Psychiatric Drugs Tutorial

Question 1

What are the common Adrenergic/Noradrenergic side effects ?

Answer 1

Sweating
Tremor
Headaches
Nausea
Dizziness

Question 2

What are the common Muscarinic side effects ?

Answer 2

Dry mouth, difficulty swallowing, thirst
Difficulty urinating, urinary retention
Hot and flushed skin
Dry skin

Question 3

What are the common histamine side effects ?

Answer 3

Dry mouth
Drowsiness
Dizziness
Nausea and vomiting

Question 4

How do antidepressants work?

Answer 4

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

Question 5

How do SSRIs work?

Answer 5

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

Question 6

Side effects of SSRIs?

Answer 6

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)

Question 7

Give 4 common SSRIs and the key things to look out for when prescribing them

Answer 7

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

Question 8

What is the value at which the QTc is prolonged?

Answer 8

450 msec for men and 470 msec for women

Question 9

How do SNRIs work? Common side effects?

Answer 9

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

Question 10

Give 2 SNRIs and their dose

Answer 10

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.

Question 11

Why might suicidal ideation go up when starting antidepressant treatment?

Answer 11

Energy levels and motivation may improve before other symptoms
May be more likely to act on existing suicidal thoughts

Question 12

How does Mirtazipine work?

Answer 12

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

Question 13

Indications for tricyclic antidepressants? Key side effects?

Answer 13

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

Question 14

What are the different categories of monoamine oxidase B inhibitors?

Answer 14

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

Question 15

Key things to know about MAOIs?

Answer 15

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)

Question 16

What should you consider when deciding which antidepressant to prescribe?

Answer 16

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

Question 17

What antidepressants are generally prescribed to someone on first presentation?

Answer 17

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

Question 18

How do you decide whether to increase the dose of an antidepressant or switch the drug?

Answer 18

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.

Question 19

What features can discontinuation syndrome present with?

Answer 19

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

Question 20

Discontinuation syndrome is more likely to occur:

Answer 20

in drugs with a short half life

Question 21

How can you reduce risk of discontinuation syndrome?

Answer 21

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

Question 22

What is Vortioxetine?

Answer 22

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

Question 23

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?

Answer 23

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

Question 24

What is the MOA of antipsychotics? General side effects?

Answer 24

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

Question 25

What is the difference between typical and atypical antipsychotics?

Answer 25

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

Question 26

Give some typical antipsychotics

Answer 26

Haloperidol
Flupenthixol
Zuclopenthixol
Chlorpromazine
Sulpiride

Question 27

Give some atypical antipsychotics

Answer 27

also called Second Generation Antipsychotics: SGAs

Clozapine, Olanzapine, Risperidone, Quetiapine, Amisulpiride, Aripiprazole – D2 partial agonist (not antagonist) fewer side effects

Question 28

Side effects of antipsychotics?

Answer 28

Typical - more likely to cause:
Extra-Pyramidal Side Effects
Dizziness
Sexual dysfunction

Atypical - more likely to cause:
Weight gain
Dyslipidaemia and diabetes

Question 29

How should patients on antipsychotics be monitored?

Answer 29

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

Question 30

What is neuroleptic malignant syndrome?

Answer 30

Rare, life-threatening reaction to antipsychotics
* Fever, confusion, muscle rigidity, sweating, autonomic instability

Death usually due to:
* Rhabdomyolysis, renal failure, seizures

Question 31

Risk factors for neuroleptic malignant syndrome?

Answer 31

High potency dopamine antagonists (typical antipsychotics) in antipsychotic naive, high doses, young men

Question 32

What tests might you do to confirm dx of NMS?

Answer 32

WCC (rule out sepsis), CRP, Creatinine Kinase (rhabdomyolysis)

Question 33

How can neuroleptic malignant syndrome be managed?

Answer 33

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

Question 34

Why do you give anticholinergics to treat EPSEs which are due to a decrease in dopamine?

Answer 34

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

Question 35

What anticholinergic is commonly used to treat extra-pyramidal side effects?

Answer 35

Procyclidine

potential for misuse, not effective for (and may exacerbate) tardive dyskinesia

Question 36

What are acute dystonias?

Answer 36

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)

Question 37

How should acute dystonias be managed?

Answer 37

Stop antipsychotic

Administer IM or IV anticholinergics – first line is procyclidine

Continue for 1 to 2 days after dystonia and consider long-term prophylactic

Question 38

MOA of clozapine?

Answer 38

atypical antipsychotic

D2 antagonist; 5HT-2 antagonist
Most efficacious antipsychotic ever!
Improvements can continue for several months

Question 39

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?

Answer 39

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

Question 40

How should agranulocytosis due to clozapine be managed?

Answer 40

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

Question 41

Purpose of olanzapine clinic?

Answer 41

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)

Question 42

Purpose of clozapine clinic?

Answer 42

Ensure FBC carried out before dose is given

Question 43

EPSEs are due to:

Answer 43

dopamine antagonism in the nigrostriatal pathway

Question 44

The 3 most common antipsychotic side effects reported by patients are:

Answer 44

weight gain, akathisia and sedation

Question 45

Most appropriate administration route for an inpatient refusing to take their antipsychotic tablet?

Answer 45

long-acting depot injection

Question 46

What are the 4 main anxiolytics?

Answer 46

Beta-blockers
Benzodiazepines
Pregabalin
Antidepressants

Question 47

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?

Answer 47

propanolol- dangerous in overdose

contraindicated in asthma, limited efficacy for enduring anxiety disorders

Question 48

What is the MOA of benzodiazepines?

Answer 48

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

Question 49

What are the problems with benzos?

Answer 49

Significant potential for tolerance and dependence
Significant potential for misuse
Use very cautiously and for no more than six weeks

Occasionally cause paradoxical disinhibition

Question 50

MOA of pregabalin?

Answer 50

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

Question 51

Side effects of pregabalin?

Answer 51

Can cause sedation and weight gain

Question 52

What are the categories of hypnotics (sleeping tablets)?

Answer 52

Benzodiazepines:
* Temazepam, Lormatazepam, Nitrazepam

Nonbenzodiazepines: usually favoured
* Act in a very similar way (positive allosteric modulators) , also called Z drugs
* Zopiclone, Zolpidem

Question 53

What are the problems with hypnotics?

Answer 53

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

Question 54

Mood stabilisers are used to treat bipolar disorder. What groups are available?

Answer 54

Lithium
Anticonvulsants
Second Generation (Atypical) Antipsychotics

Question 55

Lithium is one of the most effective mood stabilisers with an unknown mechanism of action.
What are the benefits? What is the risk?

Answer 55

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

Question 56

Side effects of lithium?

Answer 56

GI disturbance (especially on initiation), metallic taste and/or dry mouth, fine tremor, polydipsia and polyuria, weight gain

Question 57

Long term effects of lithium?

Answer 57

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

Question 58

How does lithium toxicity present?
How is it managed?
What increases the risk?

Answer 58

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

Question 59

What is the first line drug for bipolar?

Answer 59

Quetiapine - SGA

Question 60

Most common anticonvulsants in bipolar are:

Answer 60

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

Question 61

Problems with anticonvulsants?

Answer 61

Most anticonvulsants have potential to cause thrombocytopenia so check FBC

Side effects include sedation and weight gain

Question 62

What drugs can be used in ADHD? How should they be monitored in kids?

Answer 62

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