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Pharmacology (Winter) > Antipsychotic Drugs & Mood Stabilizers > Flashcards

Antipsychotic Drugs & Mood Stabilizers Flashcards

1
Q

What are the TYPICAL antipsychotics?

A

1st gen

Haloperidol, Chlorpromazine

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2
Q

What are the ATYPICAL antipsychotics?

A

2nd gen

Clozapine, Risperidone, Olanzapine, Aripiprazole, Quetiapine

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3
Q

What are the 3 Sx’s of Schizophrenia and dopaminergic pathways?

A
  1. (+) Sx’s
  2. (-) Sx’s
  3. Cognitive dysfunction
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4
Q

What are the (+) Sx’s of Schizophrenia?

A
  • Hallucinations
  • Delusions
  • Disorganized thought
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5
Q

What are the (-) Sx’s of Schizophrenia?

A
  • Affective blunting; Apathy; Anhedonia (like depression)
  • Social withdrawal
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6
Q

What are the Cognitive dysfunction Sx’s of Schizophrenia?

A
  • Declines in attention, language, memory, executive function
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7
Q

What are the 2 parts of the Dopamine hypothesis?

A

Amphetamine
- Hyperactivity, extreme anxiety, paranoid delusions, hallucinations…..
- Membrane dopamine transporter (can inhibit reuptake & therefore buildup & dopamine can cause psychosis)

Antipsychotic drugs
- Antipsychotic drugs tend to block dopamine
receptors in the dopamine pathways of the brain.

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8
Q

What 4 parts of the Dopaminergic pathways?

A
  • Mesolimbic pathway
  • Mesocortical pathway
  • Nigrostriatal pathway
  • Tuberoinfundibular pathway
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9
Q

What is the Mesolimbic pathway?

A
  • VTA (Ventral Tegmental Area) →(projects to) → Nucleus accumbens in the ventral striatum
  • Motivation, reward, addiction, reinforcing behaviour
  • HYPERACTIVITY → POSITIVE SYMPTOMS

(A Dopaminergic pathway)

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10
Q

What is the Mesocortical pathway?

A
  • VTA →(projects to) → Prefrontal cortex
  • Cognitive function, motivation and emotional response.
  • DEFICIT → NEGATIVE SYMPTOMS,
  • DEFICIT → COGNITIVE DYSFUNCTION

(A Dopaminergic pathway)

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11
Q

What is the Nigrostriatal pathway?

A
  • SNc (substantia nigra) →(projects to) → caudate nucleus and putamen in the dorsal striatum
  • MODULATE MOTOR ACTIVITY, part of the basal ganglia motor loop.

(A Dopaminergic pathway)

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12
Q

What is the Tuberoinfundibular pathway?

A
  • infundibular nucleus in hypothalamus →(projects to) → pituitary gland
  • regulates the secretion of prolactin (which)→ INHIBITS PROLACTIN RELEASE.

(A Dopaminergic pathway)

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13
Q

What are antipsychotic drugs?

A

Antipsychotic drugs are able to REDUCE PSYCHOTIC SYMPTOMS in a wide variety of conditions, including schizophrenia, bipolar disorder and others.

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14
Q

What is the classification of Antipsychotic drugs?

A
  • TYPICAL antipsychotics (1st generation):
    – chlorpromazine, haloperidol
  • ATYPICAL antipsychotics (2nd generation):
    – clozapine, risperidone, olanzapine,
    quetiapine, aripiprazole
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15
Q

What is the action sites of the TYPICAL antipsychotics (first generation): chlorpromazine, haloperidol?

A
  • BLOCK DOPAMINE D2 RECEPTOR: binding affinity is strong
  • NON-SELECTIVELY BLOCK: histamine H1 receptor; muscarinic M receptor; adrenergic α receptor

NO EFFECT ON 5-HT receptor

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16
Q

What is the therapeutic uses of TYPICAL antipsychotics (first generation): chlorpromazine, haloperidol?

A
  • Onset of action is about 1 WEEK
  • Effective for POSITIVE symptoms (block Mesolimbic pathway) but not effective for negative symptoms (NO EFFECT ON (-) & Cognitive Sx’s)
  • Inhibit D2 receptor in mesolimbic DA pathway → positive symptoms ↓
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17
Q

Why are TYPICAL antipsychotics effective for (+) Sx’s but not (-) Sx’s?

A

b/c only for psychosis; b/c blocks dopamine D2 r.; inhibiting it
- for (-) Sx’s, you’d want to UPregulate dopamine

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18
Q

What are the adverse effects of TYPICAL antipsychotics (first generation): chlorpromazine, haloperidol?

A

EXTRAPYRAMIDAL SYMPTOMS (EPS):
- block DA nigrostriatal pathway (which controls motor movement)
- Short-term Tx (hours-months):
– Parkinson’s syndrome
– Akathisia, acute dystonia
– REVERSIBLE
- Long-term treatment (months-years):
- Tardive dyskinesia (repetitive, invol, purposeless movements)
- IRREVERSIBLE

NEUROLEPTIC MALIGNANT SYNDROME:
- A rare but life-threatening reaction (high fever, rigid muscles, etc.)

GALACTORRHEA:
- block tuberoinfundibular pathway: spontaneous flow of milk from breast

OTHER:
- ANTIMUSCARINIC, ANTIHISTAMINERGIC, ANTIADRENERGIC

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19
Q

What are the action sites of ATYPICAL antipsychotics (second generation)
(clozapine, risperidone, olanzapine, quetiapine, aripiprazole)?

A
  • Block dopamine D2 receptor
  • Block 5-HT2 receptor
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20
Q

What are the therapeutic uses of ATYPICAL antipsychotics (second generation)
(clozapine, risperidone, olanzapine, quetiapine, aripiprazole)?

A
  • Onset of action is about one week
  • Useful for BOTH POSITIVE and
    NEGATIVE symptoms

For positive symptoms:
- SIMILAR EFFICACY with typical antipsychotics
- Inhibit D2 receptor in mesolimbic DA pathway → positive symptoms↓

For negative symptoms:
- Block 5-HT2 receptor → ↓Negative symptoms, cognitive dysfunction

Clozapine: reduce suicidal risk in patients with schizophrenia

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21
Q

What is unique about Clozapine (Atypical)?

A

only one that can REDUCE suicidal risk in patients with schizophrenia

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22
Q

What are the adverse effects of ATYPICAL antipsychotics (second generation)
(clozapine, risperidone, olanzapine, quetiapine, aripiprazole)?

A

Extrapyramidal symptoms (EPS)
- With lower risk of EPS
- Blocking of 5-HT2 receptor may be a requirement for the reduction in EPS

Others:
- Olanzapine and others: Weight gain, hyperlipidemia
- Clozapine: agranulocytosis; seizures (NOT 1st line (2nd gen) drug)

23
Q

Describe ATYPICAL vs. TYPICAL in terms of SE’s

A

TYPICAL:
- as antipsychotic effect increases, EPS SE’s increases

ATYPICAL:
- have to increase antipsychotic effect way more to see increase in EPS SE’s (higher therapeutic window)

24
Q

What is the drug interaction with Antipsychotic drugs?

A

Pharmacokinetic interaction:
- Some pharmacokinetic interactions have been reported, but none are of major clinical significance.

Pharmacodynamic interaction:
- Be cautious: use with anti-Parkinson’s drugs (may inhibit antipsychotic effect)
- Enhance EPS: use with metoclopramide
- Produce excess sedation: use with anxiolytics, alcohol, antidepressants, antihistamines
- Produce additive antimuscarinic effects

25
Q

In terms of drug choice, which drug is preferred?

A

ATYPICAL antipsychotics (2nd gen) are preferred over TYPICAL antipsychotics (1st gen)

26
Q

Typical & atypical antipsychotics are of _________ for treating POSITIVE Sx’s

A

EQUAL EFFICACY

27
Q

ATYPICAL antipsychotics are beneficial for:

A
  • Low risk of EPS & tardive dyskinesia
  • Lesser increases in prolactin levels
  • Negative symptoms & dysfunctional cognition
28
Q

________ (ATYPICAL antipsychotic drug) produces more weight gain, hyperlipidemia

A

Olanzapine

29
Q

_________ (ATYPICAL antipsychotic drug) produces agranulocytosis and seizures.

A

Clozapine (NOT 1st choice)

30
Q

_______ is the only second-generation antipsychotic drug approved to reduce the risk of suicide in patients with history
of schizophrenia.

31
Q

What are the bipolar drugs?

A
  • Lithium
  • Anticonvulsant mood stabilizers:
    valproate, carbamazepine
  • Atypical antipsychotic mood stabilizers: olanzapine, risperidone, quetiapine, aripiprazole
32
Q

What are the Anticonvulsant mood stabilizers?

A

valproate, carbamazepine

33
Q

What are the Atypical antipsychotic mood stabilizers?

A

olanzapine, risperidone, quetiapine, aripiprazole

34
Q

What is Bipolar disorder?

A

is a medical condition with periods of depression and elevated mood.

35
Q

What are the 4 phases of Bipolar disorder?

A

MANIC phase
- continuously high, happy, euphoric, irritable, angry and aggressive, exaggerated self-esteem, decreased need for sleep, more talkative than usual, racing thoughts, excessive energy for activities, engaging in risky behaviour…..

DEPRESSIVE phase (Tx diff. than depression tx)
- Depressed mood, loss of interest, weight loss or gain, difficulty sleeping or sleeping too much, apathy or agitation, loss of energy, feelings of worthlessness…..

MIXED EPISODE & RAPID CYCLING

EUTHYMIA

36
Q

Patients with bipolar disorder are at high risk for ______.

A

Suicide (~25-50%)

37
Q

What is the pathophys of bipolar disorder?

A

The precise causes of bipolar disorder are unknown.

Studies suggest that:
- Genetic factors interact with environmental
factors (stress…)
- Impaired neuroplasticity

38
Q

What are Mood Stabilizers?

A

are medications used in the treatment of
bipolar disorder

he mechanism is not clear for mood stabilizing treatment

39
Q

Mood stabilizer - Lithium:

A

Pharmacological mechanism is not clear

40
Q

Mood stabilizer - Anticonvulsant mood stabilizers:

A
  • Valproic acid, carbamazepine
  • Inhibit voltage-dependent Na+ channels
  • Inhibit glutamate functioning and increase GABA functioning
41
Q

Atypical Antipsychotic mood stabilizers:

A
  • Olanzapine, quetiapine, risperidone, aripiprazole (partial agonists)
  • block dopamine receptors and serotonin receptors
42
Q

What are the action sites of Lithium?

A
  • Pharmacological mechanism is not clear

No unified theory, several effects reported
- Reduced serotonin reuptake
- Reduced dopamine synthesis
- Increased GABAergic activity
- Increased glutamate reuptake
- Reduced neuronal calcium uptake

  • Major working hypothesis is that Li+ affects the IP3/DAG second messenger system by blocking inositol recycling
  • Inhibit glycogen synthase kinase 3 beta
  • Mitochondrial function and oxidative stress
43
Q

What is the therapeutic use of Lithium?

A
  • A slow onset of action
  • Used for manic phase of bipolar disorder
  • Used for maintenance treatment
  • Can reduce risk of suicide
44
Q

What is the adverse effects of Lithium?

A
  • Lithium has a low therapeutic index and a
    narrow therapeutic window.
  • Neurologic & psychiatric adverse effects
  • Decreased thyroid function
  • Renal adverse effects
  • Cardiac adverse effects
  • Drug interactions:
  • Thiazide diuretics, NSAIDS, ACEi’s (INCREASE Li)
  • Potassium-sparing diuretics (REDUCE Li)
  • Loop diuretics, Ca2+ channel blockers (INCREASE/DECREASE Li)
45
Q

What are the action sites of Valproate (anticonvulsant mood stabilizer)?

A
  • Inhibit voltage-dependent Na+ channels
  • Inhibit glutamate functioning and increase GABA functioning
46
Q

What are the therapeutic uses of Valproate (anticonvulsant mood stabilizer)?

A
  • Approved for anti-manic effects
  • Effective in patients not responsive to lithium:
  • Effective in mixed states and rapid cycling
47
Q

What are the adverse effects of Valproate (anticonvulsant mood stabilizer)?

A
  • Generally well-tolerated
  • In some patients: nausea
48
Q

What are the therapeutic uses of Carbamazepine (anticonvulsant mood stabilizer)?

A
  • Manic phase: alternative in patients not responsive to lithium:
  • Maintenance treatment of bipolar disorder.
49
Q

What are the adverse effects of Carbamazepine (anticonvulsant mood stabilizer)?

A
  • Generally well-tolerated
  • Induce CYP3A4: is a difficult drug to use with other pharmacological treatments for bipolar disorder
50
Q

What are the ATYPICAL antipsychotic mood stabilizers?

A

(olanzapine, risperidone, quetiapine, aripiprazole)
 Effective in treating manic phase
 Quetiapine, and olanzapine + fluoxetine (antidepressant): effective on bipolar depression

51
Q

What is the drugs of choice for bipolar mania and mixed episode?

A

Lithium, valproate, carbamazepine or an atypical antipsychotic medication.

52
Q

What is the drugs of choice for bipolar depression?

A

quetiapine, olanzapine/fluoxetine combination

53
Q

What are the drugs of choice for maintenance tx?

A
  • Lithium, carbamazepine,
  • Atypical antipsychotic mood stabilizers (aripiprazole, olanzapine, risperidone, quetiapine)
  • Either one (aripiprazole, olanzapine, risperidone, quetiapine) in combination with lithium

Pharmacology (Winter) (23 decks)

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