PH3113 - Psychiatric Disease and its Pharmacology 5 Flashcards
What is the pharmacological treatment for schizophrenia?
Long-term treatment with antipsychotics
- standard approach
First episode patients more sensitive to the effects (and side effects) of drugs
Compliance is important
- non-compliance major factor in relapse
- hospital
Functional tends to decline with repeated relapses
- harder to treat
Treatment resistance can develop over time
What is the prognosis for schizophrenia?
Variable but generally life-long
- associated with
- physical illness
- cardiovascular disease
- self-harm
- suicide
- victimisation
- reduced by ~ 10 years
- 1/3 recover
- 1/3 improve with significant impairment
- 1/3 require frequent hospitalisation
Prognosis better in traditional societies
- family more supportive
Prognosis worsened in
- early onset
- insidious onset
- male gender
- poor pre-morbid/cognitive functioning
- poor insight
- less willing to take meds
- social isolation/adversity
- homelessness
What are the two classes of antipsychotics?
Typical
- first generation
- older
- produce greater motor side effects
- hyperprolactinaemia
- prolonged QTc
- D2 receptor antagonist
Atypical
- second generation
- newer
- less motor side effects
- greater metabolic side effects
- D2/5-HT receptor antagonists
Before initiation need baseline observations
- weight
- blood pressure
- heart rate
- bloods
- glucose
- lipids
- prolactin
- ECG
Give examples of first generation potent D2 receptor antagonists
Benperidol
Pipothiazine
Haloperidol
Pimozide
Flupehnazine
Give examples of second generation moderately potent D2 receptor antagonists
Chlorpromazine
Perphenazine
Trifluoperazine
Zuclopentixol
Pericyazine
What are the extra-pyramidal side effects of treating schizophrenia?
Movement disorders
- disruption in dopaminergic transmission in nigrostriatal pathway
- affects all dopaminergic pathways
- correlate with D2 receptor occupancy
- 65 - 80% antipsychotic effect
- 72% increased prolactin secretion
- 80% EPSE
What are the four sub-types of extra-pyramidal side effects of treating schizophrenia?
Divided into 4 sub-types
- Pseudo-Parkinsonianism
- tremor
- rigidity
- dribbling
- treat with anticholinergic
- Akathisia
- restlessness
- linked to suicide
- treat with
- beta blockers
- 5-HT(2C) antagonists
- benzodiazepines
- Dystonia
- involuntary muscle contraction
- oculogyric crisis, torticollis
- treat with anticholinergic
Tardive dyskinesia
- involuntary muscle movements
- tongue rolling
- lip smacking
- treat with
- gradual dose reduction
- tetrabenazine
What are the other side effects of treating schizophrenia?
Sedation
- H1 receptor
- less potent D2 > potent D1
Sexual dysfunction
- hypotension
- noradrenergic alpha
- dry mouth
- constipation
- muscarinic acetyl cholinergic
- raised prolactin levels
- D2 receptor
- QT prolongation
- K+ ion channel
- weight gain
- H1 receptors
- 5-HT(2C)
- reduced seizure threshold
- increased risk of seizures
- neuroleptic malignant syndrome
Give examples of atypical second generation anti-psychotics used to treat schizophrenia
Amisulpride
Aripiprazole
Clozapine
Quetiapine
Olanzapine
Risperidone/paliperidone
Lirasidone
Zotepine
Serindole
How can non-compliance be overcome when treating schizophrenia?
Non-compliance with antipsychotics is a significant problem in practice due to
- lack of insight
- adverse effects
- symptomatology
Long-acting injections reduce “covert non-compliance”
Older drugs formulated as oily injections
- release the drug over weeks/months
- initial “test” dose
- followed by 2 - 4 weekly maintenance dosing
- after stopping, release of drug continues for up to 3 months
Newer anti-psychotics now available
- use different methods of controlled release
What is the role of using clozapine for treating resistant schizophrenia?
Different binding profile from other anti-psychotics
- relatively low affinity for D2 receptors in the striatum
- high affinity for D4 receptors in frontal cortex
- high affinity for 5-HT receptors
Two failed treatments with other antipsychotics
- one of which should be second generation anti-psychotic drug
- 1/3 will respond at 6 weeks
- 2/3 will respond at 1 year
How should clozapine be monitored when treating resistant schizophrenia?
Mandatory
- risk of agranulocytosis
- death < 1 in 10,000
Drug company records
- white blood cells
- neutrophil count
- platelets
- eosinophils
- initially weekly for 18 weeks
- fortnightly for remainder of the first year
- monthly thereafter and post-discontinuation
What are the side effects of using clozapine to treat resistant schizophrenia?
Hypersalivation
- muscarinic agonism
Constipation
- muscarinic antagonism
Sedation
- histamine H1 antagonism
Weight gain
- H1 antagonism
- 5-HT(2C) antagonism
Hypotension
- noradrenergic alpha antagonism
Hypertension
- atenolol?
Tachycardia
- atenolol
Fever
Seizures
- valproate?
What is the role of aripiprazole in treating schizophrenia, mania and bipolar disorder?
Partial agonist at dopamine D2 receptor
What are the side effects of using aripiprazole to treat schizophrenia, mania and bipolar disorder?
Nausea
Agitation
- on initiation
Akathisia
Some EPSE
Weight gain
