Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

8. Psychopharmacology > Mood stabilizers > Flashcards

Mood stabilizers Flashcards

1
Q

what is considered the gold standard mood stabilizer for bipolar disorder

A

lithium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

which has a more rapid anti-manic effect, lithium or valproate

A

valproate (therapeutic benefit seen in 3-5 days)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

list medications that fall under the “mood stabilizers and anticonvulsants” label

A

lithium

valproate

carbamazepine

gabapentin

lamotrigine

levetiracetam

phenytoin

pregabalin

oxcarbazepine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the strictest definition of mood stabilizer

A

an agent that treats and prevents acute mania and depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the broadest definition of mood stabilizer

A

an agent that is effective at either treating or preventing mania or in treating or preventing depression, and does not exacerbate symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how long do mood stabilizers generally take for a good response

A

1-2 weeks

some initial effects can take place within 48 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

why are antiepileptics used to treat bipolar disorders

A

bipolar disorder and epilepsy share common features including an EPISODIC course of illness and KINDLING phenomena

the AMYGDALA plays role in both disorders as well

however epilepsy and bipolar disorders are two distinct diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is the mechanism of action of most mood stabilizers

A

most have multiple MOAs

include modulation of GABA-ergic and glutamatergic neurotransmission and alteration of VOLTAGE GATED ION CHANNELS or intracellular signalling pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is the mechanism of action of lithium

A

“unknown and complex”

alters SODIUM TRANSPORT across cell membranes in nerve and muscle cells

alters metabolism of neurotransmitters including catecholamines and serotonin –> may alter intracellular signalling through actions on second messenger systems

specifically–> INHIBITS INOSITOL MONOPHOSPHATASE–> possibly affecting neurotransmission via phasphatidyl inositol second messenger system

also REDUCED PROTEIN KINASE C activity–> possibly affecting genomic expression associated with neurotransmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how might lithium provide neuroprotective effects (what mechanism of action)

A

–increasing glutamate clearance

–inhibiting apoptotic glycogen synthase kinase activity

–increasing levels of antiapoptotic protein Bcl-2

–enhancing the expression of neurotropic factors (including brain derived neurotropic factor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how might lithium affect genomic expression associated with neurotransmission

A

possibly by reducing protein kinase C activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

indications for lithium therapy

A

manic episodes in bipolar illness

maintenance patients with bipolar disorder

bipolar depression

MDD (adjunctive)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

onset of action of lithium

A

1-3 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how do you titrate lithium in the acute setting

A

start 300mg 2-3x/day

rapidly increase to 900-1200mg per day

(“dr lam slams it in after one day of 600mg)

THEN DO LEVELS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how do you titrate lithium in the outpatient setting

A

for low mood–> 150mg po daily for 1 week, then increase to 300mg po daily

then measure levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the benefits to converting lithium from split dosing to once daily dosing

A

ideally daily at HS

less kidney exposure to lithium, possibly less CKD and side effects overall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how do you change the dose of lithium if going from divided doses to once daily dose

A

once daily dose is 20% LOWER than in divided doses–> this is because kidneys filter lithium more slowly while u are sleeping

i.e if was on 1500mg total daily dose in divided doses, then nighttime dose would be 1200mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is the typical adult target range dose for lithium

A

300-2400mg per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is the typical adolescent dose range for lithium

A

300-1800mg per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

in what forms does lithium come

A

capsules (carbonate)

liquid (citrate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what baseline monitoring needs to be done for lithium

A

CBC/diff

electrolytes

creatinine/BUN

TSH, Ca, consider PTH

weight

beta-hcg in all women

ECG if over 40 or cardiac hx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what investigations should be ordered during maintenance phase of lithium therapy for monitoring

A

CBC.diff

electrolytes

creatinine, BUN

TSH

lithium level (minimum 5 days after dose change)

weight q6 months

calcium

PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how frequently should you measure calcium and PTH in lithium maintenance monitoring

A

calcium q2years

PTH ?q5 years and if indicated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

when should you draw lithium levels

A

12 hours post dose so a “trough” level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is the lithium level range in acute treatment

A

0.8-1.2 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is the lithium level range in maintenance therapy

A

0.6-0.8 mmol/L

(psych DB says 0.6-1.0 mmol/L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is the lithium level target range generally in peds and geri populations

A

0.3-0.7 mmol/L

(other sources say 0.4-0.8 in acute bipolar mania/depression in those above 65 years old)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

how does one daily dosing affect lithium levels compared to divided doses

A

a 10-26% INCREASE of a 12 hour level can be expected with ONCE DAILY dosing compared to a 12 hour level checked of an EQUAL dose if given twice a day–> hence why you would usually decrease the total daily dose if going from BID to OD dosing for same blood level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

list possible CNS side effects/adverse events associated with lithium

A

sedation

FINE tremor

ataxia

lethargy

pseudotumor cerebri/seizures (rare)

serotonin syndrome

cognitive dulling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how do we understand the cognitive dulling some patients complain of on lithium

A

likely the subjective loss of highly creative/brilliant thinking of manic state or being in mildly depressed phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

list possible endocrine side effects/adverse events associated with lithium

A

hypothyroidism

hyperparathyroidism

weight gain/loss

polydipsia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

why is hypothyroidism a complication of lithium therapy

A

lithium interferes with iodine uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

if someone it going to develop hypothyroidism on lithium, when will it usually happen

A

within 6-18 months of initiating treatment

women may be at higher risk–> 14% vs 5% in men

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

how do you manage hypothyroidism developing while on lithium? what is the target TSH?

A

synthroid–> target TSH of 1.0

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what is a sign of hyperparathyroidism (seen in lithium therapy)

A

hyper calcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

list possible cardiovascular side effects/adverse events associated with lithium

A

bradycardia

arrhythmias

heart failure (reversible on discontinuation of lithium)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what might you see on ECG in someone on lithium

A

diffuse slowing

flattening

t wave changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

list possible GI side effects of lithium

A

nausea

vomiting

diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

list possible genitourinary side effects/adverse events associated with lithium

A

nephrogenic diabetes insipidus

CKD

polyuria

non-specific chronic tubulointerstitial nephropathy

sexual dyfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what can you do if someone develops polyuria on lithium

A

consolidate to once daily dosing which may decrease urine output

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

list possible hematological side effects/adverse events associated with lithium

A

REVERSIBLE agranulocytosis

BENIGN leukocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

list possible derm side effects/adverse events associated with lithium

A

alopecia

new or worsening acne and psoriasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what % of people develop new or worsening acne or psoriasis on lithium? why?

A

about 45%

due to increase in neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

what fetal abnormality are you concerned about in pregnant women on lithium

A

ebsteins anomaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what is the baseline population risk of ebsteins anomaly

A

1/40 000 births

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what is the risk of ebsteins anomaly in pregnant women on lithium

A

1/10 000 (0.1%)

(vs 1/40 000 at baseline)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what factors affect risk of ebsteins anomaly in pregnant women on lithium

A

dose dependent

higher risk with doses of lithium above 900mg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what can lithium toxicity/overdose look like?

A

can look like EtOH intoxication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

what serum lithium level suggests mild toxicity

A

1.5-2.0 mmol/L

(occasionally can have signs of mild toxicity even when blood levels are in normal range)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

what serum lithium level would suggest severe toxicity

A

above 2 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

list symptoms of mild lithium toxicity

A

N/V/D

COARSE (vs fine) tremor–> this will be much worse than normal tremor

HYPERreflexia

agitation

dysarthria/slurred speech

impaired vision

muscle weakness and ataxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

list symptoms of moderate lithium toxicity

A

stupor

rigidity

hypertonia

HYPOtension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

list symptoms/signs of severe lithium toxicity

A

coma

seizures

myoclonus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

list four other meds/conditions that can increase levels of lithium

A

NSAIDs

diuretics

ACEi/ARBs

dehydration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

list four meds/conditions that can decrease lithium levels

A

caffeine

high salt diets

manic episodes

pregnancy (later in pregnancy, higher circulating blood volume)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

must you make changes to lithium dosing in liver impairment

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

what is the half life of lithium

A

18-30 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

how must you adjust lithium dosing in renal impairment

A

based on eGFR

reduce dose

if 10-50ml/min use 50-75% of standard dose

if less than 10ml/min use 25-50% of standard dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

what % of people achieve adequate relief with lithium monotherapy

A

only about 1/3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

list 7 predictors of poor efficacy related to lithium therapy

A

dysphoric/psychotic mania

mixed states

rapid cycling

multiple prior episodes

comorbid medical conditions

substance abuse

high anxiety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

list 6 predictors of positive response to lithium therapy

A

prior response to lithium

history of response in 1st degree relative–> 67% likelihood of also being responsive (vs 35% baseline likelihood)

family history of BD

classic euphoric/grandiose mania

few prior mood episodes and complete recovery between episodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

how long should you continue treatment with lithium in the case of mania

A

continue treatment until all symptoms are gone or until improvement is stable and then continue treating INDEFINITELY as long as improvement persists

continue treatment indefinitely to avoid recurrence of mania or depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

is there a significant withdrawal syndrome associated with lithiuim

A

no significant withdrawal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

what are risks associated with stopping lithium

A

risk of recurrence within MONTHS

increased risk of suicide within the first year

risk of this is increased with rapid withdrawal of lithium (ie within 2 weeks)

some patients reported to become refractory to lithium if discontinued –> this is controversial but Dr. Shabbits quotes this study to reinforce adherence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

does lithium reduce suicide risk

A

yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

what meds/substance should be counselled about when starting lithium

A

ACEi/ARB

NSAIDs

diuretics

caffeine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

what can you do to help deal with nausea associated with taking lithium

A

take with food

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

in addition to ebsteins anomaly, what other abnormality might be noted in infants born to mothers on lithium

A

hypotonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

how do you counsel women RE breastfeeding and lithium

A

lithium is found in breast milk, possibly at full therapeutic levels–> either stay off lithium or bottle feed

however, if has done well on lithium before may be best to restart lithium and bottle feed ideally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

list factors that can cause or contribute to lithium toxicity

A

overdose

volume depletion/dehydration

reduced GFR

drug interactions (thiazide diuretics, NSAIDs–> not aspirin, ACEi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

how do you manage lithium toxicity

A

lithium levels q2-4 hours

IV hydration

bowel irrigation (asymptomatic acute overdose)–> to reduce absorption

consider hemodialysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

when should you consider pursuing hemodialysis in the case of lithium toxicity

A

lithium level above 4mmol/L empirically/with ANY symptoms

lithium level above 2.5 mmol/L + serious symptoms or renal failure

if theres an increasing lithium level despite IV fluids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

what would you counsel someone if theyre home and doing okay but worried about possible signs of lithiuim toxicity

A

tell them to drink a bunch of fluid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

when do you restart lithium after an overdose/toxicity

A

since it accumulates in the CNS, the serum level will fall faster than in the tissue

restart based on CLINICAL PICTURE i.e when coarse motor tremor resolves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

what type of compound is lithium

A

alkali metal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

is lithium absorbed rapidly?

A

yes–> rapidly absorbed from the GI tract

Tmax = 1-3 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

do food or antacids affect lithium absorption

A

no dont appear to

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

is lithium protein bound

A

no–> distributes freely in the body water both intra and extracellularly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

how is lithium metabolized and excreted

A

not metabolized, almost entirely excreted by kidneys

80
Q

what types of neurotransmission are thought to be modulated by lithium

A

glutamatergic

dopaminergic

GABAergic

via alteration of sodium transport across cell membranes of muscle and nerve cells

81
Q

how does lithium increase synthesis of serotonin

A

by increasing tryptophan reuptake in synaptic terminals

82
Q

what effect does lithium have on 5HT receptors

A

downregulation of 5HT1A, 5HTB and 5HT2 receptors

83
Q

changes in what electrolyte is closely related to risk factors for developing lithium toxicity

A

changes in sodium levels or the way the body handles sodium

84
Q

what types of diuretics would worsen or risk lithium toxicity

A

thiazide and loop diuretics

85
Q

what types of diuresis could be used to help treat mild to moderate lithium toxicity

A

osmotic or alkaline diuresis

86
Q

above what lithium level is lithium toxic

A

above 1.5mmol/L (though can have sx toxicity below this so be aware)

87
Q

what is one way to figure out what dose your patient would need of lithium if their current lithium level is subtherapeutic

A

divide current dose over current lithium level, then multiple by target level

ie if dose is 600mg/day and current level is subtherapeutic at 0.5, and your target level is 0.8 then do
(600mg/0.5) x 0.8 = 960mg po daily

88
Q

do we know why there is a “rebound affect” of mood episodes associated with abrupt discontinuation of lithium

A

no–> but risk of mood episodes with abrupt stop can actually be above risk of untreated bipolar disorder

89
Q

is intermittent treatment with lithium recommended in bipolar disorder

A

no–> intermittent treatment may worsen the natural course of bipolar disorder –> some recommendations that lithium should not be started unless there is a clear intention to continue it for at least 3 years

90
Q

how does sodium depletion affect lithium uptake

A

lithium undergoes higher reabsorption in the kidneys if there is low sodium resulting in higher lithium levels

when there is high sodium intake, there is less lithium reabsorption, leading to lower levels

91
Q

what pathways are associated with lithium’s hypothesized neuroprotective effects

A

NMDA pathways

some mild evidence for lower risk of dementia in those with mood disorders treated on lithium

92
Q

which has better anti-suicidal evidence, lithium or clozapine

A

lithium

93
Q

what is the hypothesis behind why lithium protects against suicide

A

?lithium leads to a decrease in impulsivity and aggression via several influences within the nerve cell

however one recent study of lithium as an AUGMENTATION agent at SUBTHERAPEUTIC doses did NOT reduce the overall incidence of suicide related events compared to placebo

94
Q

contraindications to lithium therapy

A

first trimester of pregnancy (teratogen)

severe renal impairment

CV disease with arrhythmias (can cause reversible T waves changes or unmask Brugada syndrome)

addisons disease

untreated hypothyroidism of thyroid disorder

95
Q

list the most common side effects of lithium

A

metallic taste in the mouth

GI upset

fine tremors

polyuria and polydipsia

ankle edema

weight gain

96
Q

how is the tremor associated with lithium categorized

A

postural tremor–> produced by voluntary maintenance of a particular posture held against gravity

97
Q

what is the typical frequency of the tremor (postural) associate with lithium

A

8-12 Hz

98
Q

what is the average rate of tremor associated with lithium

A

ranges depending on study

around 27% average

99
Q

does lithium tremor (postural) improve

A

yes often improves over time

is often tolerable

100
Q

how might you manage lithium tremors

A

beta blockers (propanolol)

primidone

gabapentin

topiramate

*benzos generally not recommened

101
Q

what is nephrogenic diabetes insipidus

A

can be due to lithium

characterized by intense thirst and polyuria with inability to concentrate urine due to reduction of ADH

chronic lithium use can cause ADH RESISTANCE in the kidneys

usually REVERSIBLE in the short term but may be irreversible after long term treatment with lithium ie over 15 years

lithium levels over 0.8 assoc with higher risk of nephrotoxicity

102
Q

how do you diagnose nephrogenic diabetes insipidus

A

water restriction test

+ when theres no change in urine osmolality despite water restriction

103
Q

what is the management of nephrogenic diabetes insipidus

A

d/c lithium or reduce dailty dose or dosing schedule

diuretics can be used to treat NDI but require close monitoring of Li and K levels

104
Q

what are consequences of long term hypercalcemia (i.e due to long term lithium therapy)

A

renal stones, osteoporosis, dyspepsia, hypertension and renal impairment.

105
Q

can lithium prolong QTc

A

yes

106
Q

what is the risk of developing CKD and progressing to ESRD in patients on lithium

A

about 1.5% in long term Li users

most people on long term Li do NOT appear to develop impaired renal function

107
Q

how does drinking caffeine reduce lithium levels

A

?increasing renal Li clearance

108
Q

should lithium be held in delivery (of a baby)

A

yes–> 24 hours before

due to risks of massive fluid shifts from delivery causing lithium toxicity

109
Q

what lithium levels and doses are recommened in geriatric patients

A

For geriatric patients, lithium levels should be <0.8 mmol/L where possible (0.4 to 0.6 for depression, and 0.4 to 0.8 for mania/hypomania). Once daily dosing is best, and it is best to start at a lower dose of 150 mg per day.
Typically, 450 mg per day is enough to reach a therapeutic level for geriatric patients. In some cases, a therapeutic effect is achieved between 0.2 to 0.6 mmol/L, this is because there is a lower correlation between serum lithium levels and cerebrospinal levels in older age (due to a leakier blood brain barrier).

110
Q

what are the big possible adverse events you should know about:
lithium

A

renal impairment

nephrotoxicity

111
Q

what are the big possible adverse events you should know about:
valproic acid

A

pancreatitis

hepatotoxicity

112
Q

what are the big possible adverse events you should know about:

cabamazepine

A

agranulocytosis

asplastic anemia

hepatotoxicity

SJS

TEN

113
Q

what are the big possible adverse events you should know about:

oxcarbazapine

A

agranulocytosis

asplastic anemia

hepatotoxicity

SJS

TEN

114
Q

what are the big possible adverse events you should know about:

lamotrigine

A

SJS

TEN

115
Q

is there any blood work monitoring with lamotrigine specifically

A

no–> but monitor for rashes

116
Q

what teratogenic effects are associated with:

lithium

A

ebsteines anomaly

117
Q

what teratogenic effects are associated with:

valproic acid

A

neural tube defects

118
Q

what teratogenic effects are associated with:

carbamazepine

A

neural tube defects

cleft lip

119
Q

what teratogenic effects are associated with:

oxcarbazepine

A

neural tube defects

cleft lip

120
Q

what teratogenic effects are associated with:

lamotrigine

A

safe in pregnancy

121
Q

what is a particular drug-drug interaction to know amongst the mood stabilizers/anticonvulsants

A

combo of valproic acid with LAMOTRIGINE can cause significant and dangerous increases of lamotrigine –> due to inhibition of GLUCURONIDATION

122
Q

what mood stabilizer should you consider in those with hx of comorbid substance use or TBI

A

VPA

123
Q

what is the benefit of oxcarbazepine vs carbamazepine

A

similar to carbamazepine but NO autoinduction and much fewer CYP 450 enzyme interactions

124
Q

what is the mechanism of action of VPA

A

blocks voltage-sensitive sodium channels by unknown mechanism

acute effects–> mediated by ENHANCEMENT OF GABA-MEDIATED neurotransmission via interference with GABA metabolism and effects on signalling pathways

long term effects–> alteration in multiple gene expression–> at least partly mediated through direct inhibition of HISTONE DEACETYLASE (leads to increase acetylation of lysine residues and thus enhanced transcriptional activity)

125
Q

list 5 indications for treatment with VPA

A

manic episodes

maintenance treatment of bipolar I

bipolar depression

seizures (complex partial, simple/complex absence)

migraine prophylaxis

126
Q

how long is the onset of action of VPA for acute mania? for mood stabilization?

A

acute mania–> a few days

mood stabilization–> a few weeks

127
Q

how would you titrate VPA in the acute setting

A

start at 500-750mg /day then increase by 250-500mg q1-3 days until reach clinical effect

128
Q

how would you titrate VPA in outpatient settings

A

start at 250-500mg qHS, increase weekly, to clinical effect

129
Q

what is the target dosing range for VPA

A

1200-1500mg/day for mania–> extended release formulation with HS dosing once daily

130
Q

what is the benefit of divalproex vs valproic acid

A

less GI side effects with divalproex

131
Q

what baseline monitoring is needed before starting VPA

A

CBC/diff (platelets)

LFTs

weight

blood glucose

lipid panel

beta HCG in all women

consider serum testosterone in young females

132
Q

what is the maintenance monitoring required for VPA

A

cbc/diff (platelets)

LFTs

serum ammonia (with symptoms of lethargy, mental status change)

metabolic monitoring annually

serum testosterone if sx of hyperandrogenization/irregular menses

menstrual hx

133
Q

why do you do a menstrual hx for women on VPA

A

can cause PCOS

do it as q3-6 month intervals for first year, then annually

134
Q

when should you do a serum ammonia for someone on VPA

A

with symptoms of lethargy, mental status change

135
Q

how soon after a dose change should you do a VPA level

A

3-4 days after initiation and dose changes

draw 12 hours post dose as a trough

136
Q

what is the target VPA level

A

350-700umol/L (aim for around 500)–> this is for safety not efficacy

137
Q

is VPA dosing linear

A

no–> due to saturable protein binding

doubling the dose will double the level minus 10-20% ish

138
Q

list CNS side effects/adverse events associated with VPA

A

COGNITIVE BLUNTING

headache (30%)

sedations (up to 30%)

dizziness (up to 25%)

insomnia (15%)

tremor

encephalopathy

139
Q

list endo side effects/adverse events associated with VPA

A

hyperammonemia

metabolic acidosis

hyperosmolality

hypernatremia

hypocalcemia

WEIGHT GAIN

140
Q

list GI side effects/adverse events associated with VPA

A

N/V/D

pancreatitis

hepatotoxicity

141
Q

list heme side effects/adverse events associated with VPA

A

anemia

thrombocytopenia (dose related, up to 25%)

rare pancytopenia

142
Q

what % of people develop thrombocytopenia on VPA

A

up to 25%–> dose related

143
Q

list derm side effects/adverse events associated with VPA

A

alopecia

hypersensivitity (SJS, TEN)

144
Q

list sexual side effects/adverse events associated with VPA

A

PCOS

hyperandrogenism

1-2% risk of neural tube defects (i.e spina bifida)

145
Q

how should you adjust dose of lamotrigine if paired with VPA

A

reduce lamotrigine by 50%

146
Q

is there any adjustment in dosing needed for VPA in cases of renal impairment

A

no

147
Q

what is the half life of VPA

A

9-16 hours

148
Q

is there any dose adjustment required for VPA in cases if liver impairment

A

since metabolized primarily by liver, use with caution–> not recommended in mild/mod disease and contraindicated in severe liver disease

149
Q

what could you pair with VPA to possibly help reduce risk of alopecia

A

multivitamin with zinc and selenium

150
Q

is VPA generally recommended in kids

A

not generally recommended under age 10 except by experts and when other options have been considered

151
Q

how should you handle a pregnant patient on VPA

A

ideally, stop VPA before pregnancy to reduce risk of NTDs and other abnormalities

atypical antipsychotics are generally preferred to mood stabilizers like lithium and VPA during pregnancy

152
Q

is it generally considered safe to breastfeed on VPA

A

yes generally

may be safer than lithium during the post partum period when breast feeding

153
Q

what is the mechanism of action of lamotrigine

A

blocks the alpha subunit of voltage sensitive sodium channels which INHIBITS release of GLUTAMATE

this may modulate reuptake of serotonin and may block reuptake of dopamine

also thought to stabilize neuronal membranes and inhibit the release o excitatory amino acid neurotransmitters i.e glutamate and aspartate that are thought to play a role in the generation and spread of epileptic seizures

154
Q

how do you titrate lamotrigine

A

25mg po daily x 2 weeks

increase by 25mg every 2 weeks

155
Q

what is the target dose of lamotrigine

A

“at least” 200mg po daily

156
Q

what increases the risk of developing SJS on lamotrigine

A

also on VPA

age below 16 years

157
Q

what is the risk of SJS in lamotrigine start

A

0.8 in 1000

158
Q

what is the half life of lamotrigine

A

about 25 hours

159
Q

does lamotrigine affect contraceptive efficacy (OCP)

A

while studies have shown that lamotrigine decreases progestin levels by about 20% it is NOT thought to have an overall impact on contraception efficacy

160
Q

lamotrigine has been observed to cause false positive of what drug on urine drug screen

A

phencyclidine

161
Q

is lamotrigine safe in pregnancy

A

yes

162
Q

how do you titrate lithium

A

150mg po BID

can increase by 300mg every 1-5 days

163
Q

what is the usual dose of lithium

A

900-1800mg /day

164
Q

is lithium first line for MDD

A

no–> second line adjunct

165
Q

do you hold lithium before ECT

A

yes–> risk of delirium

hold for 24 hours prior

166
Q

VPA is particularly well suited to treated bipolar patients with what diagnostic specifier

A

rapid cycling

167
Q

can you use VPA in liver failure

A

no–> health canada warning

168
Q

what is the max dose of lamotrigine

A

400mg/day

169
Q

what % of people get a benign rash with lamotrigine

A

8-10%

170
Q

can you add epival to lamotrigine?

A

no, only add lamotrigine to epival (at reduced dose)

171
Q

does carbamazepine cause weight gain

A

no

172
Q

in which patients should you avoid using carbamazepine

A

pregnant (risk of cleft palate, NTDs, microcephaly)

EtOH abuse

173
Q

what impact does carmabazepine have on the effect of lithium

A

increases neurotixicity of lithium

174
Q

what is the starting dose of topiramate

A

50mg /day

175
Q

what is the usual dose of topiramate

A

200mg / day (max is 400mg/day)

176
Q

what are indications for use of topiramate

A

SECOND line for AUD

binge eating

bulimia

antipsychotic induced weight gain

177
Q

side effects of topiramate

A

weight loss

dizziness

sedation

paresthesias

cognitive dulling

rare metabolic acidosis

NEPHROLITHIASIS

glaucoma

178
Q

is topiramate recommended for PTSD

A

NO not recommended

179
Q

what is the starting dose of gabapentin

A

300mg/day

usual dose is 300-600mg / day

180
Q

what is the max dose of gabapentin

A

3600mg/day

181
Q

list indications for gabapentin

A

second line for AUD

used for neuropathic pain, EtOH withdrawal

182
Q

side effects of gabapentin

A

sedation

ataxia

fatigue

183
Q

should you use gabapentin/pregabalin in pregnancy or breastfeeding

A

no, avoid

184
Q

what effect does gabapentin/pregabalin have on other sedatives

A

potentiates them

185
Q

starting dose of pregabalin

A

150mg/day

usual dose is 150mg BID

186
Q

max dose of pregabalin

A

600mg/day

187
Q

indications for pregabalin

A

FIRST line for GAD, SAD, restless legs

used for neuropathic pain

188
Q

why is divalproex better for GI side effects

A

its enteric coated

189
Q

half life of VPA

A

10-16 hours

190
Q

is VPA approved for any psychiatric conditions in canada in kids/teens

A

no

often used off label for bipolar or for symptoms of impulsivity, rage, aggression

191
Q

maximum dose of VPA

A

3000mg po daily

or 60mg/kg/day

192
Q

what is the risk of NTDs in women on VPA

A

5%

193
Q

what should women taking VPA also be taking

A

OCP

194
Q

what % of people develop a tremor within 1 year of taking VPA

A

25%

dose response relationship

reducing dose or changing to slow release can help

195
Q

when is VPA induced pancreatitis most likely to occur

A

it does NOT depend on the serum level and can occur ANYTIME after the onset of therapy

196
Q

what % of people will experience hair loss/alopecia with VPA therapy? does this happen at any particular time in therapy?

A

up to 25% of people

more common in women than men

temporary

most common with long term VPA treatment

appears to be dose related

197
Q

what should you do if you see a patient who is on VPA and develops decreased LOD, focal neuro signs, cognitive slowing, vomiting, drowsiness, lethargy

A

draw ammonia level–> ?hyperammonenia encephalopathy

8. Psychopharmacology (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions