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Psychiatry > Psychopharmacology > Flashcards

Psychopharmacology Flashcards

1
Q

What are the general pharmacological strategies?

A

Indication
- establish a diagnosis and identify the target symptoms that will be used to monitor therapy response

Choice of agent and dose

  • select an agent with an acceptable side-effect profile and use the lowest effective dose
  • remember the delayed response for many psychiatry medications and drug-drug interactions

Management

  • adjust dosage for optimum benefit, safety and compliance
  • use adjunctive and combination therapies if needed, however, always strive for simplest regime
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2
Q

Indications for antidepressants

A

Unipolar and bipolar depression
Organic mood disorders
Schizoaffective disorder
Anxiety disorder including OCD, panic, social phobia, PTSD, premenstrual dysmorphic disorder and impulsivity associated with personality disorders

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3
Q

What is selection of an antidepressant based on?

A

Past history of a response, side effect profile and co-existing medical conditions

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4
Q

What is the typical delay after a therapeutic dose is achieved before symptoms improve with antidepressant therapy?

A

2-4 weeks

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5
Q

If no improvement in symptoms is seen after a trial of adequate length (at least 2 months) and adequate dose, what should be done?

A

Switch to another antidepressant or augment with another agent

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6
Q

Antibiotic prophylaxis features

A

First episode - continue for 6 months to a year
Second episode - continue for 2 years
Third episode - discuss lifelong

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7
Q

Antidepressant classifications

A 
Tricyclics
Monoamine oxidase inhibitors
Selective serotonin reuptake inhibitors 
Serotonin/noradrenaline reuptake inhibitors 
Novel agents
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8
Q

General features of TCAs

A

Very effective but potentially unacceptable side effect profile
Lethal in overdose
Can cause QT lengthening even at a therapeutic serum level

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9
Q

What is the side effect profile of TCAs?

A

Anticholinergic
Antihistaminic
Antiadrenergic

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10
Q

Features of tertiary TCAs

A

Tertiary amine side chains
Side chains prone to cross-react with other types of receptors which leads to more side effects
Have active metabolites including despiramine and nortriptyline

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11
Q

Examples of tertiary TCAs

A

Amitriptyline
Imipramine
Doxepine
Clomipramine

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12
Q

Features of secondary TCAs

A

Often metabolites of tertiary amines
Primarily block noradrenaline
Side effects same as tertiary TCAs but generally less severe

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13
Q

Examples of secondary TCAs

A

Desipramine

Nortriptyline

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14
Q

Features of MAOIs

A

Bind irreversible to monoamine oxidase preventing inactivation of amines e.g. norepinephrine, dopamine and serotonin, leading to increased synaptic levels
Very effective for resistant depression

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15
Q

Side effects of MAOIs

A 
Orthostatic hypotension
Weight gain 
Dry mouth 
Sedation 
Sexual dysfunction
Sleep disturbance
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16
Q

Examples of MAOIs

A

Phenelzine

Selegiline

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17
Q

What is the ‘cheese reaction’?

A

Hypertensive crisis that can develop when MAOIs are taken with tyramine-rich foods e.g. cheese, wine or sympathomimetics

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18
Q

What is serotonin syndrome?

A

Can develop if MAOIs taken with medications that increase serotonin or have sympathomimetic actions
Symptoms include abdominal pain, diarrhoea, sweats, tachycardia, hypertension, myoclonus, irritability and delirium
Can lead to hyperpyrexia, cardiovascular shock and death

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19
Q

How do you avoid serotonin syndrome?

A

Wait 2 weeks before switching from SSRI to MAOI

Exception is fluoxetine where you need to wait 5 weeks due to long half-life

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20
Q

Features of SSRIs

A

Block presynaptic serotonin reuptake
Treat both anxiety and depressive symptoms
Very little risk of cardio toxicity in overdose
Can develop discontinuation syndrome is stopped quickly

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21
Q

Side effects of SSRIs

A 
GI upset
Sexual dysfunction, 30+%
Anxiety 
Restlessness
Nervousness
Insomnia 
Fatigue/sedation
Dizziness

SE usually last 2 days but can last up to a month

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22
Q

Symptoms of discontinuation syndrome

A

Agitation
Nausea
Disequilibrium
Dysphoria

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23
Q

Examples of SSRIs

A 
Sertraline
Paroxetine
Fluoxetine 
Citalopram
Escitalopram
Fluvoxamine
Venflaxine 
Duloxetine
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24
Q

Features of activation and discontinuation syndromes

A

SSRIs

Activation syndrome causes increased serotonin, can be distressing for patient
Nausea, increased anxiety, panic and agitation
Typically lasts 2-10 days

Discontinuation syndrome - agitation, nausea, disequilibrium and dysphoria
More common with shorter half-life drugs so consider switching to fluoxetine

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25
Q

Pros and cons of sertraline

A

Pros

  • very weak P450 interactions
  • short half-life with lower build up of metabolites
  • less sedating when compared to paroxetine

Cons

  • max absorption requires full stomach
  • increased number of GI ADRs
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26
Q

Pros and cons of paroxetine

A

Pros

  • short half-life with no active metabolite so no build up, good if hypomania develops
  • sedating properties offer good initial relief from anxiety and insomnia

Cons

  • sedating, weight gain, more anticholinergic effects
  • likely to cause discontinuation syndrome
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27
Q

Pros and cons of fluoxetine

A

Pros

  • long half-life so decreased incidence of discontinuation syndrome
  • good for patients with medication non-compliance issues
  • initially activating so may provide increased energy
  • secondary to long half-life, can give one 20mg tab to taper someone off SSRI when trying to prevent discontinuation syndrome

Cons

  • long half-life and active metabolite may build up, not a good choice in patients with hepatic illness
  • significant P450 interactions so may not be a good choice in patients already on a number of medications
  • initial activation may increase anxiety and insomnia
  • more likely to induce mania than some other SSRIs
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28
Q

Pros and cons of citalopram

A

Pros

  • low inhibition of P450 enzymes so fewer drug-drug interactions
  • intermediate half life

Cons

  • dose-dependent QT interval prolongation with doses of 10-30mg daily, risk doses > 40mg/day not recommended
  • can be sedating
  • GI side effects but fewer than sertraline
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29
Q

Pros and cons of escitalopram

A

Pros

  • low overall inhibition of P450 enzymes so fewer drug-drug interactions
  • intermediate half life
  • more effective than citalopram in acute response and remission

Cons

  • dose-dependent QT interval prolongation with doses of 10-30mg daily
  • nausea, headache
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30
Q

Pros and cons of fluvoxamine

A

Pros

  • shortest half life
  • found to possess some analgesic properties

Cons

  • shortest half life
  • GI distress, headaches, sedation, weakness
  • strong inhibitor of CYP1S2 and CYP2C19
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31
Q

Features of SNRIs

A

Inhibit both serotonin and noradrenergic reuptake like the TCAs but without the antihistaminic, anticholinergic or antiadrenergic effects
Used for depression, anxiety and possibly neuropathic pain

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32
Q

Examples of SNRIs

A

Venlafaxine

Duloxetine

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33
Q

Pros and cons of venlafaxine

A

Pros

  • minimal drug interactions and almost no P450 activity
  • short half-life and fast renal clearance avoids build up, good for geriatric population

Cons

  • can cause 10-15mmHg dose-dependent increase in diastolic BP
  • may cause significant nausea primarily with immediate release tabs
  • can cause bad discontinuation syndrome and taper recommended after 2 weeks of administration
  • noted to cause QT prolongation
  • side effects in > 30%
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34
Q

Pros and cons of duloxetine

A

Pros

  • some data to suggest efficacy for physical symptoms of depression
  • far less BP increase compared to venlafaxine

Cons

  • CYP2D6 and CYP1A2 inhibitor
  • cannot break capsule as active ingredient is not stable within stomach
  • higher dropout rate in pooled analysis
35
Q

Examples of novel antidepressants

A

Mirtazapine

Bupropion

36
Q

Pros and cons of mirtazapine

A

Pros

  • different mechanism of action might provide good augmentation strategy to SSRIs
  • 5HT2 and 5HT3 receptor antagonist
  • can be utilised as hypnotic at lower doses, secondary to antihistaminic effects

Cons

  • increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients
  • very sedating at lower doses
  • doses 30mg + can become activating and require change of administration time to the morning
  • associated with weight gain, particularly at doses < 45mg
37
Q

Pros and cons of bupropion

A

Pros

  • good for use as augmenting agent
  • mechanism of action likely reuptake of dopamine and norepinephrine
  • no weight gain, sexual side effects, sedation or cardiac interactions
  • low induction of mania
  • second line ADHD agent so consider if co-occurring diagnosis

Cons

  • may increase seizure risk at high doses (450mg+), should be avoided in patients with traumatic brain injury, bulimia and anorexia
  • does not treat anxiety, can cause anxiety, insomnia and agitation
  • has abuse potential as it can induce psychotic symptoms at high doses
38
Q

Approach to treatment resistance

A

Combination of antidepressants
Adjunctive treatment with lithium
adjunctive treatment with atypical antipsychotic e.g. quetiapine, olanzapine, aripiprazole
ECT

39
Q

Indications for mood stabilisers

A

Bipolar
Cyclothymia
Schizoaffective

40
Q

Classes of mood stabilisers

A

Lithium
Anticonvulsants
Antipsyhoctics

41
Q

Features of lithium

A

Only medication to reduce suicide rate

Effective in long-term prophylaxis of both mania and depressive episodes in 70+% of patients with BAD

42
Q

Factors predicting positive response to lithium

A

Prior long-term response to lithium
Classic pure mania
Mania followed by depression

43
Q

How to use lithium

A

Before starting get baseline U&Es, TSH and pregnancy test
Monitor - steady state achieved after 5 days, check 12 hours after last dose, once stable check level at 3 months and TSH and creatinine at 6 months
Goal - blood level between 0.6 and 1

44
Q

Side effects of lithium

A

GI distress, including reduced appetite, nausea/vomiting, diarrhoea
Thyroid abnormalities
Non-significant leucocytosis
Polyuria/polydipsia secondary to ADH antagonism
Interstitial renal fibrosis
Hair loss
Acne
Reduces seizure threshold, cognitive slowing, intention tremor

45
Q

Features of mild lithium toxicity

A 
Level 1.5-2.0
Vomiting
Diarrhoea
Ataxia
Dizziness
Slurred speech
Nystagmus
46
Q

Features of moderate lithium toxicity

A 
Level 2.0-2.5
Nausea
Vomiting 
Anorexia
Blurred vision
Clonic limb movements
Convulsions
Delirium 
Syncope
47
Q

Features of severe lithium toxicity

A

Level > 2.5
Generalised convulsions
Oliguria
Renal failure

48
Q

Features of valproic acid

A

As effective as lithium in mania prophylaxis but not as effective in depression prophylaxis
Better tolerated than lithium

49
Q

Factors predicting positive response to valproic acid

A

Rapid cycling patients (females > males)
Co-morbid substance issues
Mixed patients
Patients with co-morbid anxiety disorders

50
Q

How to use valproic acid

A

Before started, get baseline LFTs, pregnancy test and FBC
Avoid in women of child-bearing age due to neural tube defects
Monitoring - steady state achieved after 4-5 days, check 12 hours after last dose and repeat CBC and LFTs
Goal - target level between 50-125

51
Q

Side effects of valproic acid

A 
Thrombocytopenia and platelet dysfunction 
Nausea
Vomiting 
Weight gain
Sedation 
Tremor 
Increased risk of neural tube defect
Hair loss
52
Q

Examples of anticonvulsants

A

Valproid acid
Carbamazepine
Lamotrigine

53
Q

Features of carbamazepine

A

First line agent for acute mania and mania prophylaxis

Indicated for rapid cyclers and mixed patients

54
Q

How to use carbamazepine

A

Before starting get baseline LFTs, FBC and ECG
Monitoring - steady state achieved after 5 days, check 12 hours after last dose and repeat CBC and LFTs
Goal - target level 4-12mcg/ml
Need to check level and adjust dosing after around 1 month because it induces the patient’s own metabolism

55
Q

Side effects of carbamazepine

A 
Rash - most common 
Nausea
Vomiting 
Diarrhoea 
Sedation
Dizziness
Ataxia 
Confusion 
AV conduction delay 
Aplastic anaemia and agranulocytosis 
Water retention resulting in hyponatraemia 
Drug-drug interactions
56
Q

Features of lamotrigine

A

Indication similar to other anticonvulsants
Also used for neuropathic/chronic pain
Before starting get baseline LFTs
Initiation/titration - start with 25mg daily for 2 weeks then increase to 50mg for 2 weeks, then increase to 100mg, faster titration but higher incidence of serious rash
If patient stops medication for 5 or more days then need to re-start at 25mg

57
Q

Side effects of lamotrigine

A 
Nausea
Vomiting
Sedation
Dizziness
Ataxia
Confusion 
Most severe are toxic epidermal necrolysis and Stevens Johnson's Syndrome 
Character/severity of rash if not a good predictor of severity of reaction so if any rash develops discontinue use immediately 
Blood dyscrasias - rare
58
Q

What drugs increase lamotrigine level?

A

VPA

Sertraline

59
Q

Indications for use of antipsychotics

A

Schizophrenia
Schizoaffective disorder
Bipolar disorder - for mood stabilisation and/or when psychotic features are present
Psychotic depression
Augmenting agent in treatment resistant anxiety disorders

60
Q

What are the key pathways affected by dopamine in the brain?

A

Mesocortical
Mesolimbic
Nigrostriatal
Tuberoinfundibular

61
Q

Features of mesocortical pathway

A

Projects from ventral tegmenjtum to the cerebral cortex
Felt to be where the negative symptoms and cognitive disorders arise
Problem here for a psychotic patient is too little dopamine

62
Q

Features of mesolimbic pathway

A

Projects from dopaminergic cell bodies int he ventral tegmenjtum to the limbic system
Where the positive symptoms come from e.g. hallucinations, delusions and thought disorders
Problem here for a psychotic patient is too much dopamine

63
Q

Features of nigrostriatal pathway

A

Projects from dopaminergic cell bodies in the substantial migrant to the basal ganglia
Involved in movement regulation
Dopamine hyperactivity can cause Parkinsonia movements - rigidity, bradykinesia, tremors, akathisia and dystonia

64
Q

Features of tuberoinfundibular pathway

A

Projects from hypothalamus to the anterior pituitary

Blocking dopamine in this pathway will predispose patient to hyperprolactinaemia

65
Q

Features of typical antipsychotics

A

D2 dopamine receptor antagonists
High potency typical antipsychotics bind to D2 receptor with high affinity
Higher risk of extra-pyramidal side-effets
Low potency typical antipsychotics have less affinity for D2 receptors but tend to interact with non-dopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects

66
Q

Examples of high potency typical antipsychotics

A

Fluphenazine
Haloperidol
Pimozide

67
Q

Examples of low potency typical antipsychotics

A

Chlorpromazine

Thioridazine

68
Q

Features of atypical antipsychotics

A

Atypical agents are serotonin-dopamine D antagonists
Considered atypical in the way they affect dopamine and serotonin neurotransmission int he four key dopamine pathways in the brain

69
Q

Examples of atypical antipsychotics

A 
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Clozapine
70
Q

Features of risperidone

A

Available in regular tabs, IM depots and rapidly dissolving tablet
Functions more like a typical antipsychotic at doses > 6mg
Increased extrapyramidal side effects (dose dependent)
Most likely atypical to induce hyperprolactinaemia
Weight gain and sedation - dose dependent

71
Q

Features of olanzapine

A

Available in regular tabs, immediate release IM, rapidly dissolving tablet and depot form
Weight gain - can be as much as 30-50lbs even with short-term use
May cause hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia
May cause hyperprolactinaemia
May cause abnormal LFTs

72
Q

Features of quetiapine

A

Available in regular tablet form only
May cause abnormal LFTs
May be associated with weight gain, though less than seen with olanzapine
May cause hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia but less than with olanzapine
Most likely to cause orthostatic hypotension

73
Q

Features of aripiprazole

A

Available in regular tabs, immediate release IM formation and depot form
Unique mechanism of action as D2 partial agonist
Low EPS, no QT prolongation, low sedation
CYP2D6, 3A4 interactions
Not associated with weight gain

74
Q

Features of clozapine

A

Available only in regular tablet form
Reserved for treatment of resistant patients due to side-effect profile, but highly effective
Associated with agranulocytosis and therefore requires weekly blood draws for 6 months then 2 weekly for 6 months
Increased risk of seizures, especially if lithium also being used
Associated with the most sedation, weight gain and abnormal LFTs
Increased risk of hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia, including non-ketotic hyperosmolar coma and death with/without weight gain

75
Q

What is the commonest psychotic symptom?

A

Lack of insight

76
Q

Why do people with psychotic illnesses most commonly relapse?

A

Non-compliance

77
Q

What percentage of patients take medications as prescribed?

A

30%

78
Q

Adverse effects of antipsychotics

A

Tardive dyskinesia
Neuroleptic malignant syndrome
Extrapyramidal side effects

79
Q

Agents for treatment of extrapyramidal side effects

A

Anticholinergics e.g. benzotropine, trihexyphenidyl, diphenhydramine
Dopamine facilitators e.g. amantadine
Beta blockers e.g. propranolol
Need to watch for anticholinergic side effects

80
Q

Features of anxiolytics

A

Used to treat many diagnoses including pain disorder, generalised anxiety disorder, substance-related disorders and their withdrawal, insomnias and parasomnias
In anxiety disorders, often used in combination with SSRIs or SNRIs for treatment

81
Q

Pros and cons of buspirone

A

Pros

  • good augmentation strategy, mechanism of action is 5HT1A agonist, works independently of endogenous release of serotonin
  • no sedation

Cons

  • takes around 2 weeks before patients notice results
  • will not reduce anxiety in patients that are used to taking benzodiazepines because there is no sedation effect
82
Q

Features of benzodiazepines

A

Used to treat insomnia, parasomnias and anxiety disorders

Often used for CNS depressant withdrawal protocols

83
Q

Side effects/cons of benzodiazepines

A 
Somnolence
Cognitive deficits
Amnesia
Disinhibition
Tolerance 
Dependence

Psychiatry (21 decks)

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