antipsychotics + side effects

Question 1

why were 2nd gen (atypical) antipsychotics developed?

Answer 1

due to adverse side effects of 1st gen typical

atypical = 1st line

Question 2

examples of typical (1st gen) antipsychotics

Answer 2

haloperidol
chlorpromazine
prochlorperazine

Question 3

typical (1st gn) MoA

Answer 3

dopamine D2 receptor antagonists, blocking dopaminergic transmission in mesolimbic pathways

Question 4

adverse effects of typical (1st gen) antipsychotics

Answer 4

extrapyramidal side effects
hyperprolactinaemia - infertility, galactorrhoea

Question 5

examples of atypical (2nd gen) antipsychotics

Answer 5

clozapine
risperidone
olanzapine (higher risk of obesity)

Question 6

atypical (2nd gen) antipsychotics MoA

Answer 6

act on a variety of receptors (D2, D3, D4, 5-HT)

Question 7

adverse effects of atypical (2nd gen) antipsychotics

Answer 7

metabolic, weight gain
hyperprolactinaemia
agranulocytosis - clozapine

Question 8

clozapine

Answer 8

really good but can cause agranulocytosis
full blood count monitoring is essential during treatment
baseline ECD before starting treatment - myocarditis

BNF – should be introduced if schizophrenia not controlled despite the sequential use of 2 or more antipsychotic drugs, (one of which should be 2nd Gen), each for at least 6-8weeks

Question 9

side effects of clozapine

Answer 9

agranulocytosis - neutropenic sepsis
constipation > obstruction > sepsis
myocarditis
hypersalivation
weight gain (average = 10kg in 3 months)

Question 10

aripiprazole

Answer 10

3rd generation
- partial dopamine agonist
- more sparing of prolactin
- in high dopamine dampins it + in low bring it up

-> use if experiencing extrapyramidal + raised prolactin symptoms

Question 11

mesolimbic dopamine pathway

Answer 11

overactive in schizophrenia due to too much dopamine
causes positive symptoms

Question 12

mesocortical dopamine pathway

Answer 12

UNDERactive in schizophrenia due to reduced dopamine
causes negative symptoms

Question 13

affect of antipsychotics on tuberoinfundibular dopamine pathway

Answer 13

increases prolactin
- galactorrhoea, gynaecomastia, amenorrhoea
- sexual dysfunction, decreased libido
- osteoporosis, frality fractures

(prolactin release is inhibited by dopamine -> blockade of dopamine lead to increased prolactin release)

Question 14

effects of disruption to nigrostriatal dopamine pathway by antipsychotics

Answer 14

extrapyramidial SE
- acute dystonic reaction - involuntary movement of head/face
- parkinsonism - bradykinesia, resting tremor, shuffling gait
- tardive dyskinesia - involuntary movement of face/extremities
- akathisia (severe restlessness)

Question 15

acute dystonia

Answer 15

quick onset, sustained muscle contraction - torticollis (neck spasm to one side), oculogyric crisis (eye muscles all moving), tongue protrusion

Mx = procyclidine

Question 16

tardive dyskinesia

Answer 16

late onset of choreoathetoid movements, abnormal, involuntary, may be irreversible

commonest = chewing + pouting of chaw
- grimacing, lip smacking

Question 17

management of nigrostriatal side effects

Answer 17

decrease acetylcholine levels to restore balance with dopamine (dopamine reduced by antipsychotics)

• procyclidine - PO/IM
• change antipsychotic?

(nigrostriatal SE = extrapyramidal)

Question 18

affect of antipsychotics on hypothalmic region

Answer 18

neuroepileptic malignant syndrome

Question 19

neuroleptic malignant syndrome

Answer 19

increased tone “lead-pipe rigitidy”, pyrexia, changing pulse/BP > rhabdo > AKI > coma > die

medical emergency, rare
onset 24-72hrs
fatal in 20-30% if not treated

Question 20

neuroepileptic malignant syndrome investigation + management

Answer 20

creatine kinase

stop antipsychotic
rapid cooling, renal support
skeletal muscle relaxant - dantrolene
dopamine agonists - bromocriptine

Question 21

affect of antipsychotics on spinothalamic tracts

Answer 21

akathisia/restless legs
- unable to sit - pacing, poor sleep, cant stand still
- common
manifests within days/weeks
- linked to increase suicide risk

Question 22

management of akathisia as an antipsychotic SE

Answer 22

1st = propranolol
2nd = clonazepam (benzodiazepine so addictive)

Question 23

other SE of antipsychotics

Answer 23

anticholinergic effects - dry mouth, blurred vision
5-HT2 - weight gain -> T2DM
postural hypotension
hepatotoxicity
prolon QT interval - esp haloperidol
photosensitivity

in elderly - increased stroke + DVT

Question 24

most abundant dopamine receptor subtype

Answer 24

D1 (+D5)
- fairly widespread + also occur in pituitary gland
- stimulate cAMP

Question 25

dopamine receptor subtype more pharmalogically important in CNS

Answer 25

D2 family - D2, 3 +4

Question 26

what type of receptor are dopamine receptors?

Answer 26

G coupled

Question 27

amphetamine affect on brain

Answer 27

releases dopamine in brain

D2 receptor agonists can induce psychotic symptoms