Psychiatric Drugs Tutorial Flashcards
What are the common Adrenergic/Noradrenergic side effects ?
Sweating
Tremor
Headaches
Nausea
Dizziness
What are the common Muscarinic side effects ?
Dry mouth, difficulty swallowing, thirst
Difficulty urinating, urinary retention
Hot and flushed skin
Dry skin
What are the common histamine side effects ?
Dry mouth
Drowsiness
Dizziness
Nausea and vomiting
How do antidepressants work?
Most work on serotonin activity and aim to increase activity at post synaptic receptors
Most have most of their effect in two to three weeks
Types include:
SSRIs, SNRIs, Mirtazapine, Tricyclics, MAOIs
How do SSRIs work?
Increase serotonin activity by reducing the presynaptic reuptake of serotonin after release
= more serotonin sits in the synapse
Leads to a down regulation of post-synaptic receptors
Side effects of SSRIs?
Sense of restlessness, agitation on initiation (countered by judicious use of benzodiazepines)
Nausea, GI disturbance
Headache
Weight changes
Sexual dysfunction - tends to be more enduring
Less common – bleeding and suicidal ideation (age related)
Give 4 common SSRIs and the key things to look out for when prescribing them
Sertraline (50 to 200mgs) – safest in cardiac disease, useful because incidence of depression is higher in people post-MI than with other admissions
Citalopram (20 to 40mgs)/Escitalopram (10 – 20mgs) – watch out for QTc prolongation
Fluoxetine (20 to 60mgs) – watch out for serotonin syndrome when switching
Paroxetine (20 to 60mgs) – watch out for discontinuation syndrome
What is the value at which the QTc is prolonged?
450 msec for men and 470 msec for women
How do SNRIs work? Common side effects?
Act in the same way as SSRI’s but bind to noradrenaline reuptake receptors as well.
evidence base for use in neuropathic pain
Side effects similar to SSRIs but greater potential for sedation, nausea and sexual dysfunction
Give 2 SNRIs and their dose
Duloxetine (60 to 120mgs): low dose range
Venlafaxine (75 to 375mgs): greater efficacy and can go to a higher dose
Caution with higher doses in heart disease – monitor blood pressure at doses above 225mgs.
Why might suicidal ideation go up when starting antidepressant treatment?
Energy levels and motivation may improve before other symptoms
May be more likely to act on existing suicidal thoughts
How does Mirtazipine work?
Unique class : acts as a 5HT-2 and 5HT-3 antagonist
Strong H1 (histamine) activity – hence sedation
Major side-effects are sedation and weight gain which can be used to therapeutic advantage
Indications for tricyclic antidepressants? Key side effects?
useful for those who do not respond to SSRI’s, also used at low doses for neuropathic pain
Newer tricyclics (such as lofepramine and and nortriptyline) tolerated better than older tricyclics (amitriptyline)
All tricyclics have the potential to cause muscarinic and histaminic side effects
Can be fatal in overdose – cause QTc prolongation and arrhythmias
What are the different categories of monoamine oxidase B inhibitors?
MAOI – A (work more on serotonin) and MAOI – B (work more on dopamine) - all can potentially increase adrenaline
Irreversible – more dangerous: Phenelzine; Isocarboxazid
Reversible – less dangerous: Moclobamide; Tranylcypromine
Key things to know about MAOIs?
Potential for significant and dangerous interaction with other drugs
Potential for tyramine reaction leading to hypertensive crisis – avoid cheese, pickled meats, wine and other tyramine products
If changing to another antidepressant need a washout period (up to 6 weeks)
What should you consider when deciding which antidepressant to prescribe?
What has been used before?
Was it effective and/or tolerated?
Are there particular symptoms or comorbidities you may want to address?
* Weight loss
* Insomnia
* Neuropathic pain
What antidepressants are generally prescribed to someone on first presentation?
In new cases with no previous treatment start with an SSRI unless:
there is major weight loss or major sleep difficulty, in which case consider Mirtazapine OR comorbid neuropathic pain, in which case consider an SNRI
In most cases start with an SSRI (usually sertraline), if no effect switch to a different SSRI, if no effect switch to SNRI, Venlafaxine or Mirtazapine
How do you decide whether to increase the dose of an antidepressant or switch the drug?
For depression: if an antidepressant has absolutely no benefit at atypical dose it’s not worth increasing the dose – switch. If partial benefit increase the dose.
For anxiety (especially OCD): consider increasing dose if no initial benefit.
If an antidepressant has significant side-effects these may get better in a couple of weeks but if they cause a big problem for the patient – switch.
What features can discontinuation syndrome present with?
sweating, shakes, agitation, insomnia, headaches, irritability, nausea and vomiting, paraesthesia, clonus
The shorter the half-life the bigger the problem, Paroxetine and Venlafaxine often hardest to stop
Discontinuation syndrome is more likely to occur:
in drugs with a short half life
How can you reduce risk of discontinuation syndrome?
Go slow!
Can alternate days of taking and not taking or snap tablets in half (better option)
Sometimes worth switching to Fluoxetine (very long half-life) and then reducing the Fluoxetine
What is Vortioxetine?
new antidepressant with all sorts of serotonergic activity (differs according to receptor)
Effective
Well tolerated – most common side effect is nausea (but less severe than Venlafaxine)
Evidence for improvement in difficult to treat cognitive symptoms
Serotonin syndrome occurs when there is an increase in systemic serotonin, sometimes due to switching antidepressants and 2 being present in the system at the same time (e.g. fluoxetine and one other), or due to increasing the antidepressant dose.
How does serotonin syndrome present? Mx?
Cognitive – headaches, agitation, hypomania, confusion, coma
Autonomic – shivering, sweating, hyperthermia, tachycardia, nausea and diarrhoea
Somatic – myoclonus, hyperreflexia and tremor
Treatment usually supportive: fluids and monitoring
What is the MOA of antipsychotics? General side effects?
Also called neuroleptics
All current antipsychotics reduce level of dopamine activity at D2 receptors, target dopaminergic pathways in the brain are mesocortical and mesolimbic (psychosis = increased dopamine, parkinsonism = decreased dopamine)
All antipsychotics have potential for sedation, extrapyramidal side effects and weight gain
All antipsychotics can cause acute dystonia, including oculogyric crisis
What is the difference between typical and atypical antipsychotics?
Typical older and more likely to cause extra-pyramidal side effects – remember this difference!!!
Typical tend to bind more to muscarinic and histaminic receptors
Atypical tend to have more serotonergic activity
Give some typical antipsychotics
Haloperidol
Flupenthixol
Zuclopenthixol
Chlorpromazine
Sulpiride
Give some atypical antipsychotics
also called Second Generation Antipsychotics: SGAs
Clozapine, Olanzapine, Risperidone, Quetiapine, Amisulpiride, Aripiprazole – D2 partial agonist (not antagonist) fewer side effects
Side effects of antipsychotics?
Typical - more likely to cause:
Extra-Pyramidal Side Effects
Dizziness
Sexual dysfunction
Atypical - more likely to cause:
Weight gain
Dyslipidaemia and diabetes
How should patients on antipsychotics be monitored?
Baseline: FBC; Lipids; LFT; HbA1C. Weight. ECG. Blood pressure and pulse
Weekly: Weight in an ideal world
Three months: FBC; Lipids; LFT; HbA1C. Weight. ECG. Blood pressure and pulse
Yearly: FBC; Lipids; LFT; HbA1C. Weight. ECG. Blood pressure and pulse
What is neuroleptic malignant syndrome?
Rare, life-threatening reaction to antipsychotics
* Fever, confusion, muscle rigidity, sweating, autonomic instability
Death usually due to:
* Rhabdomyolysis, renal failure, seizures
Risk factors for neuroleptic malignant syndrome?
High potency dopamine antagonists (typical antipsychotics) in antipsychotic naive, high doses, young men
What tests might you do to confirm dx of NMS?
WCC (rule out sepsis), CRP, Creatinine Kinase (rhabdomyolysis)
How can neuroleptic malignant syndrome be managed?
Emergency referral to A&E
Stop antipsychotics, give benzos for acute behavioural disturbance
Fluid resuscitation
Reduce temperature (cooling blankets)
Oxygen if necessary
- Rhabdomyolsis – fluids and sodium bicarbonate – alkalise the urine
- Relax muscles – first line: dantrolene or lorazepam; second line bromocriptine
Why do you give anticholinergics to treat EPSEs which are due to a decrease in dopamine?
ratio of dopamine: acetylcholine in nigrostriatal pathway is more important that absolute quantities
if there is too much acetylcholine in relation to dopamine, sometimes it is easier to decrease acetylcholine than increase dopamine
What anticholinergic is commonly used to treat extra-pyramidal side effects?
Procyclidine
potential for misuse, not effective for (and may exacerbate) tardive dyskinesia
What are acute dystonias?
Sustained, often painful, muscular spasms, producing twisted abnormal postures.
50% cases in first 48 hours; 90% in first 5 days
Most common: neck; tongue; jaw; oculogyric crisis (neck arched and eyes rolled back)
How should acute dystonias be managed?
Stop antipsychotic
Administer IM or IV anticholinergics – first line is procyclidine
Continue for 1 to 2 days after dystonia and consider long-term prophylactic
MOA of clozapine?
atypical antipsychotic
D2 antagonist; 5HT-2 antagonist
Most efficacious antipsychotic ever!
Improvements can continue for several months
Clozapine should be used in schizophrenia after two other antipsychotics have not been effective.
What are the dangerous side effects? How should it be monitored?
Significant potential for agranulocytosis (severe leukopenia): therefore close monitoring of FBC: weekly for first 18 weeks, then fortnightly for up to a year, then monthly
Significant potential for gastrointestinal hypo-mobility: constipation, potentially fatal bowel obstruction
Other side-effects include hypersalivation and urinary incontinence
Dose titrated slowly upward over two weeks and vital signs monitored due to potential for autonomic dysregulation
How should agranulocytosis due to clozapine be managed?
Stop Clozapine
Stop any other potentially marrow supressing drugs – e.g. Sodium Valproate
Avoid other antipsychotics for a couple of weeks where possible, though if needed Aripiprazole has less potential for bone marrow suppression
Contact Consultant Haematologist as an emergency
Avoid sources of infection and consider prophylactic broad-spectrum abx
Sometimes lithium is used to increased WCC and neutrophil count, Granulocyte colony-stimulating factor (G-CSF) has been used
Purpose of olanzapine clinic?
patients need to stay in hospital and be monitored for 3 hours after injection because of risk of tachycardia and hypotension if it enters the blood stream too quickly (generally small spheres pop and cause the drug to steadily enter the circulation over the next few hours but this can go wrong)
Purpose of clozapine clinic?
Ensure FBC carried out before dose is given
EPSEs are due to:
dopamine antagonism in the nigrostriatal pathway
The 3 most common antipsychotic side effects reported by patients are:
weight gain, akathisia and sedation
Most appropriate administration route for an inpatient refusing to take their antipsychotic tablet?
long-acting depot injection
What are the 4 main anxiolytics?
Beta-blockers
Benzodiazepines
Pregabalin
Antidepressants
Beta blockers act by reducing autonomic nervous system activation to help with bio-psycho-feedback (less physical symptoms like tachycardia = less exacerbation of anxiety).
Which is the most commonly used in psychiatry? Contraindication?
propanolol- dangerous in overdose
contraindicated in asthma, limited efficacy for enduring anxiety disorders
What is the MOA of benzodiazepines?
Most typically used are diazepam (long half-life) and lorazepam (shorter half-life)
Bind to GABA receptors to potentiate the effect of GABA and therefore reduce the excitability of neurones.
= positive allosteric modulators of GABA receptor
What are the problems with benzos?
Significant potential for tolerance and dependence
Significant potential for misuse
Use very cautiously and for no more than six weeks
Occasionally cause paradoxical disinhibition
MOA of pregabalin?
Binds to voltage gated calcium channels on neurones
Reduces neuronal activity (i.e. is a CNS depressant)
Used in anxiety, neuropathic pain and epilepsy
Aim for short term use
Side effects of pregabalin?
Can cause sedation and weight gain
What are the categories of hypnotics (sleeping tablets)?
Benzodiazepines:
* Temazepam, Lormatazepam, Nitrazepam
Nonbenzodiazepines: usually favoured
* Act in a very similar way (positive allosteric modulators) , also called Z drugs
* Zopiclone, Zolpidem
What are the problems with hypnotics?
Significant potential for misuse, dependence, rebound insomnia.
Use for only two weeks and take for only 5 out of 7 days each week to reduce potential for tolerance
Mood stabilisers are used to treat bipolar disorder. What groups are available?
Lithium
Anticonvulsants
Second Generation (Atypical) Antipsychotics
Lithium is one of the most effective mood stabilisers with an unknown mechanism of action.
What are the benefits? What is the risk?
Significant evidence that lithium reduces suicide – and it has a licence for reduction of self-harm
Also used to augment antidepressants
Narrow therapeutic window (gap between effective dose and toxic dose)
requirement for regular serum lithium levels – weekly after dose change until level stable then 3 monthly once stable
Side effects of lithium?
GI disturbance (especially on initiation), metallic taste and/or dry mouth, fine tremor, polydipsia and polyuria, weight gain
Long term effects of lithium?
Hypothyroidism – usually reversible
Renal impairment (entirely excreted by the kidneys) – usually irreversible (and occurs most at above therapeutic doses)
Therefore annual U&Es and TFTs
How does lithium toxicity present?
How is it managed?
What increases the risk?
Confusion, coarse tremor, nausea and vomiting, ataxia and seizures
Treatment:
Stop lithium, supportive measures – IV fluid, dialysis if necessary, benzodiazepines for seizures
Potential for toxicity increases with dehydration – advise to drink lots of water in hot climates
Interactions that can increase levels dangerously include: NSAIDS, Loop diuretics, ACE inhibitors
What is the first line drug for bipolar?
Quetiapine - SGA
Most common anticonvulsants in bipolar are:
Sodium Valproate – avoid in women of child bearing age due to teratogenicity, check LFTs before and soon after starting
Carbamazepine
Lamotrigine – potential for Stevens Johnson Syndrome
Problems with anticonvulsants?
Most anticonvulsants have potential to cause thrombocytopenia so check FBC
Side effects include sedation and weight gain
What drugs can be used in ADHD? How should they be monitored in kids?
CNS stimulants- hyperactivity is a stimulating behaviour
* Methylphenidate – most commonly prescribed, often given with a combination of immediate and sustained release (in the same tablet)
* Dextroamphetamine
Monitor weight, height (in children) and pulse
