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psychopharmacology Flashcards

1
Q

general pharmacology strategies - indication

A

establish a diagnosis and identify the target symptoms that will be used to monitor therapy response

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2
Q

general pharmacology strategies - choice of agent and dosage

A

select an agent w/ an acceptable side effect profile and use the lowest effective dose

remember the delayed response for many psych meds and drug-drug interactions

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3
Q

general pharmacology strategies - management

A

adjust dosage for optumum benefit, safety and compliance

use adjunctive and combination therapies if needed however always strive for the simplest regime

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4
Q

indications for antidepressants

A

unipolar and bipolar depression

organic mood disorders

schizoaffective disorder

anxiety disorders incl OCD, panic, social phobia

PTSD

premenstrual dysphoric disorder and impulsively associated with personality disorders

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5
Q

how do antidepressants work

A

not fully understood

antidepressants increase levels of neurotransmitters (serotonin, noradrenalin) in the brain

increasing these neurotransmitters changes receptors in the brain

response rate of ~60-70% and NNT 3

takes a little while for response to occur

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6
Q

general guidelines for antidepressant use

A

antidepressant efficacy is similar (there isn’t any one that is much better than the others) so selection is based on past hx of a response, side effect profile and coexisting medical conditions

delay of ~2-4wks after a therapeutic dose is achieved before symptoms improve

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

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7
Q

antidepressant classifications

A

TCAs - tricyclics
MAOIs - monoamine oxidase inhibitors
SSRIs - selective serotonin reuptake inhibitors
SNRIs - serotonin/noradrenaline reuptake inhibitors
novel antidepressants

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8
Q

TCAs - how effective

A

very effective but potentially unacceptable side effect profile

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9
Q

side effect profile of TCAs and other problems

A

side effects: antihisatminic (weight gain, sleepy), anticholinergic (blurred vision)

lethal in overdose - even a one week supply

can cause QT lengthening, even at a therapeutic serum

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10
Q

how do TCAs work

A

increase both serotonin, dopamine and noradrenaline

hit a lot of different receptors

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11
Q

what are tertiary TCAs

A

have tertiary amine side chains

side chains are prone to cross react with other types of receptors –> more side effects

e.g. imipramine, amitriptyline, doxepin, clomipramine

have active metabolites incl desipramine and nortriptyline

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12
Q

what are secondary TCAs

A

often metabolites of 3y amines

primarily block noradrenaline

side effects are the same as 3y TCAs but generally are less severe

e.g. desipramine, nortriptyline

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13
Q

how to MAOIs work

A

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

very effective for resistant depression

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14
Q

side effects of MAOIs

A

orthostatic hypotension

weight gain

dry mouth

sedation

sexual dysfunction

sleep disturbance

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15
Q

MAOIs cheese reaction

A

hypertensive crisis can develop when MAOIs are taken with tyramine rich foods or sympathomimetics

can be fatal

  • restrict diet: cheese, red wine, some processed meats
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16
Q

MAOIs and serotonin syndrome

A

serotonin syndrome can develop if take MAOI w/ meds that increase serotonin or have sympathomimetic actions

also if using combination of antidepressants

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17
Q

symptoms of serotonin syndrome

A 
abdo pain 
diarrhoea 
sweats 
tachycardia 
HT
myoclonus 
irritability 
delirium

can lead to hyperpyrexia, CV shock and death

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18
Q

how do SSRIs work

A

block the presynaptic serotonin reuptake

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19
Q

what are SSRIs used for

A

treatment of anxiety and depressive sx

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20
Q

most common side effects of SSRIs

A 
GI upset
sexual dysfunction (30%)
anxiety
restlessness
nervousness
insomnia 
fatigue or sedation 
dizziness
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21
Q

other risks from SSRIs

A

very little risk of cardiotoxicity in overdose

can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria - occurs when people stop them quickly

more common with shorter half life drugs, consider switching to fluoxetine - slowly reducing concentration and reduces problems

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22
Q

SSRIs and activation syndrome

A

caused by increased serotonin

can be distressing for patient

sx: increased anxiety, panic, agitation, nausea

typically lasts 2-10 days - warn patient

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23
Q

pros of sertraline

A

very weak P450 interactions, only slight CYP2D6 - less drug interactions

short half life with lower build up of metabolites - quick activating

less sedating when compared to paroxetine

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24
Q

cons of sertraline

A

max absorption requires a full stomach

increased number of GI adverse drug reactions

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25
pros of fluoxetine (prozac)
long half life - decreased incidence of discontinuation syndromes, good for pts w/ medication noncompliance issues initially activating - may provide increased energy 2y to long half life, can give one 20mg tab to taper someone off SSRI when trying to prevent discontinuation syndrome
26
cons of fluoxetine
long half life and active metabolite may build up - not good w/ hepatic illness significant P450 interactions - not a good choice on 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
27
what are SNRIs how do they work what are they used for
serotonin/noradrenaline reuptake inhibitors inhibit both serotonin and noradrenergic reuptake like TCAs BUT w/o antihistamine/antiadrenergic/anticholinergic side effects used for depression, anxiety and possibly neuropathic pain
28
pros of venlafaxine
minimal drug interactions and almost no P450 activity short half life and fast renal clearance avoids build up - good for geriatrics
29
cons of venlafaxine
can cause a 10-15mmHg dose dependent increase in diastolic BP may cause significant nausea, primarily w/ immediate release tabs can cause a bad discontinuation syndrome, taper recommended after 2wks of use QT prolongation sexual side effects in >30%
30
duloxetine pros
some data to suggest efficacy for the physical symptoms of depression far less BP increase as compared to venlafaxine - may change in time
31
duloxetine cons
CYP2D6 and CYP1A2 inhibitor cannot break capsule as active ingredient not stable within stomach higher drop out rate
32
what type of antidepressant is mirtazapine
novel
33
pros of mirtazapine
different mechanism of action may provide a good augmentation strategy to SSRIs can be used as a hypnotic at lower doses 2y to antihitaminic effects
34
how does mirtazapine work
5HT2 and 5HT3 receptor antagonist
35
cons of mirtazapine
increases serum cholesterol by 20% in 15% of pts and triglycerides in 6% of pts very sedating at lower doses - at doses 30mg and above it can become activating and require change of administration time to the morning associated w/ weight gain - esp at doses <45mg
36
how do we manage treatment resistant depression
combination of antidepressants e.g. SSRI/SNRI + mirtazepine adjunctive treatment w/ lithium adjunctive treatment w/ atypical antipsychotic e.g. quetiapine, olanzapine, aripiprazole ECT
37
prophylaxis following treatment w/ antidepressants
1st episode - continue for 6-12mths 2nd episode - continue for 2yrs 3rd episode - discuss life long american studies suggest: - stop before 6mths - 80% relapse - phrophylaxis >6mths - 20% relapse
38
management of anxiety
serotonergic anti-depressants e.g. SSRI/SNRI tricyclic chlomipramine adjunctive treatment: mainly antipsychotics e.g. risperidone, quetiapine try and avoid symptomatic relief e.g. diazepam
39
indications for mood stabilisers
bipolar cyclothymia schizoaffective
40
classes of mood stabilisers
lithium anticonvulsants antipsychotics
41
how to choose which mood stabiliser
depends on what you are treating and the side effect profile
42
what is the only medication to reduce suicide rate
lithium has been shown to reduce the rate of completed suicide in BAD by ~15%
43
when is lithium used as prophylaxis
effective in long term prophylaxis of both mania and depressive episodes in >70% of BAD pts
44
factors predicting positive response to lithium
prior long term response or family member with good response classic pure mania mania is follower by depression
45
what to do before starting lithium
baseline U+E and TSH in women check a pregnancy test
46
risk of lithium use during pregnancy
during the first trimester is associated w/ Ebstein's anomaly 1/1000 20x greater risk than in the general pop
47
monitoring with lithium use
steady state acheived after 5 days check 12 hrs after last dose once stable check level 3mths TSH and creatinine 6mths goal: blood level 0.6-1.2
48
lithium side effects
most common are GI distress incl reduced appetite, N+V, diarrhoea thyroid abnormalities nonsignificant leukocytosis polyuria/polydipsia 2y to ADH antagonism small number of pts - interstitial renal fibrosis hair loss, acne reduces seizure threshold, cognitive slowing, intention tremor
49
lithium toxicity
mild (1.5-2) - vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus moderate (2-2.5) - N+V, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope severe (>2.5) - generalised convulsions, oliguria, renal failure
50
examples of anticonvulsants
valproic acid (Depakote) carbamazepine (Tegretol) lamotrigine (lamictal)
51
effectiveness of valproic acid
as effective as lithium in mania prophylaxis not as effective in depression prophylaxis
52
factors predicting a +ve response to valproic acid
rapid cycling pts (F>M) comorbid substance issues mixed pts pts w/ comorbid anxiety disorders
53
how well tolerated is valproic acid
better tolerated than lithium
54
what to do before starting valproic acid
baseline LFTs pregnancy test FBC
55
why can valproic acid not be used in women of childbearing age
neural tube defects increased risk 1-2% vs 0.14-0.2% in general population 2y to reduction in folic acid
56
monitoring during valproic acid use
steady state achieved after 4-5days check 12hrs after last dose and repeat CBC and LFTs goal - target level 50-125
57
valproic acid side effects
thrombocytopaenia and platelet dysfunction N+V, weight gain sedation, tremor hair loss
58
when is carbamazepine (Tegretol) indicated
1st line for acute mania and mania prophylaxis indicated for rapid cyclers and mixed pts
59
what to do before starting carbamazepine
baseline LFT, FBC, ECG
60
monitoring during carbamazepine use
steady state acheived after 5 days check 12hrs after last dose repeat CBC and LFTs goal - target levels 4-12mcg/ml need to check level and adjust dosing ~1mth - induces own metabolism
61
carbamazepine side effects
rash - most common SE N+V, diarrhoea sedation, dizziness, ataxia, confusion AV conduction delays aplastic anaemia and agranulocytosis (<0.002%) water retention - vasopressin like effect --> hyponatraemia drug-drug interactions
62
indications for lamotrigine (lamictal)
indications similar to other anticonvulsants also used for neuropathic/chronic pain used more commonly as it doesn't cause as many problems in women of childbearing age SJS not as serious an issue
63
what to do before starting lamotrigine
baseline LFTs
64
initiation/titration of lamotrigine
start w/ 25mg daily for 2wks then increase to 50mg for 2wks then increase to 100mg faster titration has a higher incidence of SJS if the patient stops the med for ≥5 days, have to start at 25mg again
65
lamotrigine side effects
N+V sedation, dizziness, ataxia, confusion stevens Johnson's syndrome and toxic epidemal necrolysis blood dyscrasias - rare
66
severity of rash and severity of reaction w/ lamotrigine
severity/character of rash isn't a good predictor of reaction severity if any rash develops, immediately stop use
67
what drugs increase lamotrigine levels and what do we do in these cases
VPA - doubles concentration, use slower dose titration sertraline
68
approved indications in bipolar disorder
aripiprazole (abilify) - manic, mixed, maintenance risperidone (risperdal) - manic, mixed quetiapine (seroquel) - manic, mainenance* quetiapine modified release (XR) (seroquel XR) - manic, maintenance*, depressed olanzapine (zyprexa) - manic, mixed, maintenance
69
when are antipsychotics useful
acutely unwell pts when they are manic also have a sedative effect not as good for maintenance
70
prophylaxis for bipolar disorder
generally lifelong relapse is almost inevitable but impossible to predict when (could be mths or yrs)
71
indications for antipsychotic use
schizophrenia schizoaffective disorder bipolar disorder for mood stabilisation and/or when psychotic features are present psychotic depression augmenting agent in treatment resistant depressive and anxiety disorders
72
what is the mesocortical pathway
projects from the ventral tegmentum (brain stem) to the cerebral cortex is felt to be where the -ve symptoms and cognitive disorders arise problem in psychotic patients is too little dopamine
73
what is the mesolimbic pathway
projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system this is where the +ve symptoms come from (hallucinations, delusions, thought disorders) problem in psychotic patients is there is too much dopamine
74
what is the nigrostriatal pathway
projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia involved in movement regulation
75
effect of dopamine on acetylcholine activity
dopamine suppresses acetylcholine activity
76
what is the result of dopamine hypoactivity in the nigrostriatal pathway
parkinsonian movements e.g. rigidity, bradykinesia, tremors akathisia dystonia
77
what is the tuberoinfundibular pathway what does blocking dopamine lead to
projects from the hypothalamus to the anterior pituitary blocking dopamine in this pathway will predispose your patient to hyperprolactinaemia
78
effect of dopamine on prolactin
dopamine release inhibits/regulates prolactin release
79
result of hyperprolactinaemia
gynaecomastia galactorrhea decreased libido menstrual dysfunction
80
how do typical antipsychotics work examples
D2 dopamine receptor antagonists high potency typical antipsychotics bind to the D2 receptor w/ high affinity - higher risk of extrapyramidal side effects fluphenazine, haloperidol, pimozide
81
low potency typical antipsychotics | example
less affinity for D2 receptors but tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects e.g. sedation, hypotension chlorpromazine
82
how do atypical antipsychotics work
serotonin-dopamine 2 antagonists (SDAs) considered atypical in the way they affect dopamine and serotonin neurotransmission in the 4 key dopamine pathways in the brain
83
examples of atypical antipsychotics
risperidone (risperdal) olanzaprine (zyprexa) quetiapine (seroquel) aripiprazole (abilify)
84
risperidone formation effects
available in regular tablets, IM depot forms and rapidly dissolving tablet functions more like a typical antipsychotic at doses >6mg
85
side effects of risperidone
increased extrapyramidal side effects (dose dependent) most likely atypical to induce hyperprolactinaemia weight gain and sedation (dose dependent)
86
olanzapine formation
regular tablets immediate release IM rapidly dissolving tablet depot form
87
olanzapine side effects
weight gain (up to 30-50lbs even with short term use) may cause: hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia (even w/o weight gain) may cause hyperprolactinaemia (< risperidone) may cause abnormal LFTs (2%)
88
quetiapine formation
regular tablet only
89
quetiapine side effects
abnormal LFTs (6%) weight gain (less than olanzapine) hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia (even w/o weight gain) - less than olanzapine most likely to cause orthostatic hypotension
90
aripiprazole formation
regular tablets immediate release IM depot formation
91
how does aripiprazole work
unique mechanism of action as a D2 partial agonist
92
apiprazole side effects
low extrapyramidal side effects, no QT prolongation, low sedation not associated w/ weight gain could cause potential intolerability due to akathisia/activation
93
aripiprazole interactions
CYP2D6 (fluoxetine and paroxetine) and 3A4 (carbamazepine and ketoconazole) interactions - adjust dosing
94
antipsychotic efficacy
no evidence to suggest difference between 1st line agents choice based on side effect or preparation general rule of 1/3 good response, 1/3 some response, 1/3 poor response
95
what antipsychotic is used for treatment resistant patients
clozapine (clozaril)
96
what classifies someone as treatment resistant on antipsychotics
they have tried one antipsychotic for at least 8 weeks and then a 2nd for the same period of time of treatment and neither have worked
97
what formation is clozapine available in
regular tablet only
98
why is clozapine reserved for treatment resistant patients
due to its side effect profile but it is very effective
99
clozapine side effects
associated w/ agranulocytosis (0.5-2%) - wkly bloods for 6mths then 2wkly tests for 6mths then monthly increased risk of seizures (esp if also using lithium) associated w/ the most sedation, weight gain and abnormal LFTs increased risk of hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia, including nonketoic hyperosmolar coma and death, w/ or w/o weight gain
100
efficacy of clozapine
general rule of 1/3s
101
antipsychotic adverse effects
tardive dyskinesia neuroleptic malignant syndrome extrapyramidal side effects
102
what is tardive dyskinesia
involuntary muscle movements that may not resolve w/ drug discontinuation e.g. tongue protruding, lip smacking, neck movements risk ~5% per yr esp w/ typical antipsychotics
103
what is neuroleptic malignant syndrome
severe muscle rigidity fever altered mental status autonomic instability elevated WBC, CPK and LFTs - potentially fatal
104
what are extrapyramidal side effects
acute dystonia parkinson syndrome akathisia
105
agents for extrapyramidal side effects
anticholinergics e.g. benztropine, trihexyphenidyl, diphenhydramine - need to watch for anticholinergic SE esp if taken w/ other meds w/ anticholinergic activity i.e. TCAs dopamine facilitators e.g. amantadine beta blockers e.g. propranalol
106
anti-psychotic prophylaxis
life long relapse inevitable commonest psychotic symptoms is lack of insight people w/ psychotic illnesses relapse most commonly due to non-compliance only 30% of pts take medication as prescribed
107
level of functioning after schizophrenic episode
after 3rd episode of sz - clear link to reduced functioning, lower IQ and -ve symptoms consider long acting IM
108
what are anxiolytics used for
used to treat many diagnoses including panic disorder, GAD, substance related disorders and their withdrawal, insomnias and parasomnias in anxiety disorders often use anxiolytics in combination w/ SSRIs or SNRIs for treatment
109
what are benzodiazpines used for
used to treat insomnia, parasomnias and anxiety disorders often used for CNS depressant withdrawal protocols e.g. alcohol withdrawal
110
side effects of benzodiazepines
``` somnolence cognitive deficits amnesia disinhibition tolerance dependence ```
111
examples of benzodiazepines and dosage
diazepam chlordiazepoxide doses of ~20mg, 4x/day OR 10mg PRN up to 8x/day
112
different types of benzodiazepines
113
important points about benzodiazapines
remember dependence develops increased tolerance - people need more and more; also becomes less effective try and reserve for short term use only e.g. emergency sedation and withdrawal states for psychiatric disorder use meds which treat the underlying cause

Psychiatry (63 decks)

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