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PH3501- Neuropharmacology > Lec 16- Schizophrenia > Flashcards

Lec 16- Schizophrenia Flashcards

1
Q

Definitions

A
  • Schizophrenia- also called
    • Paranoid illness/ Delusional disorder/ Psychotic state/ Psychosis
  • Drug-induced psychosis- Short term only
  • Schizoaffective disorder
    • Combination of bipolar and schizophrenia
  • Psychotic depression
    • Severely depressed & loss touch with reality
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2
Q

Schizophrenia- frequency & epidemiology

A
  • Lifetime expectation- 0.5-1.0%
  • Onset usually late adolescence or early adult life
  • Affects males and females equally
  • Rate similar most countries
  • Twice the rate in immigrants
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3
Q

Thought abnormalities

A
  • Thought interference includes
    • Insertion
    • Withdrawal
    • Broadcasting- believe people can read you thought
    • Block
  • Knight’s move thinking- thinking about things that are totally unrelated
  • Concrete thought- focus on physical facts
  • The poverty of thought- not much thought
  • Speech abnormalities
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4
Q

Symptoms

A
  • What is schizophrenia
  • Lose touch with reality
  • Reality subjective
  • Abnormalities
    • Thought
    • Ideation (Delusions)
    • Perception (Hallucinations)
    • Emotion
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5
Q

Other symptoms

A
  • Delusion= false belief against reality e.g. believing you have “God-like” powers
  • Hallucination = Disorder of perception
    • 3rd person auditory most common
  • Emotion- blunted; incongruity i.e. inappropriate
  • Positive- delusions, thought disorder; hallucinations
  • Negative symptoms- social withdrawal, apathy
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6
Q

Treatment through the ages

A
  • Insulin coma shock
  • Psychosurgery
  • ECT
  • Neuroleptics
    • Typicals
    • Atypicals
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7
Q

Insulin coma therapy

A
  • The idea that you can’t get epilepsy and psychosis together (this is now known to be wrong), induce hypoglycaemia = seizures= treat psychosis
  • Quite risky as very dangerous
  • Large dose insulin induce coma & seizure
  • Given glucose recovery
  • Widely used 1930-1970
  • Often led to serious illness & even death
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8
Q

Psychosurgery

A
  • 1930s “prefrontal Lobotomy” Portuguese physician Egas Moniz
  • 1949- Nobel prize medicine
  • US 10,000-20,000 patients 1930s- 1950s
  • Adverse events- cognitive & emotional deficit
  • Still limited use
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9
Q

Electroconvulsive therapy (ECT)

A
  • Introduced 1939 Cerletti- Italy
  • Same theory as coma shock therapy= don’t get epilepsy and psychosis
  • Production fit by electricity
  • Never much help schizophrenia
  • Effective severe depression
  • It is hard to do clinical trials
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10
Q

Anti-psychotics

A
  • Typicals- Chlorpromazine, Trifluoperazine, Fluphenazine, Haloperidol, Flupenthixol, Zuclopenthixol
  • Atypicals- Risperidone, Olazapine, Quetiapine, Aripiprazole, Clozapine
  • Long acting preparations- depots/Consta
  • Generally equally effective
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11
Q

Efficacy

A
  • Generally greater efficacy +ve symptoms (exceptions clozapine)
  • Work in 3 ways
  1. Calming effect
    • Immediate sedative compounds- not true anti-psychotic effect = As required usage
  2. Symptom control
    • Symptom control can take 6-8 weeks- although some effects from 1 week
    • Patience and support required
  3. Relapse prevention
    • Maintenance treatment prevent re-lapse- long-term compliance
    • Stop medication no immediate return symptoms
      • Re-lapse delayed 2-6 months
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12
Q

typical side effects

A
  • Anti-cholinergic (also with atypicals)
    • Dry mouth, blurred vision, constipation
    • Often wear off
  • Others- Lower seizure threshold (also atypicals)
    • Numerous
  • Movement problems- Main problem
  • Acute dystonia
    • Abnormal face & body movements e.g. stiff neck
    • Potentially fatal
    • oculogyric crisis- involuntary upward movement of eyes- Can be fatal medical emergency
  • Parkinsonism- coarse tremor at rest, rigidity, slow movement
  • Treatments
    • Anticholinergics- procyclidine, benzhexol, benztropine
    • Anti-cholinergic side effects; Abuse potential
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13
Q

Typical side effects

A
  • Akathisia
    • Inner restlessness, floor pacing, crossing legs, very distressing
    • Treatments: BZs; 5-HT antagonists- Cyproheptadine, mirtazapine/ mianserin
  • Tardive Dyskinesia
    • Late-onset involuntary & repetitive facial movements
    • Lip smacking, grimacing
    • Irreversible- no effective treatments
    • A form of brain damage
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14
Q

Depots

A
  • Long-acting injection
    • Flupenthixol decanoate; Haloperidol decanoate; Fluphenazine decanoate; Zuclopenthixol
  • Given every 1-4 weeks
  • Efficacy >4 months
  • No more effective
  • May aid compliance but
    • Patients do not like depots
    • Cause more movement problems
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15
Q

Atypical neuroleptics

A
  • Search agents without movement problems typicals
  • Major advantage
    • Little or no movement disorder
    • Procyclidine type medicines not usually required
  • NICE used to recommend first-line treatment
  • Different side-effects- significant weight gain 5-10 Kg
  • Patient preferred side-effects
  • Monotherapy
  • Long-term use- atypical + typical not recommended- double side effects
  • Little evidence increase efficacy- clozapine
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16
Q

Clozapine: efficacy

A
  • Activity at many receptors- dirty drug
  • Only anti-psychotic with proven increased efficacy
    • reason unclear- due to broad activity
    • Indicated in treatment-resistant schizophrenia
  • Long-term medication
    • Up to 1 year for a maximum response
17
Q

Clozapine: side effects

A
  • Lack of EPSE
  • Neutropenia (drop WBC)- also called agranulocytosis (severe drop)
    • Risk of infection- fatalities reported
    • Not dose dependent
    • Most commonly w6-18
  • Regular blood tests
  • Blood results must be okay for drug dispensed
18
Q

Clozapine: other serious side-effects

A
  • Weight gain- significant 10-20Kg
    • Dietary advice; fruit and veg; reduce fatty food; exercise
    • Tailored programmes, dietician support
  • Diabetes
    • Related weight gain
    • Patients warned of signs
    • Regular monitoring- oral glucose tolerance test (random), HbA1C
    • May need insulin or oral agents
  • Seizures
    • Dose related- grdual titration; check plasma levels
    • Doses >600mg DD consider valproate
    • After seizure reduce damage
  • Constipation
    • 3 fatal cases
    • Usual advice: high-fibre diet; plenty of fluids
    • Laxatives may be required
19
Q

Clozapine: other serious side-effects

A
  • Tachycardia
    • Usually benign- treat with atenolol
    • If persistent at rest + five; chest pain and hypotension could indicate myocarditis- stop clozapine and referral
  • Hypersalivation
    • Can be very distressing, usually nocturnal
    • Plastic pillows but acceptability is an issue
    • hyoscine 300mcg at night- OTC Kwells
    • Other treatments- aantimuscarinics procyclidine, pirenzepine- not licensed in the UK
20
Q

Olanzapine

A
  • Activity range receptors- D (including D2); 5-HT including (5-HTA), HI, Anti-cholinergic
  • No evidence efficacy TRS
  • Lack of EPS
  • Significant weight gain
    • Mean 10Kg or ore
    • Distribution not uniform
  • Diabetes, increase serum triglyceride/ ChE
  • Regular monitoring- weight, others
  • Long-term risk cardiac disease
21
Q

Risperidone

A
  • High affinity: Serotoninergic 5-HT2 and dopaminergic D2 receptors + other activities
  • Most effective dose 4-6mg daily- lower doses in older people
  • Reduced EPSE at lower doses
  • Less weight gain than olanzapine- usually 3-5Kg
  • Initial hypotension
  • Increase serum prolactin- leading to
    • Galactorrhea, gynecomastia, amenorrhea
    • Sexual side-effects e.g. impotence
    • Risk osteoporosis
    • Linked with breast cancer
22
Q

Risperidone consta

A
  • First depot atypical
    • Unique release mechanism
  • No efficacy in resistant schizophrenia
  • Movement problems occur higher doses
  • Cold chain product- like a vaccine
  • 36-step injection & re-constitution procedure
23
Q

Release mechanism

A
  • Microsphere biodegradable polymer beads
  • Degrade releasing over sustained period
24
Q

Quetiapine

A
  • Affinity serotonin (5-HT2), dopamine D1 and D2 receptors
  • Adrenergic H1
  • Lack of EPSE
  • No evidence efficacy in TRS
  • Risk- weight gain
  • Case reports- diabetes
25
Q

Aripiprazole

A
  • Partial agonism D2, 5-HT1a receptors + antagonism 5-HT2a receptors
  • Not particularly effective
  • Less weight gain than other atypicals
  • Adverse events include- Anxiety; insomnia; akathisia; nausea; vomiting
  • Not recommended- treatment resistant

PH3501- Neuropharmacology (28 decks)

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