Neuro Drugs

Terms in this set (76)

Why are SSRIs considered first line Tx of MDD?

1. Better tolerated
2. "Safer" in OD --> generally not fatal with a patient's one-month supply of SSRI

_____ has a warning against QT interval prolongation. (SSRI)

_____ is the racemic mixture of citalopram. (SSRI)

_____ has a long half-life. What does this mean? (SSRI)

Fluoxetine
has an active metabolite norfluoxetine with a long half-life --> less likely to experience withdrawal symptoms with missed doses

_____ has a short half-life. What does this mean? (SSRI)

Paroxetine
more likely to experience withdrawal symptoms with missed doses

_____ is very anticholinergic. (SSRI)

Which 2 SSRIs are very strong CYP 2D6 inhibitors?

1. Paroxetine
2. Fluoxetine

Which SSRI is a CYP 1A2 and mild 3A4 inhibitor?

Short-term SE of SSRIs that go away with time

1. Jitteriness/anxiety (activation) - related to acutely increased serotonin levels
2. GI upset (N/V) - related to acutely increased serotonin levels
3. H/A
4. Insomnia

Long-term and sustained SE of SSRIs as long as patient is on medication

Sexual dysfunction
- does not occur to the same degree with different agents in the same class

_____ is also indicated for diabetic neuropathy, fibromyalgia, musculoskeletal pain, & osteoarthritis (SNRI)

_____ is only FDA-approved for fibromyalgia, but can be used for depression. (SNRI)

_____ is the active metabolite of venlafaxine. (SNRI)

Short-term SE of SNRIs that go away with time

1. GI upset (N/V)
2. Insomnia
3. Activation/agitation (due to dopaminergic activity)

Dose-related seizure risk of SNRIs

- 0.4% at max dose 450 mg/day
- Contraindicated in patients with eating disorders (due to electrolyte abnormalities that may result from bulimia)

Only agent in the Norepinephrine/Serotonin modulator class

_____ may be ideal for those with anorexia/cachexia

ADR of Mirtazepine

- Histaminergic --> sedation (less at higher doses because norepinephrine effects take over)
2. Weight gain (appetite stimulant)
3. Hypertriglyceridemia (mostly a concern in patients with uncontrolled hypertriglyceridemia already)

Agents that are Serotonin Modulators

Trazodone
Nefazodone
Vilazodone
Vortioxetine

_____ is used more for sleep clinically. What are sleep doses vs. depression doses?

Trazodone
- Sleep doses are 50-150 mg/night
- Depression doses are 300+ mg/day --> most patients cannot tolerate high doses and will be asleep or sedated for most of the day and night

_____ is not very used clinically due to the risk of hepatotoxicity (Black Box Warning).

ADR of Trazodone

- adrenergic (dizziness, orthostasis) and histaminic (sedation and weight gain)
- Some cognitive impairment despite minimal anticholinergic activity

_____ is mostly an SSRI with partial 5-HT1A agonism

ADR of Vilazodone

- GI upset (N/V, diarrhea)
- Insomnia
- Sexual dysfunction

_____ is a new serotonin modulator approved in September 2013. What is its MOA?

Vortioxetine
MOA: Serotonin transporter reuptake inhibitor + other serotonin effects (agonist/partial agonist/antagonist at different serotonin receptor subtypes)

How should the dose of Vortioxetine be adjusted in patients on strong CYP 2D6 inhibitors?

Reduce dose by half

Vortioxetine ADR

- less sexual SE compared to other serotonergic agents (advantage)
- GI upset (mostly nausea)
- Dizziness

_____ are fatal in overdose with as little as a ______ supply of drug. How does death occur?

TCAs
2 week supply
Death is usually by arrhythmia

_____ is one of the agents indicated for neuropathic pain

_____ levels can be monitored clinically.

Nortriptyline
Best evidence, but not always clinically necessary

TCAs w/ Secondary amines
What does this mean?

Nortriptyline, desipramine
Higher affinity for NE reuptake pump, better tolerated

TCAs w/ Tertiary amines
What does this mean?

Amitriptyline, Clomipramine, Doxepin, Imipramine
- Higher affinity for 5-HT reuptake pump
- More anticholinergic adverse effects
- More histaminergic adverse effects

- Anticholinergic --> blurred vision, urinary retention, dry mouth, confusion
- Anti-adrenergic --> orthostasis, dizziness
- Histaminic --> sedation, weight gain
- Blocking of sodium channels --> conduction abnormalities, arrhythmias, heart block
- Monitor EKG: age >50, history of cardiac risk factors
- Sexual dysfunction, weight gain, myoclonus (can cause seizures in overdose)

Increases DA, NE, and 5-HT by inhibiting metabolism through MAO enzymes

MAO-_ preferentially breaks down NE and 5-HT

MAO-_ preferentially breaks down DA

- Orthostasis, weight gain, sexual dysfunction
- Hypertensive crisis

_____ is a sedating MAOI.

_____ is a stimulating MAOI.

Tranylcypromine
(structure similar to amphetamines)

Explain Hypertensive crisis with MAOIs

- secondary to "tyramine reaction"
- Tyramine is a vasopressor
- Tyramine breakdown is reduced due to MAO-A inhibition
- Symptoms: headache, stiff neck, N/V, elevated BP
- Negative sequelae: CVA (stroke), death

Foods that can cause "tyramine reaction"

Aged cheese/meats, fermented products, fava beans, red wine, draft beers, monosodium glutamate

Selegiline patch

- 6mg/24 hour patch - no food restrictions (higher doses DO have food restrictions)
- Bypasses gut
- Selectively blocks MAO-B
- Also reduced effects on MAO-A in the gut
- Higher doses may block both MAO-A and MAO-B

Drug interactions with MAOIs that can cause Hypertensive Crisis

- NE reuptake blockers
- Sympathomimetic vasoconstrictive agents
- OTC decongestants (i.e. pseudofed)

Drug interactions that can lead to serotonin syndrome

MAOIs with serotonin increasing agents
i.e. triptans, SSRIs

_____ is a mood stabilizer used to treat BPAD that is antisuicidal

Lithium Transient ADR

- GI upset (NV, diarrhea)
- sedation
- lethargy
- muscle weakness
- polydipsia, polyuria
- headache
- tremor (fine)
- memory/cognitive impairment

Lithium Long-term ADR

- renal impairment
- hypothyroidism
- cardiac effects
- leukocytosis
- acne
- weight gain

Lithium serum levels

- Obtain initially after ~5 days (3-5 half-lives), 12 hours post-dose
- If stable, recheck in 2 weeks, then every 3-6 months or as clinically indicated
- Acute episodes: 1.0-1.2 mmol/L (or mEq/L)
- Maintenance: 0.8-1.0 mmol/L
- Elderly: 0.6-0.8 mmol/L (potentially lower for maintenance)

Lithium toxicity

- Can occur at levels >1.5 mmol/L (can be life-threatening at >2.0 mmol/L)
- Symptoms: severe GI upset, impaired coordination (hand-flapping tremor, ataxia, myoclonus, etc.), impaired consciousness (delirium, confusion, etc.)
- Dialyzable

What drugs/conditions may reduce the elimination/excretion of Lithium?

- Drugs: NSAIDs, ACEI/ARBs, thiazide diuretics
- Dehydration (e.g. from diarrhea or being out in the sun all day without drinking fluids)
- Sodium restriction

_____ is a BPAD drug that is preferred for rapid cycling/mixed states

Valproate Transient ADR

- GI upset
- ataxia
- elevations in LFTs

Valproate Long-term ADR

- fine hand tremors
- weight gain
- thrombocytopenia (dose-related)
- alopecia
- hyperammonemia

- Lamotrigine: VPA reduces clearance of lamotrigine
- Carbamazepine: VPA reduces clearance of active metabolite

Are serum levels of Valproate required?

- No, but may be done
- If monitoring, desired range: 50-125 mcg/mL
- Obtain initially after ~ 3 days
- If stable, recheck in 2 weeks, then every 3-6 months or as clinically indicated
- Consider if toxicity appears at low doses or inefficacy at high doses
- Ultimately, adjust dose based upon patient response (NOT what is recommended in seizure disorder)

Although _____ has a wide therapeutic window, coma and death may occur with toxicity.

_____ may be reserved for lithium-refractory, rapid cycling, or mixed state patients.

Carbamazepine Transient ADR

- GI upset
- sedation
- ataxia
- fatigue
- dizziness
- diplopia

Carbamazepine Long-term ADR

- weight gain
- hyponatremia

Carbamazepine hepatotoxicity and renal impairment

- may cause mild LFT elevations in 5-15% of patients
- may also cause renal dysfunction

Carbamazepine Black Box Warning

- blood dyscrasia/hematologic toxicity (leukopenia, neutropenia, thrombocytopenia) - contraindicated in patients with history of bone marrow suppression

Carbamazepine DI

- induces CYP 3A4
- Clozapine: both agents can cause bone marrow supression

Carbamazepine autoinduction

- induces its own metabolism
- complete induction in ~ 2 weeks
- may need to increase the dose of CBZ later

Are serum levels of Carbamazepine required?

- No, but may be taken
- If monitoring, desired range: 6-10 mcg/mL (per textbook) - see your own lab's normal values
- Obtain initially after ~ 4 days
- If stable, recheck in 2 weeks, then every 3-6 months or as clinically indicated
- Consider if toxicity appears at low doses or inefficacy at high doses
- Ultimately, adjust dose based upon patient response (NOT what is recommended in seizure disorder)

Carbamazepine toxicity

- ataxia
- choreiform movements
- nystagmus
- cardiac abnormalities
- seizures
- respiratory dysfunction
- coma
..... Death may occur

_____ may be preferred for Bipolar depression and maintenance

Why is lamotrigine not preferred for acute mania?

Long titration (>4 weeks to get to therapeutic dose 200 mg/day)

Lamotrigine ADR

- Nausea
- sedation
- HA
- ataxia
- dizziness
- diplopia
- rash --> SJS

_____ can lead to Stevens-Johnson Syndrome. What does this mean?

Lamotrigine
rapidly progressing rash, can lead to sloughing of skin and be life-threatening

- VPA reduces clearance of LTG --> reduce LTG doses by half
- CBZ increases metabolism of LTG --> double LTG doses
- Can alter birth control efficacy

If off of Lamotrigine for ~ 72 hours, what should you do?

restart titration

_____ is a 10-keto analogue of carbamazepine.

Oxcarbazepine
Evidence of use is not as robust as for carbamazepine

Oxcarbazepine Transient ADR

- GI upset
- sedation
- ataxia
- fatigue
- dizziness
- diplopia

Oxcarbazepine Long-term ADR

- weight gain
- hyponatremia (higher rate than carbamazepine)

Oxcarbazepine DI

- induces CYP 3A4 (to a lesser degree than carbamazepine)
- Not an autoinducer

Oxcarbazepine Toxicity symptoms

- ataxia
- choreiform movements
- nystagmus
- cardiac abnormalities
- seizures
- coma

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