Antipsychotic

Question 1

antipsychotics (overview)

Answer 1

neuroleptics/major tranquilisers
used for psychosis and delirium

high levels of dopamine in the brain lead to symptoms of psychosis. antipsychotics inhibit dopamine in the brain

they can effect the following pathways:
Nigrostriatal Pathway- Movement & motor function (EPSEs when blocked)
Mesolimbic Pathway- pleasurable feelings/positive symptoms of psychosis
Mesocortical Pathway- cognitive and affective symptoms of psychosis
Tuberoinfundibular Pathway - control prolactin secretion

two types- typical (first gen) and atypical (second gen- usually have fewer motor side effects)

Question 2

examples of typical antipsychotics

Answer 2

*first generation
chlorpromazine
haloperidol
fluphenazine
clopenthixol

Question 3

examples of atypical antipsychotics

Answer 3

*second generation
clozapine
risperidone
sertindole
olanzapine

Question 4

4 important qualities of antipsychotics

Answer 4

1. sedation
2. anticholinergic activity
3. extrapyramidal activity
4. hypotensive effects

Question 5

MOA of antipsychotics

Answer 5

blockade of dopamine receptors (and also other neurotransmitters e.g. histamine, acetylcholine, 5HT serotonin)

there are 5 dopamine receptors, antipsychotics mainly block D2

blockade of the mesolimbic and mesocortiyal regions are responsible for the antipyshcoitc effects. blockade of the nigrostriatal pathway cause the motor side effects.

initially, dopaminergic neuronal activity increases but over time (3 weeks) it decreases.

can cause unwanted extrapyramidal side effects

Question 6

clinical effects of antipsyhcotics

Answer 6

depresses emotional responses
sedation
antiemetics effect (vomiting CTZ)
antihistamine effect (allergies)

Question 7

unwanted/adverse effects of antipsychotics

Answer 7

akathisia (restlessness)
acute dystonia (bizarre and unwanted muscle movements e.g. tongue protrusion)
Parkinsonism (tremor, rigidity, bradykinesia)
tradive dyskinesia

weight gain 
drowsiness and cognitive impairment
insomnia and agitation
galactorrhea
antimuscarinic effect
postural hypotension
seizure
hypothermia
hypersenstivity
photosensitvity
agranulocytosis* (clozapine)
prolonged QT
neuroleptic malignant synrome

Question 8

NMS (neuroleptic malignant syndrome)

Answer 8

Rigidity
Delirium
Fluctuating bp
Tachycardia
Sweating
Extrapyramidal side effects (EPSE’s)
Bloods: creatinine kinase – very high!

rare and a medical emegency
treat by stopping the drug, ice packs, circulatory and ventilator support, benzodiazpeines to control agitations.

Question 9

typical antipsychotics

examples + side effects

Answer 9

Examples include Haloperidol, Chlorpromazine and Zuclopenthixol

More commonly associated with sedation and motor disturbances

Acute dystonia (Oculogyric Crisis, Torticollis)
Occurs within hours to days

Extra pyramidal side effects (EPSEs)
Onset within days to weeks
Parkinsonian clinical picture

Tardive dyskinesia
Can occur at any point, but typically months to years. Choreoathetoid movements usually within the head, face or neck.

Question 10

atypical antipsychotics

examples + side effects

Answer 10

Examples include Olanzapine, Risperidone and Aripiprazole

More selective therefore different side effect profile

Weight gain
Impaired glucose tolerance
Hyperlipidaemia
Constipation
Dry mouth (hypersalivation in clozapine)
Agranulocytosis (Particularly clozapine)
QTc prolongation
Hyperprolactinaemia (can lead to galactorrhoea, sexual dysfunction)

***important to check FBC if suspicious of agranulocytosis (sore throat, fever, flu like symptoms)