Psychopharmacology Flashcards
1
Q
what are the indications for use of antidepressant medication?
A
- Unipolar and bipolar depression
- organic mood disorders
- schizoaffective disorder
- anxiety disorders including OCD, panic, social phobia, PTSD
- premenstrual dysphoric disorder
- impulsivity associated with personality disorders
2
Q
list the different classes of antidepressant drugs
A
- SSRIs
- Tricyclics (TCAs)
- Monoamine Oxidase Inhibitors (MAOIs)
- Serotonin/noradrenaline reuptake inhibitors (SNRIs)
- novel antidepressants
3
Q
SSRIs side effects
A
Most common:
- GI upset
- sexual dysfunction (30%+)
- anxiety
- restlessness
- nervousness
- insomnia
- fatigue or sedation
- dizziness
Very little risk of cardiotoxicity in overdose.
Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria.
4
Q
what causes activation syndrome?
related to SSRIs
A
- caused by increased seretonin. Can be distressing for patient.
- nausea, increased anxiety, panic and agitation.
- typically last 2-10 days so warn patients!
5
Q
Fluoxetine (Prozac) Pros
A
- long half-life so decreased incidence of discontinuation syndromes. Good for patients 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.
6
Q
Fluoxetine (Prozac) Cons
A
- long half-life and active metabolites 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 patients already on number of meds.
- initial activation may increase anxiety and insomnia.
- more likely to induce mania than some of the other SSRIs.
7
Q
Sertraline Pros
A
- very weak P450 interactions (only slightly CYP2D6)
- short half-life with lower build up of metabolites.
- less sedating when compared to paroxetine.
8
Q
Sertraline Cons
A
- max absorption requires a full stomach
- increased number of GI adverse drug reactions.
9
Q
TCAs Cons
A
- very affective drugs but potentially unacceptable side effect profile i.e. antihistaminic, anticholinergic, antiadrenergic.
- lethal in overdose (even a one week supply can be lethal)
- can cause QT lengthening even at therapeutic serum level.
- secondary TCAs have same side effects as tertiary TCAs but are generally less severe.
10
Q
tertiary TCAs examples
A
Imipramine
Amitryptyline
Doxepin
Clomipramine
11
Q
secondary TCAs examples
A
desipramine
nortriptyline
12
Q
how do Monoamine Oxidase Inhibitors (MAOIs) work as antidepressants?
A
- bind irreversibly to MAO thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels.
- very effective for resistant depression.
13
Q
MAOIs side effects
A
- orthostatic hypotension
- weight gain
- dry mouth
- sedation
- sexual dysfunction
- sleep disturbance
14
Q
Hypertensive crisis can develop when MAOI’s are taken with…
A
tyramine-rich foods (such as cheese) or sympathomimetics (seretonin syndrome).
- To avoid seretonin syndrome 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.
15
Q
seretonin syndrome symptoms
A
- abdominal pain
- diarrhoea
- sweats
- tachycardia
- hypertension
- myoclonus
- irritability
- delirium
- can lead to hyperpyrexia, CV shock and death.
16
Q
Venlafaxine (a SNRI) Pros
A
- minimal drug interactions and almost no P450 activity
- short half-life and fast renal clearance avoids build-up (good for geriatric populations)
17
Q
Venlafaxine (a SNRI) Cons
A
- can cause 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.
- sexual side effects in > 30%.
18
Q
Duloxetine (SNRI) Pros
A
- some data to suggest efficacy for physical symptoms of depression
- thus far less BP increase as compared to venlafaxine
19
Q
Duloxetine (SNRI) Cons
A
- CYP2D6 and CYP1A2 inhibitor
- cannot break capsule, as active ingredient not stable within the stomach
- in pooled analysis had higher drop out rate
20
Q
Novel antidepressant Mitrazapine Pros
A
- 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
21
Q
Novel antidepressant Mitrazapine Cons
A
- 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)
22
Q
what are the management options for a patient with treatment resistance depression?
A
- combo of antidepressants e.g. SSRI or SNRI with Mirtazepine
- adjunctive treatment with lithium
- adjunctive treatment with atypical antipsychotic e.g. quetipaine, olanzapine or aripiprazole
- ECT
23
Q
what are the management options for a patient with treatment resistance anxiety?
A
- high dose SSRI first
- combo of antidepressants e.g. SSRI or SNRI with Mitrazepine
- adjunctive treatment with atypical antipsychotic e.g. quetiapine, olanzapine or risperidone.
- adjunctive treatment with pregabalin or buspirone
- avoid diazepam
24
Q
what are the indications for mood stabiliser drugs?
A
- bipolar
- cyclothymia
- schizoaffective disorder
25
what are the different classes of mood stabiliser drugs?
- lithium
- anticonvulsants
- antipsychotics
26
what is the only medication to reduce suicide rate?
lithium
27
factors prediciting positive response to lithium
- prior long-term response or family member with good response
- classic pure mania
- mania is followed by depression
28
what investigations should be performed before starting lithium?
- get baseline U&E and TSH
- pregnancy test in women
29
how is lithium monitored?
- steady state achieved after 5 days - check 12 hours after last dose. Once stable check level 3 months and TSH and creatinine at 6 months.
30
what is the goal level of lithium in bloods?
- 0.6-1.2
31
lithium side effects
- Most common > GI distress including reduced appetite, nause/vomiting and diarrhoea.
- thyroid abnormalities
- polyuria/polydypsia secondary to ADH antagonism. In a small no. patients can cause interstitial renal fibrosis leading to renal failure
- hair loss, acne
- reduces seizure threshold, cognitive slowing, intention tremor.
32
discuss mild, moderate and severe lithium toxicity symptoms
- Mild, levels 1.5-2: see vomiting, diarrhoea, ataxia, dizziness, slurred speech nystagmus.
- Moderate, 2-2.5: nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium and syncope.
Severe, > 2.5: generalised convulsions, oliguria and renal failure
33
what tests must be taken before commencing treatment with Valproic acid?
- baseline LFTs
- pregnancy test
- FBC
34
why would you use valproic acid instead of lithium?
- Valproic acid is as effective as Lithium in mania prophylaxis but is not as effective in depression prophylaxis.
- Better tolerated than lithium.
35
Valproic acid side-effects
- CI in women of child bearing age as increased risk of neural tube defects secondary to reduction in folic acid.
- thrombocytopenia and platelet dysfunction
- nausea, vomiting, weight gain
- sedation, tremor
- hair loss.
36
when is Carbamazepine (Tegretol) indicated?
- first-line agent for acute mania and mania prohylaxis
- indicated for rapid cyclers and mixed patients
37
what tests must be performed before commencing carbamazepine treatment?
baseline LFTs
FBC
ECG
38
carbamazepine side effects
- rash, most common SE seen
- nasuea, vomiting, diarrhoea
- sedation, dizziness, ataxia, confusion
- AV conduction delays
- aplastic anemia and agranulocytosis (< 0.002%)
- water retention due to vasopressin-like effect which can result in hyponatraemia
- drug-drug interactions
39
when is Lamotrigine indiacted (Lamictal)?
indications similar to other anticonvulsants
also used for neuropathic/chronic pain
40
Lamotrigine side effects
- nausea/vomting
- sedation, dizziness, ataxia and confusion.
- most severe: TENS and Steven Johnson's syndrome, if ANY rash devlops, discontinue use immediatly.
- valproic acid and sertraline increase lamotrigine levels.
41
Antipsychotics indications for use
- schizophrenia
- schizoaffective disorder
- bipolar disorder for mood stabilisation and/or when psychotic features are present
- psychotic depression
- augmenting agent in treatment resistant anxiety disorders
42
what dopamine pathway is responsible for positive symptoms (hallucinations, delusions and thought disorders)?
Mesolimbic: projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system.
In a psychotic patient, there is too much dopamine.
43
Which dopamine pathway is considered to be where negative symptoms and cognitive disorders (lack of executive function) arise?
Mesocortical: projects from the ventral tegmentum (brain stem) to the cerebral cortex.
Problem here for a psychotic patient, is too little dopamine.
44
Which dopamine pathway is involved in movement regulation?
Nigrostriatal: projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia.
- remember that dopamine suppressed ACh activity.
- dopamine hypoactivity can cause Parkinsonian movements, akathisia and dystonia.
45
blocking dopamine in which pathway will predispose your patient to hyperprolactinemia?
Tuberoinfundibular: projects from the hypothalamus to the anterior pituitary.
- dopamine release inhibits/regulates prolactin release.
46
what is a typical antipsychotic?
give examples of high and low potency ones
- D2 dopamine receptor antagonists.
- high potency typical antipsychotics bind to the D2 receptor with high affinity. As a result, they have higher risk of extrapyramidal side effects.
- e.g. Fluphenazine, Haloperidol, Pimozide.
- low potency typical antipsychotics have less affinity for D2 receptor but tend to interact with nondopaminergic receptors > cardiotoxic, anticholinergic adverse effects (sedation, hypotension)
- e.g. chlorpromazine and thioridazine
47
antipsychotic adverse affects
- Tardive Dyskinesia (TD) - involuntary muscle movements that may not resolve with drug discontinuation - risk approx. 5% per year.
- Neuroleptic Malignant Syndrome (NMS): characterised by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and LFTs. Potentially fatal.
- Extrapyramidal side effects (EPS): acute dystonia, Parkinson syndrome
- Akathisia be aware increased risk of suicide
48
what are atypical antipsychotics?
- seretonin-dopamine 2 antagonists (SDAs)
- less propensity for EPS
- atypical in the way they affect dopamine and seretonin neurotransmission in the four keu dopamine pathways in the brain.
49
risperidone side effects
increased extrapyramidal side effects (dose-dependent)
- most liekly atypical to induce hyperprolactinemia
- weight gain and sedation (dosage dependent)
50
olanzapine side-effects
- weight gain
- may cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain)
- may cause hyperprolactinemia (< risperidone)
- may cause abnormal LFTs
51
Quetiapine side effects
- May cause abnormal LFT’s
- May be associated with weight gain, though less than seen with olanzapine
- May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain), however less than olanzapine
- Most likely to cause orthostatic hypotension
52
how is schizophrenia classified as treatment-resistant? how is it managed?
- poor response to 2 first-line antipsychotics at adequate dose for 8 weeks
- clozapine used in this case
53
why is clozapine reserved for treatment-resistant patients?
- Is reserved for treatment resistant patients because of side effect profile but this stuff works!
- Associated with agranulocytosis (0.5-2%) and therefore requires weekly blood draws x 6 months, then Q- 2weeks x 6 months)
- Increased risk of seizures (especially if lithium is also on board)
- Associated with the most sedation, weight gain and abnormal LFT’s
- Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain
54
How is akathisia, a side-effect of antipsychotics treated?
| inability to remain physically still
propanolol or diazepam
55
Buspirone (Buspar) Pros
| an anxiolytic
- good augmentation strategy in anxiety - mechanism of action is 5HT1A agonist. It works independent of endogenous release of seretonin.
- no sedation.
56
Buspirone (Buspar) Cons
| an anxiolytic
- 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'.
57
Benzodiazepines side effects/cons
- somnolence
- cognitive deficits
- amnesia
- disinhibition
- tolerance
- dependence
