pharmacology in psychiatry (longer) Flashcards
1
Q
What are the general pharmacology strategies?
A
Indication
- diagnosis & identify target symptoms
Choice of agent and dosage
- agent with acceptable side effect profile and use lowest effective dose (delayed response for many psych meds and drug-drug interactions)
Management
- adjust dosage
- use adjunctive and combination therapies
2
Q
What are the indications for antidepressants?
A
- depression (unipolar/bipolar)
- organic mood disorders
- schizoaffective disorder
- anxiety disorders (OCD, panic, social phobia, PTSD)
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
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
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
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
wait 2 weeks before switching from a SSRI to an MAOI.
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
- 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 type of drug is paroxetine?
SSRI
32
What are the disadvantages of paroxetine?
- Sedating, wt gain, more anticholinergic effects
| - Likely to cause a discontinuation syndrome
33
What type of drug is sertraline?
SSRI
34
What are the advantages of sertraline?
- weak drug-drug interactions
- short half life with lower build-up of metabolites
- less sedating
35
What are the disadvantages of sertraline?
max absorption requires a full stomach
36
What type of drug is fluoxetine?
SSRI
37
What are the advantages of fluoxetine?
- long half-life --> little discontinuation syndromes.
| - initially activating so may provide increased energy
38
What are the disadvantages of fluoxetine?
- long half life --> active metabolite may build up
- significant drug-drug interactions so 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
39
What type of drug is citalopram?
SSRI
40
What is the mechanism of SNRIs?
Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects
41
What are SNRIs used for?
- Depression
- Anxiety
- Neuropathic pain
42
What type of drug is venlafaxine?
SNRI
43
What are the advantages of venlafaxine?
- minimal drug interactions
| - short half life (avoids build-up - good for geriatric populations)
44
What are the disadvantages of venlafaxine?
- increase in diastolic BP
- cause bad discontinuation syndrome
- sexual side effects in >30%
45
What type of drug is duloxetine?
SNRI
46
What are the advantages of duloxetine?
- efficacy for the physical symptoms of depression
| - far less BP increase
47
What are the disadvantages of duloxetine?
- drug interactions (CYP2D6 and CYP1A2 inhibitor)
- cannot break capsule as active ingredient not stable within the stomach
- higher drop out rate
48
What type of drug is mirtazapine?
Novel antidepressant
49
What are the advantages of mirtazapine?
- different mechanism of action to SSRIs.
| - can be utilised as a hypnotic at lower doses
50
What are the disadvantages of mirtazapine?
- weight gain (increases serum cholesterol)
| - very sedating at lower doses
51
What are the indications for mood stabilisers?
- bipolar
- cyclothymia
- schizoaffective
52
What is the only medication to reduce suicide rate?
Lithium
53
What is lithium effective for?
long-term prophylaxis of both mania and depressive episodes in bipolar patients
54
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
55
What should be done before starting lithium?
- baseline bloods - U&E and TSH
| - pregnancy test
56
How should lithium use be monitored?
- steady state achieved after 5 days
- check 12 hours after last dose
- once stable check level 3 months
- TSH and creatinine 6 months.
57
What is the goal with lithium use?
Blood level between 0.6-1.2
58
What are the side effects of lithium?
- GI distress: reduced appetite, nausea/vomiting, diarrhoea
- thyroid abnormalities
- nonsignificant leukocytosis
- polyuria/polydypsia secondary to ADH antagonism
- interstitial renal fibrosis
- hair loss, acne
- reduces seizure threshold, cognitive slowing, intention tremor
59
How does lithium toxicity present?
mild: vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus
moderate: nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
severe: generalised convulsions, oliguria, renal failure,
60
What type of drug is valproic acid (Depakote)?
Anticonvulsant
61
What factors predict a positive response to valproic acid?
- rapid cycling patients (females>males)
- comorbid substance issues
- mixed patients
- comorbid anxiety disorders
62
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
63
What should be done before starting valproic acid?
- Baseline LFTs
- Pregnancy test
- FBC
64
Why should valproic acid be avoided in women of child bearing age?
Can cause neural tube defects
65
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
66
What is the goal of valproic acid use?
Target blood level 50-125
67
What are the side effects of valproic acid?
- thrombocytopenia and platelet dysfunction
- nausea, vomiting, weight gain
- sedation, tremor
- hair loss
68
What is the first line agent for acute mania and mania prophylaxis?
Carbamazepine
69
What type of drug is carbamazepine (tegretol)?
Anticonvulsant
70
What is carbamazepine indicated for?
Rapid cyclers and mixed patients
71
What should be done before carbamazepine is started?
- Baseline LFTs
- FBC
- ECG
72
How should carbamazepine be monitored?
- Steady state achieved after 5 days
| - Check 12 hours after last dose and repeat CBC and LFTs
73
What is the goal of carbamazepine used?
Blood levels 4-12mcg/ml
74
Why should carbamazepine levels be checked after 1 month?
adjust dosing after around a month because induces own metabolism.
75
What are the side effects of carbamazepine?
- rash
- nausea, vomiting, diarrhoea
- sedation, dizziness, ataxia, confusion
- aplastic anaemia and agranulocytosis (<0.002%)
- water retention (--> hyponatremia_
- drug-drug interactions
76
What type of drug is lamotrigine (lamictal)??
Anticonvulsant
77
What are the indications for lamotrigine?
- Mania
| - Neuropathic/chronic pain
78
What should be done before starting lamotrigine?
Baseline LFTs
79
How should lamotrigine be initiated and titrated?
- start with 25 mg daily X 2 weeks
- increase to 50mg X 2 weeks
- then increase to 100mg
- faster titration has a higher incidence of serious rash
80
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!
81
What are the side effects of lamotrigine?
- Nausea/vomiting
- Sedation, dizziness, ataxia and confusion
- TEN and Stevens Johnson's syndrome
- Blood dyscrasias (rare)
82
What drugs can increase lamotrigine levels?
- VPA (doubles concentration, so use slower dose titration),
- Sertaline
83
Why should lamotrigine be discontinued if ANY rash develops?
character/severity of the rash is not a good predictor of severity of reaction
84
What are the indications for antipsychotic drug use
- schizophrenia
- schizoaffective disorder
- bipolar disorder- for mood stabilization and/or when psychotic features are present
- psychotic depression
- augmenting agent in treatment resistant anxiety disorders
85
What are the key pathways affected by dopamine in the brain?
- Mesocortical
- Mesolimbic
- Nigrostriatal
- Tuberoinfundibular
86
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.
87
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.
88
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.
89
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).
90
What is the mechanism of typical antipsychotics?
D2 dopamine receptor antagnoists
91
Give examples of high potency typical antipsychotics.
- Fluphenazine
- Haloperidol
- Pimozide
92
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
93
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
94
Give examples of low potency typical antipsychotics.
- Chlorpromazine
| - Thioridazine
95
What is the mechanism of atypical antipsychotics?
Serotonin-dopamine 2 antagonists (SDAs)
96
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.
97
What type of drug is risperidone (Risperdal)?
Atypical antipsychotic
98
In what forms is risperidone available?
- Regular tablet
- IM depot forms
- Rapidly dissolving tablet
99
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)
100
How does the function of risperidone change at doses greater than 6mg?
Functions more like a typical antipsychotic at doses greater than 6mg
101
What type of drug is olanzapine (Zyprexa)?
Atypical antipsychotic
102
In what forms is olanzapine available?
- Regular tablet
- Immediate release IM
- Rapidly dissolbing tab
- Depo form
103
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)
104
What type of drug is quetiapine (Seroquel)?
Atypical antipsychotic
105
In what form is quetiapine available?
Regular tablet only
106
What are the side effects of quetiapine?
- Abnormal LFTs
| - Weight gain (
107
What type of drug is aripiprazole (abilify)?
Atypical aripiprazole
108
In what forms if aripiprazole available?
- Regular tablets
- Immediate release IM formulation
- Depo form
109
What is the mechanism of ariprprazole?
Unique mechanism of action as a D2 partial agonist
110
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.
111
What is aripiprazole not associated with?
- Weight gain
| - QT prolongation
112
What type of drug is clozapine (clozaril)?
Atypical antipsychotic
113
What form is clozapine available in?
Regular tablet only
114
Who is clozapine reserved for?
Treatment resistant patients because of side effect profile but this stuff works
115
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
116
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
117
What is the commonest psychotic symptom?
Lack of insight
118
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
119
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
120
Give examples of adverse effects of antipsychotics.
- Tardive dyskinesia
| - Neuroleptic malignant syndrome
121
What is tardive dyskinesia?
-Involuntary muscle movements that may not resolve with drug
122
How does neuroleptic malignant syndrome present?
Characterised by:
- Severe muscle rigidity
- Fever
- Altered mental status
- Autonomic instability
- Elevated WBC, CPK and LFTs
- Potentially fatal
123
What extrapyramidal side effects are associated with antipsychotic use?
- Acute dystonia
- Parkinson syndrome
- Akathisia
124
What agents can be used for extrapyramidal symptoms?
- Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine
- Dopamine facilitators such as Amantadine
- Beta-blockers such as propranolol
125
What are anxiolytics used to treat?
- Panic disorder
- GAD
- Substance-related disorders and their withdrawal
- Insomnias
- Parasomnias
126
What treatment regime is common in anxiety disorders?
In anxiety disorders often use anxiolytics in combination with SSRIS or SNRIs for treatment.
127
What type of drug is buspirone (buspar)?
Non-benzodiazepine anti-anxiety drug
128
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
129
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.
130
What type of drug are benzodiazepines?
Anti-anxiety CNS depressants
131
What are benzodiazapines used to treat?
- Insomnia
- Parasomnias
- Anxiety disorder
- Often used for CNS depressant withdrawal protocols ex. ETOH withdrawal
132
What are the side effects of benzodiazapines?
- Somnolence
- Cognitive deficits
- Amnesia
- Disinhibition
- Tolerance
- Dependence
133
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
134
What are the classes of mood stabiliser?
- Lithium
- Anticonvulsants
- Antipsychotics
