8 - Psychiatric Drugs (Antipsychotics, Anxiolytics, Hypnotics) Flashcards
What is the mechanism of action of first generation (typical) antipsychotics and name 5 examples?
D2 antagonists
Takes 4-6 weeks to work
- Chlorpromazine
- Haloperidol
- Prochlorperazine
- Flupentixol
How are antipsychotics stopped?
How does prescribing antipsychotics differ in the elderly?
Elderly prone to postural hypotension and if have dementia small risk of stroke when using antipsychotics
- Antipsychotic drugs should not be used in dementia, unless they are at risk of harming themselves or others, or experiencing agitation, hallucinations or delusions that are causing them severe distress.
- Lowest effective dose for shortest period of time
- Treatment should be reviewed at least every 6 weeks
What are some patient groups you have to be careful with when prescribing antipsychotics?
- Blood dyscrasias
- Parkinson’s disease (may be exacerbated)
- QT prolongation
- Breast cancer
- Cardiovascular disease
- Depressiom
- Epilepsy
- Diabetes
- History of jaundice
- Prostatic hypertrophy
- Severe respiratory disease
- Susceptibility to angle-closure glaucoma
What are the general side effects of all antipsychotics?
- Extrapyramidal symptoms (FGA)
- Weight gain
- Sedation
- QT prolongation
- Acute dystonia
- Hyperprolactinaemia (FGA and Risperidone) (Amenorrhoea, Galactorrhea)
- Sexual dysfunction
- Neuroleptic Malignant Syndrome
- Tachycardia, arrhythmias, hypotension
- Postural hypotension (usually SGA)
- Hyperglycaemia and Diabetes
What is some general life advice to give patients on antipsychotics?
- Sedation so be careful driving
- Effects of alcohol enhanced
- Photosensitivity so be careful in sun
What are some examples of extrapyramidal symptoms?
- Parkinsonian symptoms (including bradykinesia, tremor)
- Dystonia (uncontrolled muscle spasm in any part of the body), more common in young males
- Akathisia (restlessness), within hours to weeks of starting antipsychotic treatmen
- Tardive dyskinesia (abnormal involuntary movements of lips, tongue, face, and jaw), in some patients it can be irreversible.
Hyperprolatinaemia is common with antipsychotics as dopamine inhibits prolactin release. What are some symptoms of raised prolactin?
- Sexual dysfunction
- Reduced bone mineral density
- Menstrual disturbances
- Breast enlargement
- Galactorrhoea
- Increased risk of breast cancer
When are depot injections for antipsychotics used?
- Non-adherance
- Patient preference
Higher risk of EPSE when using first-generation antipsychotics. Zuclopenthixol may be most effect FGA in depot form
What are the pros and cons of depot injections for antipsychotics?
Pros
- Better adherance
- Less hospitalisations as less relapses
Cons
- Side effects last longer
- Pain at injection site
What are the side effects of FGA and SGA separately?
FGA
- Extrapyramidal side effects
- Weight gain
- Sedation
- Hyperprolactinaemia
SGA
- Weight gain
- Dyslipidaemia
- QT prolongation
- Hyperglycaemia
- Sexual dysfunction
- Anticholinergic effects
What are some examples of atypical (second-generation) antipsychotics and how do they work?
D2 antagonist and 5HT2A antagonist
Less likely to have EPSE but more likely to have metabolic SE
What is some general monitoring that needs to be done with antipsychotics?
(Focus on image)
Weight: at the start, then weekly for the 6 weeks, then at 12 weeks, at 1 year, and then yearly.
All patients should have yearly physical review!!!!
Fasting blood glucose, HbA1c, and blood lipid concentrations: baseline, 12 weeks, 1 year, and then yearly
Prolactin: baseline
ECG: before starting
Blood pressure: before starting, at 12 weeks, at 1 year and then yearly during treatment
FBC, U+Es, LFTs: at the start then yearly thereafter
Why are the following monitored when on antipsychotic treatment?
- FBC
- LFTs
- Lipids
- HbA1c
- BP
FBC: bone marrow suppression
LFTs: steatohepatitis/metabolic syndrome
Lipids: dyslipidaemia
HbA1c: diabetes and metabolic syndrome
BP: metabolic syndrome
What are the following for Haloperidol:
- Contraindications
- Side effects
- Monitoring
- Drug Interactions
It is less sedating but high risk for sexual dysfunction
Contraindications
Long QT syndrome, Dementia with Lewy bodies, Parkinson’s disease; Progressive supranuclear palsy, QTc-interval prolongation, Recent acute MI, uncorrected hypokalaemia
Side effects
EPSE, NMS, Long QT, Sexual Dysfunction, Orthostatic HTN Depression, eye disorders, headache, hypersalivation, nausea, neuromuscular dysfunction, weight loss
Monitoring
ECG baseline essential then the rest of tests like normal monitoring for antipsychotics e.g PRL, BP, FBC etc
Drug Interactions
Smoking may change dose needed
Anticholinergics, Lithium
What are the following for Chlorpromazine:
- Contraindications
- Side effects
- Monitoring
- Drug Interactions
Contraindications
Comatose, Hypothyroidism, Phaechromocytoma
Side effects
Acute dystonia, Long QT, NMS, Anxiety, glucose tolerance impaired, muscle tone increased
Monitoring
Same as normal but following IM injection should remain supine for 30 mins with regular BP monitoring
Drug Interactions
Parkinson’s meds, Long QT meds, Alcohol and Benzos could cause respiratory depression
What are some drugs that increase the QT interval?
Which antipsychotics have a lower risk of prolonged the QT interval?
Atypical Antipsychotics
- Aripiprazole
- Clozapine
- Olanzapine
- Flupentixol
- Risperidone
What are the following for Aripiprazole:
- Contraindications
- Side effects
- Monitoring
- Drug Interactions
Less likely to cause weight gain, diabetes, hyperprolactinaemia and long QT compared to other SGAs
Contraindications
Cerebrovascular disease, elderly, risk of aspiration pneumonia
Side effects
Anxiety, appetite increase/weight gain, diabetes, GI discomfort, headache, hypersalivation, nausea, vision disorders
Monitoring
Monitor serum concentrations if signs of toxicity or taking drugs that interfere with metabolism
BP monitoring not mandatory. Rest of normal check up to be done
Drug Interactions
Be careful with other sedatives as respiratory depression
What are the following for Olanzapine:
- Contraindications
- Side effects
- Monitoring
High risk of sexual dysfunction
Contraindications
Acute MI, bradycardia, recent heart surgery, severe hypotension, unstable angina
Side effects
Anticholinergic syndrome, Appetite increased/Weight gain, Hyperglycaemia, Glycosuria, Oedema, Sexual dysfunction
Monitoring
If depot monitor BP, pulse, RR for 3 hours post-injection
Blood lipids and weight should be measured at baseline, then every 3 months for a year then yearly with antipsychotic drugs
Fasting blood glucose tested at baseline, after 1 month, then every 4–6 months.
What are the following for Risperidone:
- Contraindications
- Side effects
- Monitoring
High risk of sexual dysfunction and hyperprolactinaemia
Contraindications
Cataract surgery (risk of intra-operative floppy iris syndrome), Dehydration, Dementia with Lewy bodies, prolactin-dependent tumours
Side effects
Headache, hypertension, joint disorders; laryngeal pain, muscle spasms, nasal congestion, nausea, oedema, oral disorders, pain, sexual dysfunction; skin reactions, weight loss
Monitoring
Same as normal antipsychotic monitoring
Which antipsychotics cause the most weight gain and sexual dysfunction?
Weight gain: Olanzapine, Clozapine
Sexual Dysfunction: Risperidone, Haloperiodol, Olanzapine
What are the following for Quetiapine:
- Contraindications
- Side effects
- Monitoring
High risk of hypotension but low chance of sexual dysfunction
Contraindications
Cerebrovascular disease, elderly, treatment of depression in patients under 25 years (suicide risk)
Side effects
Weight gain, dyspnoea, headache; irritability; palpitations, suicidal behaviour, syncope, vision blurred, withdrawal syndrome
Monitoring
Same as normal antipsychotic monitoring
What are the following for Clozapine:
- Contraindications
- Side effects
- Monitoring
Contraindications
Age over 60, Prostatic hypertrophy, Susceptibility to angle-closure glaucoma, taper off other antipsychotics before starting
Side effects
AGRANULOCYTOSIS, Cardiomyopathy, Myocarditis, Constipation/ Intestinal Obstruction, weight gain, postural hypotension, hyper salivation, urinary incontinence
Monitoring
FBC (WCC) weekly for 18 weeks, then fortnightly for up to one year, and then monthly as part of the clozapine patient monitoring service
Blood clozapine concentration should be monitored in certain clinical situations
Close medical supervision during initiation (risk of collapse because of hypotension and convulsions).
Blood lipids and weight: every 3 months for the first year, then yearly.
Fasting blood glucose: baseline, after 1 month, then every 4–6 months
How can you treat hypersalivation with Clozapine treatment?
Hyoscine Hydrobromide
How are the following serious complications of clozapine treatment avoided/monitored?
- Agranulocytosis (Neutropenia)
- Cardiomyopathy
- Intestinal Obstruction
Agranulocytosis
- If leucocyte count below 3000 /mm3 or if absolute neutrophil count below 1500 /mm3 discontinue permanently
- Avoid drugs which depress leucopoiesis
- Patients should report immediately symptoms of infection, especially influenza-like illness.
Myocarditis and cardiomyopathy
- Perform physical examination and take full medical history before starting
- Persistent tachycardia especially in first 2 months should prompt observation for other indicators for myocarditis or cardiomyopathy
- Discontinue permanently in clozapine-induced myocarditis or cardiomyopathy
Intestinal obstruction
- Clozapine should be used with caution in patients receiving drugs that may cause constipation (e.g. antimuscarinic drugs) or in those with a history of colonic disease or lower abdominal surgery
- Recognise and treat constipation promptly
If SSRIs are not working for OCD, what can be used instead?
Clomipramine (TCA)
Need to warn they can be sedating unlike SSRIs so be careful driving
Why is Aripiprazole’s MOA different to other SGAs?
Partial D2 agonist not antagonist!!!
Good tolerability
What are the dopamine target pathways in antipsychotics?
Targets: Mesocortical and Mesolimbic
Unwanted SEs: Nigrostriatal and Tuberoinfundibular (HPA axis)
How can EPSEs be managed with FGA?
Procyclidine
EPSEs due to ratio of dopamine:acetylcholine so reduce quantities of Ach with above
May exacerbate tardive dyskinesia
Why is Clozapine dose slowly upped over 2 weeks when starting?
Risk of autonomic dysregulation when first starting
What are some classes of drugs used as anxiolytics?
- B-Blockers
- Benzodiazepines
- Pregablin
- Antidepressants (SSRIs - high dose in OCD)
How do B-Blockers work as an anxiolytic, what is an example, what are the contraindications and what are the side effects?
Propanolol: B-blocker, decreases ANS activation so less physical autonomic symptoms, does not treat psychological symptoms
CI: asthma, enduring anxiety
Side effects: hypotension, bradycardia, nausea, tired
How do Benzodiazepines work as an anxiolytic, what are some examples, what are the contraindications and what are the side effects?
- Bind to GABA receptors to potentiate the effect of GABA so reduce excitability of neurones. Useful for acute anxiety, only use for 2-4 weeks max
- Examples: Diazepam, Lorazepam
- CI: substance misuse history, COPD
- Side effects: dependence, paradoxical disinhibition (at low doses), sedation, confusion, respiratory depression
How does Pregablin work as an anxiolytic, what are the contraindications and what are the side effects?
- Binds to VGCC to reduce neuronal activity
- Used for anxiety, neuropathic pain, epilepsy
- Not addictive
- CI: hypersensitivity to drug, previous substance misuse
- SE: sedation, weight gain, sexual dysfunction
How are antidepressants used as anxiolytics?
Same as for depression but higher doses and stay on for 1 year instead of 6 months
What is the difference between hypnotics and anxiolytics?
Anxiolytics (‘sedatives’) will induce sleep when given at night and most hypnotics will sedate when given during the day
When can a benzodiazepine be used for insomnia?
When it is severe, disabling, or causing the patient extreme distress
2-4 weeks max
What are the symptoms of Benzodiazepine Withdrawal Syndrome and how can you withdraw someone from Benzos?
Symptoms: insomnia, anxiety, loss of appetite and weight, tremor, perspiration, tinnitus, and perceptual disturbance
Withdrawal: Short term users can be tapered off in 2-4 weeks, Long term users over a few months
How long does it take for Benzodiazepine withdrawal syndrome to occur?
Short acting (Lorazepam): One day
Long acting (Diazepam): 3 weeks
What are some examples of hypnotics?
- Benzodiazepines: Temazepam, Lormatazepam, Nitrazepam
- Non-Benzos (Z-Drugs): Zopiclone, Zolpidem
Z drugs still act on benzodiazepine receptor
What are some questions that need to be asked before prescribing a hypnotic?
- Find out cause of insomnia
- Address factors e.g unrealistic sleep expectations, alcohol consumption
Causes
Transient insomnia: normally sleep well and may be due to extraneous factors such as noise, shift work, and jet lag. Only give 1 or 2 doses
Short-term insomnia: emotional problem or serious medical illness, may last for a few weeks and may recur; a hypnotic can be useful but should not be given for more than three weeks
Chronic insomnia is rarely benefited by hypnotics and is sometimes due to mild dependence caused by injudicious prescribing of hypnotics
What is the issue of prescribing hypnotics for insomnia?
- Rebound insomnia with vivid dreams for several weeks
- Withdrawal symptoms
Should you prescribe hypnotics in the elderly?
No as greater risk of ataxia, confusion and falls
What patients are at risk of dependence when taking benzodiazepines?
- History of drug or alcohol abuse
- Personality disorder
What are some medications used for ADHD?
Work by increasing activity in the brain in the areas responsible for controlling attention and behaviour
- methylphenidate
- lisdexamfetamine
- dexamfetamine
- atomoxetine
- guanfacine
What is the mechanism of action of Methylphenidate for ADHD and what are contraindications to this?
Non-competitively blocks the reuptake of dopamine and noradrenaline into the terminal by blocking dopamine transporter (DAT) and noradrenaline transporter (NAT) increasing levels of dopamine and noradrenaline in the synaptic cleft
What are the side effects of Methylphenidate?
Non-competitively blocks the reuptake of dopamine and noradrenaline into the terminal by blocking dopamine transporter (DAT) and noradrenaline transporter (NAT) increasing levels of dopamine and noradrenaline in the synaptic cleft
Side effects
- a small increase in blood pressure and heart rate
- loss of appetite, which can lead to weight loss or poor weight gain
- insomnia
- headaches
- stomach aches
- feeling aggressive, irritable, depressed, anxious or tense
- dependance
What drugs may interact with Methylphenidate?
What monitoring needs to be done whilst on Methylphenidate?
Start: Pulse, BP, psychiatric symptoms, appetite, weight and height
Every 6 months: Pulse, BP, psychiatric symptoms, appetite, weight and height
Also monitor for development of tics
When is Atomoxetine favoured over Methylphenidate for ADHD?
History of dependence
Methylphenidate has potential for dependence
What is the mechanism of action of Atomoxetine and what are some of the side effects?
SNRI/NoRI so not addictive
Side effects:
- Suicidal thoughts
- Sexual dysfunction
- Liver impairment
- Small increase in blood pressure and heart rate
- Nausea and vomiting
- Stomach aches
- Trouble sleeping
What monitoring needs to be done whilst on Atomoxetine?
Start: Pulse, BP, psychiatric symptoms, appetite, weight and height
Every 6 months: Pulse, BP, psychiatric symptoms, appetite, weight and height
Also monitor for development of tics, depression, anxiety, suicidal thoughts!!
What are the two main things you need to warn parents of when starting ADHD medication?
- Suicidal thoughts
- Hepatic Impairment
Which ADHD medication are tics more common in?
Stimulants
