Psychopharmacology Flashcards
What important things do you need to keep in mind when choosing medications to treat mental illnesses?
Choosing an agent with acceptable side effects at lowest effective dose
Avoiding DDIs
What is the response rate to antidepressants?
40%
What conditions may you treat with antidepressants?
Unipolar and bipolar depression, organic mood disorders, schizoaffective disorder, anxiety disorders (OCD, social phobia, panic), PTSD etc.
What must you warn your patients of when starting them on antidepressants?
That they take 2-4 weeks to reach their therapeutic dose (when their symptoms will improve)
Why would you start someone on prophylactic antidepressants?
To reduce relapse and likelihood of another episode
After someone first episode of depression how long should you keep them on antidepressants for?
6m - 1y
After someone second episode of depression how long should you keep them on antidepressants for?
2y
After someone third episode of depression how long should you keep them on antidepressants for?
Consider life long
In treating depression, with an antidepressant, if no improvement is seen in ____ time then either ______ or ________
If no improvement is seen in within 2 months, either switch to another antidepressant or augment with another agent
What are the different types of antidepressants?
SSRIs - selective serotonin reuptake inhibitors
SNRIs - serotonin/noradrenaline reuptake inhibitors
MAOIs - monoamine oxidase inhibitors
TCAs - tricyclics
Novel antidepressants
What is the biggest issue with TCAs?
Lethal in OD - DON’T GIVE TO SUICIDAL PATIENT
Unacceptable side effects - antihistaminic, anticholingeric and antiadrenergic side effects
What side effects are associated with TCAs?
Antihistaminic - sedation, wt gain
Anticholingeric - dry mouth, eyes, constipation, memory deficits, delirium
Antiadrenergic - orthostatic hypotension, sedation, sexual dysfunction
How do tertiary TCAs work?
Act on serotonin receptors
What are examples of tertiary TCAs?
Amitriptyline
Imipramine
Doxepin
What are secondary TCAs?
Metabolites of tertiary amines
How do secondary TCAs work?
Block noradrenaline
What are the SEs of secondary TCAs?
Like tertiary TCAs but not as bad
Give examples of secondary TCAs
Desipramine, nortriptyline
How do MAOIs work?
Bind irreversibly to monoamine oxidase which prevents inactivation of amines, e.g. noradrenaline, dopamine and serotonin –> higher synaptic levels
What are the SEs for MAOIs?
Orthostatic hypotension, wt gain, dry mouth, sedation, sexual dysfunction, sleep disturbance
Cheese reaction when taken with tyramine rich foods
Serotonin syndrome if taken with meds increasing serotonin/have symathomimetic actions
What are the symptoms of serotonin syndrome?
Abdominal pain, diarrhoea, sweats, tachycardia, hypotension, myoclonus, irritability, delirium hyperprexia, CV shock and death
What must you do if you are switching from an SSRI to a MAOI?
Wait 2 weeks or 5 weeks if fluoxetine (longer half life)
What is used for first line treatment of depression?
SSRIs
How do SSRIs work?
Block presynaptic reuptake of serotonin
What are the SEs of SSRIs?
GI upset, sexual dysfunction, anxiety, restlessness, nervousness, insomnia, fatigue, sedation, dizziness
Activation syndrome
Discontinuation syndrome
What is activation syndrome?
For the first 2-10 days of starting SSRIs feel more anxious, agitated, nauseated and panicked
What is discontinuation syndrome?
On completing SSRI course, feel agitated, nauseated, dysphoric
What are the main pros and cons of paroxetine?
Sedating, wt gain
What are the main pros and cons of sertraline?
GI SEs
Less sedating
What are the main pros and cons of fluoxetine?
Can be used in u18s P450 interactions (avoid in those on lots of drugs) Avoid in hepatic illness
What are the main pros and cons of citalopram/escitalopram?
Fewer DDIs
QT lengthening
Sedating, GI SEs
What are the main pros and cons of fluvoxamine?
GI SEs, side effects, sedation, weakness
Inhibits liver enzymes
Analgesic
How do SNRIs work?
Inhibit both serotonin and noradrenaline uptake
What can SNRIs be used for?
Depression, anxiety, neuropathic pain
What is second line treatment for depression?
SNRIs
What are the two SNRIs?
Venlafaxine
Duloxetine
What are examples of SSRIs?
Fluoxetine Paroxetine Sertraline Citalopram/escitalopram Fluvoxamine
What are the main pros and cons of venlafaxine?
Minimal DDIs Increases diastolic BP Nausea QT prolongation Sexual SEs
What are the main pros and cons of duloxetine?
Used for stress incontinence and neuropathic pain as well
What are the two novel antidepressants?
Mitrazapine
Buproprion
What are the main pros and cons of mitrazapine?
Increases serum cholesterol
Very sedation
Wt gain
How does mirtazapine work?
5HT2 and 5HT3 receptor antagonist
What are the main pros and cons of buproprion?
May induce seizure risk in those with traumatic brain injury, bulimia, anorexia
Doesn’t treat anxiety
May cause psychosis
How do you treat treatment resistant depression?
Combine SSRI or SNRI with mirtazapine
Augment with lithium or atypical antipsychotic
ECT
What is ECT?
Electroconvulsive therapy
Stimulate an epileptic seizure under GA and muscle relaxant
What are SEs of ECT?
Memory loss and headache
What are indications for mood stabilisers?
Bipolar, cyclothymia, schizoaffective disorders
What are positive factors predicting a good response to lithium?
Previous good response
Positive response of family member
Classic pure mania
Mania followed by depression (where mania is first episode)
What must you do before starting lithium treatment?
Get baseline U&Es and TSH as kidneys and thyroid gland are affected by lithium use
What abnormality can result from lithium use during pregnancy?
Ebstein’s abnormality (heart defect) in first trimester
How does the body get rid of lithium?
Not metabolised by liver
Excreted by kidney
What must you ensure to do with lithium use?
Do regular blood tests to ensure lithium level is between 0.6-1.2
What are side effects of lithium use?
GI SEs - reduced appetite, N/V, diarrhoea
Hypothyroidism
Non-specific leucocytosis
Polyuria/polydipsia (due to ADH antagonism)
Hair loss, acne
Reduced seizure threshold, cognitive slowing, intention tremor
What happens if blood levels of lithium are between 1.5 and 2?
Vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus
What happens if blood levels of lithium are between 2 and 2.5?
Nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
What happens if blood levels of lithium are over 2.5?
Generalised convulsions, renal failure, oliguria, death
What must patients on lithium be aware of?
Illness/dehydration can cause lithium levels to increase –> lithium toxicity
What is the classification of lithium toxicity?
Mild - 1.5-2
Moderate - 2-2.5
severe >2.5
What are factors predicting a good response to valproic acid treatment?
Rapid cycling patients
Comorbid substance misuse
Mixed patients Patients with cormorbid anxiety
What must you do before you start someone on sodium valproate?
LFTs, FBC, pregnancy test
Why must sodium valproate be avoided in woman of childbearing age?
Causes neural tube defects
What is the target level of sodium valproate?
50-125 but generally more on response rather than blood level
What are the side effects of sodium valproate?
Thrombocytopenia, platelet dysfunction
N/V, wt gain
Sedation, tremor, hair loss
When might you use carbamazepine?
First line for acute mania and mania prophylaxis
Indicated for rapid cyclers/mixed patients
What must you do before starting someone on carbamazepine?
FBC, LFTs, ECG
What SEs are associated with carbamazepine?
Rash - most common N/V, diarrhoea Sedation, dizziness, ataxia, confusion AV conduction delays Aplastic anaemia, agranulocystosis Water retention due to vasopressin like effect which can lead to hyponatraemia DDIs
Apart from as a mood stabiliser and anticonvulsant, what can lamotrigine be used for?
Neuropathic/chronic pain
What must you check before you start lamotrigine?
LFTs
What are the side effects of lamotrigine?
N/V
Sedation, dizziness, ataxia, confusion
TEN/SJS
ANY RASH - STOP RX IMMEDIATELY
Apart from lithium, sodium valproate, carbamazepine and lamotrigine what else can be used as mood stabilisers?
Antipsychotics (e.g. risperidone or quetiapine)
Tend to use antipsychotics with someone who has been detained with really bad mania and then use mood stabilisers after for prophylaxis
If well enough and first episode of mania what should you give?
Lithium
If really unwell and first episode of mania what should you give?
Antipsychotic
What is an average starting dose of lithium?
800mg nocte
What are indications for use of antipsychotics?
Schizophrenia, schizoaffective disorder, bipolar disorder (for mood stabilisation/when psychotic features present), psychotic depression
What is the mesocortical pathway?
Dopaminergic neurons fire from VTA to cortex
In schizophrenia there is reduced dopaminergic firing over the mesocortical pathway –> negative symptoms
What is the mesolimbic pathway?
Dopaminergic neurons firing from the VTA to the nucleus accumbens (limbic system)
In schizophrenia there is too much dopamine in this pathway –> positive symptoms
What is the nigrostriatal pathway?
Normally responsible for co-ordination of movement
Dopaminergic neurons project from the substantia nigra to the basal ganglia
Treatment in schizophrenia reduces dopamine in this pathway which may lead to EPS
What is the tuberoinfindibular pathway?
Dopaminergic neurons fire from the hypothalamus to the anterior pituitary
Antipsychotics decrease dopamine firing from this pathway –> increased prolactin
NB - increased prolactin leads to galactorrhoea and reduced FSH (leading to amenorrhoea)
How do the typical antipsychotics work?
D2 dopamine receptor antagonists
What are examples of typicals?
Fluphenazine, haloperidol
What side effects are common from typicals?
Typicals are also anti-HAM (histamine, alpha, muscarinic) meaning they lead to sedation, weight gain, hypotension, sexual dysfunction, dry mouth, visual problems etc.
And extrapyramidal side effects & neuroepileptic malignant syndrome
How do the atypicals work?
Serotonin and dopamine 2 antagonists
What is the main difference in the atypicals and typicals?
Atypicals tend not to cause EPS but cause more weight gain, cholesterol raising and diabetes mellitus
What are the various routes of administration of antipsychotics?
Tablets, IM, rapidly dissolving
What is the issue with risperidone?
More likely to cause hyperprolactinaemia
Acts like typical >6mg
Give examples of typicals
Risperidone, olanzapine, aripiprazole, quetiapine, clozapine
What is the issue with olanzapine?
May cause irregular LFTs
What are the issues with quetiapine?
Most likely to cause orthostatic hypotension
Only available as a tablet
When should you use clozapine and why?
Treatment resistance only due to side effects
Agranulocytosis means that those on clozapine must have FBC checks
Also increased risk of seizures
How long does it tend to take for an antipsychotic to start working?
6 weeks
When is someone considered as treatment resistant?
When they have not responded to 2 antipsychotics (1 of which should be an atypical)
What are the movement disorders associated with antipsychotic use (the extrapyramidal symptoms)?
Tardive dyskinesia
Parkinsonsim
Dystonia
Akathesia
What is tardive dyskinesia?
Involuntary movements of the lips, tongue, neck e.g. lip smacking
What is parkinsonism?
Symptoms exactly same as Parkinson’s disease
Cogwheel rigidity, resting tremor, shuffling gait etc.
What is akathisia?
Restlessness, pacing, taping etc.
What is dystonia?
Sustained muscle contraction
How do you treat EPS?
Anticholingerics (e.g. benzotropine)
Dopamine facilitators, e.g. amantadine
Beta blockers for akathisia (e.g. propranolol)
What are anxiolytics used to treat?
Panic disorder, GAD, substance related disorders, insomnias, parasomnias
Usually used in combo with SSRIs/SNRIs
What are the two anxiolytics we need to know about?
Buspirone and benzodiazepines
How does buspirone work?
5HT1A agonist
Takes around 2 weeks to work!!
What are the side effects of benzodiazepines?
Somnolence, cognitive defects, amnesia, disinhibition, tolerance, dependence
Why would you try to avoid benzos?
They work very quickly, but after about 10 days their effect wears off where as fluoxetine starts working then
