Psychopharmacology Flashcards

1
Q

What are the common adrenergic/noradrenergic side effects?

A
  • Sweat
  • Tremor
  • Headaches
  • Nausea
  • Dizziness
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2
Q

What are the common muscarinic side effects?

A
  • Dry mouth, difficulty swallowing
  • Difficulty urinating and possibly retention
  • Hot and flushed skin
  • Dry skin
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3
Q

What are the common histamine side effects?

A
  • Dry mouth
  • Drowsiness
  • Dizziness
  • Nausea and vomiting
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4
Q

What do antidepressants do?

A

Modulate serotonin activity, aiming to increase activity at post-synaptic receptors

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5
Q

How quickly do antidepressants work?

A

2-3 weeks.

WARNING increase of suicidality within this time.

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6
Q

What is the most common class of antidepressants, what are some alternatives?

A

SSRIs.

  • SNRIs
  • Mirtazapine
  • Tricyclics
  • MAOIs
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7
Q

How do SSRIs work?

A
  • Reduce pre-synaptic reuptake of serotonin after release
  • Which increases serotonin activity to the post-synaptic nerve
  • More serotonin sits in the nerve junction
  • Leads to a down regulation of post-synaptic receptors
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8
Q

What are the common side effects of SSRIs?

A

On initiation:

  • Sense of restlessness, agitation on initiation
  • Nausea, GI upset
  • Headache

Long term:

  • Weight changes
  • Sexual dysfunction
  • Bleeding
  • Suicidal ideation
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9
Q

How can you get around issues of restlessness and agitation on SSRIs?

A

Benzodiazepines.

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10
Q

What is the link between antidepressants and suicide?

A

Regardless of the drug, there is a statistical increase in suicides around 2-3 weeks of treatment.

This is because within this time motivation and energy increases, but improvements in hope/optimism come noticeably later, causing increased suicidal ideation.

Get around this by arranging for a meeting at 2 weeks, check in on how they’re doing.

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11
Q

Who is especially at risk of suicide when going on antidepressants

A

Young men.

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12
Q

What are the common SSRIs?

A

Sertraline (50 to 200mgs)

Citalopram (20 to 40mgs)

Fluoxetine (20 to 60mgs)

Paroxetine (20 to 60mgs)

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13
Q

What is the ideal starting dose for Sertraline?

A

In the BNF, 50mgs. In reality you don’t really start anyone at a dosage below 100mgs.

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14
Q

What is a benefit to sertraline over other SSRIs?

A

Safest in cardiac disease.

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15
Q

What is it important to look out for with Citalopram and Escitalopram?

A

Watch out for QTc prolongation.

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16
Q

What is it important to look out for with Fluoxetine?

A

Serotonin syndrome.

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17
Q

What is it important to look out for with Paroxetine?

A

Discontinuation syndrome.

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18
Q

How do SNRIs work?

A
  • Same as SSRIs but also bind to noradrenaline reuptake receptors also.
  • Highly effective for neuropathic pain
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19
Q

What are the main side effects of SNRIs?

A

Similar to SSRIs, BUT with more issues around sedation, nausea and sexual dysfunction (both in terms of arousal and achieving orgasm).

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20
Q

What are some examples of SNRIs used in the UK?

A

Duloxetine (60 to 120mgs)

Venlafaxine (75 to 375mgs)

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21
Q

How does Mirtazapine work?

A
  • Unique class
  • Acts as a 5HT-2 and 5HT-3 antagonist
  • Works on both Noradrenaline and Serotonin
  • Strong histaminic activity even at low doses
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22
Q

What are the major side effects of Mirtazapine?

A
  • Sedation
  • Weight gain

Annoyingly these are sort of not dosage dependent, reducing a patient’s dose will not actually help them.

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23
Q

When are TCAs used?

A

Pretty much only when someone doesn’t like SSRIs nowadays.

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24
Q

What are the main side effects of TCAs?

A

Muscarinic and Histaminic side effects

Can be fatal in OD due to QTc prolongation and arrhythmias

Quite strong sedation, can be beneficial in insomnia.

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25
Q

How do MAOIs work?

A
  • Monoamine oxidase inhibitors.
  • MAOI As work on serotonin, MAOIs B work on dopamine
  • All work on adrenaline
  • Possibly most effective for atypical depression
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26
Q

What is the main issue with MAOIs

A

Severe interactions with other drugs.

One of the things it reacts with is Tyramine which is common in food and therefore restricts diet e.g. cheese, pickled meats, red wine.

Also, if changing someone from a MAOI to something else, need a 6 week washout.

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27
Q

What is Vortioxetine?

A
  • New antidepressants
  • All sorts of serotonergic activity
  • Effective
  • Well tolerated (most common side effect is nausea- less severe than Venlafaxine)
  • Effective for patients with difficult to treat cognitive symptoms (e.g. concentration and memory, which many people notice drops along with mood but might not return)
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28
Q

How do you choose which antidepressant is appropriate?

A
  • What have they used before
  • Was it effective, was it tolerated

Are there any particular symptoms or comorbidities that should be considered/addressed as part of your prescription:

  • Insomnia
  • Weight loss
  • Neuropathic pain
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29
Q

What antidepressant is most effective if patients have lost weight and are struggling to sleep due to their depression?

A

Mertazapine, causes sedation and weight gain

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30
Q

What antidepressant is most appropriate if patient has neuropathic pain issues?

A

Velafaxine or Duloxetine

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31
Q

What is the go-to first line antidepressant?

A

Sertraline.

Affective, well tolerated, no cardiac issues.

Start at 50 then work up to the therapeutic dose of 100.

32
Q

At what point, with no effect of an antidepressant, is it appropriate to switch drugs or increase dose?

A

4 weeks.

If no effect at this point it’s not going to work, try something different

(true for almost all psych, apart from anxiety and OCD)

33
Q

What advice would you give someone starting an AD about side effects?

A
  • Side effect are most pronounced at the start and tend to fade away
  • Therapeutic effect are least pronounced at the start and ramp up
  • If SEs are insurmountable we can try something else but try and hold out.
34
Q

What is discontinuation syndrome? What drugs is it seen most in? How can it be avoided?

A

Syndrome characterised by:

  • Sweating
  • Shakes
  • Agitation
  • Insomnia
  • Headaches
  • Irritability
  • Nausea
  • Vomiting
  • Paraesthesia
  • Clonus

Not an addiction reaction, not dangerous but deeply unpleasant.

Caused by half life of drugs, the shorter the more severe the problem (e.g. Paroxetine and Venlafaxine- so difficult that patients often get switched to Fluoxetine, then come off that).

Avoid by stopping these drugs slowly (half dose first- snap tablets in half)

35
Q

What are the symptoms of serotonin syndrome?

A

Vague syndrome caused by too much serotonin which can occur when serotonergic drug doses are increased

Cognitive:

  • Headaches
  • Agitation
  • Hypomania
  • Confusion
  • Coma

Autonomic:

  • Shivering
  • Sweating
  • Hyperthermia
  • Tachycardia
  • Nausea
  • Diarrhoea

Somatic:

  • Myoclonus
  • Hyper-reflexia
  • Tremor

Treatment = Supportive (fluids and monitoring)

36
Q

Define QTc prolongation?

A

Above 450 microsecs for men

Above 470 microsecs for women

37
Q

How do antipsychotics work?

A

Reduce levels of dopamine activity at the D2 receptors

38
Q

What are the 4 dopaminergic pathways?

A

Targets for APs:

  • Mesocortical
  • Mesolimbic

Unwanted effects of APs:

  • Nigrostriatal (movement)
  • Tuberoinfundibular (HPA axis)
39
Q

What are the side effects of antipsychotics?

A
  • Sedation
  • Extrapyramidal SEs
  • Weight gain
  • Dizzyness
  • Sexual dysfunction

Serious:

  • NMS
  • Acute Dystonia (including Oculogyric crisis)
  • QTc prolongation
  • Constipation leading to bowel obstruction
40
Q

What are the two classes of APs?

A
  • Typical: More likely to cause ExP side effects
  • Atypical: More likely to cause dyslipidaemia, weight gain, diabetes
  • Typical bind more to muscarinic and histaminic
  • Atypical binds more to serotonergic
41
Q

What are some examples of APs?

A

Typical:

  • Haloperidol
  • Chlorpromazine
  • Sulrpide

Atypical:

  • Clozapine
  • Olanzapine
  • Quetiapine
  • Risperidone
  • Aripiprazole
42
Q

What monitoring is required for patients going on an antipsychotic?

A

Most important relates to Diabetes and Lipids (majority of reason why these drugs are life shortening is dyslipidaemia and diabetes)

@ Baseline:

  • FBC
  • Lipids
  • LFTs
  • HbA1c
  • Weight
  • Pulse
  • BP
  • ECG

Weekly weighing. Metabolic bloods should be repeated at 3 months, 6 months and yearly, with all blood tests repeated yearly

43
Q

What is Neuroleptic Malignant Syndrome?

A

Rare, life-threatening complication of antipsychotics.

Vague presentation:

  • Fever
  • Confusion
  • Muscle rigidity
  • Sweating
  • Autonomic instability (blood pressure goes up and down rapidly)

Death by:

  • Rhabdomyolysis
  • Renal failure
  • Seizures

Key indicator = Raised Creatine Kinase.

RFs:

  • High potency dopamine antagonists e.g. TYPICAL antipsychotics in those who’ve never had APs.
  • High doses
  • Young men
  • Restrained patients
44
Q

How do you manage NMS?

A

Key investigations:

  • WCC, CRP to rule out infection
  • CK for diagnosis
  • Emergency refer to A and E
  • Stop APs
  • Give benzos
  • Fluid resus
  • Reduce temperature with cooling blankets
45
Q

What are the main extra pyramidal side effects?

A
  • Tremor
  • Slurred speech
  • Bradykinesia
  • Cog-wheeling
  • Akathesia (urge to move)
  • Dystonia
  • Anxiety
  • Paranoi
46
Q

What causes EPSEs?

A

Ratio of dopamine to acetylcholine in nigrostriatal pathway is disturbed (too much AcH)

47
Q

How do you treat EPSEs?

A

Reduce AcH activity by antagonising the receptors.

Use:

  • PROCYCLIDINE
  • Benzatropine
  • Trihexphenidyl

However these meds dont work for Tardive Dyskinesia

48
Q

What is Acute Dystonia?

A

Sustained, painful muscular spasms which cause twisted abnormal postures, caused by APs.

Most common at the neck, tongue, jaw.

Can get oculogyric crisis (neck and eyes held back)

49
Q

How do you manage Acute Dystonia?

A
  • Stop AP
  • Administer IM or IV anticholinergics (Procyclidine)
  • Continue for 1 to 2 days after dystonia and consider long-term prophylactic
50
Q

What are the main severe complications of AP therapy to look out for?

A
  • NMS
  • Extra-pyramidal side effects
  • Acute Dystonia
51
Q

What is the most effective AP to use?

A

Clozapine.

  • Most efficacious
  • Effective for both the negative and positive effects of Sz
  • ## However difficult side effect profile, therefore normally third line (only given after two unsuccessful antipsychotics)
52
Q

What are normally the two first line APs?

A
  • Haloperidol
  • Olanzapine

If both fail consider Clozapine

53
Q

When giving Clozapine, why do you start low and slow?

A
  • Risk of agranulocytosis
  • Risk of autonomic dysregulation and arrhythmia
  • Risk of GI hypo-mobility, causing constipation and potentially fatal bowel obstruction
54
Q

Why do people tend not to die of agranulocytosis in the UK?

A

Can’t physically get Clozapine without blood test results anymore.

55
Q

How do you treat agranulocytosis?

A
  • Stop clozapine
  • Stop any other marrow suppressing drugs
  • Avoid other psychotics for a couple of weeks where possible
  • Contact consultant haematologist
  • Avoid source of infection and consider broad spec antibiotics
  • Can give Lithium which increases neutrophil count
  • Can give Granulocyte Colony Stimulating Factor if massive risk of infection, but deeply unpleasant
56
Q

Define agranulocytosis?

A

Neutrophil count below 1.

57
Q

What monitoring is required on Clozapine to prevent agranulocytosis?

A

Weekly FBC for first 18 weeks, then fortnightly for the next 12, then monthly forever.

Keep checking WCC essentially

58
Q

What is unique amongst antipsychotics about Aripiprazole?

A

Dopamine partial agonist, not antagonist.

For this reason it has a reduced side effect profile, but can be less effective and takes a while to work. Good for patients not at risk with mildish symptoms.

59
Q

What are the life-threatening complications of antipsychotic therapy?

A
  • Agranulocytosis
  • Constipation
  • Autonomic instability
60
Q

Why are beta-blockers effective in managing anxiety?

A
  • Reduce autonomic nervous system activation
  • Block bio-psycho feedback
  • Most common used is Propranolol
  • Contraindicated in asthma
61
Q

What are benzodiazepines?

A

Anxiolytics which work by binding to GABA receptors to potentiate the effect of GABA, therefore reducing the excitability of neurones.

Positive allosteric modulators of GABA receptors.

Potential for misuse, tolerance and dependence, so not typically used for more than 6 weeks.

62
Q

How does pregabalin work?

A
  • Binds to VGCCs
  • Reduces neuronal activity
  • Useful in anxiety, neuropathic pain and epilepsy
  • Low potential for misuse and dependence
  • Causes sedation but does not cause weight gain
63
Q

Which antidepressants are commonly used for anxiety?

A

SSRIs most common.

64
Q

What are hypnotics anfdgive some examples?

A

Sleeping agents.

  • Benzodiazepines (Temazepam)
  • Nonbenzodiazepines (different structure but work the same way e.g. Zopiclone, Zolpidem)

No real difference between the two in terms of efficacy or potential for misuse.

65
Q

What can happen when people stop taking hypnotics?

A

Rebound insomnia, can be quite severe.

Probably mostly psychological, anxiety that they don’t have anything to help them sleep.

66
Q

What are the 3 groups of mood stabilisers?

A
  • Lithium
  • Anticonvulsants
  • Second Gen Antipsychotics
67
Q

How effective is Lithium?

A
  • Very
  • However very narrow therapeutic range which makes things difficult
  • Can cause kidney and thyroid damage
68
Q

What monitoring is required for Lithium?

A
  • Weekly Lithium levels once starting or changing dose
  • Essentially put someone on Lithium, take a level, go up or down as appropriate, test again, change again, test again etc…
  • However if someone is responding to treatment but has ‘low’ blood levels best to ignore, risk of pushing dose up outside of T range is too great.
  • Once levels are stable, 3 monthly blood test
69
Q

What are some common side effects of Lithium?

A

Short term:

  • GI D
  • Metallic taste and dry mouth
  • Fine tremor
  • Polydipsia, polyuria
  • Weight gain

Long term:

  • Hypothyroidism (reversible)
  • Renal impairment (usually irreversible, occurs most above the therapeutic dose)
  • Therefore need anual Us and Es and TFTs
70
Q

What is the upper range of Lithium T range on a blood test?

A

1.0

71
Q

What is the first line mood stabiliser for bipolar disorder?

A

Quetiapine.

Not necessarily more effective than Lithium or other SGAs, but safer as less chance of toxicity.

72
Q

What is the first line mood stabiliser for bipolar disorder?

A

Quetiapine.

Not necessarily more effective than Lithium or other SGAs, but safer as less chance of toxicity.

73
Q

What anticonvulsants are most commonly used in bipolar?

A
  • Sodium Valproate (basically never for women of child bearing age, only if on parenteral contraceptive and literally nothing else works)
  • Carbamazepine
  • Lamotrigine (potential for SJS)
74
Q

What is the main drug used to treat ADD/ADHD?

A

Methylphenidate.

  • Often given with a combination of immediate and sustained release
  • Potential for misuse and dependency
  • Must monitor weight and height (in children) + pulse
75
Q

What is an alternative to Methylphenidate used in ADD/ADHD?

A

Atomoxetine

Noradrenaline re-uptake inhibitor.

  • Used if patient is unable to tolerate stimulants
  • Or patient preference
  • Or previous issues around drug dependence (esp. amphetamines)