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CNS lectures (Bal) > Module 1.5.2 (Management of Schizophrenia) > Flashcards

Module 1.5.2 (Management of Schizophrenia) Flashcards

1
Q

What are 1st gen and 2nd gen antipsychotics

A
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2
Q

What are high potency 1st gen antipsychotics?

↑EPSE ↓ Sedation ↓ orthostatic hypotension ↓ anticholinergic side effects

A

Droperidol Flupentixol Haloperidol Trifluoperazine Zuclopenthixol

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3
Q

What are low potency 1st gen antipsychotics?

↓EPSE ↑sedation ↑ orthostatic hypotension ↑ anticholinergic side effects

A

Chlorpromazine and Pericyazine

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4
Q

What to do if EPSE occurs?

A

ideally reduce antipsychotic dose or switch to alternative antipsychotic

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5
Q

What treatment for the following EPSE?

A) Dystonias - stiffness, uncontrolled muscular spasms

B) Akathisia - inner restlessness, strong desire or compulsion to move

C) Parkinsonism - tremor and/or rigidity, mask- like face, shuffling gait, slow movements

D) Tardive Dyskinesia - involuntary abnormal movements of face, tongue, lips, hands or feet

A

A)

benzatropine (oral, inj), trihexyphenidyl (benzhexol)

B)

propranolol, clonazepam

C)

benzatropine, trihexyphenidyl

D)

Can be irreversible. Stop antipsychotic (preferred)

Treatment poor efficacy – tetrabenazine, Ginkgo biloba

anticholinergic MOA: Antagonizes acetylcholine and histamine receptors.it reduces the cholinergic effects significantly during Parkinson disease which becomes more pronounced in the nigrostriatal tract because of reduced dopamine concentrations.

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6
Q

What is first line treatment in schizophrenia?

A

2nd Generation Antipsychotics (SGAs)

  • More metabolic adverse effects
  • More expensive
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7
Q

How does cloazapine differ from other side effects of SGAs?

A

Increased sedation, weight gain and anticholinergic effects

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8
Q

Pharmacalogy of aripiprazole? What is it used to agument?

A

Is a dopamine system stabiliser (increased dopamine output when conc are low and decreased dopamine output when conc. are high)

  • Less sedation, weight gain and prolactin elevation
  • Good 1st choice antipsychotic
  • Doesn’t provide sedation if patient acutely unwell
  • May cause insomnia, akathisia and/or activation

> Often used to augment other antipsychotics

To reduce weight gain – e.g. clozapine, olanzapine

To reduce prolactin – e.g. risperidone

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9
Q

Pharmacology of brexpiprazole

A

Indicated only in schizophrenia

May have positive effects on mood

Well tolerated – little weight gain, prolactin elevation, akathisia

> best evidence of no EPSE side effects

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10
Q

Pharmaclogy of lurasidone

A

Take with food to increase absorption

Low incidence weight gain, small rise in prolactin

Theorised to improve mood & be useful in bipolar

Reports of increased irritability/rage

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11
Q

Pharmacology of olanzapine

A

Sedating – may be beneficial in acute psychosis

WEIGHT GAIN +++

  • Metabolic syndrome major concern. For this reason falling out of favour as long term treatment
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12
Q

Pharmacology of paliperidone

A
  • 9-hydroxyrisperidone
  • Active metabolite of risperidone
  • Similar adverse effects to risperidone

Swallow tablets whole –> Cannot be halved, crushed –> Empty tablet may appear in stools

  • always with food, or always on an empty stomach
  • Oral not commonly used, but depot very common
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13
Q

Pharmacology of Quietiapine

A

Commonly used antipsychotic

  • Prone to abuse – watch for doctor shopping and picking up supply earlyn
  • More sedating at lower doses
  • To get antipsychotic effect, some patients require higher dose
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14
Q

Pharmacology of risperidone

A

Adverse effects:

  • Prolactin elevation – can be severe and problematic
  • EPSE – dose related

cheaper than most SGAs

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15
Q

Pharmacology of Amisulpride? How does its MOA change from low to higher doses?

A

Indicated for treatment of schizophrenia

  • At low doses (50-300mg) it is more effective for negative symptoms
  • At higher doses (400-800mg) it is more effective for positive symptoms
  • Not metabolised in the liver; reduce dose in renal impairment
  • Dose-related EPSE & hyperprolactinemia
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16
Q

Pharmacology of Asenapine

A

Rarely used

Sublingual wafer –> do not eat or drink for 10 minutes after taking –> take after all other medications –> poor absorption if swallowed

  • Tastes awful!! Makes mouth numb/tingly up to 1 hour after taking
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17
Q

Pharmacology of Ziprasidone

A

Can cause QT prolongation, increase risk of arrythmia – monitor ECG

Little weight gain, prolactin elevation & sedation

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18
Q

Clozapine pharmacology? Why is it not 1st line?

A
  • The most effective antipsychotic
  • 50% of non-responders will improve with clozapine
  • Particularly effective for negative symptoms

Not 1st line due to serious adverse effects (Immune mediated, rather than dose-dependent)

  • Agranulocytosis
  • Neutropenia
  • Cardiomyopathy
  • Myocarditis
  • Gastrointestinal Hypomotility – i.e. constipation = highest risk of mortality
19
Q

Why is clozapine more effective than all other antipsychotic agents?

A

Clozapine differs from other neuroleptics by antagonising D1, D2 and D4 dopamine receptors, with less affinity for D2 receptors, so it is less apt to induce extrapyramidal side effects.

Clozapine also antagonises 5-HT2, α1-adrenoreceptors and histamine H1 receptors –> It has been suggested it is more effective than all other antipsychotics, particularly in the treatment of negative symptoms or in treatment resistant patients

20
Q

What is the condition of clozapine being used?

A

Must have trialled ≥2 antipsychotics prior to clozapine initiation

  • Not effective or not tolerated
  • At least 1 must be atypical antipsychotic
21
Q

What is done before treatment of clozapine can be done (monitoring)?

A

Monitoring systems record WCC and neutrophil count

  • Clopine Connect
  • Clozaril Patient Monitoring Service

Pre-treatment

  • FBP, CRP, troponin, ECG, echocardiogram ( pregnancy test)
  • Desired: LFTs, U&Es, lipids, weight, BSL/HbA1c, weight, waist circumferance,
22
Q

What ongoing monitoring for clozapine?

A

Ongoing monitoring. Medication only supplied until next blood test

  • FBP weekly for first 18 weeks
  • CRP, troponin weekly for 4 weeks

> Monthly (every 4 weeks) thereafter

23
Q

Clozapine dosing/drug concentration

A

Slow dose titration to avoid/reduce dose dependent adverse effects

  • Target drug concentration: 350-1000mcg/L
24
Q

For clozapine;

A) What to use to treat hypersalivation

B) What to use to treat GI hypomotility (constiaption)

A

A)

  • Atropine 1% eye drops sublingually
  • Hyoscine wafers
  • Ipratropium MDI sublingually
  • Moclobemide, metoclopramide

B)

  • Macrogol first line and BE AGGRESSIVE!
  • Docusate/senna first line for prophylaxis
25
Q

Why is medication used in acute agitation and arousal in patients with schizophrenia? What drugs to use?

A

Medication is used to calm/lightly sedate the patient and reduce the risk to self and/or others

> Verbal de-escalation

  • Oral benzodiazepine (lorazepam, clonazepam, diazepam)
  • Oral antipsychotic (olanzapine, risperidone, quetiapine, haloperidol)
  • IM medication (lorazepam, olanazapine, ziprasidone, haloperidol, droperidol, midazolam, clonazepam)
  • IV med –> used in EDs, not used in psychiatric inpatient wards
26
Q

Outline why certain IM medication is not used for acute agitation. Which one is preferred?

A

M diazepam not recommended as absorption is poor & erratic

IM chlorpromazine not recommended due to risk of abscess formation & catastrophic hypotension

IM clonazepam not an approved route of administration – absorption erratic

> IM lorazepam available under SAS – more predictable absorption & effect –> refrigerate, 3 months shelf life once out of fridge

27
Q

What is needed when benzodiazepines used IM/IV? When to use?

A

Have flumazenil available when benzodiazepines used IM/IV

  • Use if respiratory rate falls below 10/minute
  • Caution in patient with epilepsy & on long term benzos
  • Has short half life (shorter than diazepam) so respiratory function may recover then deteriorate again
28
Q

Pharmacology of Zuclopenthixol acetate. When are they used?

A
  • NOT a rapid tranquilising agent
  • Can only be written as a stat dos
  • Used if other short-acting treatment options for acute agitation and arousal have been ineffective
  • IM administration. Intermediate-acting injection.
  • Not for long-term use. Duration of Tx cannot exceed 2 weeks, 400mg or 4 injections
  • Max conc at about 8 hours. Effects persist for 3 days

> Paroxetine and fluoxetine are known potent inhibitors of CYP2D6, and these SSRIs apparently reduce zuclopenthixol metabolism –> increase AE of zuclopenthixiol

> Raised zuclopenthixol concentrations with the addition of fluoxetine may also increase the risk of adverse events such as movement disorders and increased risk of QT prolongation. It is also possible that the risk is greater due to additive, similar side effects.

29
Q

When is long acting (depot) antipsychotics used? How is it used?

A

Antipsychotic long-acting injections (LAIs) used where non-adherence to oral treatment is problematic, or patient prefers this formulation type

Deep intramuscular injection (gluteal or deltoid)

Medication slowly released into bloodstream, providing steady supply of medication.

LAIs do not ensure adherence: they assure awareness of adherence

Allow regular assessment of patient (due to regular injections)

30
Q

Advantages and disadvantages of LAI antipsychotics?

A

Advantages

Proven reduction in relapse

Improved adherence

Fewer hospitalisations

Less fluctuation in drug concentration

Regular contact with clinicians

Less risk of overdose

Avoids first pass metabolism

Disadvantages

Pain at injection site

Cannot be withdrawn quickly (E.g. side effects)

Patient loses control of treatment

Less dosing flexibility

Monitoring required (olanzapine)

31
Q

How is LAI antipsychotics formulated? Where is it injected?

A

All fomulated in oil

Test doses required to test tolerability to antipsychotic and oil –> Regular dosing commence 4-10 days after test dose

  • • Injected into gluteal muscle sometimes deltoid
32
Q

Pharmacology of paliperidone palmitate?

Strengths: 25mg, 50mg, 75mg, 100mg, 150mg

A

once monthly (every 4 weeks) –> IM

  • Must trial oral risperidone or paliperidone prior to initiation –> To test tolerability to medication
  • Two initiation doses, so oral administration not required once injection has commenced.
  • Deltoid gives approx 28% higher peak concentration
33
Q

Pharmacology of paliperidone palmitate?

Strengths: 175mg, 263mg, 350mg, 525mg

A

3-monthly injection

Deltoid or gluteal muscle

For patients who are clinically stable on paliperidone 1-monthly for at least 4 months

Recommended the last two injections are same dose

> Give the 1st dose in place of next 1-monthly injection

34
Q

Pharmacology of risperidone

A

First SGA long-acting injection

Refrigerate. Remove from fridge 30 minutes prior to admin

Risperidone coated in polymer to form microspheres

Must be suspended in aqueous base immediately before use

Test dose of oral risperidone

Requires oral treatment (full dose) for 3-4 weeks

Takes 3-4 weeks for 1st injection to produce therapeutic plasma levels

35
Q

Pharmacology of aripiprazole LAI?

A

Gluteal or deltoid muscle

Oral test doses of aripiprazole

Oral antipsychotic required for 14 days after LAI is commenced

Indicated for treatment of:

  • Schizophrenia
  • BPAD – maintenance treatment (not PBS)

Favourable metabolic and prolactin-sparing effects

36
Q

What is post injection syndrome? What are the symptoms? What type of IM drug does it occur in? How to prevent it?

A

Post-injection syndrome (PIS) presents with signs and symptoms of olanzapine overdose

  • Sedation (mild to coma), delirium, dizziness, agitation, hypotension, weakness, confusion

> Possibly due to inadvertent intravascular injection (more soluble in blood than muscle)

  • The risk is present for every injection of olanzapine pamoate –> maintenance treatment of schizophrenia
  • Deep IM GLUTEAL site only –> less vascular than deltoid
  • Must monitor for 2 HOURS after every injection
  • Visual, have conversation every 30 minutes
  • Cannot drive for rest of the day
37
Q

All antipsychotics can reduce the seizure threshold/ What antipsychotics to avoid?

A

Clozapine, chlorpromazine – most epileptogenic

> Depot antipsychotics – cannot be withdrawn

38
Q

What are the effects of smoking and smoking cessation with antipsychotics?

A

Cigarette smoking induces CYP1A2

  • Reduces plasma levels of drugs eg BZD, clozapine, olanzapine
  • Significant effects with clozapine and olanzapine

Smoking cessation –> increased drug plasma levels –> consider dose reduction

39
Q

What to use for smoking cessation?

A

NRT has been used effectively for smoking cessation

  • But does not affect CYP enzymes

> Varenicline – Champix® - pschiatric adverse effects reported, but can be used with careful monitoring

> Bupropion – Zyban® - not routinely used in psychiatric setting. Lowers seizure threshold

40
Q

What are effects of caffeine on antipsychotic drugs?

A

Patients with mental illness have been reported to drink large amounts of caffeinated drinks

  • Caffeine can increase drug levels –> possibly due to competitive CYP1A2 inhibition
41
Q

Why does NMS occur (Neuroleptic Malignant Syndrome)?

A

Thought to be due to a sudden over-blockade of dopaminergic function

  • A very rare life-threatening syndrome that can occur with any antipsychotic medication

antipsychotics that act on stronger dopamine receptors

42
Q

Symptoms of NMS (Neuroleptic Malignant Syndrome)? How to treat?

A

Characterised by fever, muscle stiffness, altered consciousness and problems with the autonomic nervous system

  • Can be fatal if left untreated
  • Treatment is symptomatic and antipsychotic should be ceased
43
Q

Concerns with elderly patients?

A

More susceptible to adverse effects including EPSE and TD

Lower starting doses of medications are used

There is some concern that olanzapine and risperidone may increase the chance of a stroke

Elderly patients more likely to have other illness or be on other medications

44
Q

How to deal with side effects

A) Akathisia

B) Sedation

C) nausea

D) constipation

some more not relate to questions above

Weight gain – combination of good diet and exercise – prevention better than treatment

metformin can reduce weight gain

Augmentation with aripiprazole –> can reduce weight gain

A

A)

stretching & exercise

B)

take medication at night (if once daily dose) e.g. clozapine small dose in morning and large dose at night

C)

take with or after food

D)

balanced diet, increase fibre and fluid intake

Coloxyl & Senna, Movicol

CNS lectures (Bal) (29 decks)

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