Psychopharmacology of psychosis

Question 1

What is the aim of treatment in schizophrenia? (biochemically)

Answer 1

reduce dopamine over-activity

Question 2

What are the 4 main neuronal pathways that use dopamine?

Answer 2

mesolimbic - emotions, behaviour
mesocortical - learning, memory
nigrostriatal - voluntary movement (extrapyramidal side effects related to this)
tuberoinfundibular - prolactin regulation

Question 3

What does the dopamine hypothesis of schizophrenia state?

Answer 3

states that the symptoms of schizophrenia are due to a hyperdopaminergic state in the mesolimbic system

Question 4

Another name for typical antipsychotics?

Answer 4

first generation antipsychotics

Question 5

Another name for atypical antipsychotics?

Answer 5

second generation antipsychotics

Question 6

Name some first generation antipsychotics

Answer 6

phenothiazines:
- chlorpromazine, levomepromazine, promazine, pericyazine, trifluoperazine, fluphenazine

butyrophenones:
- haloperidol, benperidol

thioxanthenes:
- flupentixol, zuclopenthixol

diphenylbutylpiperidines:
- pimozide, fluspirilene

substituted benzamides:
- sulpiride, amisulpride

Question 7

Name some second generation antipsychotics

Answer 7

risperidone
quetiapine
aripiprazole
olanzapine
clozapine
paliperidone
zotepine

Question 8

Describe how first generation antipsychotics work

Answer 8

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)

Question 9

Describe how second generation antipschotics work

Answer 9

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

Question 10

What can be done for patients with poor adherence to antipsychotics?

Answer 10

depot injections

Question 11

What antipsychotics are available as depot injections?

Answer 11

haloperidol
flupentixol
zuclopenthixol
risperidone
paliperidone
aripiprazole
olanzapine

Question 12

Side effects of antipsychotics

Answer 12

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

Question 13

How can hypersalivation due to antipsychotics be treated?

Answer 13

hyoscine hydrobromide 300mcg sucked at night

Question 14

How can constipation due to antipsychotics be treated?

Answer 14

osmotic or stimulant laxatives

Question 15

How can tachycardia due to antipsychotics be treated?

Answer 15

persistent benign tachycardia may be treated with cardio-selective beta-blockers

Question 16

What extrapyramidal side effects can occur with antipsychotics and how can these be managed?

Answer 16

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

Question 17

What causes extrapyramidal side effects when on antipsychotics?

Answer 17

D2 antagonism in striatum

Question 18

What causes hyperprolactinaemia when on antipsychotics?

Answer 18

D2 antagonism in tuberoinfundibular results in increased prolactin secretion

Question 19

Short term effects of hyperprolactinaemia

Answer 19

menstrual disturbance
gynaecomastia
galactorrhoea
sexual dysfunction
infertility

Question 20

Long term effects of hyperprolactinaemia

Answer 20

reduced bone mineral density - osteoporosis
cancer
cardiovascular disease

Question 21

What cardiovascular side effects can occur when on antipsychotics?

Answer 21

hypotention
tachycardia
myocarditis + cardiomyopathy
prolonged QT interval

Question 22

What antipsychotics have a high, medium and low risk of weight gain?

Answer 22

high = clozapine, olanzapine
medium = chlorpromazine, quetiapine, risperidone
low = amisulpride, aripiprazole, haloperidol, sulpiride, trifluoperazine, ziprasidone

Question 23

Which antipsychotics are reported to cause glucose intolerance and potentially diabetes?

Answer 23

phenothiazines
haloperidol
clozapine
olanzapine
quetiapine
risperidone

Question 24

What is neuroleptic malignant syndrome?

Answer 24

idiosyncratic dose-dependent adverse drug reaction
sudden loss of control of body temperature

Question 25

Main symptoms of neuroleptic malignant syndrome

Answer 25

hyperthermia
fever
muscular rigidity
confusion
tremor
fluctuating consciousness
tachycardia
fluctuating BP

Question 26

Risk factors for neuroleptic malignant syndrome

Answer 26

high potency antipsychotics (including depot)
recent rapid dose increase
rapid dose reduction
abrupt withdrawal of anticholinergics

Question 27

Management for neuroleptic malignant syndrome

Answer 27

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

Question 28

When is clozapine indicated?

Answer 28

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

Question 29

Dangers of clozapine

Answer 29

neutropenia
agranulocytosis
cardiomyopathy + myocarditis
seizures at high doses (above 600mg)
postural hypotension
significant weight gain
hypersalivation
drowsiness
constipation
diabetes

Question 30

What monitoring should a pt have when on clozapine?

Answer 30

weekly bloods for 18 weeks
2 weely bloods for 34 weeks
monthly thereafter
cannot dispense without satisfactory bloods

Question 31

What is the traffic light system for monitoring clozapine?

Answer 31

green = safe to dispense
amber = absolute neutrophil count 1.5-2, increase monitoring to twice weekly
red = neutrophil <1.5, stop clozapine

Question 32

Management of neutropenia caused by clozapine

Answer 32

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

Question 33

What tools can be used to assess for side effects in patients on antipsychotics?

Answer 33

GASS - glasgow antipsychotic side effects scale
LUNSERS - liverpool university neuroleptics side effects rating scale

Question 34

What health monitoring should be done for patients with schizophrenia?

Answer 34

annual physical health monitoring by GP
weight + BMI
waist circumference
heart rate, BP
lifestyle review - smoking, alcohol etc.

Question 35

When is it appropriate to use high dose or combination of antipsychotics?

Answer 35

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