticholinergic effects

41
Q

What are the two typical antipsychotics similar to phenothiazines?

What is pimozide?

What is pimozide approved to treat?

A

Thioxanthines, Butyrophenone

A powerful neuroleptic antipsychotic

Approved to treat Tourette’s that doesn’t respond to haloperidol

42
Q

What are some advantages of atypical antipsychotics?

A
  • Fewer extrapyramidal symptoms
  • Lower incidence of tardive dyskinesia
  • Improved treatment of negative symptoms
  • Improved treatment of resistant positive symptoms
  • Fewer cognitive side effects
43
Q

Clozapine

What receptors does clozapine affect?

What symptoms does it treat?

What side effects does it have?

A

Antagonizes muscarinic receptors, D4 receptors, and 5-HT2 receptors

Treats recalcitrant positive symptoms, negative symptoms, and lowers seizure threshold

Fatal agranulocytosis

44
Q

Olanzapine

What receptors does olanzapine affect?

What side effects are seen?

A

Affects 5-HT2, D1and2, some D4

weight gain, diabetes, and possibility of abuse

45
Q

Risperidone

What receptors does risperidone affect?

What symptoms does risperidone treat?

A

Antaognizes D2 and 5-HT2 receptors

Greatly reduces negative symptoms with few extrapyramidal symptoms

46
Q

Quetiapine

What is quetiapine approved to treat?

What side-effects does it have?

A

Treats negative schizophrenia symptoms and augmentation in depression

Some risk of abuse, weight gain, and diabetes

47
Q

What receptors does ziprasidone affect?

What receptors does aripiprazole affect?

A

5-HT2, D2, and 5-HT1a

5-HT2, D2

M2 Neuro/Psych (45 decks)

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