Psychotic symptoms Flashcards
What is the extrapyramidal syste
neural network within the brain that helps regulate and control motor activity, including posture, locomotion, and coordination
What is akathisia
subjective feeling of restlessness with an urge to move around
What is akathisia
subjective feeling of restlessness with an urge to move around
What are dystonias
range of movement disorders characterized by sustained or intermittent muscle contractions causing abnormal movements or postures
What is parkinsonism
characterized by the triad of tremor, rigidity (lead pipe or cogwheel), and bradykinesia
EPSE’s are thought to be due to
antagonism of dopaminergic D2 receptors in the basal ganglia
EPSE’s are thought to be due to
antagonism of dopaminergic D2 receptors in the basal ganglia
Name the types of dystonia
Torticollis - cervical muscles spasms, resulting in a twisted posturing of the neck.
Trismus (lock jaw) - contraction of the jaw musculature.
Opisthotonus - arched posturing of the head, trunk, and extremities.
Laryngeal dystonia - difficulty in breathing
Oculogyric crises - involuntary contraction of one or more of the extraocular muscles, which may result in a fixed gaze with diplopia
Name the types of dystonia
Torticollis - cervical muscles spasms, resulting in a twisted posturing of the neck.
Trismus (lock jaw) - contraction of the jaw musculature.
Opisthotonus - arched posturing of the head, trunk, and extremities.
Laryngeal dystonia - difficulty in breathing
Oculogyric crises - involuntary contraction of one or more of the extraocular muscles, which may result in a fixed gaze with diplopia
Which antipsychotic carries the highest risk of epses
Haloperidol
What is the most resistant epse to treat
Akathisia
Dystonia Prevalence?
Approximately 10%
But more common in
- young males
- neuroleptic-naive
- high potency drugs (e.g. haloperidol)
Acute dystonia can develop within XXXXX of starting antipsychotics
minutes or hours
Which medications are used to manage acute dystonia?
Anticholinergics used include trihexyphenidyl, procyclidine, orphenadrine, benztropine. The antihistamine, diphenhydramine, is also used due to its anticholinergic properties
Pseudo-parkinsonism (e.g. tremor) prevalence
Approximately 20%
But more common in
- elderly females
- those with pre-existing neuro damage (e.g. stroke)
Pseudo-parkinsonism develops XXXXXX after antipsychotic started or dose increased
Days to weeks
Akathisia prevalence?
25%
Tardive dyskinesia prevalence?
5% of patients per year of antipsychotic exposure
But more common in
- elderly women
- those with affective illness
- those who have had EPSE early on in treatment
Tardive dyskinesia develops over?
Months to years
Prolactin sparing antipsychotics?
Clozapine
Aripiprazole
Asenapine
Quetiapine
High risk / major change prolactin antipsychotics?
All the typical antipsychotics
Risperidone
Amisulpride
Paliperidone
Sulpiride
Psychiatric patients with long standing hyperprolactinaemia have an increased risk of:-
Osteoporosis
Breast cancer
Hyperprolactinaemia is only very occasionally seen with antidepressants.
True
Sexual dysfunction is common in the general population (estimated 30%) but is thought to be increased in people with psychiatric illness
True
Which scale does maudesy suggest use for measuring sexual dysfunction?
Arizona Sexual Experiences Scale (ASEX)
The propensity for the antipsychotics to cause sexual dysfunction appears related, in part, to their effect on
prolactin levels
Relationship of Risperidone / paliperidone with sexual dysfunction.
The atypical with the highest prolactin elevation.
Increase is dose dependent.
Approx 70% of people using risperidone report sexual dysfunction in the first year of use.
Causes reduced libido, erectile dysfunction, vaginal dryness, and ejaculatory disorder.
Relationship of Haloperidol with sexual dysfunction
Causes significant prolactin increase.
Approx 70% of people using haloperidol report sexual dysfunction in the first year of use.
Causes reduced libido, erectile dysfunction, vaginal dryness, and ejaculatory disorder.
Effect of Clozapine on sexual dysfunction.
Associated with relatively low effect on prolactin. However, sexual dysfunction related to anti-adrenergic and anticholinergic effects (erectile and ejaculatory problems as well as priapism) does occur with clozapine.
Rates of sexual dysfunction less than risperidone and haloperidol.
Effect of Clozapine on sexual dysfunction.
Associated with relatively low effect on prolactin. However, sexual dysfunction related to anti-adrenergic and anticholinergic effects (erectile and ejaculatory problems as well as priapism) does occur with clozapine.
Rates of sexual dysfunction less than risperidone and haloperidol.
Effect of olanzapine on sexual dysfunction.
Causes a temporary increase in prolactin which then returns to normal within 6 weeks (in most cases).
Still associated with high rates of sexual dysfunction (approx 50%) but significantly less than haloperidol and risperidone.
Effect of olanzapine on sexual dysfunction.
Causes a temporary increase in prolactin which then returns to normal within 6 weeks (in most cases).
Still associated with high rates of sexual dysfunction (approx 50%) but significantly less than haloperidol and risperidone.
Effect of Quetiapine on sexual dispunction
Not thought to raise prolactin at therapeutic doses.
Associated with a lower sexual dysfunction rate than risperidone and haloperidol.
Probably low risk for sexual dysfunction.
Effect of Quetiapine on sexual dispunction
Not thought to raise prolactin at therapeutic doses.
Associated with a lower sexual dysfunction rate than risperidone and haloperidol.
Probably low risk for sexual dysfunction.
Which antipsychotics have no effect on sexual dysfunction
Aripirazole
Arsenapine
Lurasidone
What is the mechanism of Valproate
GABA modulation (increases GABA in the brain), sodium channel inhibition and NMDA antagonist
What is the mechanism of Gabapentin
Binds to the alpha-2-delta subunit of voltage-gated calcium channels, which reduces the release of certain neurotransmitters, including glutamate and substance P, and can help reduce neuronal excitability.
What is the mechanism of Topiramate
GABA modulator, NMDA antagonist, and Na channel stabiliser
What is the mechanism of Carbamazepine
Stabilises Na channels
What is the mechanism of Phenytoin
Stabilises Na channels
What is the mechanism of Pregabalin
Binds to the alpha-2-delta subunit of voltage-gated calcium channels, which reduces the release of certain neurotransmitters, including glutamate and substance P, and can help reduce neuronal excitability.
What is the mechanism of Lamotrigine
NMDA receptor modulation, stabilises Na channels and blocks calcium channels, some GABA modulation
Mechanism of Amisulpride ?
D2/D3 selective antagonist (low affinity selective antagonist of ‘D2 like’ receptors (D2=D3>D4) it has little affinity for D1 like’ receptors (D1 and D5) or non dopaminergic receptors (serotonin, histamine, adrenergic, and cholinergic)
What is the mechanism of Olanzapine
Dopamine and 5HT2 antagonism
What is the mechanism of Aripiprazole
Partial agonist at 5HT1A and D2, and 5HT2A antagonist
What is the mechanism of Clozapine
Dopamine and serotonin antagonist (5HT2A)
High affinity for D4, (to a lesser extent D1, D2, D3, D5) which may explain less EPSEs
5-HT 1A partial agonist which may explain reduction of negative symptoms
Muscarinic M1, M2, M3, M5, histamine, and alpha-1 adrenergic-receptor antagonist
Norclozapine, the metabolite of clozapine, actively works on the M1 and M4 receptors.
What is the mechanism of Lurasidone
Dopamine D2, 5-HT2A, 5-HT7, alpha2A- and alpha2C- adrenoceptor antagonist, and is a partial agonist at 5-HT1a receptors. Lurasidone does not bind to histaminergic or muscarinic receptors.
What is the mechanism of Cariprazine
D3/D2 partial agonist, 5-HT1A partial agonism, 5-HT2B and 5-HT2A antagonism
What is the mechanism of Raclopride
D2/D3 antagonist (used in PET scans not therapeutically
What is the mechanism of Benzodiazepines
Enhance action of GABA by action of non-specific positive allosteric modulation of GABA-A, in the absence of GABA they have no effect on GABA functioning
What is the mechanism of Z-drugs
Enhance action of GABA by action of specific positive allosteric modulation of GABA-A (high affinity for α1-containing GABA-A receptors)
What is the mechanism of Buspirone
5HT1A partial agonist
What is the mechanism of Flumazenil
Benzodiazepine antagonist
Action to be taken if QTC <440ms (men) <470ms (women)
No action required unless T-wave morphology
Action to be taken if QTC >440ms (men) >470ms (women)
Consider reducing dose or switching to drug of lower QTc effect, repeat ECG and refer to cardiology
Action to be taken if QTC >500ms (men and women)
Stop causative drug and then switch to drug of lower effect and refer to cardiology
non-psychotopic drugs can cause QTc prolongation Antibiotics
Antibiotics Ampicillin
Erythromycin
non-psychotopic drugs can cause QTc prolongation Antiarrthythmics
Amiodarone
Sotalol
non-psychotopic drugs can cause QTc prolongation Antimalarials
Chloroquine
Quinine
Cardiac risk factors QTC prolongation
Long QT syndrome
Bradycardia
Ischemic heart disease
Myocarditis
Myocardial infarction
Left ventricular hypertrophy
Electrolyte derangement causing QTC prolongation
Hypokalaemia
Hypomagnesaemia
Hypocalcaemia
What is the mechanism of clozapine?
D1 (dopamine 1), D2, 5-HT2A, alpha1-adrenoceptor, and muscarinic-receptor antagonist.
Clozapine Has a particularly high affinity for.
D4 receptor and exerts only a weak blockade of D2 receptors.
Clozapine is mainly metabolised by
CYP1A2
Clozapine side effects
Drowsiness/ sedation
Constipation
Salivation
Weight gain
Dizziness
Insomnia
Nausea
Vomiting
Dyspepsia
Clozapine is a potentially dangerous drug. It is associated with the following adverse events:-
Agranulocytosis
Myocarditis, pericarditis / pericardial effusion, cardiomyopathy
Seizures
Severe orthostatic hypotension with or without syncope
Increased mortality in elderly patients with dementia related psychosis
Colitis
Pancreatitis
Thrombocytopenia
Thromboembolism
Insulin resistance and diabetes mellitus (Approx 33 percent developed diabetes mellitus over a ten year period (Henderson, 2005))
Clozapine BNF advices caution in the following circumstances:
prostatic hypertrophy
susceptibility to angle-closure glaucoma
adult over 60 years
When using clozapine, valproate should be considered if
Using high doses
Plasma levels > 0.5 mg/l
Patient experiences seizures
What is the half life of diazepam
Twenty to one hundred hours
Several antipsychotic drugs are associated with postural hypotension. These include:-
Risperidone
Clozapine
Olanzapine
Paliperidone
Quetiapine
Ziprasidone
The Maudsley Guidelines provides the following list of antipsychotics to try when postural hypotension is a problem:-
Amisulpride
Aripiprazole
Haloperidol
Sulpiride
Trifluoperazine
