Antipsychotics - Bloom

Question 1

Give 4 major behavioral features of psychosis

Answer 1

• Derangement of personality
• Loss of contact with reality
• Delusions
• Hallucinations

Question 2

Give 3 possible core positive symptoms of schizophrenia

Give 5 negative symptoms

Answer 2

Positive

• Delusions
• Hallucinations
• Disorganized speech

Negative

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

Question 3

What is the dopamine hypothesis?

Answer 3

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

Question 4

Mesolimbic tract

• Origin?
• Function?
• Result of dopamine hyperactivity?

Answer 4

• A10
• Arousal, memory, stimulus processing, locomotor activity, motivational behavior
• Dopamine hyperactivity results in positive schizophrenic symptoms

Question 5

Mesocortical tract

• Origin?
• Function?
• Result of diminished dopaminergic activity?

Answer 5

• A10
• Cognition, communication, social activity
• Diminished dopaminergic activity leads to negative schizophrenic symptoms

Question 6

Nigrostriatal pathway

• Origin?
• Course?
• Does dopamine blockade increase or decrease extrapyramidal symptoms (EPS)?
• What happens if 5-HT_2alpha is blockaded here?

Answer 6

• A9
• Substantia nigra to basal ganglia
• Increased EPS
• Decreased EPS, parkinsonism (possibly)

Question 7

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

Answer 7

Increased prolactin release

Question 8

Gs or Gi?

• D1
• D2
• D3
• D4
• D5

Answer 8

• G2
• Gi
• Gi
• Gi
• Gs

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

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

Answer 11

• chlorpromazine
• fuluphenazine, trifluoperazine
• thioridazine
• thiothixene
• haloperidol

Question 12

Name (3) atypical antipsychotics

Answer 12

• risperidone
• clozapine
• olanzepine

Question 13

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

Answer 13

Positive

Question 14

Describe the major features of the extrapyramidal effects of antipsychotic drugs

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

Answer 14

• 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

Question 15

Which typical antipsychotic may produce severe cardiac side effects?

Answer 15

thioridazine

Question 16

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

Answer 16

Weight gain

Olanzapine in particular

Question 17

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

Answer 17

phenothiazines

Question 18

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

Describe its symptoms

How do you treat it?

Answer 18

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)

Question 19

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

Answer 19

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.]

Question 20

Name a drug useful in the treatment of schizoaffective disorder.

Answer 20

Paliperidone

Question 21

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

Answer 21

1. quetiapine
2. aripiprazole
3. olanzapine

Quick Add-Ons

Question 22

Name two drugs useful for treating Tourette’s Syndrome.

Answer 22

1. Haloperidol
2. Pimozide

Question 23

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

Answer 23

1. Piperazine phenothiazines (e.g. fluphenazine)
2. Butyrophenone

Question 24

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

Answer 24

• Aliphatic phenothiazines
  
  • e.g. Chlorpromazine

Question 25

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

Answer 25

* Aliphatic phenothiazines (e.g. chlorpromazine) * High hypotensive side effects

Question 26

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?

Answer 26

1. 2.6% of adult US population 2. The majority (83%) are classified as severe 3. 25 years old

Question 27

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

Answer 27

**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

Question 28

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

Answer 28

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 **hypo**mania. 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).

Question 29

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?

Answer 29

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

Question 30

What is a potential mechanism of action of lithium? Aside from that mechanism, what enzyme is litium also known to affect?

Answer 30

* 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)**

Question 31

What group of the periodic table is lithium part of?

Answer 31

Group 1 (first column), aka **alkali metals**

Question 32

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

Answer 32

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

Question 33

Lithium - Pharmacokinetics 1. When are peak serum levels seen? 2. What is lithium's half-life?

Answer 33

1. Peak serum levels in 2-4 hours 2. Serum t_1/2: 18-24hrs in young adults, 30-36hrs elderly pts

Question 34

Lithium - Pharmacokinetcs 1. Is lithium bound to plasma proteins? If so, which ones? 2. What is lithium's volume of distribution?

Answer 34

1. Not bound to plasma proteins 2. VoD = Total Body Water

Question 35

Lithium - Pharmacokinetics 1. How much of lithium makes it to the CNS? 2. How is lithium eliminated?

Answer 35

1. CSF concentration is **40-50%** of plasma concentration 2. 95% eliminated in urine

Question 36

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

Answer 36

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.)

Question 37

What are the more common side effects of lithium? What toxic reactions can occur at excessive Li levels. How much is an "excessive" level?

Answer 37

* 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

Question 38

What are the clinical uses of lithium? Are there any off label uses of lithium?

Answer 38

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

Question 39

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

Answer 39

* 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*)

Question 40

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?

Answer 40

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

Question 41

What are the two typical antipsychotics similar to phenothiazines? What is pimozide? What is pimozide approved to treat?

Answer 41

Thioxanthines, Butyrophenone A powerful neuroleptic antipsychotic Approved to treat Tourette's that doesn't respond to haloperidol

Question 42

What are some advantages of atypical antipsychotics?

Answer 42

* Fewer extrapyramidal symptoms * Lower incidence of tardive dyskinesia * Improved treatment of negative symptoms * Improved treatment of resistant positive symptoms * Fewer cognitive side effects

Question 43

_Clozapine_ What receptors does clozapine affect? What symptoms does it treat? What side effects does it have?

Answer 43

Antagonizes muscarinic receptors, D₄ receptors, and 5-HT₂ receptors Treats recalcitrant positive symptoms, negative symptoms, and lowers seizure threshold Fatal agranulocytosis

Question 44

_Olanzapine_ What receptors does olanzapine affect? What side effects are seen?

Answer 44

Affects 5-HT₂, D_1and2, some D₄ weight gain, diabetes, and possibility of abuse

Question 45

_Risperidone_ What receptors does risperidone affect? What symptoms does risperidone treat?

Answer 45

Antaognizes D₂ and 5-HT₂ receptors Greatly reduces negative symptoms with few extrapyramidal symptoms

Question 46

_Quetiapine_ What is quetiapine approved to treat? What side-effects does it have?

Answer 46

Treats negative schizophrenia symptoms and augmentation in depression Some risk of abuse, weight gain, and diabetes

Question 47

What receptors does ziprasidone affect? What receptors does aripiprazole affect?

Answer 47

5-HT₂, D₂, and 5-HT_1a 5-HT₂, D₂