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PR3136 therapeutics > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

How may iatrogenic causes lead to psychotic symptoms?

A

Increase dopaminergic transmission (levodopa, dopamine agonists) or serotonergic neurotransmission

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2
Q

How may alcohol and psychoactive substance misuse lead to psychosis?

A

Drug withdrawal and alcohol withdrawal can predispose person to psychosis

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3
Q

3 examples of drugs that can lead to schizophrenia?

A

Alcohol, benzodiazepines, barbiturates, antidepressants, corticosteroids, CNS stimulants (Amphetamines), hallucinogens (LSD, cannabis, volatiles), beta blockers (propanolol), dopamine agonists (levodopa, bromocriptine)

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4
Q

Factors that prolong the course of schizophrenia?

A

Poor adherence with antipsychotic medications

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5
Q

Non pharmacological treatment for schizophrenia

A

Individual Cognitive behavioral therapy
Electroconvulsive therapy (ECT) - for TR schizophrenia
Repetitive Transcranial magnetic stimulation (rTMS)
Psychosocial rehabilitation programs: improving patient’s adaptive functioning

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6
Q

Therapeutic goals of schizophrenia

A
  1. Acute stabilisation (minimise threat to self and others, minimise acute symptoms)
  2. Stabilisation (minimise/prevent relapse, maintain baseline functioning)
  3. Stable/maintenance phase (improve functioning and quality of life)
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7
Q

What do antipsychotic medications do?

A

Tranquilise without impairing consciousness and without causing paradoxical excitement
In the short term, they are used to calm disturbed patients whatever the underlying psychopathology which may be (schizophrenia, mania, toxic delirium, agitated depression)

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8
Q

What do antipsychotics do in schizophrenia?

A

Relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse

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9
Q

When is long-term treatment indicated?

A

After the first episode of psychosis and to prevent the illness from becoming chronic

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10
Q

Why is relapse often delayed after several weeks after cessation of treatment?

A

Adipose tissues act as depot reservoir after chronic regular usage of antipsychotics.
The antipyschotic stored in fat cells then diffuses back into bloodstream after treatment cessation, until depletion

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11
Q

Will a patient relapse immediately after stopping treatment?

A

No, relapse is often delayed after several weeks after cessation of treatment

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12
Q

Methods to overcome poor treatment adherence

A

IM long-acting injections
Community psychiatric nurse
Patient and family (caregiver) education

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13
Q

Mechanism of action of antipsychotics

A

Dopamine receptor antagonism - antagonises all dopamine receptors in all dopaminergic tracts in the brain

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14
Q

Blockade of dopamine receptors in which tract is the most common mechanism of all antipsychotics in reducing positive symptoms?

A

Mesolimbic tract

Overactivity in this region is responsible for positive symptoms of schizophrenia

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15
Q

What are the dopaminergic tracts in the brain?

A

Mesolimbic tract
Mesocortical tract
Nigrostriatal tract
Tuberoinfundibular tract

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16
Q

Blockade of dopamine receptors in which tracts causes adverse effects?

A

Mesocortical tract - dopamine blockade or hypofunction in this region results in negative symptoms
Nigrostriatal tract - modulates body movement; antipsychotic-induced dopamine blockade in this region causes EPS
Tuberoinfundibular tract - dopamine blockade in this region of the anterior pituitary leads to hyperprolactinemia → gynecomastia

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17
Q

What does D2 antagonism do in terms of therapeutic effects and postulated side effects?

A

Improve + symptoms

EPSE, hyperprolactinemia

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18
Q

Do all antipsychotics have serotonin modulating effects?

A

No, only SGA have additional mechanism on serotonin modulation

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19
Q

What does 5HT2A antagonism do in terms of therapeutic effects?

A

Improve negative symptoms

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20
Q

What other receptor affinities do antipsychotics have and their postulated side effects?

A

H1 - sedation, weight gain
alpha1 - orthostasis, sedation
M1 - memory dysfunction, peripheral anticholinergic effects
QTc interval prolongation

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21
Q

What does 5HT2C antagonism do?

A

Weight gain

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22
Q

What is the algorithm for schizophrenia?

A

Diagnosis of schizo → use a single FGA or SGA (except clozapine) → Inadequate or no response → use another single FGA or SGA (except clozapine) not previously tried → clozapine
If adequate response and no intolerable side effects and compliant → continue treatment

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23
Q

How is medication selection individualised for a patient?

A

Based on physician’s assessment of clinical circumstances, past response/failures on antipsychotics, patient needs, efficacy and side effect profiles of the therapy

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24
Q

What is an adequate trial of antipsychotic? What is the adequate trial of clozapine?

A

Antipsychotic of at least 2-6 weeks at optimal therapeutic doses
3 months

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25
Q

When should you consider a long-acting injectable antipsychotic?

A

if inadequately compliant, or if patient prefers

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26
Q

Long-acting injectable antipsychotics

A

IM haloperidol decanoate

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27
Q

What should you do before any IM injection?

A

Check platelet count to check for thrombocytopenia

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28
Q

When do you consider clozapine?

A

In those who are treatment-resistant, ie those had failed >=2 adequate trials of different antipsychotics (at least 1 should be a SGA)

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29
Q

What do we need to look for in FBC when put on clozapine?

A

Neutrophils (to check for agranulocytosis), RBCs and Hb for anemia, Platelets (for thrombocytopenia)

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30
Q

How often do we need to monitor for clozapine FBC monitoring?

A

Baseline, then weekly for first 18 weeks, then every monthly thereafter for as long as they are on the medication

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31
Q

Precautions to antipsychotic use

A

Cardiovascular disease (QTc prolongation)
Parkinsons disease - EPSE worsened by antipsychotics (dont give strong D2 antagonists that will worsen tremors - give those with low affinity, commonly quetiapine)
Prostatic hypertrophy
Angle closure glaucoma
Severe respiratory disease
Blood dyscrasias - esp for clozapine (look out for signs of infection)
Elderly with dementia - increased risks for mortality and stroke

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32
Q

Adjunctive treatments for acute agitation (psychiatric emergency) if patient is cooperative

A

Consider oral medication
(A) oral lorazepam or
(B) oral antipsychotic: risperidone

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33
Q

Adjunctive treatments for acute agitation (psychiatric emergency) if patient is uncooperative

A

If remains agitated/aggressive:

  • Consider fast-acting IM injection
    (a) IM lorazepam
    (b) IM olanzapine
    (c) IM haloperidol
    (d) IM promethazine
34
Q

Adjunctive treatments for catatonia (group of symptoms that usually involve a lack of movement and communication, and also can include agitation, confusion and restlessness)

A

Benzodiazepines

35
Q

Adjunctive treatments for depression symptoms and/or negative symptoms of chronic schizophrenia

A

Depression: treat with suitable antidepressant - mirtazipine

Negative sx: mild-moderate efficacy with antidepressants eg some SSRIs

36
Q

Which antipsychotics have to be taken with food?

A

Lurasidone and ziprasidone

37
Q

What are examples of FGA?

A

Haloperidol

38
Q

What are examples of SGA?

A

Clozapine, olanzapine, quetiapine, risperidone

39
Q

What are examples of FGA IM long acting antipsychotics?

A

Haloperidol decanoate

40
Q

How long are IM long acting antipsychotics typically dosed?

A

Typically dosed once a month; paliperidone is dosed every 3 months

41
Q

Why does SGA have lower incidence of movement SEs?

A

Not as potent D2 receptor antagonism as FGA

42
Q

In terms of metabolic side effects, which are the biggest offenders in causing weight gain?

A

Olanzapine and clozapine

43
Q

FGAs are associated with what side effects compared to SGAs?

A

ESPE and hyperprolactinemia

44
Q

In terms of metabolic side effects, which drugs are the safest?

A

Aripiprazole, ziprasidone, brexipiprazole

45
Q

What is dystonia defined by? What are the risks and how to manage?

A

Type of EPSE - Muscle spasms
Risk with high-potency antipsychotics (eg haloperidol)
Management: IM anticholinergics eg bentropine or switch to lower potency antipsychotics

46
Q

What is pseudo-parkinsonism defined by? How to manage?

A

Tremors, rigidity
Decrease antipsychotic dose (not practical), or switch to SGA
Anticholinergics PRN eg benztropine to treat the tremors, swithc to lower potency antipsychotics

47
Q

What is akathisia defined by? How to manage?

A

Restlessness
Decrease antipsychotic dose, or switch to SGA
Clonazepam (low dose) PRN and/or propanolol OR switch to a SGA or lower-potency antipsychotic

48
Q

What is tardive dyskinesia defined by? What are the risk factors and how to manage?

A

Involuntary movements, irreversible during onset (usually after taking more than 6 months).
Risk: FGA > SGA (lower potency at D2 receptors), worsens with anticholinergic drugs
Management: discontinue any anticholinergics, reduce antipsychotic dose, or switch to SGA, clonazepam PRN, treat with valbenazine

49
Q

How do you manage hyperprolactinaemia?

A

Switch to aripiprazole (partial agonist at D2, can reverse effects of hyperprolactinemia)

50
Q

What are metabolic side effects of antipsychotics? What are the high and low risk agents? How to manage?

A

Weight gain, diabetes, hyperlipidemia
High risk: olanzapine, clozapine
Low risk: lurasidone, ziprasidone, haloperidol
Management: diet, exercise
treat diabetes (eg with metformin), hyperlipidemia
Switch to lower risk agents (eg aripiprazole, brexipiprazole, lurasidone)

51
Q

What are the types of side effects experienced with antipsychotics?

A

EPSE (dystonia, pseudoparkinsonism, akathisia, tardive dykinesia), hyperprolactinemia, metabolic, cardiovascular, CNS, hematological

52
Q

What are the cardiovascular side effects of antipsychotics? How to manage?

A

Orthostatic hypotension - get up slowly from sitting or lying position
QTc prolongation
VTE/PE: aripiprazole lowest risk; manage emergent DVT

53
Q

Which CNS side effect of antipsychotics is a medical emergency? Risk factors and management?

A

Neuroleptic malignant syndrome (NMS): muscle rigidity, fever, autonomic dysfunction, altered consciousness, increased CK
Risk: High-potency antipsychotics
Management: IV dantrolene (skeletal muscle relaxant), oral dopamine agonist (to reverse efx of dopamine antagonist),
Switch to SGA (give a low potency one, not haloperidol)

54
Q

Hepatological side effect of antipsychotics - description, risks, management

A

Decreased WBC, Agranulocytosis (decreased neutrophil count)
Risk: clozapine
Management: discontinuation if severe

55
Q

Monitoring parameters for side effects of antipsychotics

A

BMI, Fasting blood sugar, lipid panel, blood pressure, EPSE exam
Clozapine - WBC and ANC

56
Q

How often should BMI be monitored?

A

Every3 months

57
Q

How often should fasting blood sugar be monitored?

A

Every 3 months after initiating SGA, then annually

58
Q

How often should blood pressure be monitored?

A

3 months after initiating SGA then annually

59
Q

How often should WBC and ANC be monitored?

A

Weekly for first 18 weeks, then monthly

60
Q

Treatment considerations for elderly

A

Avoid drugs with high propensity for alpha1-adrenergic blockade (orthostatic hypotension) or anticholinergic side effect (constipation, urinary retention, delirium)
Start low go slow
Simplify regime
Avoid long half life drugs

61
Q

Drug disease interaction of antipsychotics

A

Antipsychotics worsen Parkinson’s disease symptoms

62
Q

What is the interaction between drugs with CNS depressant effects?

A

Additive CNS effects

eg benzodiazepine and clozapine

63
Q

Additive adverse effects with ___ agents

A

Antimuscarinic, antihistaminic, alpha1-adrenergic blockade or dopamine blockade

64
Q

Is there an interaction between levodopa and antipsychotics?

A

Yes, mutual antagonism with antipsychotics

65
Q

What is the potential effects of administering an antihypertensive together with antipsychotics?

A

Increased hypotensive effects

66
Q

What are common CYP1A2 inhibitors

A

Fluvoxamine, quinolones, macrolides

67
Q

Which drug is affected by CYP1A2 inhibition?

A

Clozapine.

Cannot use fluvoxamine with Clozapine

68
Q

What is a CYP1A2 inducer?

A

Cigarettes

- will decrease concentration of clozapine

69
Q

Can you give carbamazepine together with clozapine?

A

No

Increased risk of agranulocytosis with clozapine

70
Q

How to evaluate therapeutic outcomes of antipsychotics?

A

Monitor for effectiveness of therapy
-Mental status exam
-Psychiatric rating scales
Monitor for adverse effects
-metabolic parameters: fasting blood glucose, lipids, body weight, BP etc
-EPSE: presence and severity of any treatment-emergent EPSE (drug induced pseudoparkinsonism, akathisia, tardive dyskinesia)

71
Q

When can you see a reduction in agitation, aggression, hostility?

A

1st week

72
Q

What improvements do you see in 2-4 weeks of treatment?

A

Decreased paranoia, hallucinations

73
Q

What are late improvements seen with antipsychotics and when do they occur?

A

6-12 weeks: reduced delusions

3-6 months: cognitive symptoms may improve (with SGAs)

74
Q

Key clinical features of schizophrenia

A

Positive symptoms, negative symptoms, functional impairment

75
Q

What is the MOA that improves positive symptoms?

A

D2 antagonism (both FGA and SGA)

76
Q

What is the MOA that improves mood symptoms (and possibly also negative symptoms)?

A

5HT2A antagonism

77
Q

Clinical differences between SGA and FGA

A

SGA effective for both positive and mood symptoms; FGA effective mainly for positive symptoms

FGA generally has more muscle side effects; SGA generally has more metabolic side effects (weight gain, dyslipidemia, diabetes) except aripiprazole, brexipiprazole, lurasidone.

78
Q

Which SGAs tend to be more sedating and more weight gain?

A

the “ines” - Clozapines, olanzapines, quetiapine

79
Q

When is IM rapid acting used? 2 examples?

A

IM haloperidol or IM olanzapine.

Used when not cooperative and cannot comply orally

80
Q

What is considered treatment resistant schizophrenia? Drug of choice and monitoring?

A

Not responsive to at least 2 adequate trials of antipsychotics (2-6 weeks at recommended dosing), of which one is a SGA.
Clozapine is drug of choice for TRS - monitor baseline and periodic FBC with ANC due to risks for agranulocytosis

81
Q

How do manage a patient who is acutely agitated or aggressive?

A
  1. De-escalate
  2. Consider oral antipsychotic +/- benzodiazapine
  3. If refuse or not possible to administer oral medications, consider fast acting IM alternatives with monitoring: eg IM haloperidol 5mg with ECG + IM lorazepam 2mg
  4. monitor for treatment emergent adverse effects (eg dystonia, psuedoparkinsonian side effects) - treat accordingly (eg with oral or IM benztropine 2mg)
82
Q

During the stabilisation phase, what can we do if poor adherence to oral medications or if patient prefers?

A

IM long acting antipsychotic (LAI) eg IM haloperidol decanoate
Community psychiatric nurse referral

PR3136 therapeutics (6 decks)

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