antipsychotics + side effects Flashcards
why were 2nd gen (atypical) antipsychotics developed?
due to adverse side effects of 1st gen typical
atypical = 1st line
examples of typical (1st gen) antipsychotics
haloperidol
chlorpromazine
prochlorperazine
typical (1st gn) MoA
dopamine D2 receptor antagonists, blocking dopaminergic transmission in mesolimbic pathways
adverse effects of typical (1st gen) antipsychotics
extrapyramidal side effects
hyperprolactinaemia - infertility, galactorrhoea
examples of atypical (2nd gen) antipsychotics
clozapine
risperidone
olanzapine (higher risk of obesity)
atypical (2nd gen) antipsychotics MoA
act on a variety of receptors (D2, D3, D4, 5-HT)
adverse effects of atypical (2nd gen) antipsychotics
metabolic, weight gain
hyperprolactinaemia
agranulocytosis - clozapine
clozapine
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
side effects of clozapine
agranulocytosis - neutropenic sepsis
constipation > obstruction > sepsis
myocarditis
hypersalivation
weight gain (average = 10kg in 3 months)
aripiprazole
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
mesolimbic dopamine pathway
overactive in schizophrenia due to too much dopamine
causes positive symptoms
mesocortical dopamine pathway
UNDERactive in schizophrenia due to reduced dopamine
causes negative symptoms
affect of antipsychotics on tuberoinfundibular dopamine pathway
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)
effects of disruption to nigrostriatal dopamine pathway by antipsychotics
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)
acute dystonia
quick onset, sustained muscle contraction - torticollis (neck spasm to one side), oculogyric crisis (eye muscles all moving), tongue protrusion
Mx = procyclidine
tardive dyskinesia
late onset of choreoathetoid movements, abnormal, involuntary, may be irreversible
commonest = chewing + pouting of chaw
- grimacing, lip smacking
management of nigrostriatal side effects
decrease acetylcholine levels to restore balance with dopamine (dopamine reduced by antipsychotics)
- procyclidine - PO/IM
- change antipsychotic?
(nigrostriatal SE = extrapyramidal)
affect of antipsychotics on hypothalmic region
neuroepileptic malignant syndrome
neuroleptic malignant syndrome
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
neuroepileptic malignant syndrome investigation + management
creatine kinase
stop antipsychotic
rapid cooling, renal support
skeletal muscle relaxant - dantrolene
dopamine agonists - bromocriptine
affect of antipsychotics on spinothalamic tracts
akathisia/restless legs
- unable to sit - pacing, poor sleep, cant stand still
- common
manifests within days/weeks
- linked to increase suicide risk
management of akathisia as an antipsychotic SE
1st = propranolol
2nd = clonazepam (benzodiazepine so addictive)
other SE of antipsychotics
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
most abundant dopamine receptor subtype
D1 (+D5)
- fairly widespread + also occur in pituitary gland
- stimulate cAMP
dopamine receptor subtype more pharmalogically important in CNS
D2 family - D2, 3 +4
what type of receptor are dopamine receptors?
G coupled
amphetamine affect on brain
releases dopamine in brain
D2 receptor agonists can induce psychotic symptoms
