Psychopharmacology Flashcards
Explain antipsychotics
- First generation antipsychotics: FGAs (‘Typical antipsychotics’)
- Chlorpromazine, haloperidol, flupentixol, zuclopenthixol, sulpiride
- Second generation antipsychotics: SGAs (‘Atypical antipsychotics’)
- Olanzapine, quetiapine, risperidone, paliperidone, clozapine, aripiprazole, lurasidone, amisulpride
- Depot antipsychotics (Long Acting Injectable, LAI)
- Aripiprazole, flupentixol, zuclopenthixol, risperidone, paliperidone, olanzapine, haloperidol
- Note: not all antipsychotics are available as a depot formulation
- Aripiprazole, flupentixol, zuclopenthixol, risperidone, paliperidone, olanzapine, haloperidol
Explain antipsychotics MOA
What pathways do antipsychotics work on?
- Nigrostriatal (fine tuning)
- Mesolimbic → antipsychotic effect (EMOTION)
- Mesocortical → antipsychotic effect (personality???)
- Tuberoinfundibular system
Explain the MOA of 1st generation antipsychotics and their efficacy
- Therapeutic effect due to D2 receptor blockade in the meso-limbic and meso-cortical dopamine pathways
- Trials suggest that efficacy of FGAs is equivalent to that of SGAs
- Clozapine is the only antipsychotic to have demonstrated superior efficacy over other antipsychotics
- Side-effects can be problematic and can lead to poor adherence
What are the side effects of 1st generation antipsychotics?
- Blockade of D2 receptors in nigro-striatal area can cause extrapyramidal side effects
- Length of time to onset
- Within hours to days
- Acute dystonia (including oculogyric crisis)
- Akathisia
- Medium term
- Parkinsonism
- Long term
- Tardive dyskinesia
- Within hours to days
Manage acute dystonia and parkinsonism with Procyclidine (anticholinergic agent)
MORE
- D2 receptor antagonism at the tubero-infundibular pathway = hyperprolactinaemia
- Increase in prolactin levels (dopamine is inhibitory of prolactin release)
- Amenorrhoea, gynaecomastia, galactorrhoea, sexual dysfunction.
- Increase in prolactin levels (dopamine is inhibitory of prolactin release)
- Long term effects (regardless of the presence of symptoms) include a reduction in bone mineral density and an increase risk of breast cancer.
- Muscarinic effects
- Constipation, dry mouth, blurred vision, cognitive impairment
- Histaminergic effects
- Sedation
How to 2nd generation antipsychotics works and their efficacy
- Efficacy arising from D2 and 5HT2A receptor antagonism
- Wide spectrum of activity across a range of neurotransmitter receptor sites
What are the side effects of 2nd generation antipsychotics?
- Metabolic side-effects
- Weight gain
- Impaired glucose tolerance
- Dyslipidaemia
- Less likely to cause extrapyramidal side-effects than FGAs
- Aripiprazole and Lurasidone have less metabolic effects and arguably the best side-effect profile of any antipsychotics
Explain clozapine and the side effects and monitoring
- Licensed for ‘treatment-resistant schizophrenia’ as well as psychosis in Parkinson’s disease
- Side-effects:
- Profound sedation
- Hypersalivation
- Hypo/hypertension
- Fever
- Seizures
- Weight gain
- Myocarditis/Cardiomyopathy
- Neutropenia/agranulocytosis (1/10,000 mortality in the UK)
- Constipation
- Clozapine monitoring service – require regular FBC results for continuation of dispensing. Plasma level monitoring can guide dosing.
- Plasma level is affected by gender and tobacco smoking
Antipsychotics and ECG
- QTc prolongation may present as flutter, collapse or death
- Risk is compounded by additional meds that prolong the QT interval
- Antipsychotics
- Some antidepressants
- Antihistamines
- Lithium
- Methadone
- Erythromycin
- Grapefruit and liquorice consumption
- The risk between individual antipsychotics varies greatly – some have ‘no effect’ on the QT interval, some can prolong it by >20ms at therapeutic doses.
Explain neuroleptic malignant syndrome (NMS) (symptoms, blood tests, risk factors)
It is related to the level of dopamine blockade
Monitoring in antipsychotic medications
Baseline:
- Physical history, family history and examination
- Blood pressure and pulse
- Weight, height, BMI
- Bloods: fasting glucose/ HbA1C / fasting lipids / LFT / U&E / Prolactin
- ECG
Regularly monitoring is required thereafter with a full screen every 12 months as a minimum
Explain antidepressants
- First line:
- Selective serotonin reuptake inhibitors (SSRIs) (sertraline, fluoxetine, citalopram…)
- Other groups SNRIs, NASSAs…
- Tricyclics (TCAs) (Imipramine, clomipramine)
- Monoamine oxidase inhibitors (MAOIs) (Phenelzine or moclobemide)
NICE recommends an SSRI as first line option, no clear rationale for antidepressant choice thereafter but consider combined side effects, drug interactions, co-morbidities and risk of overdose.
List classes and examples of antidepressants
- TCAs: Lofepramine, Clomipramine, Amitriptyline, Imipramine
- SSRIs: Fluoxetine, Citalopram, Escitalopram, Sertraline, Paroxetine
- MAOIs: Phenelzine, Moclobemide
- SNRIs: Venlafaxine, Duloxetine
- NaSSAs: Mirtazapine
- NDRIs: Bupropion
- SARIs: Trazodone
- NARIs: Reboxetine
- Miscellaneous (e.g. Agomelatine, Vortioxetine, ECT, TMS, VNS, DBS)
What are the side effects of tricyclic antidepressants
- Histamine
- Sedation
- Muscarinic
- Dry mouth
- Constipation
- Blurred vision
- α-adrenoceptor
- Postural hypotension
What are the side effects of SSRIs?
- Very common (>10% incidence, the highest frequency category)
- Nausea
- Diarrhoea
- Headache
- Dry mouth
- Sexual Dysfunction (~60% incidence)
- All phases of sexual response (most common decreased libido & delayed orgasm)