Final Exam: NR546/ NR 546 (Latest Update 2024/ 2025) Psychopharmacology for the Psychiatric-Mental Health Nurse Practitioner Guide |Weeks 5-8 Covered| Questions and Verified Answers| 100% Correct- Chamberlain
Final Exam: NR546/ NR 546 (Latest Update
2024/ 2025) Psychopharmacology for the
Psychiatric-Mental Health Nurse
Practitioner Guide |Weeks 5-8 Covered|
Questions and Verified Answers| 100%
Correct- Chamberlain
Q: Medication Management
Answer:
SSRI-Selective Serotonin Reuptake Inhibitors
*Inhibit 5 HT reuptake
SNRI-Serotonin Norepinephrine Reuptake Inhibitors
*inhibit 5-HT reuptake
*inhibit NE reuptake (increase energy, focus)
*increase DA in prefrontal cortex (increase cognition)
NDRI-Norepinephrine Dopamine Reuptake inhibitors
*inhibit DA reuptake (increase alertness, motivation)
*inhibit NE reuptake (increase energy)
SARI-Serotonin Antagonist Reuptake Inhibitors
Q: Selective Serotonin Reuptake Inhibitors (SSRIs): Most adverse effects will subside after 4-5
days once the body adjusts to increased serotonin levels.
Answer:
diarrhea
headache
weight gain
sexual side effects
Q: Serotonin Norepinephrine Reuptake Inhibitors (SNRIs): Medications should not be abruptly
stopped to avoid discontinuation symptoms. NE effects of the medication may increase anxiety
in some clients. Report worsening anxiety to the provider.
Answer:
elevated blood pressure
anxiety
insomnia
constipation
Q: Norepinephrine Dopamine Reuptake Inhibitors (NDRI): Take medication in the morning.
Stop taking medication if seizures occur. Stop taking medication if anxiety is noted.
Answer:
agitation
headache
dry mouth
constipation
weight loss
Q: escitalopram (Lexapro) SSRI
Answer:
no known drug interactions
best tolerated SSRI
27-32 hour half-life good for forgetful prone clients
least CYP reactions
Substrate for 3A4
Q: citalopram (Celexa) SSRI
Answer:
mild antihistamine effects; Half-Life: 23-45 hours
Weak Inhibitor of 2D6
Q: fluoxetine (Prozac) SSRI
Answer:
longest half-life
Use caution in patients with comorbid anxiety due to risk for activation and panic attacks
Half-Life: 2-3 days parent, 2 week metabolite
Inhibits 2D6 and 3A4
Q: paroxetine (Paxil) SSRI
Answer:
also treats social anxiety and insomnia
associated with weight gain
will experience withdrawal with missed dose or abrupt stop
Half-Life: 24 hours
Inhibits 2D6
Q: fluvoxamine (Luvox) SSRI
Answer:
treats anxious depression smokers require an increased dose
Half-Life: 9-28 hours
Inhibits 3A4, 2C9, 1A2
Q: sertraline (Zoloft) SSRI
Answer:
also treats social anxiety and hypersomnolence
Half-Life: 22-36 hour parent; 62-104 hour metabolite
Inhibits 2D6 and 3A4 weakly at low doses
Q: venlafaxine (Effexor)
Answer:
treats both depression and anxiety disorders, ensure trial of higher dose before switching to a
different medication
Half-life: Parent drug 3-7 hour; metabolite has 9-13 hour
Q: duloxetine (Cymbalta) SNRI
Answer:
effective for atypical pain at higher doses; appropriate for clients who present with somatic
symptoms of depression; effective for atypical pain, such as fibromyalgia and diabetic
neuropathy
Half-Life: 12 hours
Inhibitor of 2D6
Q: bupropion (Wellbutrin)
Answer:
NDRI may improve energy, alertness, and motivation; not first-line treatment for anxiety;
contraindicated in clients with a history of seizures
Avoid in patients with comorbid anxiety
Half-Life: Parent 10-14 hours; Metabolite 20-27 hours
Inhibits 2D6
Q: Serotonin Antagonist and Reuptake Inhibitors (SARIs)
Answer:
SARIs potently block 5-HT2A and 5HT 2C receptors, which allow more 5-HT to interact at
postsynaptic 5-HT1A sites. Serotonin blockade and reuptake inhibition is present at higher doses.
Q: Trazodone
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Prefrontal Cortex Symptoms of MDD
Concentration
Mental Fatigue
Mood
PFC & Amygdala Symptoms of MDD
Guilt
Suicidality
Worthlessness
Striatum Symptoms of MDD
Physical fatigue
Nucleus Accumbens Symptoms of MDD
Pleasure interests
Hypothalamus Symptoms of MDD
Sleep
Appetite
Thalamus & Hypothalamus Symptoms of Mania
Decreased sleep/arousal
Striatum Symptoms of Mania
Motor/agitation
Prefrontal cortex (PFC) Symptoms of Mania
Risk-taking
Talkative/pressured speech
Nucleus Accumbens & PFC Symptoms of Mania
Racing thoughts, grandiosity
PFC & Amygdala Symptoms of Mania
Mood
Medication Management
SSRI-Selective Serotonin Reuptake Inhibitors
*Inhibit 5 HT reuptake
SNRI-Serotonin Norepinephrine Reuptake Inhibitors
*inhibit 5-HT reuptake
*inhibit NE reuptake (increase energy, focus)
*increase DA in prefrontal cortex (increase cognition)
NDRI-Norepinephrine Dopamine Reuptake inhibitors
*inhibit DA reuptake (increase alertness, motivation)
*inhibit NE reuptake (increase energy)
SARI-Serotonin Antagonist Reuptake Inhibitors
Selective Serotonin Reuptake Inhibitors (SSRIs): Most adverse effects will subside after 4-5 days once the body adjusts to increased serotonin levels.
diarrhea
headache
weight gain
sexual side effects
Serotonin Norepinephrine Reuptake Inhibitors (SNRIs): Medications should not be abruptly stopped to avoid discontinuation symptoms. NE effects of the medication may increase anxiety in some clients. Report worsening anxiety to the provider.
elevated blood pressure
anxiety
insomnia
constipation
Norepinephrine Dopamine Reuptake Inhibitors (NDRI): Take medication in the morning. Stop taking medication if seizures occur. Stop taking medication if anxiety is noted.
agitation
headache
dry mouth
constipation
weight loss
escitalopram (Lexapro) SSRI
no known drug interactions
best tolerated SSRI
27-32 hour half-life good for forgetful prone clients
least CYP reactions
Substrate for 3A4
citalopram (Celexa) SSRI
mild antihistamine effects; Half-Life: 23-45 hours
Weak Inhibitor of 2D6
fluoxetine (Prozac) SSRI
longest half-life
Use caution in patients with comorbid anxiety due to risk for activation and panic attacks
Half-Life: 2-3 days parent, 2 week metabolite
Inhibits 2D6 and 3A4
paroxetine (Paxil) SSRI
also treats social anxiety and insomnia
associated with weight gain
will experience withdrawal with missed dose or abrupt stop
Half-Life: 24 hours
Inhibits 2D6
fluvoxamine (Luvox) SSRI
treats anxious depression smokers require an increased dose
Half-Life: 9-28 hours
Inhibits 3A4, 2C9, 1A2
sertraline (Zoloft) SSRI
also treats social anxiety and hypersomnolence
Half-Life: 22-36 hour parent; 62-104 hour metabolite
Inhibits 2D6 and 3A4 weakly at low doses
venlafaxine (Effexor)
treats both depression and anxiety disorders, ensure trial of higher dose before switching to a different medication
Half-life: Parent drug 3-7 hour; metabolite has 9-13 hour
duloxetine (Cymbalta) SNRI
effective for atypical pain at higher doses; appropriate for clients who present with somatic symptoms of depression; effective for atypical pain, such as fibromyalgia and diabetic neuropathy
Half-Life: 12 hours
Inhibitor of 2D6
bupropion (Wellbutrin)
NDRI may improve energy, alertness, and motivation; not first-line treatment for anxiety; contraindicated in clients with a history of seizures
Avoid in patients with comorbid anxiety
Half-Life: Parent 10-14 hours; Metabolite 20-27 hours
Inhibits 2D6
Serotonin Antagonist and Reuptake Inhibitors (SARIs)
SARIs potently block 5-HT2A and 5HT 2C receptors, which allow more 5-HT to interact at postsynaptic 5-HT1A sites. Serotonin blockade and reuptake inhibition is present at higher doses.
Trazodone
The most common SARI, also blocks histaminergic and α-adrenergic receptors.
Half-Life: 3-6 hours
Serotonin Antagonist and Reuptake Inhibitors (SARIs)
Common Adverse Effects
· sedation
· drowsiness
· blurred vision
· constipation
· dry mouth
Serious Adverse Effect
priapism
Serotonin norepinephrine receptor agonist, alpha2 receptor agonist
Mirtazapine
Serotonin multimodal (SMM)/serotonin partial agonist reuptake inhibitor (SPARI)
Vilazodone (Viibryd)
· Inhibits serotonin reuptake with partial 5HT1A agonism
Appropriate for depression/comorbid anxiety, its action is similar to a combination of SSRI and buspirone
Serotonin multimodal (SMM)
Vortioxetine (Trintellix)
· Acts as SSRI plus 5HT1A partial agonism
· Improves depression-related cognition
Tricyclic antidepressants (TCAs)
Tricyclic antidepressants (TCAs) possess both SRI and NRI properties, but they also block other receptors, including α1-adrenergic, histamine-1, and muscarinic cholinergic receptors. TCAs are not used first-line because of the high incidence of adverse effects and the risk of potential overdose and death due to overdose
Tricyclic antidepressants (TCAs)
Drugs:
· amitriptyline (Elavil)
· desipramine (Norpramin)
· doxepin (Sinequan)
· imipramine (Tofranil)
· nortriptyline (Pamelor)
Tricyclic antidepressants (TCAs)
Common adverse effects of TCAs
Alpha-1 adrenergic effects-Orthostatic hypotension
Histamine effects-Sedation
Histamine effects-Weight gain
Anticholinergic effects-Blurred vision
Anticholinergic effects-Urinary retention
Anticholinergic effects-Constipation
Anticholinergic effects-Dry mouth
MAOIs
Last choice medication class for depression due to the many potential, serious side effects. MAOIs have specific dietary restrictions that when ignored, may be very uncomfortable or very serious for clients.
MAOIs
Drugs:
· phenelzine (Nardil)
· selegiline (Emsam) – MAOI-B
· tranylcypromine (Parnate)
· isocarboxazid (Marplan)
MAOI’s Key Points
· Clients taking MAOIs are at high risk for hypertensive crisis if tyramine is ingested.
· Do not prescribe any serotonergic agents within 2 weeks of MAOI discontinuation due to an increased risk of serotonin syndrome.
Wait at least 5 half-lives after discontinuing a serotonergic medication before initiating an MAIO.
Foods to Avoid When Taking MAO-A Medications
· Red wine (Avoid)
· Sauerkraut (Avoid)
· Cheese (Avoid)
· Soy (Avoid)
· Smoked meats (Avoid)
Foods to Avoid When Taking MAO-A Medications
Rationale: Limiting the consumption of tyramine is necessary for orally available MAOIs due to inhibition of MAO-A in the gut. Dietary restrictions are not required for the transdermal formulation of selegiline.
Tyramine is present in many aged or preserved foods including aged cheeses, tap and non-pasteurized beers, aged or smoked meat or fish, sauerkraut, kimchee, soy products, and tofu.
Foods to be avoided when taking MAO-A medications include wine, meats, sauerkraut, cheese, and soy.
Newer Treatments for Resistant Depression
· The goal of antidepressant treatment is the remission of symptoms; however, the current treatment response of clients with mood disorders varies widely and is often unsatisfactory.
· For example, in clients with MDD, the treatment efficacy of selective serotonin reuptake inhibitors (SSRIs), the most used first-line pharmacological agent is between 48 and 64% with reported remission rates as low as 23.5%.
· Treatment-resistant depression occurs when depression persists after the client has adequately trialed at least two antidepressant therapies.
Newer Treatments for Resistant Depression
Esketamine (Spravato)-N-methyl-D-aspartate (NMDA) receptor inhibitor
Dextromethorphan/quinidine (Nuedexta)-under investigation for Resistant depression
Esketamine (Spravato)-N-methyl-D-aspartate (NMDA) receptor inhibitor
Nasal spray for the treatment of major depressive disorder (MDD) with acute suicidal ideation or behavior.
Esketamine reaches peak onset in the body in between 20-40 minutes.
Due to the risk of adverse outcomes due to sedation and dissociation, esketamine must be administered in a supervised healthcare setting
Initiating Medication
· Start patients on a single drug for 4-8 weeks to assess efficacy
· Start with the lowest recommended dose to reduce side effects
· If not achieving efficacy follow the process below:
Increase the dose gradually to the efficacious dose range
Switch to a different drug within the same class after an adequate trial which includes higher dosing and a minimum of eight weeks of trial
Switch to a drug in a different class after an adequate trial which includes higher dosing and a minimum of eight weeks of trial
Add a second medication as an adjunct
If not achieving efficacy for MDD follow the process below:
-Increase the dose gradually to the efficacious dose range
-Switch to a different drug within the same class after an adequate trial which includes higher dosing and a minimum of eight weeks of trial
-Switch to a drug in a different class after an adequate trial which includes higher dosing and a minimum of eight weeks of trial
-Add a second medication as an adjunct
Discontinuing Medications
· Clients should be advised not to suddenly stop any medication or omit doses due to the risk of discontinuation syndrome.
· Paroxetine has the highest risk of discontinuation syndrome due to serotonin transporter inhibition and anticholinergic rebound.
· If a treatment course has lasted 8 weeks, discontinuation over 1-2 weeks is safe. Once symptoms are in remission, continue treatment for 4-9 months to reduce the risk of relapse.
Black Box Warning: Suicide Risk with Antidepressant Drugs
· Clients with depression may consider or attempt suicide.
· The risk for suicide may increase at the start of treatment with antidepressants.
-Antidepressant-induced suicide is more prevalent in children, adolescents, and adults younger than 25 years
Serotonin Syndrome
Symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Concerns for Sexual Side Effects
Bupropion has fewer sexual side effects than other first-line treatments. Bupropion can also be prescribed as an adjunct to a SSRI.
Complaining of Brain Fog as part of Depression Symptoms
Vortioxetine can improve the speed of processing and cognitive function due to its unique mechanism of action.
Patient often forgets to take pills
Fluoxetine has a 2-3 days half-life, an excellent option for forgetful people
Pregnancy Considerations for Depression
Paroxetine is contraindicated in pregnancy due to the risk of congenital defects, including atrial septal defects.
Prescribing for older adults with depression
Citalopram and escitalopram should be dosed at 1/2 dose due to the risk of QTc prolongation
-Avoid paroxetine in clients with a history of falls/fractures.
-Avoid tricyclic antidepressants prescribed with other central nervous system (CNS) depressants.
MEDICATION MANAGEMENT FOR BIPOLAR DISORDER
· Treatment of bipolar disorder (BD) varies depending on the presenting symptoms.
· Some medications are more appropriate for symptoms of mania, while others are better for symptoms of depression.
· Medication classes used include mood stabilizers, anticonvulsants, and atypical antipsychotics.
Lithium
ACTION:
alters cation transport in the nerve and muscle (downstream signal transduction cascades) Lithium may work by affecting signal transduction, perhaps through its inhibition of second messenger enzymes such as inositol monophosphatase, by modulation of G proteins, or by interaction at various sites within downstream signal transduction cascades, including glycogen synthetase kinase 3 (GSK3).
Lithium
INDICATIONS:
-euphoric mania
-rapid cycling
-maintenance therapy
HALF-LIFE: 18-30 hours
Lithium Therapeutic Levels
Therapeutic levels:
1.0 and 1.5 mEq/L for acute treatment, 0.6 and 1.2 mEq/L for chronic treatment)
Lamotrigine (Lamictal)
ACTION:
affects sodium channel ion transport and enhances the activity of y-aminobutyric acid (GABA)
Lamotrigine (Lamictal)
INDICATION:
-maintenance therapy
-monotherapy for bipolar disorder
HALF LIFE: 33 hours
Lamotrigine (Lamictal)
PRESCRIBING PEARLS:
This drug is equal in efficacy to lithium.
Educate clients and assess for rash at each visit. Ten percent of rashes are benign.
There is a risk for rare Stevens-Johnson Syndrome rash and multi-organ failure.
Take at bedtime due to sedation side effect.
Lamotrigine (Lamictal)
Therapeutic levels:
Not monitored
Valproic acid (Depakene)
ACTION:
affects ion transport and enhances the activity of y-aminobutyric acid (GABA)
Valproic acid (Depakene)
INDICATION:
acute mania
mixed mood
comorbid substance use
multiple prior episodes
HALF LIFE: 9-16 hours
Valproic acid (Depakene)
Therapeutic levels:
50-100mcg/mL; Toxic Levels: >175 mcg/mL
Valproic acid (Depakene)
If using with Lamitrogine decrease dose by 50%
Second generation antipsychotics
aripiprazole (Abilify)
cariprazine (Vraylar)
lurasidone (Latuda)
quetiapine (Seroquel)
asenapine (Saphris)
risperidone (Risperdal)
olanzapine (Zyprexa)
ziprazadone (Geodon)
Second generation antipsychotics
ACTION:
DA, NE, and 5-HT receptor antagonists
Second generation antipsychotics
INDICATION:
acute bipolar depression
acute manic or mixed episodes
bipolar maintenance/adjunct
Second generation antipsychotics
ADVERSE EFFECTS:
weight gain
sedation
GI effects
Second generation antipsychotics
PRESCRIBING PEARLS:
Indications vary with each medication.
Check for monotherapy vs. adjunct indication.
Monitor for extrapyramidal effects.
XR form may improve adherence.
Monthly injection may improve adherence.
Select second generation antipsychotics first to decrease risk of side effects and long-term adverse effects.
Carbamazepine (Tegretol)
ACTION:
glutamate voltage gated sodium and calcium channel blocker (Glu-CB)
Carbamazepine (Tegretol)
INDICATION:
acute mania
mixed mood
HALF LIFE: 26-65 hours
Carbamazepine (Tegretol)
ADVERSE EFFECTS:
GI effects
Sedation
Hyponatremia
Neutropenia
rash (Stevens-Johnson Syndrome)-Consider genotyping clients with Asian ancestry; the HLA-B 2501 allele increases risk of Steven-Johnson Syndrome
Carbamazepine (Tegretol)
Therapeutic levels:
4-12 mcg/mL;
Toxic levels: >12mcg/mL
FIRST LINE COMBINATION THERAPY FOR BPI D/O, Current manic episode, with depressive features
Lithium + Lamotrigine
Lithium + Aripiprazole
Lithium + Risperdal
OR
Valproic Acid + Lamotrigine
Valproic Acid + Aripiprazole
Valproic Acid + Risperdal
MANAGEMENT OF ACUTE AGITATION (pacing or fidgeting in mild cases or uncooperative threatening and aggressive behaviors in severe cases)
-In the inpatient setting, the use of rapid-acting oral antimanic medications is preferred.
-When agitation persists, additional rapidly acting pharmacologic therapies may be needed.
-A loading dose of divalproex, oral formulations of atypical antipsychotics, conventional antipsychotics such as haloperidol or loxapine, and/or benzodiazepines such as lorazepam may be appropriate
-If oral medications are ineffective or if the agitation is severe, the client is refusing oral medications, or when oral therapy cannot be safely or reliably administered, an IM or inhaled formulation should be considered.
-IM options include olanzapine, aripiprazole, or haloperidol. Inhaled loxapine may also be given
INITIAL TREATMENT SELECTION for a client with bipolar disorder should follow a stepwise approach beginning with a thorough assessment
Assess
· client safety
· comorbidities
· treatment adherence
Initiate/optimize therapy
· choose monotherapy or combination
· optimize dose
· check for adherence
Add-on or switch therapy
· use an alternative first-line agent or add on an additional first-line agent
· if first-line agents are not effective, may switch to second-line agents
NONADHERENCE RISK FACTORS
Medication factors
· adverse effects
· low treatment doses
Manifestation of BD
· mixed episodes
· rapid cycling
· hallucinations
· BD I
Comorbidities
· substance use
· obsessive-compulsive disorder
Demographics
· male
· younger
· lower education level
· single
Other
· poor insight
· negative attitude
· low self-esteem
PRESCRIBING PEARLS
· Lurasidone (Latuda) should be taken with food, at least 350 calories, for maximum absorption.
· Lithium carbonate (Lithobid) starting dose is reduced by at least 50% in clients with renal impairment.
· Lithium levels can be increased by nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors and decreased by caffeine and mania.
Lithium Lab Monitoring
· serum lithium level
· renal function
· thyroid function
Rationale: Lithium has a narrow therapeutic index and should be monitored carefully.
Serum levels should be evaluated 5 days after any dosage change and regularly at 6-month intervals. Lithium can cause renal and thyroid toxicity.
Renal and thyroid function should be evaluated every 6 months.
Valproic Acid Lab Monitoring
· serum valproate level
· liver function
· CBC
Rationale: Valproic acid and its derivatives can cause leukopenia, thrombocytopenia, and hepatotoxicity.
Monitor CBC and liver function tests (LFTs) every 3 months for 1 year and then annually
Carbamazepine Lab Monitoring
· serum carbamazepine level
· renal function
· liver function
· CBC
Rationale: Carbamazepine can cause blood dyscrasias, hepatotoxicity, and renal failure.
Order a CBC, LFT, and renal function every 3 months for 1 year and then annually.
Atypical antipsychotic medications Lab Monitoring
· CBC
· HbA1C
Rationale: Atypical antipsychotics can cause increased blood glucose and an increased risk of developing diabetes mellitus (DM) II.
Measure HbA1C every 3 months for 1 year and then annually. Certain medications, such as Clozapine, may cause blood dyscrasias and CBC should be monitored closely.
SPECIAL CONSIDERATIONS: Pregnancy
· Lithium, valproic acid, and carbamazepine are teratogenic and are contraindicated during pregnancy.
· Lurasidone has been used in pregnancy without teratogenic effects.
SPECIAL CONSIDERATIONS: Breast Feeding
Breast Feeding
Avoid breastfeeding for clients prescribed carbamazepine, lithium, and lamotrigine
SPECIAL CONSIDERATIONS: Older Adult
Use caution. Reduced renal and hepatic function may impact metabolism and elimination. Reduce dose as necessary.
· Avoid carbamazepine (may cause syndrome of inappropriate antidiuretic hormone secretion [SIADH]).
· Use caution with antipsychotic medications (may increase the risk of falls).
· Antipsychotic medications may increase the risk of stroke, cognitive decline, and death in dementia clients.
Avoid lithium in clients taking ACE inhibitors or loop diuretics
SPECIAL CONSIDERATIONS: Children
Age 10 +:
· lurasidone (bipolar depression)
· aripiprazole (acute and mixed mania)
· quetiapine (monotherapy and adjunct for acute mania)
· asenapine (acute and mixed mania)
· risperidone (monotherapy and adjunct for acute and mixed mania)
Age 13 +:
· olanzapine (acute and mixed mania)
BIPOLAR 1
· The diagnosis of bipolar I disorder requires at least one episode of mania for at least one week (or any duration if hospitalization due to symptoms is required).
· Mania is characterized by a persistently elevated, expansive, or irritable mood.
· Related symptoms may include inflated self-esteem, increased goal-directed activity or energy, including grandiosity, decreased need for sleep, excessive talkativeness, racing thoughts, flight of ideas (FOI), distractibility, psychomotor agitation, and a propensity to be involved in high-risk activities.
· Mania leads to significant functional impairment and may include psychotic features or necessitate hospitalization
BIPOLAR 1
Mania diagnosed by having (1) of either Elevated/expansive mood OR Irritable mood AND (3) or more of:
1.) Inflated self-esteem/grandiosity
2.) Increased goal-directed activity or agitation
3.) Risk Taking
4.) Decreased need for sleep
5.) Distractible/Concentration
6.) More talkative pressured speech
7.) Flight of ideas/racing thoughts.
*If mood is only irritable, must have 4 symptoms present above.
BP TYPE II
· A diagnosis of bipolar II disorder requires a current or past hypomanic episode and a current or past major depressive episode.
· Symptoms last for at least 4 days but fewer than seven.
· Hypomanic symptoms are not of sufficient duration or severity to cause significant functional impairment, psychosis, or hospitalization.
· Anger and irritability are common.
Clients often enjoy the elevation of mood and are reluctant to report these symptoms, making bipolar more difficult to diagnose if the client presents in the depression phase
Cyclothymia
· Cyclothymia involves the chronic presentation of hypomanic and depressive symptoms that do not meet the diagnostic criteria for a major depressive or manic/hypomanic episode.
Decreased positive affect: DA, NE Dysfunction
· depressed mood
· loss of joy
· lack of interest
· loss of energy
· decreased alertness
· decreased self-confidence
· appetite changes
Increased negative affect: 5HT, NE Dysfunction
· depressed mood
· guilt
· fear/anxiety
· hostility
· irritability
· loneliness
· appetite changes
Neural Networks
The classic monoamine hypothesis of depression posits that depression occurs as a result of a deficiency of one or all three monoamine transmitters (serotonin, norepinephrine, and dopamine), while mania may result from an excess; however, this hypothesis has limitations.
Neural Signaling
Three principal neurotransmitters, norepinephrine (NE), dopamine (DA), and serotonin 5HT, have implications for the pathophysiology and treatment of mood disorders. Norepinephrine, dopamine, and serotonin are monoamines. Monoamines work in concert and comprise the monoamine neurotransmitter system
Monoamine transmitters
serotonin, norepinephrine, and dopamine
Lithium
Levels can be increased by NSAIDs and ACE inhibitors
Decreased by caffeine and mania
Unchanged by amiloride, furosemide, and sulindac
Lithium
Well established to help prevent suicide in clients with mood disorders
MAOI’s Duration of action
Drugs:
· phenelzine (Nardil)-Clinical Duration of action up to 14 days
· selegiline (Emsam) – MAOI-B-Clinical Duration of action up to 14 days
· tranylcypromine (Parnate)-Clinical Duration of action 14- 30 days
· isocarboxazid (Marplan)-Clinical Duration of action up to 14 days
L-Methylfolate in Depression
Enhances antidepressant response. Methylfolate crosses the blood brain barrier and is a cofactor required for the complete synthesis of serotonin, norepinephrine, and dopamine in the brain. Supplementation with L-methylfolate in addition to SSRIs or SNRIs shows symptom reduction in MDD, and may be an effective monotherapy in MDD.
Morphine-Prototype opioid agonist
Morphine binds to opioid receptors in the central nervous system (CNS), inhibiting ascending pain pathways, and altering the perception and response to pain
Morphine
The onset of action of immediate release formulation is patient-dependent, with variable absorption. The onset of action intravenously is 5-10 minutes, with a duration 3-5 hours. Also available in controlled release formulation (MS Contin) and extended-release morphine (Avinza)
Fentanyl
Almost immediate onset of action when given IV, with a duration of 0.5-1 hour
Fentanyl
More potent than morphine, but short duration of action. This medication is the preferred opioid for those unable to tolerate morphine or hydromorphone and in those with severe hepatic and renal disease
Hydromorphone
Similar opioid agonist as morphine but more potent. Oral and parenteral doses are not equivalent (parenteral doses up to 5 times more potent)
Methadone
In addition to its opioid receptor activity, it is also an antagonist of the N-methyl-D-aspartate (NMDA) receptor
Methadone
Utilized in detoxification and maintenance treatment of opioid addiction and heroin addiction, with high variability among patients
Methadone
This is a long acting opioid that binds to and occupies mu-opioid receptors, reducing craving for opioids and prevents withdrawal symptoms for 24 hours
Half-life: 8-59 hours
Ketamine
Medication useful in general anesthesia and procedural sedation, but also off label usage as infusions for acute pain, as both a stand-alone treatment, as an adjunctive option with opioids, as well as an intranasal formulation
Tramadol
Opioid agonist, with similar indications and side effect profile as other opioids, but that also blocks reuptake of serotonin and norepinephrine. Indicated for acute pain management, with added benefit for patients with neuropathic pain and nociceptive pain. Has a lower risk of constipation and dependence than other opioids, but does have risk of serotonin syndrome
Naloxone
-This is a pure antagonist, with clinical indication for treatment of acute opioid overdose.
-IV naloxone can dramatically reverse opioids, even in comatose states, with recent widespread community availability of intramuscular and intranasal administration options available given the prescription and recreational opiate crisis, and related deaths.
-Given the short duration of action, patients can relapse into coma or previous overdose state, and may need continued monitoring and potentially further doses or constant infusion.
Clonidine
Antihypertensive agent, and Alpha2-Adrenergic Agonist
Thought to produce analgesia at presynaptic and post junction alpha-2 adrenoceptors in the spinal cord, with pain transmission to the brain prevented.
Clonidine
Off-label adjunctive treatment for medically supervised opioid withdrawal. Initial treatment is 0.1mg-0.2mg, with ability to repeat up to 4 doses until symptoms resolve
Maintenance would be determined by severity of symptoms, with treatment every 6-8 hours.
Mesolimbic dopamine pathway
-Identified as the key pathway that mediates reward
-Connects the ventral tegmental area of the midbrain to the ventral striatum of the basal ganglia
-Begins in the ventral tegmental area (VTA) and connects to the ventral striatum/nucleus accumbens, amygdala, hippocampus, and prefrontal cortex (PFC)
Ventral tegmental area (VTA)
One of the major dopamine-producing areas of the brain
Nucleus accumbens
Area found within the ventral striatum and has a strong association with motivation and reward
Prefrontal cortex/striatal circuitry
Conditions that involve impulsive or compulsive behaviors, such as substance use disorder, obsessive-compulsive disorder (OCD), and obesity may relate to inefficient processing in the prefrontal cortex/striatal circuitry.
Mesolimbic dopamine pathway
Drugs and alcohol act directly on brain receptors leading to a release of dopamine, the neurotransmitter associated with reward.
As substance use increases, brain circuits adapt by reducing sensitivity to dopamine, leading to tolerance and the need to increase the use of a substance to achieve the same high
Dopamine Effects on Addictive Drugs
Addictive drugs cause a surge of dopamine in the ventral striatum or nucleus accumbens.
Repeated use can lead to changes in brain circuitry, leading to craving, addiction, dependence, and withdrawal.
Medications which treat addiction target dopamine.
Tolerance
With repeated ingestion of a drug, the drug shows decreased effect. Increasing doses are required to achieve the effects noted with the original administration.
Dependence
State of adaptation produced with repeated administration of certain drugs so that physical symptoms occur when the drug is discontinued abruptly.
Addiction
A change in behavior caused by biochemical changes in the brain after continued substance use characterized by preoccupation with and repeated use of a substance despite negative outcomes
Withdrawal
Physiological and psychological reactions that occur when the use of a substance is stopped abruptly
Intoxication
Condition following the ingestion of a substance resulting in changes in level of consciousness, cognition, perception, judgment, and behavior.
SAMHSA (2022a) identified the goals of MAT to include
· improved survival
· improved treatment retention
· decreased illegal activity
· increased quality of life
· improved birth outcomes in people who use substances while pregnant
· reduced HIV and Hepatitis B & C infections
OCD/Impulsive Control Disorders
Studies indicate dopaminergic activity in the activation of the right ventral striatum in response to images of food in individuals with binge-eating disorders.
OCD/Impulsive Control Disorders
Pharmacologic management is often used in combination with psychotherapy to address eating disorders
Obesity
-Phentermine or phentermine/topiramate
-Bupropion or bupropion/naltrexone
-Lorcaserin
-Zonisamide
Anorexia
-Olanzapine
-Avoid bupropion in individuals with anorexia nervosa and bulimia nervosa as bupropion lowers the seizure threshold in these individuals putting them at significantly increased risk for new-onset seizures
Bulimia
-High Dose Fluoxetine
-Avoid bupropion in individuals with anorexia nervosa and bulimia nervosa as bupropion lowers the seizure threshold in these individuals putting them at significantly increased risk for new-onset seizures
Binge Eating Disorder
-Topiramate
-Bupropion
-Lisdexamfetamine
SCENARIO: Bernita is a 64-year-old who has been using heroin for 6 years. She is currently unemployed and lives with her daughter in the city center. She does not have health insurance
MAT: Methadone
SCENARIO: Antoine is a 34-year-old who has been abusing prescription oxycodone. He is employed but is on probation at work for increased absenteeism. He desires MAT but is concerned about his roommates stealing his medication to get high
MAT: Buprenorphine plus naloxone (Suboxone)
-Suboxone is a good option for a client who may not be able to leave work for medication dosing, as it does not need to be taken under direct observation.
-If one tries to administer the buprenorphine/naloxone formulation intravenously, naloxone will prevent any rewarding effects from buprenorphine, making this drug a less desirable street drug
Lisa is a 29-year-old who admits to using “pills, heroin, and booze” regularly. She lives in a rural area and is employed part-time. She has a history of poor compliance with past treatments.
MAT: Naltrexone
RATIONALE:Naltrexone blocks mu-opioid receptors, preventing exogenous opioids from binding there and thus preventing the pleasurable effects of opioid consumption.
This medication also reduces alcohol consumption through the modulation of opioid systems, thereby reducing the reinforcing effects of alcohol.
For those clients with alcohol use disorder, who have poor adherence to a regimen, and are unable to maintain abstinence, a long-acting injection of naltrexone (Vivitrol) administered monthly can be efficacious
Miranda is a 20-year-old who is 18 weeks pregnant and uses heroin. She wants to get clean “for her baby.”
MAT: Buprenorphine
RATIONALE:Buprenorphine is a partial opioid agonist which binds with a strong affinity to the mu-opioid receptor, preventing exogenous opioids from binding at the receptor site, and preventing the pleasurable effects of opioid consumption. While either methadone or buprenorphine may be prescribed in pregnancy, buprenorphine does not require daily visits to an opioid treatment program and requires less need for dosage adjustments during pregnancy
SCENARIO: John is a 56-year-old with a history of seizure disorder who has smoked 1 pack-per-day (PPD) for 30 years. He has tried to quit using nicotine gum without success. He is committed to quitting smoking but feels he would benefit from medication to help.
MAT: varenicline
RATIONALE: Varenicline is an appropriate medication option for clients who want to quit using tobacco products. Bupropion is contraindicated in clients with seizure disorder.
SCENARIO: Ellen is a 35-year-old who has a history of drinking 4-5 alcoholic beverages per day. She was admitted to the hospital for a respiratory infection and was treated with benzodiazepines using the CIWA-Ar scale. She has abstained from alcohol for 8 days and is committed to maintaining abstinence but would like to take a medication to help her stay away from alcohol
MAT: disulfiram
RATIONALE: Disulfiram creates unpleasant physical symptoms when taken with alcohol. This mild negative stimulus can help reinforce the client’s abstinence from drinking alcohol.
SCENARIO: Nori is a 24-year-old who has a history of abusing opioid medications and binge drinking. She is not committed to abstain from using at this time.
MAT: naloxone
RATIONALE: Since Nori is not committed to abstaining at this time, it is important to provide naloxone along with education to help her remain safe from overdose.
SCENARIO: Juan is a 19-year-old who has a history of using oxycodone that he has taken from his grandfather and drinking occasional alcohol. He wants to stop using both substances.
MAT: naltrexone
RATIONALE:Naltrexone is a good option for clients who use opioids and alcohol and are committed to abstinence
Pregnancy with Buprenorphine
Buprenorphine is an acceptable treatment during pregnancy; however, there is an increased risk of a neonatal withdrawal syndrome in newborns.
Pregnancy with Suboxone (buprenorphine/naloxone)
Suboxone (buprenorphine/naloxone) cannot be used in pregnancy
Pregnancy with Naloxone
Naloxone increases the risk of neonatal abstinence syndrome. Pregnant clients must be switched to buprenorphine (Subutex) monotherapy.
Pregnancy with Methadone
Methadone is approved in pregnancy for heroin-addicted women. Dosing requires adjustment.
Pregnancy in MAT
Short-term newborn withdrawal effects may be seen and may require neonatal intensive care unit (NICU) admission for treatment.
Breast Feeding with Naltrexone and Buprenorphine
Not recommended
Breast Feeding with Methadone
Can be prescribed with special consideration given to feeding intervals (breastfeed prior to or 2-6 hours after dose).
Older Adult with Buprenorphine
Use in the elderly may lead to confusion and drowsiness
Older Adult with Methadone
Methadone has a high potential for drug interactions, associated with QT prolongation.
It is difficult to titrate in the elderly and has a risk for accumulation due to the long half-life
MAT for Chronic Alcohol Use Disorder
Medication selections for MAT should be based on clinical presentation, history of alcohol use/abuse with comorbid liver disease or renal impairment, concurrent opioid use disorder, and other unique client characteristics
Naltrexone (Revia, Vivitrol):
Initial treatment for alcohol use disorder
-Start while still drinking
-Can treat concurrent opioid use disorder
-Contraindicated in liver disease
-May be given in monthly long-acting injections (Vivitrol)
Acamprosate (Campral)
· Modulates glutamine transmission, and resembles gamma-aminobutyric acid (GABA)
· Good option for clients who must take opioids for chronic pain
· Treats withdrawal symptoms
· Abstain prior to beginning treatment
No affect on Opioids
Disulfiram (Antabuse):
-Blocks oxidation of alcohol
-Creates unpleasant symptoms when the client drinks while taking medication
-Palpitations
-Headache
-Nausea/vomiting
-Flushing
·-Abstain from alcohol for at least 12 hours prior to treatment to avoid a reaction
-a disulfiram reaction can occur for up to 14 days after alcohol is consumed
Topiramate (Topamax)
· An anticonvulsant that blocks sodium channels and enhances GABA-A
· Reduces cravings for alcohol
Chlorpromazine (Librium)
· Benzodiazepine for acute and chronic alcohol use
· Can cause benzodiazepine (BZO) withdrawal symptoms when stopped abruptly
· Avoid in older adults
Alcohol Withdrawal- Mild
Mild
· Anxiety
· Irritability
· Headache
· Insomnia
· Tremors
· Nausea/vomiting
Alcohol Withdrawal-Moderate
Moderate
· Increased blood pressure (BP)
· Increased heart rate (HR)
· Confusion
· Mild hyperthermia
· Rapid breathing
Alcohol Withdrawal- Severe
Severe
· Hallucinations
· Seizures
· Disorientation
· Impaired attention
· Delirium tremens
· Death
Alcohol Withdrawal Moderate to Severe
The use of pharmacologic interventions should be considered for individuals with withdrawal symptoms due to the risk of increased morbidity and mortality during withdrawal.
Alcohol Withdrawal Symptom-Triggered Regimen
· Administer benzodiazepine when CIWA-Ar score is 8 or above.
· PO lorazepam (Ativan), diazepam (Valium), or chlordiazepoxide (Librium) for symptom-triggered therapy
· Reassess CIWA-Ar every hour.
Administer CIWA-Ar
· every 4-8 hours until score is lower than 8-10 for 24 hours
You are discharging this client from the hospital following admission for alcohol withdrawal syndrome. He has no further withdrawal symptoms and he would like to abstain from alcohol use. He informs you that has abused opioids in the past, but he has not used them in the last several months. He is concerned that he is at risk of abusing opioids again. Which of the following is the best pharmaceutical option for this client?
-naltrexone (ReVia) common initial treatment for alcohol use disorder.
-Can be initiated while the client is still drinking.
-Can also be utilized in those with opioid use disorder, as the drug can treat both conditions
should be opioid-free for at least 7-10 days to avoid withdrawal
Alcohol Treatment in Pregnancy
· Teratogenic effects of alcohol on the developing fetus are well known; however, there is limited data on the safety of withdrawal medications in pregnancy.
· Naltrexone is commonly used to treat alcohol use disorder in pregnant women, but its effects on the fetus remain largely unknown.
· Acamprosate is not recommended in pregnancy but may be necessary if the mother cannot stop drinking alcohol.
Disulfiram’s safety in pregnancy is not established
Alcohol treatment for Older Adult
· Frequent monitoring is necessary when prescribing benzodiazepines for alcohol withdrawal in older adults. Acamprosate should be used with caution in older adults.
Nicotine Replacement Therapy
· Gradual, controlled reduction of nicotine to avoid withdrawal symptoms
· bupropion (Zyban)
-Tobacco-free by 7 to 12 weeks of therapy
· varenicline (Chantix)
-Tobacco-free by 12 weeks
Nicotine Replacement Therapy
· Use for clients who smoke more than 20 cigarettes per day
· Over-the-counter (OTC) drugs
-Gum: Nicorette
-Patch: Nicotrol, Nicoderm, Habitrol
-Lozenge: Commit
· Prescription drugs
-Nasal spray: Nicotrol NS
-Inhaler: Nicotrol
Nicotine Replacement in Pregnancy
Gum is pregnancy category C
Transdermal patch is pregnancy category D
Nicotine Replacement Contraindicated
Immediately after a myocardial infarction
Immediately after a stroke
Nicotine Gum
· Improves cessation success
· Buccal absorption
· Client needs to follow directions or nicotine will release too quickly, increasing adverse drug reactions (ADRs)
· Dosing: For people who smoke within 30 minutes of awakening: the 4 mg dose is recommended; For people who wait more than 30 minutes after awakening to smoke: the 2 mg dose is recommended
· Client weans dose after 2 to 3 months of abstinence
Nicotine Lozenge
· Lozenge slowly dissolves in mouth
· Advise not to chew lozenge
· Dose: 1 lozenge every 1 to 2 hours
· Use 4 mg if client smokes within 30 minutes of waking
· Client should not eat or drink while lozenge is in mouth
· Wean after 6 weeks of abstinence
Nicotine Patch
· Transdermal absorption
· 16-hour and 24-hour patches
· Slow onset, steady state once at peak
· Dose of patch is determined by number of cigarettes the client smokes per day
· Patch dose is decreased gradually
· Client cannot smoke while using patch
· ADRs: Monitor for nicotine toxicity
· Advise to dispose of patches safely
Nicotine Nasal Spray
· Intranasal administration
· Rapid onset and peak
· Client education
-Proper administration
-ADRs
-Abuse potential
Nicotine Inhaler
· Inhaled drug
· Client puffs on inhaler for 20 minutes
· Dose is weaned down gradually over 12 weeks
· ADRs
-Cough
-Mouth irritation
-Dyspepsia
bupropion (Zyban)
· Unknown action but believed to enhance the noradrenergic and dopaminergic release
· Start 1 to 2 weeks before quit date
· Dose: 150 mg daily for 3 days then increase to 150 mg twice daily
· Continue therapy for 7 to 12 weeks, may need longer
· May use with nicotine replacement products
· Avoid in pregnancy
varenicline (Chantix)
· Highly selective to the alpha-4 beta-2 nicotinic receptor and moderately selective to the 5-HT3 receptor
· Start a week before quit date
· Dosing: 0.5 mg by mouth daily for the first 3 days; then 0.5 mg twice daily on days 4 to 7; increase to 1.0 mg twice daily on day 8
· Continue therapy for 12 weeks
· Combining with other nicotine replacement products does not improve results
Combination Nicotine Therapy
· Long-term (more than 14 weeks) nicotine patch + other nicotine replacement therapy (gum and spray)
· Nicotine patch + nicotine inhaler
· Nicotine patch + bupropion sustained-release
· Nonpharmacological treatment of nicotine addiction
-Individual or group counseling
-Support via a telephone hotline or online support group
Nicotine replacement therapy in Pregnancy
-Nicotine replacement products not recommended
-bupropion (Zyban) not recommended
-varenicline (Chantrix) not recommended
FDA Approved for:
Maintenance of alcohol abstinence
Disulfiram (Antabuse)
Acamprosate (Campral)
FDA Approved for:
-Alcohol dependence
-Blockade of effects of exogenously administered opioids (oral)
-Prevention of relapse to opioid dependence (injection)
Naltrexone (revia
Methadone (Dolophine, Methadose)
FDA Approved for:
Moderate-to-severe chronic pain Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services
Buprenorphine/Naloxone (Suboxone, Zubsolv, Bunavail)
FDA Approved for:
-Maintenance treatment of opioid dependence
-Induction of treatment for opioid dependence (Bunavail only)
Buprenorphine (Subutex)
FDA approved for:
-Induction of treatmentfor opioid dependence (Bunavail only)
-Maintenance treatment of opioid dependence (sublingual)
-Maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses (no more than 8 mg) of a transmucosal buprenorphine- containing product (implant)
-Moderate to severe opioid use disorder in patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days (injection)
First Line treatment for OCD
SSRI’s
Primary action of hallucinogenic drugs such as LSD, mescaline, psilocybin, and MDMA
Agonism of 5HT2A receptors
Hallucinogens may have additional actions at other serotonin receptors (particularly 5HT1A and 5HT2C) and at other neurotransmitter systems, and MDMA in particular also blocks the serotonin transporter (SERT)
Hypothalamus-Brain Center
Controls appetite by utilizing a complex set of circuits and regulators.
One formulation of how the hypothalamus does this is the notion that there is a major appetite-stimulating pathway whose actions are mediated by two peptides (neuropeptide Y and agouti-related protein)..
Appetite is regulated by
The balance between an appetite-stimulating pathway (on the left) that releases agouti-related peptide (AgRP) and neuropeptide Y (NPY), and an appetite-suppressing pathway (on the right) that releases α-melanocyte-stimulating hormone
Appetite-stimulating pathway
On the left, that releases agouti-related peptide (AgRP) and neuropeptide Y (NPY)
Appetite-suppressing pathway
On the right that releases α-melanocyte-stimulating hormone
Weight Gain Can Occur
Either by excessive activity of the appetite-stimulating pathway, by deficient activity of the appetite-suppressing pathway, or both
Phentermine MOA
Phentermine acts much like amphetamine, blocking both the dopamine transporter (DAT) and the norepinephrine transporter (NET) and, at high doses, the vesicular monoamine transporter (VMAT).
Bupenorphrine <18 yo
Buprenorphine is approved for persons < 18 years of age
Hallucinogen intoxication
Can cause what is perceived as a panic attack, often called a “bad trip.”
As intoxication escalates, one can experience an acute state of confusion (delirium) where the abuser is disoriented and agitated
Disulfiram
Irreversibly inhibits aldehyde dehydrogenase resulting in build of toxic levels of acetaldehyde
Acamprosate
Reduces glutamate release associated with alcohol withdrawal
Naltrexone
Blocks the enjoyment of heaving drinking through its action on reward circuitry, sedative hypnotics act at GABA A receptor sites in reward circuits
Attention-deficit/hyperactivity disorder (ADHD)
One of the most common neurodevelopmental disorders
Norepinephrine (NE) and dopamine (DA) play a role in the symptoms and treatment of ADHD
ADHD symptoms
Selective Attention
· lack of attention to detail
· careless mistakes
· not listening
· losing things
· diverting attention
· forgetfulness
ADHD symptoms
Lack of Sustained Attention
· poor problem solving
· difficulty completing tasks
· disorganization
· difficulty sustaining mental effort
ADHD symptoms
Impulsivity
· excessive talking
· blurting things out
· not waiting one’s turn
interrupting
Hyperactivity
· fidgeting
· leaving one’s seat
· running, climbing
· trouble playing quietly
ADHD symptoms
Adults struggling with executive functioning difficulties and disorganization may experience occupational stress or anxiety
ADHD Genetics
The major genes implicated in ADHD are those linked to DA, though the α2A-adrenergic receptor, serotonin receptors, among others
ADHD Neuroanatomy
Specific ADHD symptoms may arise from abnormalities within circuits in the prefrontal cortex (PFC), which affect executive function
ADHD Neural Networks
-Possibly due to abnormalities in the prefrontal cortex circuits or errors in the synaptic pruning process
-Both selective and sustained attention are modulated by the corticostriatal-thalamocortical (CSTC) loop, the same loop that is associated with anxiety
ADHD Neural Signaling
Norepinephrine (NE) (too low) and dopamine (DA (too low) are associated with inefficient information processing in the prefrontal circuits- OUT OF TUNE
Agents that can increase the firing of both DA and NE may help increase prefrontal activity.
ADHD medications commonly target both dopamine and norepinephrine.
Stimulants, including stimulant medications, caffeine, and nicotine enhance DA release and arousal.
The PMHNP is considering treatment options for an 18-year-old man with ADHD who has a history of alcohol and marijuana abuse. Which of the following accurately explains the effects of different stimulant formulations on neuronal firing
Pulsatile stimulation amplifies undesirable phasic DA and NE firing, which can lead to euphoria and abuse
Pulsatile stimulation amplifies undesirable phasic DA and NE firing, which can lead to euphoria and abuse
Rationale: Phasic firing is hypothetically associated with reward, feelings of euphoria, and abuse potential.
Immediate-release stimulants rapidly increase DA and NE, especially increasing phasic firing, not tonic firing (Therefore, immediate-release stimulants have a higher risk of abuse). Extended-release formulations of stimulants lead to a gradual and sustained increase in NE and DA, enhancing tonic firing, which is hypothetically linked to the therapeutic effects of stimulants.
They are amplifying tonic NE and DA signals, which are thought to be low in ADHD. The extended-release formulations occupy the NE transporter in the prefrontal cortex with slow enough onset and for long enough to enhance tonic NE and DA signaling; however, they do not block DA transporters fast or long enough in the nucleus accumbens to increase phasic signaling, thus reducing abuse potential.
Why does atomoxetine lack abuse potential
It increases dopamine levels in the prefrontal cortex but not in the nucleus accumbens
Why does atomoxetine lack abuse potential
The prefrontal cortex lacks high concentrations of dopamine transporters (DAT), so in this brain region, DA gets inactivated by norepinephrine transporters (NET). Therefore, inhibiting NET in the prefrontal cortex increases both DA and NE. As only a few NET exist in the nucleus accumbens, atomoxetine does not induce an increase in DA and NE in the nucleus accumbens, the reward center of the brain, thus atomoxetine does not have abuse potential.
Chris is a 44-year-old client presenting with comorbid alcohol abuse, generalized anxiety, and ADHD. Which disorder should be treated first?
Alcohol abuse
Rationale: It is important to treat identified diagnoses in terms of the highest degree of impairment. Alcohol abuse should be treated prior to any mood and anxiety disorders, then any remaining ADHD symptoms can be treated
Pharmacologic Treatment of ADHD
Stimulants- When NE and DA are out of balance, information processing in the prefrontal cortex can be affected leading to the symptoms of ADHD. Medications that stimulate the release of NE and DA or boost the firing of associated neurons may help improve information processing. Stimulant medications are effective for 70-80% of clients with ADHD and are typically the first choice of medications for children
Pharmacologic Treatment of ADHD
Non-stimulants- Non-stimulant medications work by selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex and enhancement of norepinephrine neurotransmission. Non-stimulants can help lower distractibility and improve attention, working memory, and impulsivity.
Pharmacologic Treatment of ADHD
A combination of stimulant and non-stimulant medications is sometimes used when ADHD includes argumentative or oppositional symptoms
Methylphenidate-Stimulant
· Ritalin
available in immediate-release (IR) and extended-release (XR)
available in beads that may be sprinkled on food for children who cannot swallow pills
· Concerta
biphasic – combined immediate and delayed release in one medication
· Daytrana
patch applied in the morning and removed after 9 hours Class: dopamine, norepinephrine reuptake inhibitor and releaser (DN-RIRe), Multimodal
Stimulant
dexmethylphenidate (Focalin)-Stimulant
· Available in immediate release and extended release
· More potent than Ritalin
· High risk of adverse effects
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant
amphetamine (Adzenys)-Stimulant
· It is available in an orally-disintegrating extended-release formula for children who cannot swallow pills.
· Avoid prescribing when an MAOI has been used within 14 days.
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant
dextroamphetamine (Adderall)-Stimulant
· Available in immediate and extended-release formulations
· Often dosed in AM (IR or XR) with a PM or PM PRN (IR) dose if medication effects diminish prior to the end of school, study, or the workday
· Most abused and diverted prescription stimulants
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant
lisdexamfetamine (Vyvanse)-Stimulant
· Biologically inactive until metabolized by the body (Prodrug)
· Less abuse and diversion potential than other stimulants
· Higher-cost medication
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant
Prescribing Pearls-Stimulants
· An EKG is required if cardiac history is present in a first-degree relative.
· Blood pressure, height, and weight should be monitored regularly during treatment.
Abrupt withdrawal after prolonged use can result in irritability and rebound symptoms.
· When switching stimulants, discontinue the current medication and start the new medication at a starting dose the next day.
Non-stimulants
· low risk of abuse or diversion
· often prescribed for adults with ADHD
Non-stimulant-noradrenergic (NRI)-ADHD
Atomoxetine (Strattera)-Selective norepinephrine reuptake inhibitor (NRI)
drug of choice for adults with ADHD
no abuse potential
tolerated well when prescribed in twice daily dosing
appropriate choice for comorbid substance abuse
may augment the effects of antidepressants and antianxiety medications
can be dosed at bedtime if fatigue is noted
unlikely to worsen tics
Non-Stimulants-α 2 agonists-ADHD
· clonidine-Class:Selective norepinephrine receptor agonist (N-RA)
enhances precortical function for better mental focus
appetite neutral
may help with sleep disturbances, administer at bedtime
adverse effects: sedation, brain fog
monitor of BP closely during initial titration
tapered to avoid rebound hypertension post discontinuation
· guanfacine-Class:Selective norepinephrine receptor agonist (N-RA); Centrally acting alpha 2A agonist
may also be used for children with tics, sleep disturbances, or aggression
tolerability and convenience enhanced by once-daily oral controlled-release formulation
adverse effects: sedation, headache, decreased appetite
reduced side-effect profile comparable to clonidine
bedtime administration to avoid daytime sedation
Non-Stimulant-Norepinephrine Dopamine Reuptake Inhibitor
bupropion (Wellbutrin) -Class:
(D-RIRe-dopamine reuptake inhibitor and releaser)
(NDRI-norepinephrine and dopamine reuptake inhibitor)
off-label use for ADHD in adults
appropriate for clients with concurrent depression or tobacco abuse
Prescribing Pearls-non-stimulants
Use when clients are too young for stimulants but need medication, intolerant of or have contraindications for stimulants have a client history of dependency or drug abuse or lack of response to stimulants alone
Monitor for abrupt behavior changes, suicidal ideation or self-harm, aggression, seizures, prolonged QT interval, increased peripheral vascular resistance, heart rate, and blood pressure
· Concurrent use is contraindicated with MAO inhibitors (within the past 14 days), glaucoma, a history of pheochromocytoma, and cardiac or vascular disorders.
· Non-stimulant medications may exacerbate depression in clients with a history of the disorder.
· Non-stimulant medications can take longer to achieve desired effects than stimulants.
· Withdrawal needs to be tapered to prevent rebound hypertension and neurological side effects.
increase GABA’s inhibitory activity, leading to the decreased output of excitatory neurotransmitters resulting in the adverse effects related to BZO use
ORDER OF TREATMENT
· Alcohol/stimulant/substance abuse
· Mood disorders
· Anxiety disorders
· ADHD
· Nicotine dependence
Lifespan Considerations in ADHD
Pregnancy
· Stimulants may cause fetal harm including increases in low birth weight and pregnancy.
Breastfeeding
· Stimulants are not recommended while breastfeeding.
Children
· ADHD medications are not approved for children under 6. Consider short-acting medications for children who have significant appetite loss or are underweight; this may improve appetite for lunch and dinner.
Neurotransmitters and Sleep
Sun:
· acetylcholine
· norepinephrine
· histamine
· serotonin
· orexin
· dopamine
· TMN-Tuberomammillary nucleus turns on when its time to wake up
Moon:
· Gamma aminobutyric acid (GABA)
· Melatonin
· VLPO-VENTROLATERAL PREOPTIC AREA-turns on when its time to go to sleep
Insomnia causes
Insomnia is frequently triggered by acute stress and resolves when the stress resolves. Many coexisting medical conditions, such as pain, thyroid abnormalities, asthma, and gastroesophageal reflux, and medications such as selective serotonin reuptake inhibitors (SSRIs), steroids, stimulants, and β-agonists, can cause insomnia
SLEEP MEDICATIONS-Over-the-Counter Sleep Aids
Antihistamines such as diphenhydramine (Benadryl) are commonly used for short-term difficulty sleeping. Diphenhydramine is FDA-approved for the treatment of insomnia and can be effective at reducing sleep latency and increasing sleep time. However, diphenhydramine has undesirable anticholinergic effects and carryover sedation which limits its use, especially in older adults.
SLEEP MEDICATIONS-Over-the-Counter Sleep Aids
Valerian root is an herbal over-the-counter medication that is sometimes used to promote sleep. Studies indicate that it may reduce the amount of time it takes to fall asleep and may improve sleep; however, it should be used with caution. Valerian may increase the effects of other sleep medications and increase the sedative effect of depressants, such as alcohol, benzodiazepines, and narcotics.
SLEEP MEDICATIONS-Melatonin Agonist Medications
Melatonin is a hormone produced in the body by the pineal gland to help regulate the sleep-wake cycle. Melatonin agonists mimic melatonin to help reset the body’s natural sleep-wake cycle. These medications improve sleep onset but are not effective for sleep maintenance. These agents may be used for acute or chronic insomnia and are available over-the-counter (OTC) and by prescription
SLEEP MEDICATIONS-Melatonin Agonist Medications
ramelteon (Rozerem)
· Prescription melatonin receptor 1 and 2 agonists
· Low incidence of adverse effects
SLEEP MEDICATIONS-Orexin Receptor Antagonists
Orexin is a neurotransmitter that assists with alertness and wakefulness. Dual orexin receptor antagonists (DORA) promote sleep by blocking orexin
SLEEP MEDICATIONS-Orexin Receptor Antagonists
Suvorexant (Belsomra): improves sleep maintenance. Mild adverse effects are similar to those of z-drugs (zolpidem, eszopiclone, and zaleplon). Studies indicated suvorexant is well-tolerated in older adult. The suvorexant dose should be decreased when given with drugs that inhibit CYP3A4, such as diltiazem, erythromycin, and ketoconazole.
Lemborexant (Dayvigo) is FDA approved for the treatment of adults with insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Adverse effects include daytime somnolence. Avoid the use of lemborexant with strong or moderate CYP3A inhibitors and inducers.
SLEEP MEDICATIONS-Sedating Antidepressants
Medications
· trazodone (Desyrel)
· amitriptyline (Elavil)
· mirtazapine (Remeron)
Sleep Medications-Z-Drugs
Sedative/hypnotic drugs, or z-drugs, act on the brain to produce a calming effect. These agents may be prescribed to help clients who are unable to fall asleep as well as those who have difficulty maintaining sleep or returning to sleep once awake. Z-drugs bind to benzodiazepine sites on GABA receptors
Sleep Medications-Z-Drugs
zolpidem (Ambien)
zaleplon (Sonata)
eszopiclone (Lunesta)
Prescribe for PRN use.
· These are a schedule IV controlled substance.
· There is some potential for abuse/dependence.
· The safety of use longer than 4-6 weeks is unclear.
Sleep Medications-Benzos
Although benzodiazepines have been approved for use with insomnia, they are not considered a first-line treatment due to the potential for misuse; however, when first-line agents fail, benzodiazepines may be used with caution for insomnia
Lifespan Considerations with Sleep meds
Pregnancy
· Consider the risk-benefit ratio.
· Avoid z-drugs when possible; use them for the shortest duration possible.
Older Adult
· Consider nonpharmacologic strategies.
· Avoid combining z-drugs with other central nervous system (CNS) medications to prevent falls.
· Avoid using z-drugs or antihistamines in clients with dementia, cognitive impairment, or a history of falls.
· Consider melatonin as an alternative.
Restless Legs Syndrome
RLS typically occurs in the evening or at night and causes the uncomfortable uncontrollable urge to move the legs. RLS may be idiopathic or associated with other conditions such as pregnancy, end-stage renal disease, fibromyalgia, iron deficiency, arthritis, or peripheral neuropathy
Restless Legs Syndrome-Medications
Dopamine agonists
· pramipexole (Mirapex), ropinirole (Requip)
· adverse effects: daytime somnolence, nausea
Iron
· Check serum iron levels.
· Provide supplementation if needed.
Gabapentin/ pregabalin
· severe or painful RLS
Jessica is a 28-year-old client with a diagnosis of generalized anxiety disorder. Her anxiety is well-controlled with escitalopram and therapy. She presents with new complaints of insomnia and states, “I have constant itching and need to move my legs while I am in bed.”
Which of the following diagnostic tests should be completed next? Select all that apply.
· caffeine intake
· ferritin level
· pregnancy test
Rationale: Caffeine, alcohol, and nicotine may all increase the risk for RLS. Pregnancy and iron deficiency anemia may cause RLS. Foods high in tyrosine are not associated with RLS. A CT scan is not indicated for this client.
Jessica’s lab work is within normal limits, and her pregnancy test is negative. She reports drinking two cups of coffee each morning and denies alcohol or nicotine use. Based on her assessment and diagnostic data, which of the following is the best medication choice to treat Jessica’s RLS?
· ropinirole
Rationale: Ropinirole is a first-line agent for RLS. Iron is not appropriate in a client unless serum ferritin indicates deficiency. Gabapentin is appropriate for RLS but is a second-line medication. Diazepam is not appropriate for this client.
Hyperactivity is modulated by the prefrontal cortex
TRUE
Impulsivity is modulated by the orbitofrontal cortex
TRUE-dACC is associated with impulsivity
Alzheimer’s Association has identified a list of 10 early warning signs and symptoms which include
· memory loss
· challenges in planning or solving problems
· trouble understanding visual and spatial relationships
· difficulty completing familiar tasks
· disorientation
· problems with word finding
· misplacing things
· impaired judgment
· social withdrawal
· changes in mood
The etiology of AD
Genes appear to play a strong role, with late-onset AD showing heritability of 58-79% and early-onset AD showing over 90%
The etiology of AD
Neurons in the brains of clients who develop AD may also have genetic coding abnormalities associated with amyloid precursor protein, while mutations of at least three different chromosomes, 21, 14, and 1, are associated with early-onset AD
Neuroanatomy of AD
Two hallmarks of AD are amyloid plaques and neurofibrillary tangles. Toxic amyloid plaques are believed to form in the brain of clients with AD due to the abnormal processing of amyloid precursor protein
Neuroanatomy of AD
Cell death leads to the atrophy of brain tissue, which affects the areas responsible for memory and higher-level thinking, such as the hippocampus and cerebral cortex.
Neural Networks of AD
In addition to the development of amyloid plaques and neurofibrillary tangles, multiple cellular changes are associated with AD, including damage to synapses, mitochondrial abnormalities, and inflammatory processes. These changes are associated with neurotransmitter failure and neuronal death.
Neural Signaling in AD
Acetylcholine (ACh) is a neurotransmitter necessary for processing memory and learning. AD leads to decreased acetylcholinesterase activity and a permanent loss of cholinergic neurons.
Neural Signaling in AD
Decreased cholinergic function is linked to memory dysfunction, particularly short-term memory. Neuronal damage may also occur due to abnormal activation of N-methyl-d-aspartate (NMDA) receptors by glutamate
Diagnosis of AD
AD is currently diagnosed through the exclusion of other causes of dementia, such as vascular disease, Lewy body dementia, Parkinson’s disease, and Creutzfeldt-Jacob disease.
Early symptoms of AD
Early AD may include anxiety, irritability, and sleep disruption, which could be the presenting symptoms that bring clients to providers for treatment.
Stages of AD
Preclinical (asymptomatic but brain amyloid is increased)
Mild cognitive impairment (neurodegeneration due to elevated tau and brain volume loss)
Severe cognitive deficits-(dementia)
Treatment of dementia begins in what stage?
Mild stage. Pharmacologic treatment focusing on helping the client manage symptoms and behavioral issues that may present.
Medications for Alzheimer’s Disease
Treatment for AD includes cholinesterase inhibitors (ChEIs) and memantine.
First-line treatment of AD
Use of a cholinesterase inhibitor, which increases the availability of acetylcholine, and may help maintain functional ability, and slow cognitive decline.
First-line treatment of AD
ChEIs are likely to be most effective in the early stages of AD when postsynaptic cholinergic receptors are still available; however, once neurons are destroyed by the disease, ChEIs are no longer effective
Cholinesterase Inhibitors (ChEIs) function
ChEIs increase levels of the neurotransmitter acetylcholine
ChEIs do not change the progression of AD; they provide some alleviation of symptoms
Aricept Mechanism of Action
Inhibits centrally active acetylcholinesterase
Aricept Common Side Effects
· gastrointestinal symptoms (nausea and diarrhea)
· headache
· dizziness
· muscle weakness
Aricept Precautions
· sick sinus syndrome
· seizure disorder
· Cholinesterase inhibitors are not recommended in pregnancy and lactation.
Aricept Prescribing Pearls
· Taper to avoid withdrawal effects.
· donepezil (Aricept) is approved to treat moderate to severe AD at 23 mg/day dose, but there is minimal improvement in cognitive functioning when compared to a 10 mg/day dose. At the higher dose, donepezil has a higher incidence of adverse effects.
Aricept Metabolism
When donepezil (Aricept) is added to CYP2D6 or CYP3A4, there is a possibility of peripheral side effects, and inducers of CYP2D6 and CYP3A4 may increase the rate of elimination
Rivastigmine (Exelon) Mechanism of Action
· rivastigmine (Exelon) acts centrally for both acetylcholinesterase and butyrylcholinesterase, thereby potentially increasing its efficacy.
Rivastigmine (Exelon) Common Side Effects
· gastrointestinal symptoms (anorexia, nausea, vomiting, or diarrhea)
· weakness
· dizziness
· tremor
Rivastigmine (Exelon) Precautions
· asthma or chronic obstructive pulmonary disorder (COPD)
· sick sinus syndrome
· gastrointestinal (GI) Bleeding
· weight < 50 kg
· asthma or chronic obstructive pulmonary disorder (COPD)
· sick sinus syndrome
· gastrointestinal (GI) Bleeding
· weight < 50 kg
· Cholinesterase inhibitors are not recommended in pregnancy and lactation.
Rivastigmine (Exelon) Prescribing Pearls
· rivastigmine (Exelon) is administered orally or topically (transdermal patch).
· The transdermal patch is used for dementia associated with Parkinson’s disease.
Rivastigmine (Exelon) Metabolism
Medications that induce or inhibit CYP450 metabolism will not modify rivastigmine (Exelon) metabolism
Galantamine (Razadyne, Razadyne ER) Mechanism of Action
galantamine (Razadyne, Razadyne ER) acts by elevating acetylcholine (Ach) in the cerebral cortex, modulating the nicotinic Ach receptors to increase Ach release from existing presynaptic nerve terminals. It also increases glutamate and serotonin levels; however, the benefits of this action are unknown
Galantamine (Razadyne, Razadyne ER) Side Effects
· gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia, and weight loss)
· headache
· dizziness
· fatigue
Galantamine (Razadyne, Razadyne ER) Precautions
· nonsteroidal anti-inflammatory drug (NSAID) use
· GI bleed
· asthma or COPD
· concurrent use with medications that slow or decrease heart rate
Galantamine (Razadyne, Razadyne ER) Contraindications
· severe hepatic impairment
· severe renal impairment
Galantamine (Razadyne, Razadyne ER) Metabolism
There are two major metabolizing enzymes CYP3A4 and CYP2D6 that increase galantamine (Razadyne, Razadyne ER) concentrations or reductions in clearance and anticholinergic side effects when given concurrently with inhibitors of these enzymes
Medications that induce or inhibit CYP450 metabolism will not modify rivastigmine metabolism
N-Methyl-D-Aspartate NMDA receptor antagonist
Memantine is the only NMDA approved to manage moderate to severe AD. Based on clinical trials, improvement is modest
Memantine (Namenda) Mechanism of Action
This drug prevents glutamate, an excitatory neurotransmitter, from binding at the receptor site. NMDA receptors control activity throughout the brain by regulating how much calcium enters the nerve cell
Memantine (Namenda) Mechanism of Action
An overproduction of the NMDA receptor and excess glutamate can lead to excessive calcium entering the cell and disrupting information processing. Blocking NMDA receptors protects neurons from the effects of too much glutamate without affecting normal neurotransmission
Memantine (Namenda) Common Side Effects
· gastrointestinal symptoms (constipation, diarrhea, and weight gain)
· urinary frequency
· confusion
· dizziness
· headache
· cough
Memantine (Namenda) Precautions
· concurrent use with (amantadine, rimantadine, ketamine, or dextromethorphan)
· severe hepatic impairment
· severe renal impairment
· medications or conditions that increase the pH of the urine
Memantine (Namenda) Prescribing Pearls
· This is used as monotherapy or in conjunction with ChEIs; when given with ChEIs, fall precautions are required and driving is forbidden due to delayed reactions.
Memantine (Namenda) Metabolism
· Minimal inhibition of CYP450 enzymes CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 occurs, which means there are no pharmacokinetic interactions with medications metabolized by these enzymes
Memantine (Namenda) Efficacy
Memantine is associated with an increased life expectancy when compared to donepezil.
If treatment failure occurs, 50% of individuals respond to a different agent.
The current gold standard of treatment for cognitive symptoms includes:
Pharmacologic management with a cholinesterase inhibitor (ChEIs) and an N-methyl-D-aspartate (NMDA) receptor antagonist.
The first-line pharmacologic treatment of aggression and agitation in dementia is:
SSRI/SNRI therapy. NOT AN ANTIPSYCHOTIC!
Cleo is a 65-year-old male diagnosed with mild cognitive changes related to Alzheimer’s disease. He also has anxiety, and COPD, and smokes cigarettes. Which of the following medications is appropriate for Cleo?
· rivastigmine
· donepezil (Correct answer)
· galantamine
Rationale: It is approved by the FDA for the treatment of mild dementia and is not affected by nicotine. Donepezil also treats psychological symptoms of AD such as anxiety, depression, apathy, delusions, and pacing. Rivastigmine should be avoided in clients with COPD. Nicotine can also increase the clearance of the medication. Galantamine is also FDA-indicated for mild to moderate dementia but will not address his anxiety.
Aricept
Not affected by nicotine
Aricept
Treats psychological symptoms of AD such as anxiety, depression, apathy, delusions, and pacing
Rivastigmine
Should be avoided in clients with COPD
Rivastigmine
Nicotine can also increase the clearance of the medication.
Galantamine
FDA-indicated for mild to moderate dementia but will not address anxiety.
A client diagnosed with Alzheimer’s disease has decided to stop treatment. The nurse practitioner (NP) has educated the client that medication discontinuation will result in the return of cognitive symptoms and the medication may not work as well if restarted. The client would still like to stop the medication due to the gastrointestinal side effects. Which of the following medications requires tapering?
· rivastigmine
· donepezil (Correct answer)
· galantamine
Rationale: Donepezil requires tapering. Rivastigmine and galantamine do not require tapering.
Starting doses for AD
Donepezil-5mg may increase to 10mg after 4-6 weeks
Namenda-5mg, increase by 5mg each week, max 10mg BID
Galantimine-IR-4mg BID after 4 weeks may increase to 8mg BID, after 4 more weeks may increase to 12mg BID; ER same titration schedule but dosed once daily, 8, 16, 24mg
Rivastigimine-1.5mg BID, increase by 3mg every 2 weeks, titrate to tolerability max 6mg BID; transdermal 4.6/24hours, after 4 weeks increase to 9.5/24 hours max dose 13.3mg