Psychopharmacology of psychosis Flashcards
What is the aim of treatment in schizophrenia? (biochemically)
reduce dopamine over-activity
What are the 4 main neuronal pathways that use dopamine?
mesolimbic - emotions, behaviour
mesocortical - learning, memory
nigrostriatal - voluntary movement (extrapyramidal side effects related to this)
tuberoinfundibular - prolactin regulation
What does the dopamine hypothesis of schizophrenia state?
states that the symptoms of schizophrenia are due to a hyperdopaminergic state in the mesolimbic system
Another name for typical antipsychotics?
first generation antipsychotics
Another name for atypical antipsychotics?
second generation antipsychotics
Name some first generation antipsychotics
phenothiazines:
- chlorpromazine, levomepromazine, promazine, pericyazine, trifluoperazine, fluphenazine
butyrophenones:
- haloperidol, benperidol
thioxanthenes:
- flupentixol, zuclopenthixol
diphenylbutylpiperidines:
- pimozide, fluspirilene
substituted benzamides:
- sulpiride, amisulpride
Name some second generation antipsychotics
risperidone
quetiapine
aripiprazole
olanzapine
clozapine
paliperidone
zotepine
Describe how first generation antipsychotics work
all are dopamine D2 antagonists
D2 antagonism in mesolimbic system is responsible for antipsychotic effect
D2 antagonism in other dopamine systems is responsible for common side effects (higher risk of extrapyramidal side effects)
Describe how second generation antipschotics work
D2 and 5HT2A antagonism
little to no extrapyramidal side effects as 5HT2A antagonism in nigrostriatal and tuberoinfundibular reverses D2 antagonism
minimal effect of prolactin levels
higher risk of metabolic side effects
What can be done for patients with poor adherence to antipsychotics?
depot injections
What antipsychotics are available as depot injections?
haloperidol
flupentixol
zuclopenthixol
risperidone
paliperidone
aripiprazole
olanzapine
Side effects of antipsychotics
dopamine related = EPSE, raised prolactin
anticholinergic = dry mouth, blurred vision, constipation, urinary retention, cognitive impairment
antiadrenergic = postural hypotension, tachycardia, sexual dysfunction
antihistaminic = sedation, weight gain
idiosyncratic = altered glucose tolerance, dyslipidaemia, weight gain, photosensitivity, contact sensitivity
How can hypersalivation due to antipsychotics be treated?
hyoscine hydrobromide 300mcg sucked at night
How can constipation due to antipsychotics be treated?
osmotic or stimulant laxatives
How can tachycardia due to antipsychotics be treated?
persistent benign tachycardia may be treated with cardio-selective beta-blockers
What extrapyramidal side effects can occur with antipsychotics and how can these be managed?
parkinsonism - tremor, rigidity, bradyphrenia, bradykinesia - reduce dose, change drug, anticholinergic eg. procyclidine
dystonia - sustained abnormal posture or muscle spasm - anticholinergic eg. procyclidine
akathisia - motor restlessness (inability to sit still) - reduce dose, change drug, beta-blockers eg. propranolol, benzodiazepines
dyskinesia - involuntary repetitive purposeless movements eg, lip smacking, tongue protrusion - stop any anticholinergics, reduce dose, change drug
What causes extrapyramidal side effects when on antipsychotics?
D2 antagonism in striatum
What causes hyperprolactinaemia when on antipsychotics?
D2 antagonism in tuberoinfundibular results in increased prolactin secretion
Short term effects of hyperprolactinaemia
menstrual disturbance
gynaecomastia
galactorrhoea
sexual dysfunction
infertility
Long term effects of hyperprolactinaemia
reduced bone mineral density - osteoporosis
cancer
cardiovascular disease
What cardiovascular side effects can occur when on antipsychotics?
hypotention
tachycardia
myocarditis + cardiomyopathy
prolonged QT interval
What antipsychotics have a high, medium and low risk of weight gain?
high = clozapine, olanzapine
medium = chlorpromazine, quetiapine, risperidone
low = amisulpride, aripiprazole, haloperidol, sulpiride, trifluoperazine, ziprasidone
Which antipsychotics are reported to cause glucose intolerance and potentially diabetes?
phenothiazines
haloperidol
clozapine
olanzapine
quetiapine
risperidone
What is neuroleptic malignant syndrome?
idiosyncratic dose-dependent adverse drug reaction
sudden loss of control of body temperature
Main symptoms of neuroleptic malignant syndrome
hyperthermia
fever
muscular rigidity
confusion
tremor
fluctuating consciousness
tachycardia
fluctuating BP
Risk factors for neuroleptic malignant syndrome
high potency antipsychotics (including depot)
recent rapid dose increase
rapid dose reduction
abrupt withdrawal of anticholinergics
Management for neuroleptic malignant syndrome
stop antipsychotics
monitor temp, pulse + BP
cool
rehydration if necessary
if worsens:
- diazepam for muscle stiffness and sedation
- dantrolene for muscle stiffness and hyperthermia (skeletal muscle relaxant)
bromocriptine
amantadine
L-dopa
When is clozapine indicated?
treatment-resistant schizophrenia - lack of improvement after adequate doses of at least 2 different antipsychotics including an atypical agent for an adequate duration
patients with severe, untreatable neurological adverse reactions to other antipsychotics
psychotic disorders occurring during the course of parkinson’s disease
Dangers of clozapine
neutropenia
agranulocytosis
cardiomyopathy + myocarditis
seizures at high doses (above 600mg)
postural hypotension
significant weight gain
hypersalivation
drowsiness
constipation
diabetes
What monitoring should a pt have when on clozapine?
weekly bloods for 18 weeks
2 weely bloods for 34 weeks
monthly thereafter
cannot dispense without satisfactory bloods
What is the traffic light system for monitoring clozapine?
green = safe to dispense
amber = absolute neutrophil count 1.5-2, increase monitoring to twice weekly
red = neutrophil <1.5, stop clozapine
Management of neutropenia caused by clozapine
if well + no fever:
- stop clozapine
- monitor WBC until return to normal
- see dr if any signs of infection, fever or sore throat
- liaise with psychiatric team for alternative antipsychotic
- clozapine must not be restarted, even at lower doses
if unwell or has fever:
- stop clozapine
- admit
- infection screen - blood cultures, MSU, swabs, sputum, CXR
- start IV broad-spectrum abx before results back
- any other supportive management
What tools can be used to assess for side effects in patients on antipsychotics?
GASS - glasgow antipsychotic side effects scale
LUNSERS - liverpool university neuroleptics side effects rating scale
What health monitoring should be done for patients with schizophrenia?
annual physical health monitoring by GP
weight + BMI
waist circumference
heart rate, BP
lifestyle review - smoking, alcohol etc.
When is it appropriate to use high dose or combination of antipsychotics?
failure to respond to clozapine
failure to tolerate clozapine
patients refusing to try clozapine
clozapine partial response, as augmentation
during a switch from one antipsychotic to another
as a temporary measure during an acute exacerbation of illness
