Psychopharmacology Flashcards by Tommy Mackie

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

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Explain antipsychotics MOA

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What pathways do antipsychotics work on?

Nigrostriatal (fine tuning)
Mesolimbic → antipsychotic effect (EMOTION)
Mesocortical → antipsychotic effect (personality???)
Tuberoinfundibular system

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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

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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

Manage acute dystonia and parkinsonism with Procyclidine (anticholinergic agent)

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D2 receptor antagonism at the tubero-infundibular pathway = hyperprolactinaemia
- Increase in prolactin levels (dopamine is inhibitory of prolactin release)
  - Amenorrhoea, gynaecomastia, galactorrhoea, sexual dysfunction.
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

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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

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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

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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

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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.

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Explain neuroleptic malignant syndrome (NMS) (symptoms, blood tests, risk factors)

It is related to the level of dopamine blockade

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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

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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.

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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)

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What are the side effects of tricyclic antidepressants

Histamine
- Sedation
Muscarinic
- Dry mouth
- Constipation
- Blurred vision
α-adrenoceptor
- Postural hypotension

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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)

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What is a red flag that SSRIs can cause and explain who is at risk and symptoms

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3 things

HYPONATRAEMIA

Not dose related
Usually presents within 30 days of initiation with the following symptoms:
- Headache, nausea, vomiting, cramps, lethargy, confusion
- Seizures, coma
High risk groups
- Elderly
- Female
- Low body weight
- Hx of hyponatraemia
- Low baseline sodium
- Concomitant drugs which also cause hyponatraemia:
  - Thiazide diuretics, NSAIDs, carbamazepine
- Reduced renal function
- Medical comorbidities (hypothyroidism, diabetes, COPD, CVA, cancers)
- Warm weather

INCREASED BLEEDING RISK

Serotonin is released from platelets in response to injury →vasoconstriction and platelet aggregation.
- SSRIs inhibit this process.
SSRI use associated with increased risk of
- Upper GI bleed (significant risk)
- Lower GI & uterine bleed.
- Blood loss in surgery.
Caution
- If patients also take an NSAID, warfarin or steroids
- Peptic ulcer
- Very old age
- History of GI bleed
- Haemostatic defects e.g. cirrhosis

SUICIDALITY

Antidepressant treatment linked with an increased risk of suicidal thoughts and acts during the first few weeks of treatment, particularly those <30 y/o
All antidepressants implicated
Absolute risk is very small
Most effective way to prevent acts is to treat depression
Toxicity in overdose
Important counselling point – highlight this risk to the patients. Ask them to contact services if their feelings become unbearable

Findings in a patient with moderately severe serotonin syndrome

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Explain antidepressant withdrawal

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NICE guidelines suggest that for some, withdrawal symptoms can be mild and resolve relatively quickly without the need for any help. Other people can have more severe symptoms which last much longer (sometimes months or more)
Withdrawal symptoms include:
- Fluctuating anxiety levels
- Insomnia, agitation, low mood, anger, suicidal ideation
- Lability of mood
- Loss of co-ordination, dizziness
- Electric-shock like sensation, sometimes described as “brain zaps”. Particularly common in SSRI withdrawal
- Derealisation
- Akathisia

How long should an antidepressant be prescribed for?

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Treat a single episode of depression until symptoms resolve
Maintain treatment for 6-9 months after remission of symptoms to reduce the risk of relapse
Increase the length if multiple previous episodes of depression (up to 2 years if there’s a history of significant functional impairment as a result of depression)

What should be mentioned in counselling for antidepressants?

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Relief of symptoms is a gradual process and is usually extended when antidepressants are used in the management of anxiety disorders (up to 12-16 weeks for full benefits to be shown)
- Do not expect an instant effect
Discuss side-effects
Drug interactions
Discuss the importance of good compliance and the need to maintain treatment even after symptoms resolve
Antidepressants are not addictive but can cause withdrawal effects, particularly if they are stopped suddenly – reiterate the importance of not suddenly discontinuing medications unless this has been authorised and discussed with a prescriber

How to manage generalised anxiety disorder?

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Generalised anxiety disorder: offer an SSRI first line. Consider sertraline due to it being the most cost-effective option (note that this is an off-label use)
- Consider an alternative SSRI or an SNRI if ineffective
- Consider pregabalin is SSRI/SNRIs aren’t tolerated

How to manage social anxiety disorder?

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Social anxiety disorder: SSRI (sertraline or escitalopram) recommended first line.

How to manage PTSD?

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PTSD:

Avoid chronic use of benzodiazepines. Consider venlafaxine (SNRI) or an SSRI if the person has a preference for drug treatment. Consider antipsychotics (i.e. risperidone) if there are disabling symptoms and behaviours e.g. hyperarousal or psychotic symptoms and if symptoms have not responded to other drugs.

How to manage OCD and BDD?

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OCD & BDD:

Offer an SSRI if the disease is associated with functional impairment. NICE recommends either fluoxetine, fluvoxamine, paroxetine, sertraline or citalopram.

What drink contained lithium (mood stabiliser)?

7UP

Lithium (class of drug, MOA, licenced indications)

Explain the monitoring of lithium

* Narrow therapeutic index * Plasma levels should be taken 12 hours after the last dose, just before a further dose (if BD dosing) – known as a “trough” level * Minimum effective range for prophylaxis = 0.4 mmol/L * Optimal range between 0.6-1.0 mmol/L * Toxicity occurs at levels \> 1.2 mmol/L * Serious risk of harm \>1.5 mmol/L (necessitates immediate action) They have a purple lithium book which is a comprehensive guide to lithium treatment

What are the side effects of lithium?

* GI disturbances * Tremor (increasing intensity as dose/plasma level increases) * Weight gain * Polyuria and polydipsia * Reduction in kidney function * Hypothyroidism * Hyperparathyroidism * Teratogenic

What are the drug interactions of lithium?

* Serious interaction when used with ACE inhibitors, thiazide diuretics and NSAIDs * Can result in a 4x increase in plasma levels. Avoid concurrent use * Caution when using amiodarone, angiotensin 2 receptor antagonists, anti-epileptics (carbamazepine, phenytoin and topiramate), calcium channel blockers to name a few * Fluid intake and sodium balance – important counselling points. Patients should be told to maintain an adequate and regular intake of water as well as being told to avoid variations in sodium intake * Both can have a profound effect on lithium plasma levels * The body is unable to differentiate between sodium and lithium

Explain benzodiazepines

* Short half-life agents are known as hypnotics (medications that cause sedation) * Longer acting drugs are anxiolytics * Short term use is recommended due to the potential for tolerance and dependence (max 4 weeks – BNF) * Withdrawal symptoms can occur on cessation following 4-6 weeks of regular use * To withdraw, convert to diazepam (extended half-life) and reduce gradually

Explain rapid tranquillisation

* Should only be used when all other interventions of calming a patient and managing the acute disturbance have been tried and failed or have not been possible * Commonly used drugs include IM lorazepam, promethazine or haloperidol•IM aripiprazole or olanzapine can also be used (licensed but not within NICE guidelines) * Ensure that IM olanzapine and IM lorazepam are not given within an hour of each other due to the risk of cardiorespiratory depression, excessive sedation, hypotension and very rarely, death

Explain ECT (indications, contradictions, cautions)

Electroconvulsive therapy * Indications: Severe depression, Severe mania, Catatonia * Contraindications: Relatively few (? SOL); Those of GA * Caution: MI, cardiac surgery, valvular disease, AAA Most commonly used for depression. It is also used to treat catatonia * ECT can help symptoms of schizophrenia which have not improved with medication, but the long-term benefits are not known so it is not often used * Indicated if the condition is life-threatening, severe and likely to get worse Good option where rapid improvement is needed * For use where there has been a poor response to other treatments i.e. medication and/or psychological therapy

What are the side effects of ECT?

* Short-term side effects * Headache * Aching in the muscles and/or jaw * Tiredness while the effects of the anaesthetic wear off * Confusion, particularly if you are elderly. This usually wears off after 30 minutes * Sickness or nausea * 40% of patients can have temporary memory problems while they are having ECT * ~2% of people complain of severe memory problems directly after ECT * A small number of patients report gaps in their memory about events in their life that happened before they had ECT * Some patients feel that they have suffered brain damage following a course of ECT and that have suffered long-term and life-changing side effects * Some people also experience a change in their personality or lack of emotions * It is difficult to separate out the effects of ECT from the effects of the illnesses it is treating

Why do people use ECT?

* Evidence based * RCTs, Systemic reviews * Good tolerability * Improved safety of anaesthesia, muscle relaxants, monitoring * Technologically refined * Lower voltage, brief pulse current * Effective * In severe depression, mania, catatonia (**a group of symptoms that usually involve a lack of movement and communication, and also can include agitation, confusion, and restlessness)**

What is neuro-modulation? & other treatments

the alteration of nerve activity through targeted delivery of a stimulus, such as electrical neurostimulation or chemical agents ***_OTHER TREATMENTS_*** * Transcranial magnetic stimulation * Esketamine * Psychedelics

Psychopharmacology Flashcards

(35 cards)