Psycho-Pharmacology Flashcards
(152 cards)
1
Q
What are the general pharmacology strategies?
A
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
Q
What are the indications for antidepressants?
A
- 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
Q
What is selection of antidepressant based on?
A
- Past history of response
- Side effect profile
- Coexisting medical conditions
4
Q
How long before symptoms start to improve on antidepressants?
A
There is a delay typically of 2-4 weeks after a therapeutic dose is achieved before symptoms improve.
5
Q
What should be done if no improvement is seen on antidepressants?
A
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
Q
How should antidepressants be used prophylactically?
A
- First episode continue for 6mth to a year
- Second episode continue for 2 years
- Third episode discuss life long
7
Q
What are the classifications of antidepressants?
A
- Tricyclics (TCAs)
- Monoamine Oxidase Inhibitors (MAOIs)
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
- Novel antidepressants
8
Q
What side effects can TCAs have?
A
- Antihistaminic, anticholinergic, antiadrenergic
- Lethal in overdose (even 1 week supply can be lethal)
- Prolonged QT complex
9
Q
Describe the components of tertiary TCAs
A
- Have tertiary amine side chains
- Have active metabolite including despipramine and nortripytline
10
Q
Why do tertiary TCAs have more side effects than others?
A
Side chains are prone to cross react with other types of receptors which leads to more side effects
11
Q
Give examples of tertiary TCAs.
A
- Imipramine,
- Amitriptyline
- Doxepin,
- Clomipramine
12
Q
What are secondary TCAs?
A
They are often metabolites of tertiary amines
13
Q
Give examples of secondary TCAs
A
- Desipramine
- Nortriptyline
14
Q
What side effects do secondary TCAs have?
A
Same as tertiary TCAs but less severe
15
Q
What is the mechanism of secondary TCAs?
A
Primarily block noradrenaline
16
Q
What is the mechanism of monoamine oxidase inhibitors?
A
Bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels
17
Q
What are MAOIs particularly effective in?
A
Resistant depression
18
Q
What side effects do MAOIs have?
A
- Orthostatic hypotension
- Weight gain
- Dry mouth
- Sedation
- Sexual dysfunction
- Sleep disturbance
19
Q
What is the cheese reaction?
A
Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or sympathomimetics
20
Q
When can serotonin syndrome develop?
A
Serotonin Syndrome can develop if take MAOI with meds that increase serotonin or have sympathomimetic actions
21
Q
What are the symptoms of serotonin syndrome?
A
- Abdominal pain
- Diarrhoea
- Sweats
- Tachycardia
- HTN
- Myoclonus
- Irritability
- Delirium
- Can lead to hyperpyrexia, cardiovascular shock and death
22
Q
How is serotonin syndrome avoided?
A
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
Q
What is the mechanism of SSRIs?
A
They block presynaptic serotonin reuptake
24
Q
What are SSRIs used for?
A
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
