https:\/\/learnexams.com\/search\/study?query=aqa<\/a><\/p>\n\n\n\nPrefrontal Cortex Symptoms of MDD
Concentration
Mental Fatigue
Mood<\/p>\n\n\n\n
PFC & Amygdala Symptoms of MDD
Guilt
Suicidality
Worthlessness<\/p>\n\n\n\n
Striatum Symptoms of MDD
Physical fatigue<\/p>\n\n\n\n
Nucleus Accumbens Symptoms of MDD
Pleasure interests<\/p>\n\n\n\n
Hypothalamus Symptoms of MDD
Sleep
Appetite<\/p>\n\n\n\n
Thalamus & Hypothalamus \u200bSymptoms of Mania
Decreased sleep\/arousal<\/p>\n\n\n\n
Striatum\u200b Symptoms of Mania
Motor\/agitation<\/p>\n\n\n\n
Prefrontal cortex (PFC) Symptoms of Mania
Risk-taking
Talkative\/pressured speech<\/p>\n\n\n\n
Nucleus Accumbens & PFC Symptoms of Mania
Racing thoughts, grandiosity<\/p>\n\n\n\n
PFC & Amygdala Symptoms of Mania
Mood<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
citalopram (Celexa) SSRI
mild antihistamine effects; Half-Life: 23-45 hours
Weak Inhibitor of 2D6<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
fluvoxamine (Luvox) SSRI
treats anxious depression smokers require an increased dose
Half-Life: 9-28 hours
Inhibits 3A4, 2C9, 1A2<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Trazodone
The most common SARI, also blocks histaminergic and \u03b1-adrenergic receptors.
Half-Life: 3-6 hours<\/p>\n\n\n\n
Serotonin Antagonist and Reuptake Inhibitors (SARIs)
Common Adverse Effects
\u00b7 sedation
\u00b7 drowsiness
\u00b7 blurred vision
\u00b7 constipation
\u00b7 dry mouth
Serious Adverse Effect
priapism<\/p>\n\n\n\n
Serotonin norepinephrine receptor agonist, alpha2 receptor agonist
Mirtazapine<\/p>\n\n\n\n
Serotonin multimodal (SMM)\/serotonin partial agonist reuptake inhibitor (SPARI)
Vilazodone (Viibryd)
\u00b7 Inhibits serotonin reuptake with partial 5HT1A agonism
Appropriate for depression\/comorbid anxiety, its action is similar to a combination of SSRI and buspirone<\/p>\n\n\n\n
Serotonin multimodal (SMM)
Vortioxetine (Trintellix)
\u00b7 Acts as SSRI plus 5HT1A partial agonism
\u00b7 Improves depression-related cognition<\/p>\n\n\n\n
Tricyclic antidepressants (TCAs)
Tricyclic antidepressants (TCAs) possess both SRI and NRI properties, but they also block other receptors, including \u03b11-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<\/p>\n\n\n\n
Tricyclic antidepressants (TCAs)
Drugs:
\u00b7 amitriptyline (Elavil)
\u00b7 desipramine (Norpramin)
\u00b7 doxepin (Sinequan)
\u00b7 imipramine (Tofranil)
\u00b7 nortriptyline (Pamelor)<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
MAOIs
Drugs:
\u00b7 phenelzine (Nardil)
\u00b7 selegiline (Emsam) – MAOI-B
\u00b7 tranylcypromine (Parnate)
\u00b7 isocarboxazid (Marplan)<\/p>\n\n\n\n
MAOI’s Key Points
\u00b7 Clients taking MAOIs are at high risk for hypertensive crisis if tyramine is ingested. \u200b
\u00b7 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.<\/p>\n\n\n\n
Foods to Avoid When Taking MAO-A Medications
\u00b7 Red wine (Avoid)
\u00b7 Sauerkraut (Avoid)
\u00b7 Cheese (Avoid)
\u00b7 Soy (Avoid)
\u00b7 Smoked meats (Avoid)<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Newer Treatments for Resistant Depression
\u00b7 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.
\u00b7 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%.
\u00b7 Treatment-resistant depression occurs when depression persists after the client has adequately trialed at least two antidepressant therapies.<\/p>\n\n\n\n
Newer Treatments for Resistant Depression
Esketamine (Spravato)-N-methyl-D-aspartate (NMDA) receptor inhibitor
Dextromethorphan\/quinidine (Nuedexta)-under investigation for Resistant depression<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Initiating Medication
\u00b7 Start patients on a single drug for 4-8 weeks to assess efficacy
\u00b7 Start with the lowest recommended dose to reduce side effects
\u00b7 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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Discontinuing Medications
\u00b7 Clients should be advised not to suddenly stop any medication or omit doses due to the risk of discontinuation syndrome.
\u00b7 Paroxetine has the highest risk of discontinuation syndrome due to serotonin transporter inhibition and anticholinergic rebound.
\u00b7 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.<\/p>\n\n\n\n
Black Box Warning: Suicide Risk with Antidepressant Drugs
\u00b7 Clients with depression may consider or attempt suicide.
\u00b7 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<\/p>\n\n\n\n
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).<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Patient often forgets to take pills
Fluoxetine has a 2-3 days half-life, an excellent option for forgetful people<\/p>\n\n\n\n
Pregnancy Considerations for Depression
Paroxetine is contraindicated in pregnancy due to the risk of congenital defects, including atrial septal defects.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
MEDICATION MANAGEMENT FOR BIPOLAR DISORDER
\u00b7 Treatment of bipolar disorder (BD) varies depending on the presenting symptoms.
\u00b7 Some medications are more appropriate for symptoms of mania, while others are better for symptoms of depression.
\u00b7 Medication classes used include mood stabilizers, anticonvulsants, and atypical antipsychotics.<\/p>\n\n\n\n
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).<\/p>\n\n\n\n
Lithium
INDICATIONS:
-euphoric mania
-rapid cycling
-maintenance therapy
HALF-LIFE: 18-30 hours<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
Lamotrigine (Lamictal)
ACTION:
affects sodium channel ion transport and enhances the activity of y-aminobutyric acid (GABA)<\/p>\n\n\n\n
Lamotrigine (Lamictal)
INDICATION:
-maintenance therapy
-monotherapy for bipolar disorder
HALF LIFE: 33 hours<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Lamotrigine (Lamictal)
Therapeutic levels:
Not monitored<\/p>\n\n\n\n
Valproic acid (Depakene)
ACTION:
affects ion transport and enhances the activity of y-aminobutyric acid (GABA)<\/p>\n\n\n\n
Valproic acid (Depakene)
INDICATION:
acute mania
mixed mood
comorbid substance use
multiple prior episodes
HALF LIFE: 9-16 hours<\/p>\n\n\n\n
Valproic acid (Depakene)
Therapeutic levels:
50-100mcg\/mL; Toxic Levels: >175 mcg\/mL<\/p>\n\n\n\n
Valproic acid (Depakene)
If using with Lamitrogine decrease dose by 50%<\/p>\n\n\n\n
Second generation antipsychotics
aripiprazole (Abilify)
cariprazine (Vraylar)
lurasidone (Latuda)
quetiapine (Seroquel)
asenapine (Saphris)
risperidone (Risperdal)
olanzapine (Zyprexa)
ziprazadone (Geodon)<\/p>\n\n\n\n
Second generation antipsychotics
ACTION:
DA, NE, and 5-HT receptor antagonists<\/p>\n\n\n\n
Second generation antipsychotics
INDICATION:
acute bipolar depression
acute manic or mixed episodes
bipolar maintenance\/adjunct<\/p>\n\n\n\n
Second generation antipsychotics
ADVERSE EFFECTS:
weight gain
sedation
GI effects<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Carbamazepine (Tegretol)
ACTION:
glutamate voltage gated sodium and calcium channel blocker (Glu-CB)<\/p>\n\n\n\n
Carbamazepine (Tegretol)
INDICATION:
acute mania
mixed mood
HALF LIFE: 26-65 hours<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Carbamazepine (Tegretol)
Therapeutic levels:
4-12 mcg\/mL;
Toxic levels: >12mcg\/mL<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
INITIAL TREATMENT SELECTION for a client with bipolar disorder should follow a stepwise approach beginning with a thorough assessment
Assess \u200b
\u00b7 client safety\u200b
\u00b7 comorbidities\u200b
\u00b7 treatment adherence\u200b
Initiate\/optimize therapy\u200b
\u00b7 choose monotherapy or combination
\u00b7 optimize dose
\u00b7 check for adherence
Add-on or switch therapy\u200b
\u00b7 use an alternative first-line agent or add on an additional first-line agent
\u00b7 if first-line agents are not effective, may switch to second-line agents\u200b<\/p>\n\n\n\n
NONADHERENCE RISK FACTORS
Medication factors
\u00b7 adverse effects
\u00b7 low treatment doses
Manifestation of BD
\u00b7 mixed episodes
\u00b7 rapid cycling
\u00b7 hallucinations
\u00b7 BD I
Comorbidities
\u00b7 substance use
\u00b7 obsessive-compulsive disorder
Demographics
\u00b7 male
\u00b7 younger
\u00b7 lower education level
\u00b7 single
Other
\u00b7 poor insight
\u00b7 negative attitude
\u00b7 low self-esteem<\/p>\n\n\n\n
PRESCRIBING PEARLS
\u00b7 Lurasidone (Latuda) should be taken with food, at least 350 calories, for maximum absorption.
\u00b7 Lithium carbonate (Lithobid) starting dose is reduced by at least 50% in clients with renal impairment.
\u00b7 Lithium levels can be increased by nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors and decreased by caffeine and mania.<\/p>\n\n\n\n
Lithium Lab Monitoring
\u00b7 serum lithium level
\u00b7 renal function
\u00b7 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.<\/p>\n\n\n\n
Valproic Acid Lab Monitoring
\u00b7 serum valproate level
\u00b7 liver function
\u00b7 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<\/p>\n\n\n\n
Carbamazepine Lab Monitoring
\u00b7 serum carbamazepine level
\u00b7 renal function
\u00b7 liver function
\u00b7 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.<\/p>\n\n\n\n
Atypical antipsychotic medications Lab Monitoring
\u00b7 CBC
\u00b7 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.<\/p>\n\n\n\n
SPECIAL CONSIDERATIONS: Pregnancy
\u00b7 Lithium, valproic acid, and carbamazepine are teratogenic and are contraindicated during pregnancy.
\u00b7 Lurasidone has been used in pregnancy without teratogenic effects.<\/p>\n\n\n\n
SPECIAL CONSIDERATIONS: Breast Feeding
Breast Feeding
Avoid breastfeeding for clients prescribed carbamazepine, lithium, and lamotrigine<\/p>\n\n\n\n
SPECIAL CONSIDERATIONS: Older Adult
Use caution. Reduced renal and hepatic function may impact metabolism and elimination. Reduce dose as necessary.
\u00b7 Avoid carbamazepine (may cause syndrome of inappropriate antidiuretic hormone secretion [SIADH]).
\u00b7 Use caution with antipsychotic medications (may increase the risk of falls).
\u00b7 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<\/p>\n\n\n\n
SPECIAL CONSIDERATIONS: Children
Age 10 +:
\u00b7 lurasidone (bipolar depression)
\u00b7 aripiprazole (acute and mixed mania)
\u00b7 quetiapine (monotherapy and adjunct for acute mania)
\u00b7 asenapine (acute and mixed mania)
\u00b7 risperidone (monotherapy and adjunct for acute and mixed mania)
Age 13 +:
\u00b7 olanzapine (acute and mixed mania)<\/p>\n\n\n\n
BIPOLAR 1
\u00b7 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).
\u00b7 Mania is characterized by a persistently elevated, expansive, or irritable mood.
\u00b7 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.
\u00b7 Mania leads to significant functional impairment and may include psychotic features or necessitate hospitalization<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
BP TYPE II
\u00b7 A diagnosis of bipolar II disorder requires a current or past hypomanic episode and a current or past major depressive episode.
\u00b7 Symptoms last for at least 4 days but fewer than seven.
\u00b7 Hypomanic symptoms are not of sufficient duration or severity to cause significant functional impairment, psychosis, or hospitalization.
\u00b7 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<\/p>\n\n\n\n
Cyclothymia
\u00b7 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.<\/p>\n\n\n\n
Decreased positive affect: DA, NE Dysfunction
\u00b7 depressed mood
\u00b7 loss of joy
\u00b7 lack of interest
\u00b7 loss of energy
\u00b7 decreased alertness
\u00b7 decreased self-confidence
\u00b7 appetite changes<\/p>\n\n\n\n
Increased negative affect: 5HT, NE Dysfunction
\u00b7 depressed mood
\u00b7 guilt
\u00b7 fear\/anxiety
\u00b7 hostility
\u00b7 irritability
\u00b7 loneliness
\u00b7 appetite changes<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Monoamine transmitters
serotonin, norepinephrine, and dopamine<\/p>\n\n\n\n
Lithium
Levels can be increased by NSAIDs and ACE inhibitors
Decreased by caffeine and mania
Unchanged by amiloride, furosemide, and sulindac<\/p>\n\n\n\n
Lithium
Well established to help prevent suicide in clients with mood disorders<\/p>\n\n\n\n
MAOI’s Duration of action
Drugs:
\u00b7 phenelzine (Nardil)-Clinical Duration of action up to 14 days
\u00b7 selegiline (Emsam) – MAOI-B-Clinical Duration of action up to 14 days
\u00b7 tranylcypromine (Parnate)-Clinical Duration of action 14- 30 days
\u00b7 isocarboxazid (Marplan)-Clinical Duration of action up to 14 days<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
Fentanyl
Almost immediate onset of action when given IV, with a duration of 0.5-1 hour<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Hydromorphone
Similar opioid agonist as morphine but more potent. Oral and parenteral doses are not equivalent (parenteral doses up to 5 times more potent)<\/p>\n\n\n\n
Methadone
In addition to its opioid receptor activity, it is also an antagonist of the N-methyl-D-aspartate (NMDA) receptor<\/p>\n\n\n\n
Methadone
Utilized in detoxification and maintenance treatment of opioid addiction and heroin addiction, with high variability among patients<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
Ventral tegmental area (VTA)
One of the major dopamine-producing areas of the brain<\/p>\n\n\n\n
Nucleus accumbens
Area found within the ventral striatum and has a strong association with motivation and reward<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Dependence
State of adaptation produced with repeated administration of certain drugs so that physical symptoms occur when the drug is discontinued abruptly.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Withdrawal
Physiological and psychological reactions that occur when the use of a substance is stopped abruptly<\/p>\n\n\n\n
Intoxication
Condition following the ingestion of a substance resulting in changes in level of consciousness, cognition, perception, judgment, and behavior.<\/p>\n\n\n\n
SAMHSA (2022a) identified the goals of MAT to include
\u00b7 improved survival
\u00b7 improved treatment retention
\u00b7 decreased illegal activity
\u00b7 increased quality of life
\u00b7 improved birth outcomes in people who use substances while pregnant
\u00b7 reduced HIV and Hepatitis B & C infections<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
OCD\/Impulsive Control Disorders
Pharmacologic management is often used in combination with psychotherapy to address eating disorders<\/p>\n\n\n\n
Obesity
-Phentermine or phentermine\/topiramate
-Bupropion or bupropion\/naltrexone
-Lorcaserin
-Zonisamide<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Binge Eating Disorder
-Topiramate
-Bupropion
-Lisdexamfetamine<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Pregnancy with Buprenorphine
Buprenorphine is an acceptable treatment during pregnancy; however, there is an increased risk of a neonatal withdrawal syndrome in newborns.<\/p>\n\n\n\n
Pregnancy with Suboxone (buprenorphine\/naloxone)
Suboxone (buprenorphine\/naloxone) cannot be used in pregnancy<\/p>\n\n\n\n
Pregnancy with Naloxone
Naloxone increases the risk of neonatal abstinence syndrome. Pregnant clients must be switched to buprenorphine (Subutex) monotherapy.<\/p>\n\n\n\n
Pregnancy with Methadone
Methadone is approved in pregnancy for heroin-addicted women. Dosing requires adjustment.<\/p>\n\n\n\n
Pregnancy in MAT
Short-term newborn withdrawal effects may be seen and may require neonatal intensive care unit (NICU) admission for treatment.<\/p>\n\n\n\n
Breast Feeding with Naltrexone and Buprenorphine
Not recommended<\/p>\n\n\n\n
Breast Feeding with Methadone
Can be prescribed with special consideration given to feeding intervals (breastfeed prior to or 2-6 hours after dose).<\/p>\n\n\n\n
Older Adult with Buprenorphine
Use in the elderly may lead to confusion and drowsiness<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
Acamprosate (Campral)
\u00b7 Modulates glutamine transmission, and resembles gamma-aminobutyric acid (GABA)
\u00b7 Good option for clients who must take opioids for chronic pain
\u00b7 Treats withdrawal symptoms
\u00b7 Abstain prior to beginning treatment
No affect on Opioids<\/p>\n\n\n\n
Disulfiram (Antabuse):
-Blocks oxidation of alcohol
-Creates unpleasant symptoms when the client drinks while taking medication
-Palpitations
-Headache
-Nausea\/vomiting
-Flushing
\u00b7-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<\/p>\n\n\n\n
Topiramate (Topamax)
\u00b7 An anticonvulsant that blocks sodium channels and enhances GABA-A
\u00b7 Reduces cravings for alcohol<\/p>\n\n\n\n
Chlorpromazine (Librium)
\u00b7 Benzodiazepine for acute and chronic alcohol use
\u00b7 Can cause benzodiazepine (BZO) withdrawal symptoms when stopped abruptly
\u00b7 Avoid in older adults<\/p>\n\n\n\n
Alcohol Withdrawal- Mild
Mild
\u00b7 Anxiety
\u00b7 Irritability
\u00b7 Headache
\u00b7 Insomnia
\u00b7 Tremors
\u00b7 Nausea\/vomiting<\/p>\n\n\n\n
Alcohol Withdrawal-Moderate
Moderate
\u00b7 Increased blood pressure (BP)
\u00b7 Increased heart rate (HR)
\u00b7 Confusion
\u00b7 Mild hyperthermia
\u00b7 Rapid breathing<\/p>\n\n\n\n
Alcohol Withdrawal- Severe
Severe
\u00b7 Hallucinations
\u00b7 Seizures
\u00b7 Disorientation
\u00b7 Impaired attention
\u00b7 Delirium tremens
\u00b7 Death<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Alcohol Withdrawal Symptom-Triggered Regimen
\u00b7 Administer benzodiazepine when CIWA-Ar score is 8 or above.
\u00b7 PO lorazepam (Ativan), diazepam (Valium), or chlordiazepoxide (Librium) for symptom-triggered therapy
\u00b7 Reassess CIWA-Ar every hour.
Administer CIWA-Ar
\u00b7 every 4-8 hours until score is lower than 8-10 for 24 hours<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Alcohol Treatment in Pregnancy
\u00b7 Teratogenic effects of alcohol on the developing fetus are well known; however, there is limited data on the safety of withdrawal medications in pregnancy.
\u00b7 Naltrexone is commonly used to treat alcohol use disorder in pregnant women, but its effects on the fetus remain largely unknown.
\u00b7 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<\/p>\n\n\n\n
Alcohol treatment for Older Adult
\u00b7 Frequent monitoring is necessary when prescribing benzodiazepines for alcohol withdrawal in older adults. Acamprosate should be used with caution in older adults.<\/p>\n\n\n\n
Nicotine Replacement Therapy
\u00b7 Gradual, controlled reduction of nicotine to avoid withdrawal symptoms
\u00b7 bupropion (Zyban)
-Tobacco-free by 7 to 12 weeks of therapy
\u00b7 varenicline (Chantix)
-Tobacco-free by 12 weeks<\/p>\n\n\n\n
Nicotine Replacement Therapy
\u00b7 Use for clients who smoke more than 20 cigarettes per day
\u00b7 Over-the-counter (OTC) drugs
-Gum: Nicorette
-Patch: Nicotrol, Nicoderm, Habitrol
-Lozenge: Commit
\u00b7 Prescription drugs
-Nasal spray: Nicotrol NS
-Inhaler: Nicotrol<\/p>\n\n\n\n
Nicotine Replacement in Pregnancy
Gum is pregnancy category C
Transdermal patch is pregnancy category D<\/p>\n\n\n\n
Nicotine Replacement Contraindicated
Immediately after a myocardial infarction
Immediately after a stroke<\/p>\n\n\n\n
Nicotine Gum
\u00b7 Improves cessation success
\u00b7 Buccal absorption
\u00b7 Client needs to follow directions or nicotine will release too quickly, increasing adverse drug reactions (ADRs)
\u00b7 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
\u00b7 Client weans dose after 2 to 3 months of abstinence<\/p>\n\n\n\n
Nicotine Lozenge
\u00b7 Lozenge slowly dissolves in mouth
\u00b7 Advise not to chew lozenge
\u00b7 Dose: 1 lozenge every 1 to 2 hours
\u00b7 Use 4 mg if client smokes within 30 minutes of waking
\u00b7 Client should not eat or drink while lozenge is in mouth
\u00b7 Wean after 6 weeks of abstinence<\/p>\n\n\n\n
Nicotine Patch
\u00b7 Transdermal absorption
\u00b7 16-hour and 24-hour patches
\u00b7 Slow onset, steady state once at peak
\u00b7 Dose of patch is determined by number of cigarettes the client smokes per day
\u00b7 Patch dose is decreased gradually
\u00b7 Client cannot smoke while using patch
\u00b7 ADRs: Monitor for nicotine toxicity
\u00b7 Advise to dispose of patches safely<\/p>\n\n\n\n
Nicotine Nasal Spray
\u00b7 Intranasal administration
\u00b7 Rapid onset and peak
\u00b7 Client education
-Proper administration
-ADRs
-Abuse potential<\/p>\n\n\n\n
Nicotine Inhaler
\u00b7 Inhaled drug
\u00b7 Client puffs on inhaler for 20 minutes
\u00b7 Dose is weaned down gradually over 12 weeks
\u00b7 ADRs
-Cough
-Mouth irritation
-Dyspepsia<\/p>\n\n\n\n
bupropion (Zyban)
\u00b7 Unknown action but believed to enhance the noradrenergic and dopaminergic release
\u00b7 Start 1 to 2 weeks before quit date
\u00b7 Dose: 150 mg daily for 3 days then increase to 150 mg twice daily
\u00b7 Continue therapy for 7 to 12 weeks, may need longer
\u00b7 May use with nicotine replacement products
\u00b7 Avoid in pregnancy<\/p>\n\n\n\n
varenicline (Chantix)
\u00b7 Highly selective to the alpha-4 beta-2 nicotinic receptor and moderately selective to the 5-HT3 receptor
\u00b7 Start a week before quit date
\u00b7 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
\u00b7 Continue therapy for 12 weeks
\u00b7 Combining with other nicotine replacement products does not improve results<\/p>\n\n\n\n
Combination Nicotine Therapy
\u00b7 Long-term (more than 14 weeks) nicotine patch + other nicotine replacement therapy (gum and spray)
\u00b7 Nicotine patch + nicotine inhaler
\u00b7 Nicotine patch + bupropion sustained-release
\u00b7 Nonpharmacological treatment of nicotine addiction
-Individual or group counseling
-Support via a telephone hotline or online support group<\/p>\n\n\n\n
Nicotine replacement therapy in Pregnancy
-Nicotine replacement products not recommended
-bupropion (Zyban) not recommended
-varenicline (Chantrix) not recommended<\/p>\n\n\n\n
FDA Approved for:
Maintenance of alcohol abstinence
Disulfiram (Antabuse)
Acamprosate (Campral)<\/p>\n\n\n\n
FDA Approved for:
-Alcohol dependence
-Blockade of effects of exogenously administered opioids (oral)
-Prevention of relapse to opioid dependence (injection)
Naltrexone (revia<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Buprenorphine\/Naloxone (Suboxone, Zubsolv, Bunavail)
FDA Approved for:
-Maintenance treatment of opioid dependence
-Induction of treatment for opioid dependence (Bunavail only)<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
First Line treatment for OCD
SSRI’s<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
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)..<\/p>\n\n\n\n
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 \u03b1-melanocyte-stimulating hormone<\/p>\n\n\n\n
Appetite-stimulating pathway
On the left, that releases agouti-related peptide (AgRP) and neuropeptide Y (NPY)<\/p>\n\n\n\n
Appetite-suppressing pathway
On the right that releases \u03b1-melanocyte-stimulating hormone<\/p>\n\n\n\n
Weight Gain Can Occur
Either by excessive activity of the appetite-stimulating pathway, by deficient activity of the appetite-suppressing pathway, or both<\/p>\n\n\n\n
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).<\/p>\n\n\n\n
Bupenorphrine <18 yo
Buprenorphine is approved for persons < 18 years of age<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Disulfiram
Irreversibly inhibits aldehyde dehydrogenase resulting in build of toxic levels of acetaldehyde<\/p>\n\n\n\n
Acamprosate
Reduces glutamate release associated with alcohol withdrawal<\/p>\n\n\n\n
Naltrexone
Blocks the enjoyment of heaving drinking through its action on reward circuitry, sedative hypnotics act at GABA A receptor sites in reward circuits<\/p>\n\n\n\n
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<\/p>\n\n\n\n
ADHD symptoms
Selective Attention
\u00b7 lack of attention to detail
\u00b7 careless mistakes
\u00b7 not listening
\u00b7 losing things
\u00b7 diverting attention
\u00b7 forgetfulness<\/p>\n\n\n\n
ADHD symptoms
Lack of Sustained Attention
\u00b7 poor problem solving
\u00b7 difficulty completing tasks
\u00b7 disorganization
\u00b7 difficulty sustaining mental effort<\/p>\n\n\n\n
ADHD symptoms
Impulsivity
\u00b7 excessive talking
\u00b7 blurting things out
\u00b7 not waiting one’s turn
interrupting
Hyperactivity
\u00b7 fidgeting
\u00b7 leaving one’s seat
\u00b7 running, climbing
\u00b7 trouble playing quietly<\/p>\n\n\n\n
ADHD symptoms
Adults struggling with executive functioning difficulties and disorganization may experience occupational stress or anxiety<\/p>\n\n\n\n
ADHD Genetics
The major genes implicated in ADHD are those linked to DA, though the \u03b12A-adrenergic receptor, serotonin receptors, among others<\/p>\n\n\n\n
ADHD Neuroanatomy
Specific ADHD symptoms may arise from abnormalities within circuits in the prefrontal cortex (PFC), which affect executive function<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.\u200b
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.<\/p>\n\n\n\n
Why does atomoxetine lack abuse potential
It increases dopamine levels in the prefrontal cortex but not in the nucleus accumbens<\/p>\n\n\n\n
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.\u200b<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
Pharmacologic Treatment of ADHD
A combination of stimulant and non-stimulant medications is sometimes used when ADHD includes argumentative or oppositional symptoms<\/p>\n\n\n\n
Methylphenidate-Stimulant
\u00b7 Ritalin\u200b
available in immediate-release (IR) and extended-release (XR)\u200b
available in beads that may be sprinkled on food for children who cannot swallow pills \u200b
\u00b7 Concerta\u200b
biphasic – combined immediate and delayed release in one medication\u200b
\u00b7 Daytrana\u200b \u200b
patch applied in the morning and removed after 9 hours \u200bClass: dopamine, norepinephrine reuptake inhibitor and releaser (DN-RIRe), Multimodal
Stimulant<\/p>\n\n\n\n
dexmethylphenidate (Focalin)-Stimulant
\u00b7 Available in immediate release and extended release\u200b
\u00b7 More potent than Ritalin\u200b
\u00b7 High risk of adverse effects
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant<\/p>\n\n\n\n
amphetamine (Adzenys)-Stimulant
\u00b7 It is available in an orally-disintegrating extended-release formula for children who cannot swallow pills. \u200b
\u00b7 Avoid prescribing when an MAOI has been used within 14 days.
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant<\/p>\n\n\n\n
dextroamphetamine (Adderall)-Stimulant
\u00b7 Available in immediate and extended-release formulations\u200b
\u00b7 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\u200b
\u00b7 Most abused and diverted prescription stimulants
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant<\/p>\n\n\n\n
lisdexamfetamine (Vyvanse)-Stimulant
\u00b7 Biologically inactive until metabolized by the body (Prodrug)\u200b
\u00b7 Less abuse and diversion potential than other stimulants\u200b
\u00b7 Higher-cost medication
Class: dopamine, norepinephrine reuptake inhibitor andreleaser (DN-RIRe),
Stimulant<\/p>\n\n\n\n
Prescribing Pearls-Stimulants
\u00b7 An EKG is required if cardiac history is present in a first-degree relative. \u200b
\u00b7 Blood pressure, height, and weight should be monitored regularly during treatment.
Abrupt withdrawal after prolonged use can result in irritability and rebound symptoms.
\u00b7 When switching stimulants, discontinue the current medication and start the new medication at a starting dose the next day.<\/p>\n\n\n\n
Non-stimulant\u200bs
\u00b7 low risk of abuse or diversion\u200b
\u00b7 often prescribed for adults with ADHD<\/p>\n\n\n\n
Non-stimulant-noradrenergic (NRI)-ADHD
Atomoxetine (Strattera)\u200b-Selective norepinephrine reuptake inhibitor (NRI)
drug of choice for adults with ADHD\u200b
no abuse potential \u200b
tolerated well when prescribed in twice daily dosing\u200b
appropriate choice for comorbid substance abuse\u200b
may augment the effects of antidepressants and antianxiety medications\u200b
can be dosed at bedtime if fatigue is noted \u200b
unlikely to worsen tics<\/p>\n\n\n\n
Non-Stimulants-\u03b1 2 agonists-ADHD
\u00b7 clonidine\u200b-Class:Selective norepinephrine receptor agonist (N-RA)
enhances precortical function for better mental focus\u200b
appetite neutral\u200b
may help with sleep disturbances, administer at bedtime\u200b
adverse effects: sedation, brain fog\u200b
monitor of BP closely during initial titration\u200b
tapered to avoid rebound hypertension post discontinuation\u200b
\u00b7 guanfacine\u200b-Class:Selective norepinephrine receptor agonist (N-RA); Centrally acting alpha 2A agonist
may also be used for children with tics, sleep disturbances, or aggression\u200b
tolerability and convenience enhanced by once-daily oral controlled-release formulation \u200b
adverse effects: sedation, headache, decreased appetite\u200b
reduced side-effect profile comparable to clonidine\u200b
bedtime administration to avoid daytime sedation<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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
\u00b7 Concurrent use is contraindicated with MAO inhibitors (within the past 14 days), glaucoma, a history of pheochromocytoma, and cardiac or vascular disorders. \u200b
\u00b7 Non-stimulant medications may exacerbate depression in clients with a history of the disorder. \u200b
\u00b7 Non-stimulant medications can take longer to achieve desired effects than stimulants. \u200b
\u00b7 Withdrawal needs to be tapered to prevent rebound hypertension and neurological side effects.\u200b
increase GABA’s inhibitory activity, leading to the decreased output of excitatory neurotransmitters resulting in the adverse effects related to BZO use<\/p>\n\n\n\n
ORDER OF TREATMENT
\u00b7 Alcohol\/stimulant\/substance abuse
\u00b7 Mood disorders
\u00b7 Anxiety disorders
\u00b7 ADHD
\u00b7 Nicotine dependence<\/p>\n\n\n\n
Lifespan Considerations in ADHD
Pregnancy
\u00b7 Stimulants may cause fetal harm including increases in low birth weight and pregnancy.
Breastfeeding
\u00b7 Stimulants are not recommended while breastfeeding.
Children
\u00b7 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.<\/p>\n\n\n\n
Neurotransmitters and Sleep
Sun:
\u00b7 acetylcholine
\u00b7 norepinephrine
\u00b7 histamine
\u00b7 serotonin
\u00b7 orexin
\u00b7 dopamine
\u00b7 TMN-Tuberomammillary nucleus turns on when its time to wake up
Moon:
\u00b7 Gamma aminobutyric acid (GABA)
\u00b7 Melatonin
\u00b7 VLPO-VENTROLATERAL PREOPTIC AREA-turns on when its time to go to sleep<\/p>\n\n\n\n
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 \u03b2-agonists, can cause insomnia<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
SLEEP MEDICATIONS-Melatonin Agonist Medications
ramelteon (Rozerem)
\u00b7 Prescription melatonin receptor 1 and 2 agonists
\u00b7 Low incidence of adverse effects<\/p>\n\n\n\n
SLEEP MEDICATIONS-Orexin Receptor Antagonists\u200b
Orexin is a neurotransmitter that assists with alertness and wakefulness. Dual orexin receptor antagonists (DORA) promote sleep by blocking orexin<\/p>\n\n\n\n
SLEEP MEDICATIONS-Orexin Receptor Antagonists\u200b
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.<\/p>\n\n\n\n
SLEEP MEDICATIONS-Sedating Antidepressants\u200b
Medications
\u00b7 trazodone (Desyrel)
\u00b7 amitriptyline (Elavil)
\u00b7 mirtazapine (Remeron)<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Sleep Medications-Z-Drugs
zolpidem (Ambien)
zaleplon (Sonata)
eszopiclone (Lunesta)
Prescribe for PRN use.
\u00b7 These are a schedule IV controlled substance.
\u00b7 There is some potential for abuse\/dependence.
\u00b7 The safety of use longer than 4-6 weeks is unclear.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Lifespan Considerations with Sleep meds
Pregnancy
\u00b7 Consider the risk-benefit ratio.
\u00b7 Avoid z-drugs when possible; use them for the shortest duration possible.
Older Adult
\u00b7 Consider nonpharmacologic strategies.\u200b
\u00b7 Avoid combining z-drugs with other central nervous system (CNS) medications to prevent falls.\u200b
\u00b7 Avoid using z-drugs or antihistamines in clients with dementia, cognitive impairment, or a history of falls. \u200b
\u00b7 Consider melatonin as an alternative.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Restless Legs Syndrome-Medications
Dopamine agonists\u200b
\u00b7 pramipexole (Mirapex), ropinirole (Requip)\u200b
\u00b7 adverse effects: daytime somnolence, nausea\u200b
Iron\u200b
\u00b7 Check serum iron levels. \u200b
\u00b7 Provide supplementation if needed.\u200b
Gabapentin\/ pregabalin\u200b
\u00b7 severe or painful RLS<\/p>\n\n\n\n
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.
\u00b7 caffeine intake
\u00b7 ferritin level
\u00b7 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. \u200b<\/p>\n\n\n\n
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?
\u00b7 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.<\/p>\n\n\n\n
Hyperactivity is modulated by the prefrontal cortex
TRUE<\/p>\n\n\n\n
Impulsivity is modulated by the orbitofrontal cortex
TRUE-dACC is associated with impulsivity<\/p>\n\n\n\n
Alzheimer’s Association has identified a list of 10 early warning signs and symptoms which include
\u00b7 memory loss
\u00b7 challenges in planning or solving problems
\u00b7 trouble understanding visual and spatial relationships
\u00b7 difficulty completing familiar tasks
\u00b7 disorientation
\u00b7 problems with word finding
\u00b7 misplacing things
\u00b7 impaired judgment
\u00b7 social withdrawal
\u00b7 changes in mood<\/p>\n\n\n\n
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%<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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)<\/p>\n\n\n\n
Treatment of dementia begins in what stage?
Mild stage. Pharmacologic treatment focusing on helping the client manage symptoms and behavioral issues that may present.<\/p>\n\n\n\n
Medications for Alzheimer’s Disease
Treatment for AD includes cholinesterase inhibitors (ChEIs) and memantine.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Aricept Mechanism of Action
Inhibits centrally active acetylcholinesterase<\/p>\n\n\n\n
Aricept Common Side Effects
\u00b7 gastrointestinal symptoms (nausea and diarrhea)
\u00b7 headache
\u00b7 dizziness
\u00b7 muscle weakness<\/p>\n\n\n\n
Aricept Precautions
\u00b7 sick sinus syndrome
\u00b7 seizure disorder
\u00b7 Cholinesterase inhibitors are not recommended in pregnancy and lactation.<\/p>\n\n\n\n
Aricept Prescribing Pearls
\u00b7 Taper to avoid withdrawal effects.
\u00b7 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.<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Rivastigmine (Exelon) Mechanism of Action
\u00b7 rivastigmine (Exelon) acts centrally for both acetylcholinesterase and butyrylcholinesterase, thereby potentially increasing its efficacy.<\/p>\n\n\n\n
Rivastigmine (Exelon) Common Side Effects
\u00b7 gastrointestinal symptoms (anorexia, nausea, vomiting, or diarrhea)
\u00b7 weakness
\u00b7 dizziness
\u00b7 tremor<\/p>\n\n\n\n
Rivastigmine (Exelon) Precautions
\u00b7 asthma or chronic obstructive pulmonary disorder (COPD)
\u00b7 sick sinus syndrome
\u00b7 gastrointestinal (GI) Bleeding
\u00b7 weight < 50 kg
\u00b7 asthma or chronic obstructive pulmonary disorder (COPD)
\u00b7 sick sinus syndrome
\u00b7 gastrointestinal (GI) Bleeding
\u00b7 weight < 50 kg
\u00b7 Cholinesterase inhibitors are not recommended in pregnancy and lactation.<\/p>\n\n\n\n
Rivastigmine (Exelon) Prescribing Pearls
\u00b7 rivastigmine (Exelon) is administered orally or topically (transdermal patch).
\u00b7 The transdermal patch is used for dementia associated with Parkinson’s disease.<\/p>\n\n\n\n
Rivastigmine (Exelon) Metabolism
Medications that induce or inhibit CYP450 metabolism will not modify rivastigmine (Exelon) metabolism<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Galantamine (Razadyne, Razadyne ER) Side Effects
\u00b7 gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia, and weight loss)
\u00b7 headache
\u00b7 dizziness
\u00b7 fatigue<\/p>\n\n\n\n
Galantamine (Razadyne, Razadyne ER) Precautions
\u00b7 nonsteroidal anti-inflammatory drug (NSAID) use
\u00b7 GI bleed
\u00b7 asthma or COPD
\u00b7 concurrent use with medications that slow or decrease heart rate<\/p>\n\n\n\n
Galantamine (Razadyne, Razadyne ER) Contraindications
\u00b7 severe hepatic impairment
\u00b7 severe renal impairment<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
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<\/p>\n\n\n\n
Memantine (Namenda) Common Side Effects
\u00b7 gastrointestinal symptoms (constipation, diarrhea, and weight gain)
\u00b7 urinary frequency
\u00b7 confusion
\u00b7 dizziness
\u00b7 headache
\u00b7 cough<\/p>\n\n\n\n
Memantine (Namenda) Precautions
\u00b7 concurrent use with (amantadine, rimantadine, ketamine, or dextromethorphan)
\u00b7 severe hepatic impairment
\u00b7 severe renal impairment
\u00b7 medications or conditions that increase the pH of the urine<\/p>\n\n\n\n
Memantine (Namenda) Prescribing Pearls
\u00b7 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.<\/p>\n\n\n\n
Memantine (Namenda) Metabolism
\u00b7 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<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
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.<\/p>\n\n\n\n
The first-line pharmacologic treatment of aggression and agitation in dementia is:
SSRI\/SNRI therapy. NOT AN ANTIPSYCHOTIC!<\/p>\n\n\n\n
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?
\u00b7 rivastigmine
\u00b7 donepezil (Correct answer)
\u00b7 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.<\/p>\n\n\n\n
Aricept
Not affected by nicotine<\/p>\n\n\n\n
Aricept
Treats psychological symptoms of AD such as anxiety, depression, apathy, delusions, and pacing<\/p>\n\n\n\n
Rivastigmine
Should be avoided in clients with COPD<\/p>\n\n\n\n
Rivastigmine
Nicotine can also increase the clearance of the medication.<\/p>\n\n\n\n
Galantamine
FDA-indicated for mild to moderate dementia but will not address anxiety.<\/p>\n\n\n\n
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?
\u00b7 rivastigmine
\u00b7 donepezil (Correct answer)
\u00b7 galantamine
Rationale: Donepezil requires tapering. Rivastigmine and galantamine do not require tapering.<\/p>\n\n\n\n
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<\/p>\n","protected":false},"excerpt":{"rendered":"
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 Update2024\/ 2025) Psychopharmacology for thePsychiatric-Mental Health NursePractitioner Guide |Weeks 5-8 Covered|Questions and Verified Answers| 100%Correct- ChamberlainQ: Medication ManagementAnswer:SSRI-Selective Serotonin Reuptake Inhibitors*Inhibit 5 […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[25],"tags":[],"class_list":["post-131996","post","type-post","status-publish","format-standard","hentry","category-exams-certification"],"_links":{"self":[{"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/posts\/131996","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/comments?post=131996"}],"version-history":[{"count":0,"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/posts\/131996\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/media?parent=131996"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/categories?post=131996"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.learnexams.com\/blog\/wp-json\/wp\/v2\/tags?post=131996"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}