Psychopharmacology 1 Flashcards
1
Q
List the indications for prescribing antidepressants
A
Unipolar/bipolar depression, organic mood disorders, schizoaffective disorder, anxiety disorders including OCD, panic, social phobia and PTSD
2
Q
How long does it typically take for antidepressants to start improving symptoms?
A
3-6 weeks
3
Q
Name the classifications of antidepressant medications
A
- Tricyclics
- Monoamine Oxidase Inhibitors (MAOIs)
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
4
Q
What are the drawbacks of TCAs?
A
- Potentially unacceptable side effect profile
- Lethal in overdose
- Can cause QT lengthening
5
Q
Describe the mechanism of tertiary TCAs
A
- They have amine side chains with can react with a variety of receptors
- Acts predominantly on serotonin receptors
6
Q
List the possible side effects of TCAs
A
- Anti-histaminic: sedation and weight gain
- Anti-cholinergic: dry mouth, dry eyes, constipation, memory deficits and delirium
- Anti-adrenergic: orthostatic hypotension, sedation and sexual function
7
Q
Give four examples of tertiary TCAs
A
Imipramine, amitryptyline, doxepin and chlomipramine
8
Q
Describe the features of secondary TCAs
A
- Often metabolites of tertiary amines
- Primarily block noradrenaline
- Side effects are the same as tertiary TCAs but generally less severe
9
Q
Give two examples of secondary TCAs
A
Desipramine and nortriptyline
10
Q
Describe the mechanism of monoamine oxidase inhibitors
A
They bind irreversibly to monoamine oxidase thereby preventing inactivation of amines (noradrenaline, dopamine and serotonin etc.) to increase synaptic levels
11
Q
List the possible side effects of monoamine oxidase inhibitors
A
Orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance
12
Q
What is the potential dangerous consequence of monoamine oxidase inhibitors and what causes it?
A
Hypertensive crisis - caused by taking MAOIs with tyramine rich foods (cheese, wine etc.)
13
Q
Name the cause of serotonin syndrome and how it presents
A
- MAOIs being taken alongside meds that increase serotonin or have sympathomimetic actions
- Abdominal pain, diarrhoea, sweats, tachycardia, HTN, myoclonus, irritability and delirium
- Can lead to hyperpyrexia, CVS shock and death
14
Q
Describe the mechanism of selective serotonin reuptake inhibitors and the indications for use
A
- Block the presynaptic serotonin reuptake
- Anxiety and depression
15
Q
List the most common side effects of SSRIs
A
GI upset, sexual dysfunction, anxiety, restlessness, nervousness, insomnia, fatigue/sedation and dizziness
16
Q
What can happen if an SSRI is stopped suddenly?
A
-Discontinuation syndrome: agitation, nausea, disequilibrium and dysphoria
17
Q
What are the pros and cons of Paroxetine?
A
- Pros: short half life and sedation properties (good for anxiety and insomnia)
- Cons: significant CYP2D6 inhibition, sedation, weight gain, anticholinergic effects and likely to cause discontinuation syndrome
18
Q
What are the pros and cons of sertraline?
A
- Pros: weak P450 interactions, short half life and less sedating compared to paroxetine
- Cons: max absorption requires a full stomach and there is an increased number of GI adverse drug reactions
19
Q
What are the pros and cons of fluoxetine (prozac)?
A
Pros
- Long half life (decreased incidence of discontinuation syndrome)
- Initially activating so may provide increased energy
Cons
- Long half life may cause active metabolite to build up
- Significant P450 interactions (not a good choice in patients on multiple meds)
- Initial activation may increase anxiety and insomnia
- More likely to induce mania than other SSRIs
20
Q
What are the pros and cons of citalopram?
A
Pros
- Low inhibition of P450 enzymes so fewer drug interactions
- Intermediate half life
Cons
- Dose dependant QT interval prolongation (>40 mg not recommended)
- Can be sedating
- GI side effects
21
Q
What are the pros and cones of escitalopram?
A
Pros
- Low overall inhibition of P450 enzymes
- Intermediate half life
- More effective than citalopram in acute response and remission
Cons
- Does dependent QT interval prolongation with doses of 10-30mg daily
- Nausea, headaches
22
Q
What are the pros and cons of fluvoxamine?
A
Pros
- Shortest half life
- Found to possess some analgesic properties
Cons
- Shortest half life
- GI distress, headaches, sedation and weakness
- Strong inhibitor of CYP1A2 and CYP2C19
23
Q
What are the benefits of serotonin/noradrenaline reuptake inhibitors?
A
-Inhibit both serotonin and noradrenergic reuptake but without the antihistamine, antiadrenergic or anticholinergic side effects that TCAs have
24
Q
What are the indications for SNRIs?
A
Depression, anxiety and neuropathic pain
25
Give the common examples of SNRIs
Venlafaxine, duloxetine
26
What are the pros and cons of venlafaxine?
Pros
- Minimal drug interactions and P450 activity
- Short half life and fast renal clearance
Cons
- Can cause an increase in diastolic BP
- May cause significant nausea
- Can cause a bad discontinuation syndrome (taper recommended)
- QT prolongation
- Sexual side effects in >30%
27
What are the pros and cons of duloxetine?
Pros
- Data may suggest efficacy for the physical symptoms of depression
- Less BP increase compared to venlafaxine
Cons
- CYP2D6 and CYP1A2
- Cannot break capsule - active ingredient is not stable within the stomach
- Higher drop out rate (in pooled analysis)
28
What are the pros and cons of mirtazapine?
Pros
- Different mechanism of action may provide good augmentation strategy to SSRIs
- Can be utilised as a hypnotic at lower doses
Cons
- Increases serum cholesterol and triglycerides in some patients
- Very sedating at lower doses
- Associated with weight gain
29
What are the pros and cons of buproprion?
Pros
- Good for use as an augmenting agent
- No weight gain, sexual side effects etc.
- Low induction of mania
- Second line ADHD agent
Cons
- May increase seizure risk
- Should be avoided in patients with traumatic brain injury, bulimia and anorexia
- Does not treat anxiety
- Has abuse potential
30
What are the management options for treatment resistant depression?
- Combination of antidepressants e.g. SSRI or SNRI with Mirtazepine
- Adjunctive treatment with lithium
- Adjunctive treatment with an atypical antipsychotic e,g, quetapaine, olanzapine or aripiprazole
- ECT
31
Name the commonly used SSRIs
Paroxetine, sertraline, fluoxetine, citalopram, escitalopram, fluvoxamine
32
What are the indications for mood stabilisers?
Bipolar disorder, cyclothymia and schizoaffective
33
What are the classes of mood stabilisers?
Lithium, anticonvulsants and antipsychotics
34
What are the benefits of using lithium?
- Only medication to reduce suicide rate
| - Effective in long term prophylaxis of both mania and depressive episodes
35
Which 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
36
What should be done before starting a patient on lithium?
- Baseline U&Es and TSH
| - Pregnancy test
37
What should be done after starting a patient on lithium?
- Check levels 12 hrs after day 5 dose
- Check q 3months and TSH and creatinine levels at 6 months
- Blood level should be between 0.6-1.2
38
What are the potential side effects of lithium?
Reduced appetite, nausea/vomiting, diarrhoea, thyroid abnormalities, nonsignificant leukocytosis, polyuria/polydipsia secondary to ADH antagonism, hair loss, acne, reduced seizure threshold, cognitive slowing and intention tremor
39
Describe the features of mild, moderate and severe lithium toxicity
- Mild (1.5-2.0): vomiting, diarrhoea, ataxia, dizziness, slurred speech and nystagmus
- Moderate (2.0-2.5): Nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium and syncope
- Severe (>2.5): generalised convulsions, oliguria and renal failure
40
Name the commonly used anticonvulsants
Valproic acid (Depakote), carbamazepine, lamotrigine
41
What are the benefits and downsides to using valproic acid?
- As effective as lithium in mania prophylaxis
- Better tolerated than lithium
- Not as effective in depression prophylaxis
42
Which factors predict a positive response to valproic acid?
- Rapid cycling patients (females > males)
- Comorbid substance issues
- Mixed patients
- Comorbid anxiety disorders
43
What needs done before and after starting a patient on valproic acid?
- Before: LFTs, pregnancy test and FBC
- After: Folic acid supplement in women and monitoring
- Monitoring: check 12hrs after dose on day 4/5 and repeat FBC and LFTs
- Target level: 50-125
44
What are the potential side effects of valproic acid?
Thrombocytopenia, platelet dysfunction, nausea, vomiting, weight gain, sedation, tremor, increased risk of neural tube defect and hair loss
45
What are the indications for carbamazepine?
- First line for acute mania and mania prophylaxis
| - Indicated for rapid cyclers and mixed patients
46
What should be done before and after starting a patient on carbamazepine?
- Before: LFTs, FBC and ECG
- Monitoring: check levels 12 hrs after day 5 dose and repeat FBC and LFTs
- Target Levels: 4-12mcg/ml
- Check level and adjust does after 1 month (induces own metabolism)
47
What are the potential side effects of carbamazepine?
Rash, nausea, vomiting, diarrhoea, sedation, dizziness, ataxia, confusion, AV conduction delays, aplastic anaemia, agranlulocytosis, water retention leading to hyponatremia and drug-drug interactions
48
List the drugs which can increase carbamazepine levels/toxicity?
Acetazolamide, cimetidine, clozapine, diltiazem, INH, fluvoxamine, fluoxetine, erythromycin, clarithromycin, fluconazole, itraconazole, metronidazole, propoxyphene, verapamil and ketoconazole
49
Which drugs decrease carbamazepine levels?
Neuroleptics, barbiturates, phenytoin and TCAs
50
Which drugs can carbamazepine increase the metabolism of?
Oestrogen, progesterone, warfarin, methadone, antidepressants, antipsychotics, BZDs, immunosuppressants and theophylline etc.
51
What are the potential side effects of lamotrigine?
Nausea, vomiting, sedation, dizziness, ataxia, confusion, toxic epidermal necrolysis and Steven Johnson's syndrome and blood dyscrasias
52
What are the indications for the use of antipsychotics?
Schizophrenia, schizoaffective disorder, bipolar disorder (for mood stabilisation and/or any psychotic features), psychotic depression and as an augmenting agent in treatment resistant anxiety disorders
53
Where does the mesocortical pathway run and why is it relevant to psychotic patients?
- Projects from the ventral tegmentum (brain stem) to the cerebral cortex)
- Where negative symptoms and cognitive disorders (lack of executive function) arise: too little dopamine is the problem
54
Where does the mesolimbic pathway run and why is it relevant to psychotic patients?
- Projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system
- Where the positive symptoms come from (hallucinations, delusions and thought disorders): too much dopamine
55
Where does the nigrostriatal pathway run and why is it relevant to ?
- Projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia
- Involved in movement regulation
- Dopamine hypoactivity causes: parkinsonian movements e.g. rigidity, bradykinesia, tremors, akathisia and dystonia
56
Where does the tuberoinfundibular pathway run and why is it relevant?
- Projects from the hypothalamus to the anterior pituitary
- Dopamine regulates prolactin release
- Blocking dopamine in this pathway will predispose the patient to hyperprolactinaemia (gynaecomastia/ galactorrhoea/ decreased libido/ menstrual dysfunction)
57
How do high potency typical antipsychotics work?
- They are D2 dopamine receptor antagonists
| - They bind to the D2 receptor with high affinity
58
Give 3 examples of high potency typical antipsychotics
- Fluphenazine
- Haloperidol
- Pimozide
59
How do low potency typical antipsychotics work?
-They have less affinity for the D2 receptors but tend to interact with nondopaminergic receptors (has more cardiotoxic and anticholinergic adverse effects)
60
What are the potential side effects
Sedation and hypotension
61
Give two examples of low potency typical antipsychotics
- Chlorpromazine
| - Thioridazine
62
How do atypical antipsychotics work?
- They are serotonin-dopamine 2 antagonists
- They are atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain
63
In which forms is risperidone (risperdal) available in?
Regular tabs, IM depot and rapidly dissolving tablet
64
What happens when the dose of risperidone is greater than 6mg?
It functions more like a typical antipsychotic
65
What are the downsides to using risperidone?
- Side effects: extra pyramidal
- Most likely to induce hyperprolactinaemia
- Causes weight gain and sedation
66
Which forms is Olanzapine (zyprexa) available in?
Regular tabs, immediate release IM, rapidly dissolving tablets and depo form
67
What are the downsides to using olanzapine (zyprexa)?
- Weight gain
- Hypertriglyceridemia, hypercholesterolemia and hyperglycaemia
- May cause hyperprolactinemia
- May cause abnormal LFTs
68
What are the downsides to using quetiapine (seroquel)?
- May cause abnormal LFTs
- May be associated with weight gain
- May cause hypertriglyceridemia, hypercholesterolemia and hyperglycaemia
- Most likely to cause orthostatic hypotension
69
How does aripiprazole (abilify) work?
It is a partial D2 agonist
70
What are the benefits of using aripiprazole?
- Low EPS
- No QT prolongation
- Low sedation
- Not associated with weight gain
71
What are the downsides to using ariprazole?
- CYP2D6 (fluoxetine and paroxetine) and 3A4 (carbamazepine and ketoconazole_ interactions - recommended to adjust the dosing
- Potential intolerability due to akathisia/activation
72
When is clozapine used?
For treatment resistant patients
73
What are the downsides to using clozapine?
- Associated with agranulocytosis
- 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
74
List the possible anti-psychotic adverse effects
- Tardive dyskinesia (involuntary muscle movements)
- Neuroleptic Malignant Syndrome: severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and LFTs -potentially fatal
- Extrapyramidal side effects: acute dystonia, Parkinson syndrome and akathisia
75
How can EPS be managed?
- Anticholinergics e.g. benztropine
- Dopamine facilitators e.g. amatadine
- Beta blockers e.g. propranolol
- Watch for other meds with anticholinergic activity
76
Which baseline drugs should be done before starting someone on an anti-psychotic?
- Fasting lipid profile
- Fasting blood sugar
- LFTs
- FBC
77
What are the indications for anxiolytics?
Panic disorder, generalised anxiety disorder, substance related disorders + their withdrawal, insomnias and parasomnias
78
What are the pros and cons of buspirone (buspar)?
- Pros: good augmentation strategy and no sedation
- Cons: takes roughly 2 weeks before patients notice the results and does not reduce anxiety in patients that are used to BZDs
79
Give examples of anxiolytics
Buspirone
80
What are the indications for benzodiazapines?
- Insomnia, parasomnias and anxiety disorders
| - CNS depressant withdrawal protocols
81
List the side effects/cons of using benzodiazapines
- Somnolence
- Cognitive deficits
- Amnesia
- Disinhibition
- Tolerance
- Dependence
