Psychopharmacology Flashcards

1
Q

What are some generalised Pharmacology strategies?

A

Indication - establish diagnosis and identify symptoms that will be used to monitor therapy response.

Choice of Agent and dosage - select an agent with acceptable side effect profile and use lowest effective dose.

Management - Adjust dose for optimum benefit, safety and compliance. Strive for the simplest regime.

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2
Q

What are some indications for the use of antidepressants?

A

Unipolar and bipolar depression
Organic mood disorders
Schizoaffective disorder Anxiety disorders including OCD, panic, social phobia and PTSD.

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3
Q

What are the general guidelines for antidepressant use?

A

Antidepressant selection is based on past Hx of a response, side effect profile and coexisting medical conditions.
Delay of 3-6weeks before symptoms improve
If no improvement after at least 2 months then switch to another antidepressant or augment with another agent.

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4
Q

What are some different types of Antidepressants?

A
Tricyclic antidepressants
Monoamine Oxidase Inhibitors
Selective serotonin Reuptake Inhibitors.
Serotonin/Noradrenaline reuptake inhibitors (SNRIs).
Novel antidepressants.
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5
Q

What are some disadvantages of Tricyclic antidepressants?

A

Have may side effects including antihistaminic, anticholinergic and antiadrenergic.
Lethal in overdose even if it is a week long supply.
Can cause QT lengthening.

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6
Q

What are some examples of Tertiary TCAs?

A

Imipramine
Amitriptyline
Doxepin
Clomipramine

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7
Q

What are some characteristics of tertiary TCAs?

A

Act predominantly on serotonin receptors.
Have active metabolites including desipramine and nortiptyline.
Side chains are prone to cross react with other types of receptors which leads to more side effects.

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8
Q

What are some characteristics of secondary TCAs?

A

Often metabolites of tertiary amines.
Primarily block noradrenaline.
Side effects are same as tertiary but generally less severe.
Examples include Desipramine, Nortriptyline

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9
Q

What are some characteristics of Monoamine Oxidase Inhibitors?

A

Bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as dopamine, norepinephrine and serotonin leading to increased synaptic levels.

Very effective for depression

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10
Q

What are some disadvantages of Monoamine Oxidase Inhibitors?

A

Side effects include orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance.

Hypertensive crisis can develop if they are taken with tyramine rich foods or sympathomimetics e.g. cheese.

Serotonin syndrome can develop if taken with meds that increase serotonin or have sympathomimetic actions. To avoid wait 2 weeks before switching from SSRI to MAOI. Fluoxetine need to wait 5 weeks as long half-life.

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11
Q

What are the symptoms of Serotonin syndrome?

A
Abdominal pain
Diarrhoea
Sweats
Tachycardia
HTN
Myoclonus
Irritability
Delirium 
Hyperpyrexia
Cardiovascular shock
Death
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12
Q

What are some characteristics of Selective Serotonin Reuptake Inhibitors?

A

Block pre-synaptic serotonin reuptake.
Treat both anxiety and depressive symptoms.
Very little risk of cardio toxicity in overdose.

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13
Q

What are some disadvantages of SSRIs?

A

Side effects - GI upset, sexual dysfunction, anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness.

Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria.

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14
Q

What are the advantages of Paroxetine?

A

Short half-life with no active metabolite

Sedating properties offers good initial relief from anxiety and insomnia.

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15
Q

What are the disadvantages of Paroxetine?

A

Significant CYP2D6 inihibtion.
Sedating, weight gains and more anticholingeric effects.
Likely to cause discontinuation syndrome.

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16
Q

What are the disadvantages of Sertraline?

A

Max absorption requires a full stomach.

Increased number of GI adverse drug reactions.

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17
Q

What are the advantages of Sertraline?

A

Very weak P450 interactions
Short half-life with lower build up of metabolites.
Less sedating than paroxetine.

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18
Q

What are the advantages of Fluoxetine (Prozac)?

A

Long half-life so decreased incidence of discontinuation syndromes.
Good for patients with noncompliance issues.
Initially activating so may provide increased energy.
Can give 1 20mg tablet to taper someone off SSRI.

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19
Q

What are the disadvantages of Fluoxetine?

A

Long half-life and active metabolite build up. Not a good choice in patient with hepatic illness.
Significant P450 interactions so not good for patients on a number of meds.
Initial activation may increase anxiety and insomnia.
More likely to induce mania than some other SSRIs.

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20
Q

What are the advantages of Citalopram?

A

Low inhibition of p450 enzymes so fewer drug-drug interactions.
Intermediate half-life

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21
Q

What are the disadvantages of Citalopram?

A

Dose dependent QT interval prolongation with doses of 10-30mg daily due to this risk doses of >40mg are not recommended.
Can be sedating (has mild antagonism at H1 histamine receptors)
GI side effects (but less than sertraline).

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22
Q

What are the advantages of Escitalopram?

A

Low overall inhibition of P450s enzymes so fewer drug-drug interactions.
Intermediate half-life
More effective than citalopram in acute response and remission.

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23
Q

What are the disadvantages of Escitalopram?

A

Dose-dependent Qt interval prolongation with doses <40mg daily
Nausea
Headache

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24
Q

What are the advantages of Fluvoxamine?

A

Shortest half-life

Found to possess soma analgesic properties

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25
Q

What are the disadvantages of Fluvoxamine?

A
Shortest half-life
GI distress
Headaches
Sedation
Weakness
Strong inhibitor of CYP1A2 and CYP2C19
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26
Q

What is the action of serotonin/Norepinephrine reuptake inhibitors (SNRIs)?

A

Inhibit both serotonin and noradrenergic reupatke like TCA but without the antihistamine, anticholinergic and antiadrenergic side effects.
Used for depression, anxiety and possibly neuropathic pain.

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27
Q

What are the advantages of Venlafaxine?

A

Minimal drug interactions and almost no P450 activity.

Short half-life and renal clearance avoids build-up.

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28
Q

What are the disadvantages of Venlafaxine?

A

Can cause a 10-15mmHg dose dependent increase in diastolic BP.
May cause nausea, primarily with immediate release tabs.
Discontinuation syndrome
Noted to cause QT prolongation
Sexual side effects

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29
Q

What are the advantages of duloxetine?

A

Efficacy for physic symptoms of depression

Less BP increase compared to venlafaxine.

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30
Q

What are the disadvantages of Duloxetine?

A

CYP2D6 and CYP1A2 inhibitors
Cannot break capsule as active ingredient not stable within stomach.
Higher drop out rate.

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31
Q

What are the advantages of the novel antidepressant Mirtazapine?

A

Different mechanism of action may provide good augmentation strategy to SSRIs. 5HT2 and 5HT3 receptor antagonist
Can be utilised as a hypnotic at lower doses secondary to antihistaminic effects.

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32
Q

What are the disadvantages of Mirtazapine?

A

Increases serum cholesterol by 20% in 15% of patients and increases triglycerides in 6%.
Very sedating at lower doses
Associated with weight gain, particularly with doses<45mg.

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33
Q

What are the advantages of Buproprion?

A

Good augmenting agent
mechanism of action is likely reuptake inhibition of dopamine and norepinephrine.
No weight gain, sexual side effects, sedation or cardiac interactions.
Low induction of mania
2nd line ADHD agent so consider if co-occuring diagnosis.

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34
Q

What are the disadvantages of Buprprion?

A

May increase seizure risk at high doses and should avoid in patients with traumatic brain injury, bulimia, and anorexia.
Does not treat anxiety and can actually cause it and agitation and insomnia.
Has abuse potential because can induce psychotic symptoms at high doses.

35
Q

What is the treatment for treatment resistance disorders?

A

Combination of antidepressants e.g. SSRI/SNRI + Mirtazapine

Adjunctive treatment with Lithium.
Adjunctive treatment with atypical antipsychotic e.g quetiapine, Olanzapine or Aripiprazole.

ECT

36
Q

What are the indications for the use of mood stabilisers?

A

Bipolar disorder
Cyclothymia
Schizoaffective disorder.

37
Q

What are the different classes of Mood Stabiliser?

A

Lithium
Anticonvulsants
Antipsychotics

38
Q

What are some features of Lithium?

A

Only med to reduce suicide rate.

Effective long-term prophylaxis of both mania and depressive episodes.

39
Q

What are some factors that predict a positive response to lithium?

A

Prior long-term response or family member good response.
Classic pure mania
Mania is followed by depression.

40
Q

What must you do before starting Lithium treatment?

A

Get baseline U&E and TSH

Pregnancy test - Associated with Ebstein’s anomaly.

41
Q

How long does it take to achieve a steady state after initiating Lithium treatment?

A

5days

Check regularly U&Es 3 months and TSH and creatinine every 6 months.

42
Q

What is the goal of lithium treatment for blood?

A

Blood level between 0.6 and 1.2

43
Q

What are some side effects of Lithium?

A

GI distress - reduced appetite, nausea and vomiting, diarrhoea.
Thyroid abnormalities
Nonsignificant leukocytosis
Polyuria/polydypsia secondary to ADH antagonism.
HAir loss
Acne
Reduces seizure threshold, cognitive slowing and intention tremor.

44
Q

What are some features of Valproic acid?

A

Effective as lithium in mania prophylaxis but not as effective in depression.
Better tolerated than Lithium.

45
Q

What are some factors that predict a good response to Valproic acid?

A

Rapid cycling patients (females>males)
Comorbid substance issues
Mixed patients
Patients with comorbid anxiety disorders.

46
Q

What must you do before you start valproic acid?

A

Baseline LFTs
Pregnancy test
FBC

47
Q

How long does it take to achieve a steady state after initial valproic acid treatment?

A

4-5days

48
Q

What is the target level for valproic acid?

A

50-125

49
Q

What are some side effects of Valproic acid?

A
Thrombocytpenia and platelet dysfunction
Nausea, vomiting, weight gain
Sedation, tremor
Neural tube defects
Hair loss
50
Q

What is the 1st line treatment for acute Mania and Mania prophylaxis?

A

Carbamazepine (Tegretol)

51
Q

What must you do before starting Carbamazepine?

A

Baseline LGFTS, FBC and ECG.

52
Q

How long does it take to achieve a steady state with Carbamazepine?

A

5days

53
Q

What is the target levels of Carbamazepine?

A

4-12mcg/ml

Need to check dose after a month as it induces its own metabolism.

54
Q

What are the side effects of Carbamazepine?

A
Rash
Nausea, Vomiting, diarrhoea
Sedation, dizziness, ataxia, confusion
AV conduction delays
Aplastic anaemia and agranulocytosis
Water retention due to vasopressin-like effect which can result in hyponatraemia. 
Drug-drug interactions.
55
Q

What are some examples of drugs that interact with Carbamazepine and increase it levels/toxicity?

A
Acetazolamide
Cimetidine
Clozapine
Diltiazem
INH
Fluvoxamine
Fluoxetine
Erythromycin
Metronidazole
56
Q

What are some drugs that reduce the effects of Carbamazepine?

A

Neurleptics
Barbituates
Phenytoin
TCAs

57
Q

What drugs can Carbamazepine increase the metabolism of?

A
Oestrogen
Progesterone
Warfarin
Methadone
Psychotropics
Cyclosporine
Theophylline
58
Q

What are the side effects of Lamotrigine?

A
Nausea
Vomiting
Sedation
Dizziness
Ataxia
Confusion
Toxic epidermal necrolysis
Stevens Johnson's Syndrome
Blood dycrasias
59
Q

Which drugs increase Lamotrigine levels?

A

VPA (doubles its conc)

Sertraline

60
Q

What are some approved antipsychotics for the use in Bipolar disorder?

A
Aripiprazole
Risperdone
Quetiapine
Quetiapine XR
Olanzapine
61
Q

What are the indications for Antipsychotic use?

A
Schizophrenia
schizoaffective disorder
Bipolar disorder for mood stabilisation
Psychotic depression
Augment agent in treatment resistant anxiety disorders.
62
Q

What is the Mesocortical Pathway?

A

Projects from ventral tegmentum (brain stem) to the cerebral cortex.
Where negative symptoms and cognitive disorders arise.
Problem here for a psychotic patient is too little dopamine.

63
Q

What is the Mesolimbic pathway?

A

Projects from dopaminergic cell bodies in the ventral tegmentum to the limbic system.
Positive symptoms come form here.
Problem here in psychotic patient is there is too much dopamine.

64
Q

What is the Nigrostriatal pathway?

A

Projects from dopaminergic cell bodies in substantial nigra to the basal ganglia.
Involved in movement regulation (dopamine suppresses acetylcholine activity).
Dopamine hyperactivity can cause parkinsonian movements, akathisia and dystonia.

65
Q

What is the tuberoinfundibulnar pathway?

A

Projects from the hypothalamus to the anterior pituitary. Dopamine release inhibits prolactin release. Blocking dopamine in this pathway predisposes patient too hyperprolactinaemia.

66
Q

What is the method of action of typical antipsychotics?

A

D2 dopamine receptor antagonists.

Bind with high affinity and as a result have higher risk of extrapyramidal side effects.

67
Q

What are some examples of typical antipsychotics?

A

Fluphenazine
Haloperidol
Pimozide

68
Q

What are some features of low potency typical antipsychotics?

A

Less affinity for D2 receptors but tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic side effects.
E.g. Chlorpromazine, Thioridazine.

69
Q

What is the method of action of atypical antipsychotics?

A

Serotonin-dopamine 2 antagonists (SDAs). Atypical in the way they affect dopamine and serotonin neurotransmission in the 4 key dopamine pathways in brain.

70
Q

What are some characteristics of Risperidone?

A

Functions more like a typical antipsychotic at doses >6mg.
Increased extra pyramidal side effects
Most likely atypical
Weight gain and sedation are side effects.

71
Q

What are some characteristics of Olanzapine?

A

Weight gain
May cause hypertriglyceridaemia, hypercholesterolaemia and hyperglycaemia.
May cause hyperporlactinaemia
May cause abnormal LFTs

72
Q

What are some characteristics of quetiapine?

A
Reg tablet form only.
May cause abnormal LFTs
Weight gain
May cause hypertriglyceridaemia, hypercholesterolaemia and hyperglycaemia but less os than olanzapine. 
Orthostatic hypotension.
73
Q

What are some characteristics of Aripiprazole?

A

Low EPS, no QT prolongation, low sedation.
CYP2D6 and 3A4 interactions.
Could cause potential intolerability due to akathisia/activation.
NO associated weight gain

74
Q

What are some characteristics of Clozapine?

A

Reserved for treatment resistant patients
Associated with agranulocytosis so requires weekly blood raws every 6 months.
Increased risk of seizures
Associated with the most sedation, weight gain and abnormal LFTs.
Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain.

75
Q

What are some adverse effects of antipsychotics?

A

Tardive Dyskinesia - involuntary muscle movements that may not resolve.
Neuroleptic malignant syndrome characterised by severe muscle rigidity, fever, altered mental status, autonomic instability. raised WBC, CPK and LFTs.
Extrapyramidal side effects - acute dystonia, Parkinson snydrome, akathisia.

76
Q

What agents would be suitable for EPS?

A

Anticholinergics e.g. benztropine, trihexyphenidyl, diphenhydramine.
Dopamine facilitators e.g. Amantadine
Beta-blockers e.g. propranolol

77
Q

What blood work is needed before administering an atypical antipsychotic?

A

Fasting lipid profile
Fasting blood sugar
LFTs
CBC

78
Q

When are anxiolytics used/

A
Panic disorder
Generalised anxiety disorder
Substance related disorders
Insomnias
Parasomnias

Often used in combination with SSRIs and SNRIs in anxiety disorders.

79
Q

What are the advantages of Buspirone?

A

Good augment agent - 5HT1A agonist.

No sedation

80
Q

What are the disadvantages of Buspirone?

A

Takes around 2 weeks before patients notice results.

Will not reduce anxiety in patients that are used to taking BZDs because there is no sedation effect to take edge off.

81
Q

When are benzodiazepines indicated?

A

Insomnia
Parasomnias
Anxiety disorders
CNS depressant withdrawal protocols.

82
Q

What are the side effects of benzodiazepines?

A
Somnolence
Cognitive deficits
Amnesia
Disinibition
Tolerance
Dependence
83
Q

What are some examples of benzodiazepines?

A
Alprazolam
Clonazepam
Diazepam
Flurazepam
Lorazepam
Oxazepam
Temazepam
Triazolam
Chlordiazepoxide