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Systems: Psychiatry AB > Psycho-Pharmacology > Flashcards

Flashcards in Psycho-Pharmacology Deck (152):
1

What are the general pharmacology strategies?

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

Choice of agent and dosage
-Select an agent with an acceptable side effect profile and use the lowest effective dose. Remember the delayed response for many psych meds and drug-drug interactions.

Management
-Adjust dosage for optimum benefit, safety and compliance. Use adjunctive and combination therapies if needed however always strive for the simplest regime.

2

What are the indications for antidepressants?

-Unipolar and bipolar depression
-Organic mood disorders
-Schizoaffective disorder
-Anxiety disorders (OCD, panic, social phobia, PTSD)
-Premenstrual dysphoric disorder
-Impulsivity associated with personality disorders

3

What is selection of antidepressant based on?

-Past history of response
-Side effect profile
-Coexisting medical conditions

4

How long before symptoms start to improve on antidepressants?

There is a delay typically of 2-4 weeks after a therapeutic dose is achieved before symptoms improve.

5

What should be done if no improvement is seen on antidepressants?

If no improvement is seen after a trial of adequate length (at least 2 months) and adequate dose, either switch to another antidepressant or augment with another agent.

6

How should antidepressants be used prophylactically?

-First episode continue for 6mth to a year
-Second episode continue for 2 years
-Third episode discuss life long

7

What are the classifications of antidepressants?

-Tricyclics (TCAs)
-Monoamine Oxidase Inhibitors (MAOIs)
-Selective Serotonin Reuptake Inhibitors (SSRIs)
-Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
-Novel antidepressants

8

What side effects can TCAs have?

-Antihistaminic, anticholinergic, antiadrenergic
-Lethal in overdose (even 1 week supply can be lethal)
-Prolonged QT complex

9

Describe the components of tertiary TCAs

-Have tertiary amine side chains
-Have active metabolite including despipramine and nortripytline

10

Why do tertiary TCAs have more side effects than others?

Side chains are prone to cross react with other types of receptors which leads to more side effects

11

Give examples of tertiary TCAs.

-Imipramine,
-Amitriptyline
-Doxepin,
-Clomipramine

12

What are secondary TCAs?

They are often metabolites of tertiary amines

13

Give examples of secondary TCAs

-Desipramine
-Nortriptyline

14

What side effects do secondary TCAs have?

Same as tertiary TCAs but less severe

15

What is the mechanism of secondary TCAs?

Primarily block noradrenaline

16

What is the mechanism of monoamine oxidase inhibitors?

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

17

What are MAOIs particularly effective in?

Resistant depression

18

What side effects do MAOIs have?

-Orthostatic hypotension
-Weight gain
-Dry mouth
-Sedation
-Sexual dysfunction
-Sleep disturbance

19

What is the cheese reaction?

Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or sympathomimetics

20

When can serotonin syndrome develop?

Serotonin Syndrome can develop if take MAOI with meds that increase serotonin or have sympathomimetic actions

21

What are the symptoms of serotonin syndrome?

-Abdominal pain
-Diarrhoea
-Sweats
-Tachycardia
-HTN
-Myoclonus
-Irritability
-Delirium
-Can lead to hyperpyrexia, cardiovascular shock and death

22

How is serotonin syndrome avoided?

To avoid need to wait 2 weeks before switching from an SSRI to an MAOI. The exception of fluoxetine where need to wait 5 weeks because of long half-life.

23

What is the mechanism of SSRIs?

They block presynaptic serotonin reuptake

24

What are SSRIs used for?

Anxiety and depression symptoms

25

What side effects do SSRIs have?

-GI upset
-Sexual dysfunction
-Anxiety
-Restlessness
-Nervousness
-Insomnia
-Fatigue or sedation
-Dizziness
-Cardiotoxicity (very little risk in overdose)

26

What are the symptoms of SSRI associated activation syndrome?

-Nausea
-Increased anxiety
-Panic
-Agitation

27

Why does activation syndrome occur with SSRIs?

Increase in serotonin

28

What are the symptoms of SSRI associated discontinuation syndrome?

-Agitation
-Nausea
-Disequilibrium
-Dysphoria

29

How long can SSRI associated activation syndrome last?

2-10 days

30

When is SSRI discontinuation syndrome more likely to occur?

More common with shorter half life drugs so consider switching to fluoxetine

31

What are the advantages of paroxetine?

-Short half life with no active metabolite means no build-up (which is good if hypomania develops)
-Sedating properties (dose at night) offers good initial relief from anxiety and insomnia

32

What type of drug is paroxetine?

SSRI

33

What are the disadvantages of paroxetine?

-Sedating, wt gain, more anticholinergic effects
-Likely to cause a discontinuation syndrome

34

What type of drug is sertraline?

SSRI

35

What are the advantages of sertraline?

-Very weak P450 interactions (only slight CYP2D6)
-Short half life with lower build-up of metabolites
-Less sedating when compared to paroxetine

36

What are the disadvantages of sertraline?

-Max absorption requires a full stomach
-Increased number of GI adverse drug reactions

37

What type of drug is fluoxetine?

SSRI

38

What are the advantages of fluoxetine?

-Long half-life so decreased incidence of discontinuation syndromes. Good for pts with medication noncompliance 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 SSRI Discontinuation Syndrome

39

What are the disadvantages of fluoxetine?

-Long half life and active metabolite may build up (e.g. not a good choice in patients with hepatic illness)
-Significant P450 interactions so this may not be a good choice in pts already on a number of meds
-Initial activation may increase anxiety and insomnia
-More likely to induce mania than some of the other SSRIs

40

What type of drug is citalopram?

SSRI

41

What are the advantages of citalopram?

-Low inhibition of P450 enzymes so fewer drug-drug interactions
-Intermediate ½ life

42

What are the disadvantages of citalopram?

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

43

What type of drug is escitalopram?

SSRI

44

What are the advantages of escitalopram?

-Low overall inhibition of P450s enzymes so fewer drug-drug interactions
-Intermediate 1/2 life
-More effective than Citalopram in acute response and remission

45

What are the disadvantages of escitalopram?

-Dose-dependent QT interval prolongation with doses of 10-30mg daily
-Nausea, headache

46

What type of drug is fluvoxamine?

SSRI

47

What are the advantages of fluvoxamine?

-Shortest ½ life
-Found to possess some analgesic properties

48

What are the disadvantages of fluvoxamine?

-Shortest ½ life
-GI distress, headaches, sedation, weakness
-Strong inhibitor of CYP1A2 and CYP2C19

49

What is the mechanism of SNRIs?

Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects

50

What are SNRIs used for?

-Depression
-Anxiety
-Neuropathic pain

51

What type of drug is venlafaxine?

SNRI

52

What are the advantages of venlafaxine?

-Minimal drug interactions and almost no P450 activity
-Short half life and fast renal clearance avoids build-up (good for geriatric populations)

53

What are the disadvantages of venlafaxine?

-Can cause a 10-15 mmHG dose dependent increase in diastolic BP.
-May cause significant nausea, primarily with immediate-release (IR) tabs
-Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration
-Noted to cause QT prolongation
-Sexual side effects in >30%

54

What type of drug is duloxetine?

SNRI

55

What are the advantages of duloxetine?

-Some data to suggest efficacy for the physical symptoms of depression
-Thus far less BP increase as compared to venlafaxine, however this may change in time

56

What are the disadvantages of duloxetine?

-CYP2D6 and CYP1A2 inhibitor
-Cannot break capsule, as active ingredient not stable within the stomach
-In pooled analysis had higher drop out rate

57

What type of drug is mirtazapine?

Novel antidepressant

58

What are the advantages of mirtazapine?

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

59

What are the disadvantages of mirtazapine?

-Increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients
-Very sedating at lower doses. At doses 30mg and above it can become activating and require change of administration time to the morning.
-Associated with weight gain (particularly at doses below 45mg

60

What type of drug is buproprion?

Novel antidepressant

61

What are the advantages of burproprion?

-Good for use as an augmenting agent
-Mechanism of action likely reuptake inhibition of dopamine and norepinephrine
-No weight gain, sexual side effects, sedation or cardiac interactions
-Low induction of mania
-Is a second line ADHD agent so consider if patient has a co-occurring diagnosis

62

What are the disadvantages of buproprion?

-May increase seizure risk at high doses (450mg+) and should avoid in patients with Traumatic Brain Injury, bulimia and anorexia.
-Does not treat anxiety unlike many other antidepressants and can actually cause anxiety, agitation and insomnia
-Has abuse potential because can induce psychotic sx at high doses

63

What are the indications for mood stabilisers?

-Bipolar
-Cyclothymia
-Schizoaffective

64

What is the only medication to reduce suicide rate?

Lithium

65

What is lithium effective for?

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

66

What factors predict a positive response to lithium?

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

67

What should be done before starting lithium?

-Get baseline U&E and TSH.
-In women check a pregnancy test- during the first trimester is associated with Ebstein’s anomaly 1/1000 (20X greater risk than the general population)

68

How should lithium use be monitored?

-Steady state achieved after 5 days- check 12 hours after last dose.
-Once stable check level 3 months and TSH and creatinine 6 months.

69

What is the goal with lithium use?

Blood level between 0.6-1.2

70

What are the side effects of lithium?

-Most common are GI distress including reduced appetite, nausea/vomiting, diarrhoea
-Thyroid abnormalities
-Nonsignificant leukocytosis
-Polyuria/polydypsia secondary to ADH antagonism. In a small number of patients can cause interstitial renal fibrosis.
-Hair loss, acne
-Reduces seizure threshold, cognitive slowing, intention tremor

71

How does mild lithium toxicity present?

Levels 1.5-2
-Vomiting
-Diarrhoea
-Ataxia
-Dizziness
-Slurred speech
-Nystagmus

72

How does moderate lithium toxicity present?

Levels 2-2.5
-Nausea
-Vomiting
-Anorexia
-Blurred vision
-Clonic limb movements
-Convulsions
-Delirium
-Syncope

73

How does severe lithium toxicity present?

Levels >2.5
-Generalised convulsions
-Oliguria
-Renal failure

74

What type of drug is valproic acid (Depakote)?

Anticonvulsant

75

What factors predict a positive response to valproic acid?

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

76

How does valproic acid compare to lithium?

-Valproic acid is as effective as Lithium in mania prophylaxis but is not as effective in depression prophylaxis.
-Better tolerated than lithium

77

What should be done before starting valproic acid?

-Baseline LFTs
-Pregnancy test
-FBC

78

Why should valproic acid be avoided in women of child bearing age?

Can cause neural tube defects

79

How should valproic acid use be monitored?

-Steady state achieved after 4-5 days
-Check 12 hours after last dose and repeat CBC and LFTs

80

What is the goal of valproic acid use?

Target blood level 50-125

81

What are the side effects of valproic acid?

-Thrombocytopenia and platelet dysfunction
-Nausea, vomiting, weight gain
-Sedation, tremor
-Increased risk of neural tube defect 1-2% vs 0.14-0.2% in general population secondary to reduction in folic acid
-Hair loss

82

What is the first line agent for acute mania and mania prophylaxis?

Carbamazepine

83

What type of drug is carbamazepine (tegretol)?

Anticonvulsant

84

What is carbamazepine indicated for?

Rapid cyclers and mixed patients

85

What should be done before carbamazepine is started?

-Baseline LFTs
-FBC
-ECG

86

How should carbamazepine be monitored?

-Steady state achieved after 5 days
-Check 12 hours after last dose and repeat CBC and LFTs

87

What is the goal of carbamazepine used?

Blood levels 4-12mcg/ml

88

Why should carbamazepine levels be checked after 1 month?

Need to check level and adjust dosing after around a month because induces own metabolism.

89

What are the side effects of carbamazepine?

-Rash- most common SE seen
-Nausea, vomiting, diarrhoea
-Sedation, dizziness, ataxia, confusion
-AV conduction delays
-Aplastic anaemia and agranulocytosis (<0.002%)
-Water retention due to vasopressin-like effect which can result in hyponatremia
-Drug-drug interactions!

90

What type of drug is lamotrigine (lamictal)??

Anticonvulsant

91

What are the indications for lamotrigine?

-Mania
-Neuropathic/chronic pain

92

What should be done before starting lamotrigine?

Baseline LFTs

93

How should lamotrigine be initiated and titrated?

-Start with 25 mg daily X 2 weeks then increase to 50mg X 2 weeks then increase to 100mg
-Faster titration has a higher incidence of serious rash

94

What happens if a patient stops taking their lamotrigine?

If the patient stops the med for 5 days or more have to start at 25mg again!

95

What are the side effects of lamotrigine?

-Nausea/vomiting
-Sedation, dizziness, ataxia and confusion
-TEN and Stevens Johnson's syndrome
-Blood dyscrasias (rare)

96

What drugs can increase lamotrigine levels?

-VPA (doubles concentration, so use slower dose titration),
-Sertaline

97

Why should lamotrigine be discontinued if ANY rash develops?

-The character/severity of the rash is not a good predictor of severity of reaction
-Therefore, if ANY rash develops, discontinue use immediately.

98

What antipsychotic drugs are approved for use in bipolar disorder for mania?

-Aripiprazole
-Risperdone
-Quetiapine
-Quetiapine XR
-Olanzipine

99

What antipsychotic drugs are approved for use in bipolar disorder for mixed symptoms?

-Aripiprazole
-Risperdone
-Olanzipine

100

What antipsychotic drugs are approved for use in bipolar disorder for maintenance?

-Aripiprazole
-Quetiapine
-Quetiapine XR
-Olanzipine

101

What antipsychotic drugs are approved for use in bipolar disorder for depression?

Quetiapine XR

102

What are the indications for antipsychotic drug use in mod stabilisation?

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

103

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

-Mesocortical
-Mesolimbic
-Nigrostriatal
-Tuberoinfundibular

104

Describe the mesocortical pathway and its role in mood disorders.

-Projects from the ventral tegmentum (brain stem) to the cerebral cortex.
-This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise.
-Problem here for a psychotic patient, is too little dopamine.

105

Describe the mesolimbic pathway and its role in mood disorders.

-Projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system.
-This pathway is where the positive symptoms come from (hallucinations, delusions, and thought disorders).
-Problem here in a psychotic patient is there is too much dopamine.

106

Describe the nigrostriatal pathway and its role in mood disorders.

-Projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia.
-This pathway is involved in movement regulation.
-Remember that dopamine suppresses acetylcholine activity. -Dopamine hypoactivity can cause Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia and dystonia.

107

Describe the tuberoinfundibular pathway and its role in mood disorders.

-Projects from the hypothalamus to the anterior pituitary.
-Remember that dopamine release inhibits/regulates prolactin release.
-Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia (gynecomastia/ galactorrhea/ decreased libido/ menstrual dysfunction).

108

What is the mechanism of typical antipsychotics?

D2 dopamine receptor antagnoists

109

Give examples of high potency typical antipsychotics.

-Fluphenazine
-Haloperidol
-Pimozide

110

Explain the effects of high potency typical antipsychotics.

-High potency typical antipsychotics bind to the D2 receptor with high affinity.
-As a result they have higher risk of extrapyramidal side effects

111

Explain the effects of low potency typical antipsychotics.

-Low potency typical antipsychotics have less affinity for the D2 receptors
-They tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects including sedation, hypotension

112

Give examples of low potency typical antipsychotics.

-Chlorpromazine
-Thioridazine

113

What is the mechanism of atypical antipsychotics?

Serotonin-dopamine 2 antagonists (SDAs)

114

In what way are atypical antipsychotics considered atypical?

They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

115

What type of drug is risperidone (Risperdal)?

Atypical antipsychotic

116

In what forms is risperidone available?

-Regular tablet
-IM depot forms
-Rapidly dissolving tablet

117

What are the side effects of risperidone?

-Increased extrapyramidal side effects (dose dependent)
-Most likely atypical to induce hyperprolactinemia
-Weight gain and sedation (dosage dependent)

118

How does the function of risperidone change at doses greater than 6mg?

Functions more like a typical antipsychotic at doses greater than 6mg

119

What type of drug is olanzapine (Zyprexa)?

Atypical antipsychotic

120

In what forms is olanzapine available?

-Regular tablet
-Immediate release IM
-Rapidly dissolbing tab
-Depo form

121

What are the side effects of olanzapine?

-Weight gain (can be as much as 30-50lbs with even short term use)-Hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain)
-Hyperprolactinemia (< risperidone)
-Abnormal LFT’s (2% of all patients)

122

What type of drug is quetiapine (Seroquel)?

Atypical antipsychotic

123

In what form is quetiapine available?

Regular tablet only

124

What are the side effects of quetiapine?

-Abnormal LFTs
-Weight gain (

125

What type of drug is aripiprazole (abilify)?

Atypical aripiprazole

126

In what forms if aripiprazole available?

-Regular tablets
-Immediate release IM formulation
-Depo form

127

What is the mechanism of ariprprazole?

Unique mechanism of action as a D2 partial agonist

128

What are the possible interactions of ariprprazole?

-CYP2D6 (fluoxetine and paroxetine), 3A4 (carbamazepine and ketoconazole) interactions that the manufacturer recommends adjusted dosing.
-Could cause potential intolerability due to akathisia/activation.

129

What is aripiprazole not associated with?

-Weight gain
-QT prolongation

130

What type of drug is clozapine (clozaril)?

Atypical antipsychotic

131

What form is clozapine available in?

Regular tablet only

132

Who is clozapine reserved for?

Treatment resistant patients because of side effect profile but this stuff works

133

What are the side effects of clozapine?

-Agranulocytosis
-Increased risk of seizures
-Sedation, weight gain abnormal LFTs
-Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain

134

Due to its association with agranulocytosis, what should be done monitoring wise for clozapine use?

Requires weekly blood draws for 6 months then fortnightly for 6 months

135

What is the commonest psychotic symptom?

Lack of insight

136

What problem can psychosis present in terms of medication?

-People with psychotic illnesses relapse most commonly due to non compliance
-Only 30% of patients take medication as prescribed

137

What should be considered after a 3rd episode of schizophrenia?

-There is a clear link to reduced functioning, lower IQ and negative symptoms
-Consider long acting IM

138

Give examples of adverse effects of antipsychotics.

-Tardive dyskinesia
-Neuroleptic malignant syndrome

139

What is tardive dyskinesia?

-Involuntary muscle movements that may not resolve with drug

140

How does neuroleptic malignant syndrome present?

Characterised by:
-Severe muscle rigidity
-Fever
-Altered mental status
-Autonomic instability
-Elevated WBC, CPK and LFTs
-Potentially fatal

141

What extrapyramidal side effects are associated with antipsychotic use?

-Acute dystonia
-Parkinson syndrome
-Akathisia

142

What agents can be used for extrapyramidal symptoms?

-Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine
-Dopamine facilitators such as Amantadine
-Beta-blockers such as propranolol

143

What are anxiolytics used to treat?

-Panic disorder
-GAD
-Substance-related disorders and their withdrawal
-Insomnias
-Parasomnias

144

What treatment regime is common in anxiety disorders?

In anxiety disorders often use anxiolytics in combination with SSRIS or SNRIs for treatment.

145

What type of drug is buspirone (buspar)?

Non-benzodiazepine anti-anxiety drug

146

What are the advantages of buspirone?

-Good augmentation strategy- Mechanism of action is 5HT1A agonist. It works independent of endogenous release of serotonin.
-No sedation

147

What are the disadvantages of buspirone?

-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 the edge off.

148

What type of drug are benzodiazepines?

Anti-anxiety CNS depressants

149

What are benzodiazapines used to treat?

-Insomnia
-Parasomnias
-Anxiety disorder
-Often used for CNS depressant withdrawal protocols ex. ETOH withdrawal

150

What are the side effects of benzodiazapines?

-Somnolence
-Cognitive deficits
-Amnesia
-Disinhibition
-Tolerance
-Dependence

151

How do you deal with treatment resistance with antidepressants?

-Start with SSRI
-Combine SSRI with SNRI
-Adjunctive treatment with lithium
-Adjunctive treatment with atypical antipsychotic
-ECT

152

What are the classes of mood stabiliser?

-Lithium
-Anticonvulsants
-Antipsychotics