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Mental Health > Mood Stabilizers + Other Drugs used in Bipolar > Flashcards

Mood Stabilizers + Other Drugs used in Bipolar Flashcards

1
Q

Timeline for medication response to mania is about ____ weeks.

A

1-2 weeks, to see decrease in symptoms

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2
Q

Main goals of therapy with bipolar treatment include…

There are 2 main ones, and then a few other ones that may be important

A

Eliminated mood episode with complete remission of symptoms, ongoing; acute treatment

Prevent recurrences or relapses of mood episodes, ongoing; maintenance treatment

May also improve QoL and optimize psychosocial functioning
Minimizing harm to self + others
Maximizing adherence and minimizing adverse effects
Minimizing risk factors for mood episodes
Providing care for comorbid conditions

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3
Q

Timeline for a full clinical benefit from medications for mania symptoms is about ____ weeks.

A

3-4 weeks

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4
Q

Timeline for medication response to bipolar depression is about ____ weeks.

A

2-4 weeks

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5
Q

Timeline for a full clinical benefit from medication, for bipolar depressive symptoms is about ____ weeks.

A

6-12 weeks

Usually longer than unipolar depression

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6
Q

Some key non-pharmacological therapies that may help with bipolar treatment include…

A

Exercise
Adequate sleep
Healthy diet
Decreased substance use
Decreased caffeine, nicotine, alcohol

May also involve psychoeducation, supportive counselling, psychotherapy…
ECT for extremes of mania or psychotic depression

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7
Q

A relapse prevention plan is important in bipolar treatment, since…

A

It outlines early warning symptoms and tools they can use when threat of a crisis starts to come on; and what they will do/who to entrust when they are in crisis

Also references what they have to do to stay well, and their responsibilities

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8
Q

Our most commonly used mood stabilizers for bipolar include these 3…

A

Lithium
Valproic acid
Lamotrigene

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9
Q

MOA of lithium is…

A

Exact mechanism not fully understood
Interaction with downstream signalling cascades
Enhancement of GABA activity (inhibit)
Decreased CNS adrenergic activity

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10
Q

Lithium distributes evenly in the total body water space. This is an important factor to consider because…

A

There will be decreases in Vd in elderly, due to decreased % of total body water and lean body mass

Results in increased lithium concentrations

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11
Q

The half-life of lithium for an individual with normal renal function is…

A

12-27 hours (range 5-79)

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12
Q

Elimination of lithium is mainly via…

A

Renal excretion

Freely filtered by glomerulus, like sodium and potassium

Also 80% reabsorbed in proximal tubules, with sodium

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13
Q

When considering lithium PK, we can think of lithium like…

A

A salt, similar to sodium

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14
Q

If the amount of filtered sodium decreases, this results in an increase in sodium reabsorption, which would affect lithium via…

A

Increases in lithium reabsorption and potential lithium toxicity

Hence hyponatremia decreases clearance

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15
Q

Factors that may decrease clearance of lithium include…

KIDNEY related - why?

A

Hyponatremia
Dehydration
Renal failure/dysfunction
Decreasd renal blood flow

Lithium relies on total body water/fluid status

Therefore, lower body water = higher concentration of lithium

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16
Q

What is the therapeutic range of lithium for acute mania?

A

0.8 to 1.2 mmol/L

Narrow TR; so possibility for toxicity with even 1.2…

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17
Q

The therapeutic range of lithium for maintenance therapy is…

A

0.6 to 1.0 mmol/L

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18
Q

The therapeutic range of lithium for maintenance in elderly patients is…

A

0.6 to 0.8 mmol/L

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19
Q

When should lithium levels be sampled?

A

12 hours post dose, OR stat if toxicity/non-adherence is suspected

12 hours - complete absorption/distribution

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20
Q

How often should lithium levels be taken?

Starting dose/changes; physiological conditions?

A

5-7 days after starting therapy/changing dose, then once weekly until at stable dose for 2 weeks.

Then monthly for up to 3 months, then at least every 6 months

More frequent during times of infection, debiliation, diet changes, symptoms recurrence, noncompliance, signs of toxicity

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21
Q

Lithium doses are titrated and started BID because of…

A

Increase likelihood of GI side effects

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22
Q

Initial dosing of lithium for acute mania is usually started at…

What about the elderly?

A

600-900mg per day, in 1-2 divided doses

300mg/day for elderly

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23
Q

Subsequent doses of lithium for acute mania are guided by…

A

Plasma levels and clinical response

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24
Q

Usual doses of lithium for acute mania is…

What about elderly?

A

900-2100 mg/day, in two divided doses

300-1200mg/day for elderly

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25
Q

Lithium dosing for maintenance therapy is usually…

Whats the target plasma level?

A

900mg in divided doses (600-1800mg/day)

Target plasma level of 0.6 to 1 mmol/L

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26
Q

Once a patient is stabilized on their maintenance dose, this could be done to the regimen…

A

Switch to once daily at bedtime, if able to tolerate

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27
Q

A potential benefit of switching to once daily dosing of lithium is…

A

Decrease in urine volume, and decreased renal toxicity/dysfunction

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28
Q

Patients who are sensitive to peak related side effects such as tremors, urinary frequency may benefit from…

A

Switching to the extended release formulation

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29
Q

Lithium dosing in renal impairment…

A

Needs to be reduced; is CI in acute renal failure

CrCl 10-50 mL/min: 50-75% of normal dose
CrCl below 10mL/min: 25-50% of normal dose

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30
Q

If a toxic plasma level of lithium is obtained, we should…

A

HOLD DOSE
Repeat plasma level next day
Restart therapy when within target range

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31
Q

Pregnancy will ____ lithium concentrations, because…

A

Decrease; increase in blood volume and renal clearance

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32
Q

Sodium supplementation will ____ lithium concentrations, because…

A

Decrease; will result in increased secretion of sodium, and lithium follows

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33
Q

Dialysis will ____ lithium concentrations, because…

A

Decreased; removal of drug from blood

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34
Q

Caffeine will ____ lithium concentrations because…

A

Decreased; likely due to increased renal clearance

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35
Q

Dehydration will ____ lithium concentrations, because…

A

Increased; less fluid volume (total body water) means increased concentration of lithium

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36
Q

Renal impairment will ____ lithium concentrations, because…

A

Increase; lithium is primarily renally excreted

Distributed in total body water; impaired fluid excretion in CKD

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37
Q

Sodium loss will ____ lithium concentrations, because…

A

Increase; retention of sodium will occur, lithium will follow

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38
Q

Increased age will ____ lithium concentrations, because…

A

Increased; decreased total body water as well as decreased kidney function

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39
Q

Strenuous exercise will ____ lithium concentrations, because…

A

Increase; sweat and dehydration lower fluid volume, leading to increased lithium concentrations

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40
Q

Cirrhosis will ____ lithium concentrations, because…

A

Increase; connection to hepatorenal syndrome

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41
Q

NSAID’s will ____ lithium concentrations, because…

A

Increase; affects the kidney via vasoconstriction of the afferent arteriole, leading to decreased pressure, decreased blood flow to kidney

Decreased excretion

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42
Q

Thiazide diuretics will ____ lithium concentrations, because…

A

Increase; decrease in blood volume

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43
Q

ACEI’s and ARB’s will ____ lithium concentrations, because…

A

Increase; dilate the efferent arteriole and reduce kidney pressure for filtration

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44
Q

SSRI’s and SNRI’s have a potential drug interaction with lithium, which is…

A

Theoretical risk of serotonin syndrome

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45
Q

Usage of antipsychotics with lithium may increase risk of…

A

Neurotoxicity

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46
Q

Loop diuretics and CCB’s will ____ lithium concentrations, because…

A

Increase or decrease - impact it has on fluid volumes

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47
Q

Common adverse effects of lithium that are DOSE-RELATED include…

A

Increased thirst + urinary frequency
Fine tremors to hands/arms
Headache, sedation, weakness
GI upset
Skin changes (acne, psioriasis), alopecia

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48
Q

Lithium causes weight gain, of about ____ kg.

A

4-6kg in the first 2 years

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49
Q

One of the first signs of lithium toxicity is…

A

GI upset - nausea, diarrhea

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50
Q

Some serious adverse effects that may result from lithium include…

Affects variety of body systems

A

Hypothyroidism
Renal injury
Blood dyscrasias
Bradycardias/conduction abnormalities
Nephrogenic diabetes insipdus

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51
Q

What is nephrogenic diabetes insipidus? Why can it occur with lithium usage?

A

Inability to concentration urine; lithium may be interfering with antidiuretic hormone

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52
Q

Nephrogenic diabetes insipidus with lithium usage will result in…

A

Severely increased thirst + urination; leads to volume depletion and lithium reabsorption, toxicity

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53
Q

This is the drug of choice for lithium-induced nephrogenic diabetes inspidius…

A

Amiloride - potassium sparing diuretic

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54
Q

Mild lithium toxicity symptoms may manifest as…

Think of the dose-related side effects that may be common

A

Ataxia, fine tremors, GI issues, muscle weakness, fatigue

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55
Q

Moderate lithium toxicity symptoms may manifest as…

A

Sedation, lethargy, ataxia + involuntary muscle movements, impaired senses, hyperthermia, coarse tremors

56
Q

Severe lithium symptoms may manifest as…

A

Coarse tremors, delirium, seizures, coma, respiratory complications, AKI
ECG changes, pulse irregularities
Death

57
Q

What should be monitored with lithium usage?

A

Symptoms of mania/depression
Labs
Adherence/side effects of lithium usage

58
Q

Lab values that should be monitored lithium usage include…

Think about what affects lithium concentrations/side effects

A

CBC with differential
Electrolytes (sodum)
Thyroid function
Renal function
ECG
Weight
Plasma lithium conc.

59
Q

In order to maintain adequate lithium concentrations, patients should…

A

Maintain adequate/consistent hydration, sodium, and caffeine intake

No drastic changes, or else lithium concentrations will change

60
Q

A woman should consider ____ on lithium, due to…

A

Contraception - potential heart anomoly may develop in children

61
Q

Valproic acid indications include…

A

Seizures
Bipolar disorder (acute mania treatment + maintenance)

62
Q

The MOA of valproic acid includes…

A

Exact MOA is unknown
Inhibition of voltage-gated sodium channels
Increasing action of GABA
Modulation of signal transduction cascades + gene expression
May effect neuronal excitation

Also affects other neurotransmitters

63
Q

Valproic acid relationship to protein binding is…

A

85-90% bound to serum albumin

Important when considering drug interactions

64
Q

Valproic acid is primarily eliminated via…

A

Hepatic metabolism, via glucoronidation, beta-oxidation, and alpha-hydroxylation

65
Q

The half-life of valproic acid is…

A

12-18 hours

66
Q

Therapeutic range of valproic acid is…

A

350-700 micromol/L of total valproic acid; guideline only and needs to be individualized

67
Q

Valproic acid levels should be taken…

A

At a steady state trough level; 3-4 days after initial therapy

Or at suspected s/sx’s of valproic acid toxicity

For seizures… needs to be measured at time of serizure to determine seizure threshold

68
Q

If valproic acid needs to be used for acute mania treatment, this is what needs to be given as a loading dose…

A

20-30 mg/kg/day

69
Q

Empiric doses of valproic acid should start at…

A

10-15 mg/kg/day
or
500-750 mg/day; increase by 5-10mg/kg/day (250-500 mg/day) using response, levels, and tolerance

MAX = 60 mg/kg/day

70
Q

Dosing frequency of valproic acid is…

A

Usually BID/TID

71
Q

Therapeutic doses of valproic acid is usually…

A

1500-2500 mg/day

72
Q

Hepatic disease affects valproic acid dosing via…

A

Decreased protein binding + clearance; may reuslt in increased unbound drug while total concentrations may remain unchanged

AVOID in hepatic disease

73
Q

Valproic acid PK changes in elderly, because…

How does this affect dosing?

A

Protein binding and clearance is decreased; use lower initial doses

74
Q

Does renal impairment affect valproic acid dosing?

A

No dosage adjustment necssary, but may decrease protein binding (resulting in increased unbound drug concentration)

75
Q

Common drugs that may increase valproate levels include…

A

Antibiotics - macrolides
ASA/salicylates

76
Q

Common drugs that may decrease valproic acid levels include…

A

Antibiotics - carbapenems
Anticonvulsants (carbamazepine, phenytoin)

Carbapenem interaction is very relevant

77
Q

Common drugs that are increased by valproic acid include…

A

Anticonvulsants: carbamazepine, phenytoin, phenobarb
Lamotrigine

78
Q

Lamotrigine and valproic acid have a key drug interaction in that…

And what do we have to do about it?

A

Lamotrigine concentrations are increased by ~50%, so we have to decrease lamotrigene dose by 50%

79
Q

Dose related side effects of valproic acid include…

Two systems are involved

A

GI: N/V/D, constipation, anorexia
CNS: Tremor, sedatoiin, ataxia, dizziness
Thrombocytopenia

Lots, so important to find lowest effective dose + continuously monitor

80
Q

Some serious adverse effects include…

Lots are hepatically related

A

Increased transanimases, LDH; hepatotoxicity
Pancreatitis
Hyperammonemia
Leukopenia
Skin rash (increased with lamotrigene usage)

81
Q

With chronic usage of valproic acid, the following may occur…

A

Weight gain (up to 8-14kg)
Menstrual disturbances; PCOS
Alopecia

Menstrual disturbances could mean spotting, amenorrhea, more bleeding…

82
Q

Contraception is warranted with valproic acid use, because…

A

Valproic acid is teratogenic; will cause neural tube deficits

83
Q

The following should be monitored with valproic acid usage…

A

Sedation
Rash
CBC, platelets, and LFT’s
Ammonia levels (unexplained lethargy, confusion, vomiting)
Valproate levels

84
Q

How often should valproate levels be tested?

A

2-4 days after a dose change or an interacting drug is started, then in 1-2 weeks to ensure stability

Then PRN

85
Q

Indications for lamotrigine include…

A

Seizures
Acute + maintenance therapy for bipolar depression

86
Q

Lamotrigene is not recommended in…

A

Acute mania

87
Q

Lamotrigine MOA is…

A

Blockage of sodium channels + reducing glutamate release
Weak serotonin receptor inhibitory effect

88
Q

Lamotrigine has a half-life of…

A

25-33 hours

Peak at 1-5 hours

This is with NO interacting drugs

89
Q

Lamotrigine is metabolized via…

A

Both hepatic and renal metabolism

90
Q

A key aspect of lamotrigine dosing is…

And what happens if we miss dose for long time?

A

SLOW titration

If dose is missed for 5+ days, need to restart titration

91
Q

Lamotrigine titration is usually as follows…

A

Week 1-2: 25mg once daily
Week 3-4: 50mg once daily
Week 5: 100mg once daily
Then increase dose by 50mg-200mg every 1-2 weeks

92
Q

Usual dosing for lamotrigine is…

A

225-375 mg/day, divided BID

93
Q

Common AE’s that occur with lamotrigine include…

A

Sedation, headaches, nausea, dizziness

Overall quite well tolerated

94
Q

A serious, but rare AE that we must monitor for includes…

A

Life-threatening SJS/TENS

95
Q

85% patients on lamotrigene who experience SJS rash have prodromal symptoms, which involve…

A

Flu-like symptoms

96
Q

The following needs to be monitored while on lamotrigine…

A

Obtain baseline hepatic + renal function
Monitor for rash

Avoid new soaps/detergent that may cause skin reaction in 1st month

97
Q

Does lamotrigine need serum level monitoring?

A

No - relationship between clinical efficacy and plasma concentration is not clearly established

Will only indicate adherence

98
Q

Other lamotrigine DI’s that are important to note include…

A

Other anticonvulsants
Estrogen products

Both decrease lamotrigine levels

Always check for DI’s

99
Q

With medications that have indication for seizure, we want to ____, because…

EVEN if its not being used for seizures

A

Taper off; because we want to prevent seizure occurrence

Threshold of seizure protection, to no protection at all

100
Q

Lamotrigine onset of effect is usually…

A

Several weeks, especially due to slow titration

101
Q

Carbamazepine MOA is…

A

Signal transduction modulation (blockage of sodiium channels; NMDA glutamate, modulate aspartate + glutamate release)
Stimulates release of ADH, promoting reabsorption of water

102
Q

Indications for carbamazepine include…

A

Seizures
BD - acute mania treatment + maintenance
Trigeminal neuralgia

Neuropathic pain (off-label)

103
Q

Carbamazepine is primarily metabolized via…

Also which enzyme?????

A

Hepatically - CYP3A4

Therefore, not recommended in decompensated liver disease

104
Q

Carbamazepine is uniquely metabolized, in that…

Onset? Duration?

A

It can induce its own metabolism, resulting in increased clearance + decreased half-life with continued dosing

Onset is within 1-5 days; time to completion in 1-5 weeks

Makes it difficult to reach target levels

105
Q

Clearance and half-life of carbamazepine are variable, due to…

A

Autoinduction

106
Q

Therapeutic range of carbamazepine is ____, however…

A

17-51 micromol/L - is a guideline extrapolated from seizure guidelines and does not correlate well with efficacy in BD (look for clinical response)

107
Q

If we are obtaining carbamazepine serum concentrations, this is when we need to sample, and how often.

A

Trough, within 1 hour prior to dose.
Every 1-2 weeks during auto-induction to prevent toxicity, and steady state trough after 5 weeks

108
Q

Routine monitoring of serum levels isn’t necessary for carbamazepine; it is usually done when…

A

Non-adherence suspected, or signs/symptoms of toxicity
Potential DI’s, or altered PK
Conversion between dosage forms
Establish drug concentration that resulted in mood stability

109
Q

Empiric, initial dosing of carbamazepine for BD is…

A

100-200mg PO BID, increase by 100-200mg/day q1w to target

110
Q

Maintenance dosing range is ____, and a common target is…

A

300-1600 mg/day, absolute max of 1800mg/day

Common target is 400-600mg BID

111
Q

Carbamazepine dosing is usually given in ____, and is best given at…

A

Divided doses in BID or TID, and is best given at mealtime

112
Q

Carbamazepine formulations are available in…

A

Oral suspension
IR tablets
CR tablets
Chewable tablets

113
Q

Everytime carbamazepine is started or stopped, this should be done…

A

Drug interaction check

114
Q

Common drugs that will increase carbamazepine levels include…

A

Macrolides
Antifungals
CCB’s
Grapefruit juice

115
Q

Common drugs that may decrease carbamazepine levels include…

A

Other anticonvulsants

116
Q

Common drugs that have their serum levels decreased include…

A

Anticoagulants
Antipsychotics
Antidepressants
Estrogen/progesterone

117
Q

Dose related AE’s with carbamazepine include…

3 related systems

A

GI - N/V, constipation, dry mouth
CNS - lethargy, sedation, dizziness, blurred vision, ataxia
CV - tachycardia, hypotension, conduction abnormalities

118
Q

Some idiosyncratic AE’s with carbamazepine include…

A lot of these require lab monitoring

A

Hyponatremia
Blood dyscrasias
Rash + hypersensitivity rxns
Weight gain
Hepatic and thyroid issues
Menstrual disturbances

119
Q

These lab values should be monitored with carbamazepine usage…

A

LFT’s + Thyroid
Renal fx
CBC with diff + platelets, electrolytes
ECG
Bone mineral density

120
Q

These patients have increased risk of rash + hypersensitivity reactions with carbamazepine:

A

Asian ancestry + HLA-B1502
Caucasian + HLA-A3101

121
Q

Chronic usage of carbamazepine may lead to…

A

Osteomalacia
Vitamin D deficiency

122
Q

CI’s for carbamazepine include…

Think of some of the idiosyncratic AE’s and lab monitoring needed

A

Hx of hepatic disease, CVD, blood dyscrasias, and bone-marrow depression

CANNOT be used with clozapine

123
Q

While on carbamazepine, a patient should monitor themselves for…

A

Sedation, tremor, cognitive changes
Rashes/hypersensitvity rxns

124
Q

Carbamazepine will decrease efficacy of estrogen/progestin, therefore…

A

Need to recommend alternative methods of birth control

125
Q

Atypical antipsychotics include the 6 following drugs…

A

Risperidone
Quetiapine
Olanzapine
Aripiprazole
Lurasidone
Asenapine

126
Q

Antipsychotics primary MOA is…

A

Dopamine blockade

And other receptors

127
Q

These types of antipsychotics are preferred for BD because…

A

Lower risk of EPS and hyperprolactinemia

128
Q

EPS with antipsychotics refers to…

A

Involuntary movement that individual cannot control

129
Q

Doses of atypical antipsychotics are lower for bipolar compared to patients with psychosis, because…

A

BD patients are more likely to show EPS when treated with comparable doses of antipsychotics

Also patients on typical antipsychotic is more likely to switch into depression, compared to lithium/VPA

130
Q

General AE’s of atypical antipsychotics include…

Lots of different AE’s

A

Anticholinergic, antihistaminergic, alpha1 blockade; Sedation
Metabolic disturbances
EPS
Sexual dysfxn, QT prolongation, seizures

131
Q

The following should be monitored with atypical antipsychotics:

Think of some of the general AE’s

A

BMI, vitals
A1C and lipids
ECG
Liver + renal fxn, electrolytes, and CBC
Prolactin

132
Q

Antidepressants in BD should be…

A

Avoided as monotherapy, without an antimanic agent

Cautioned in history of AD-induced mania, mixed features, or cycling

133
Q

Antidepressant usage in BD should be discontinued during…

A

An acute manic episode - preferably taper, or abrupt discontinuation if severe mania

134
Q

Once depression symptoms are eliminated in an individual using antidepressants, we should…

A

Consider tapering off once asymptomatic for 6-12 weeks

135
Q

If we are going to use an antidepressant in bipolar, we should avoid…

A

TCA’s > SNRI’s > SSRI’s

136
Q

Antidepressants are safest in this type of BD; and these are the best ones to use

A

BD2; bupropion > sertraline, the fluoxetine/other SSRI’s

PAROXETINE NOT recommended

137
Q

In BD, using short courses of antidepressant for ____ because…

A

3-4 months; prolonged use beyond 1 year may increase mania risk

Mental Health (8 decks)

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