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AC- CNS lectures > Management of schizophrenia 1.5.2 > Flashcards

Management of schizophrenia 1.5.2 Flashcards

1
Q

What are the principles of antipsychotic treatment?

A
  • drug tx tailored to individual (consider side effects)
  • Use lowest effective dose
  • Use monotherapy where possible
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2
Q

Which are the high potency FGA antipsychotics?

A
  • droperidol
  • flupentixol
  • haloperidol
  • trifluoperazine
  • zuclopenthixol
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3
Q

What are the features of the high potency FGA?

A
  • ↑EPSE
  • ↓ Sedation
  • ↓ orthostatic hypotension
  • ↓ anticholinergic side effects
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4
Q

Which are the low potency FGA?

A
  • chlorpromazine
  • pericyazine
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5
Q

What are the feautures of the low potency FGA?

A
  • ↓EPSE
  • ↑sedation
  • ↑ orthostatic hypotension
  • ↑ anticholinergic side effects
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6
Q

Which antipsychotics have better efficacy on negative symptoms?

A
  • second generation antipsychotics
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7
Q

What are the side effects of SGAs?

A
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8
Q

Why do we not use clozapine first line?

A
  • agranulolcytosis
  • myocarditis
  • cardiomypathy
  • gastrointestinal hypomotility
    • constipation
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9
Q

How are FGA used in schizophrenia?

A
  • Used 2nd line due to side effects – largely extrapyramidal side effects
  • Effective for positive symptoms, little effect on negative symptoms
  • Haloperidol, droperidol used for acute psychosis (inpatients)
  • Use if had previous good response to these agents, or if poor response to several SGAs
  • Zuclopenthixol depot used commonly
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10
Q

What are examples of EPSE?

A
  • Dystonias - stiffness, uncontrolled muscular spasms
    • Treatment: benzatropine (oral, inj), trihexyphenidyl (benzhexol)
  • Akathisia - inner restlessness, strong desire or compulsion to move
    • Treatment: propranolol, clonazepam
  • Parkinsonism - tremor and/or rigidity, mask- like face, shuffling gait, slow movements
    • treatment: benzatropine, trihexyphenidyl
  • tardive Dyskinesia - involuntary abnormal movements of face, tongue, lips, hands or feet n Can be irreversible. Stop antipsychotic (preferred)
    • Treatment poor efficacy – tetrabenazine, Ginkgo biloba
  • If EPSE occurs, ideally reduce antipsychotic dose or switch to alternative antipsychotic
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11
Q

What do we do if EPSE occurs?

A
  • ideally reduce antipsychotic dose OR
  • switch to alternative antipsychotic
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12
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

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13
Q

How does cloazapine differ from other side effects of SGAs?

A

Increased sedation, weight gain and anticholinergic effects

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14
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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15
Q

Pharmacology of brexpiprazole

A

Indicated only in schizophrenia

May have positive effects on mood

Well tolerated – little weight gain, prolactin elevation, akathisia

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16
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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17
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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18
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
19
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
20
Q

Pharmacology of risperidone

A

Adverse effects:

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

cheaper than most SGAs

21
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
22
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
23
Q

Pharmacology of Ziprasidone

A

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

Little weight gain, prolactin elevation & sedation

24
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
25
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
26
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,
27
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
28
Q

What is clozapine dosing/drug concentration?

A

Slow dose titration to avoid/reduce dose dependent adverse effects

  • Target drug concentration: 350-1000mcg/L
29
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

30
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
31
Q

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

A

IM 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

32
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
33
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
34
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)
35
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)
36
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

37
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
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

AC- CNS lectures (28 decks)

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