Antipsychotic Medications and Anxiety Disorders: Mechanisms, Treatments, and Side Effects, Exams of Nursing

Download Antipsychotic Medications and Anxiety Disorders: Mechanisms, Treatments, and Side Effects and more Exams Nursing in PDF only on Docsity! NR546 Midterm Exam Questions And Answers 2023 Update A+ What should the PMHNP consider when prescribing chemical restraints? - Answer-- NR546 MIDTERM EXAM QUESTIONS AND ANSWERS 2023 UPDATE A+ allergy status -prior med hx for adverse drug reactions r/t the meds ordered in the chemical restraint -state regulations regarding chemical restrains must be reviewed Are the PMHNP and other staff liable if the client has an allergic reaction or adverse side effects to the drugs used for chemical restraint? - Answer-No. The client has been court-ordered to take the prescribed medications and the standing order for chemical restraints is approved. The PMHNP and other staff are not liable if the patient has an allergic reaction or adverse side effects. How does reviewing the genetic makeup of a client help guide the PMHNP in selecting medication for clients? - Answer--Genetic testing can assist by providing more information on how clients may respond to certain psychotropic medications -provides information on how a client may break down and metabolize medications based on the cytochrome P450 system. Tanrıkulu and Erbaş (2020) investigated identical twins to determine the presence of an inherited link for schizophrenia and why one twin may develop schizophrenia when the other does not. When two people have 100% identical DNA, why don't both persons develop the exact illnesses? Studies of identical Danish twins found that if one twin had schizophrenia, the other twin had a 50% lifetime risk of developing schizophrenia (Lemvigh et al., 2020). Why is there only half the risk? - Answer-Both environmental and psychosocial stressors can impact mental health. Although twins may have identical genes, their gene expression may be different. There may be an environmental exposure that turned a gene "on" that should have been "off" for one twin to develop schizophrenia and not the other. central sulcus - Answer-separates the frontal lobe from the parietal lobe frontal lobe - Answer-associated with movement, intelligence, abstract thinking broca's area - Answer-speech production temporal lobe - Answer-involves object identification and auditory signals cerebellum - Answer-coordination wernicke's area - Answer-speech comprehension Adherence - Answer-Persistence -taking med over intended time period Compliance -taking med as prescribed left hemisphere - Answer--speech comprehension -word recognition -grammar -sequential processing -recognition of detail -conscious mental processing right hemisphere - Answer--prosody of speech -emotional modulation -visual-spatial skills -recognition of facial expression -music -abstract mathematical skills -holistic processing -unconscious mental processing Pharmacokinetics - Answer-the study of what happens to a drug from the time of administration until the parent drug and all metabolites leave the body CYP450 - Answer-CYP450 enzymes in the gut wall or liver convert drug substrate into a biotransformed product in the bloodstream, responsible for degradating of a large # of psychotropic drugs -Not all ind. have same genetic form of CYP450 enzymes, determined with pharmacogenetic testing *Most individuals have "normal" rates of drug metabolism from the major CYP450 enzymes and are said to be "extensive metabolizers", most drug doses are set for these individuals. *genetic variants of these enzymes can make poor metabolizers or ultra rapid metabolizers Five of the most important: CYP450 1A2, 2B6, 2D6, 2C9, 2C19, and 3A4. ultra rapid metabolizers - Answer-elevated enzyme activity subtherapeutic drug levels poor efficacy with standard doses genotyping - Answer-the patient for pharmacogenomic use -genes for these CYP450 enzymes can now be readily measured and used to predict which patients might need to have dosage adjustments -measurement of genes for drug metabolism most common targets of psychotropic drugs - Answer-G-protein receptors -Drug actions at these receptors occur in a spectrum, from full agonist actions, to partial agonist actions, to antagonism, and even to inverse agonism. Pharmacokinetics concepts - Answer-absorption distribution metabolis m excretion Flockhart Table - Answer-drug interactions that are mediated by cytochrome P450 enzymes comprehensive list of drugs and the interactions related to the cytochrome P450 system Neurotransmitters - Answer-chemicals released by neurons to send communication across synaptic clefts to other neurons -impact human emotion and behavior Neurotransmission: - Answer-the chemical transmission of information between neurons and their target cells -the chemicals, or neurotransmitters, are released from their transport vesicles to bind with receptor sites to perform their duties, which are excitatory or inhibitory -neurotransmitter then either returned and stored for future use (reuptake) or inactivated and dissolved by enzymes -Types: Classic, Retrograde, Volume Classic neurotransmission - Answer-neurons send electrical impulses from one part of the cell to another part of the same cell via their axons -one neuron hurling a chemical messenger, or neurotransmitter, at the receptors of a second neuron -electrical impulse converted chemical signal at the synapse in a process known as excitation-secretion coupling, the first stage of chemical neurotransmission, then back into electrical impulse in second neuron -chemical information from the first neuron triggering a cascade of further chemical messages within the second neuron to change that neuron's molecular and genetic functioning Retrograde neurotransmission - Answer-postsynaptic neurons "talk back" to their presynaptic neurons -second neuron to the first at the synapse between them -Chemicals produced specifically as retrograde neurotransmitters at some synapses include: endocannabinoids, gaseous neurotransmitter nitric oxide (NO), nerve growth factor (NGF). Volume neurotransmission - Answer-Neurotransmission without a synapse or nonsynaptic diffusion neurotransmission -Chemical messengers sent by one neuron to another can spill over to sites distant to the synapse by diffusion -neurotransmission can occur at any compatible receptor within the diffusion radius of the neurotransmitter -neurotransmission occurs in chemical "puffs" -sophisticated "chemical soup." -example: dopamine action in the prefrontal cortex, at the sites of autoreceptors on monoamine neurons Excitatory neurotransmitters: - Answer-increase the likelihood that the neuron will fire an action potential inhibitory neurotransmitters: - Answer-decrease the likelihood that a neuron will fire an action neurotransmitters that most impact mental health can be classified into four major categories: - Answer-cholinergics -acetylcholine monoamines -norepinephrine, dopamine, serotonin, histamine amino acids -gamma- amino-butyric acid and glutamate neuropeptides Inhibitors: VISA CKGQ - Answer-Valproate Isoniazid Sulfonamides Amiodarone Chloramphenic ol Ketoconazole Grapefruit Juice Quinidine -decrease medication metabolism Inducers: CRAP GPS - Answer- Carbamazepine Rifampin Alcohol Phenytoin Griseofulvin Phenobarbital -blocks the action of a neurotransmitter agonists - Answer-fully stimulate G-protein-linked receptors partial agonists - Answer-stimulate receptors to a lesser degree than an agonist or natural neurotransmitter SSRIs, SNRIs, and tricyclic antidepressants increase levels. do not impact serotonin levels. - Answer-increase serotonin levels. Benzodiazepines do not impact serotonin levels. Is nicotine an inducer or an inhibitor of the CYP 1A2 enzyme? - Answer- inducer Nicotine is an inducer of the CYP 1A2 enzyme. Does the PMHNP anticipate Joshua may need a higher or lower dose of olanzapine to achieve a therapeutic response? - Answer-Higher -Nicotine is an inducer of the CYP 1A2 enzyme, so it lowers the concentration of drugs. Therefore, a higher dose of olanzapine may be needed to control his symptoms. Ernesto, a 60-year-old, presents to the PMHNP with report of having anxiety, frequent occurrences of feeling frozen in place and like his heart is pounding out of his chest, as well as having difficulty sleeping. The PMHNP suspects the client has an elevated level of which neurotransmitter? - Answer-Norepinephrine -responsible for the regulation of fight or flight responses and can impact mood and sleep. Which of the following is the best medication class for the PMHNP to prescribe for Ernesto to address his elevated norepinephrine levels? - Answer-selective serotonin reuptake inhibitor would block the reuptake of serotonin, leaving a larger amount of serotonin available. Increasing the amount of serotonin would help regulate the feelings of fear and anxiety. Reducing the occurrence of fear would help reduce the release of norepinephrine. A serotonin and norepinephrine reuptake inhibitor would prevent the reuptake of norepinephrine, which would not reduce the level of norepinephrine as needed. Benzodiazepines increase the levels of GABA and do not impact norepinephrine. A monoamine oxidase inhibitor would increase levels of norepinephrine. During a follow up appointment after 4 weeks, the PMHNP should assess for the need to add which medication to Ernesto's treatment plan? - Answer-The nurse should assess for sexual dysfunction and anticipate the potential need for a phosphodiesterase inhibitor such as sildenafil (Viagra). -After 4 to 6 weeks, the client should be experiencing full effects of the SSRI, so the need for a short-term medication like a benzodiazepine or a beta blocker are not anticipated. St. John's Wort is contraindicated with an SSRI and can cause serotonin syndrome. Glu - Answer-Glutamate -amino acid -excitatory neurotransmitter -"workhorse" of the brain-can affect almost every neuron in the brain -affects: energy, memory, learning, neural plasticity -relay sensory info. and regulate spinal and motor reflexes -too much: schizophrenia, epilepsy, mania -receptors: NMDA, AMPA GABA - Answer-inhibitory neurotransmitter -decrease neuroexcitability across the brain -"chill", take the edge off stress, help people calm down, relax, destress, sleep -to little: may experience anxiety or schizophrenia -slows down everything, even breathing -affect executive function and motor coordination, increase risk for accidents -Increased levels of gamma-aminobutyric acid have a calming effect. 5HT - Answer-Serotonin -help regulate mood -makes relaxed, comfortable, decreases stress, regulate sleep, arousal, libido, aggression, pain perception NE - Answer-norepinephrine -monoamine neurotransmitter -focus and productivity -too much due to stress, meds, caffein, stimulants can cause: nervous, antsy, affect focus DA - Answer-dopamine -monoamine neurotransmitter -regulate mood -associated with executive function, ability to perform well, be organized, emotional intelligence -movement and coordination -to little: lose pleasure, interest, alertness, self-confidence, parkinson's disease -to much: schizophrenia and psychosis -reward center: can lead to addiction -has own pathways Ach - Answer-acetylcholine -in CNS: affects arousal, motivation, attention, learning, REM sleep, impacts sleep, pain perception, memory -in PNS: makes you sweat and salivate -link between brain and muscles -not enough: Alzheimer's, Parkinson's, Schizophrenia One-third of psychotropic drugs bind to a , and one-third bind to -too much: Depression -Role in addiction -Receptors: nicotinic & muscarinic Histamine (Neurotransmitter) - Answer-Histamine impacts alertness, pain sensation, and inflammatory responses; increased levels result in depression. Melatonin (neurotransmitter) - Answer-Act at MT1-3 G-protein coupled receptors Sleep/wake cycle insomnia: melatonin agonists Psychotropic drug metabolism may be impacted by factors such as: - Answer--age -smoking -caffeine intake -other medications -Some drugs or foods may inhibit or induce the rate of drug metabolism. The six main neurotransmitters are: - Answer-serotonin (5HT) norepinephrine (NE) dopamine (DA) acetylcholine (Ach) glutamate (Glu) gamma-aminobutyric acid (GABA) Signal transduction cascades can produce: - Answer-downstream (delayed) and/or long-lasting effects -explains why some psychopharmacological drugs do not provide an immediate response but require time to see the drug effects Signal transduction cascades - Answer-communication from the genome of the presynaptic neuron to the genome of the postsynaptic neuron, and then back from the genome of the postsynaptic neuron to the genome of the presynaptic neuron via retrograde neurotransmission -process involves long strings of chemical messages within both presynaptic and postsynaptic neurons -initial events occur in less than a second, but the long-term consequences are mediated by downstream messengers that take hours to days to activate, yet can last for many days or even for the lifetime of a synapse or neuron -somewhat akin to a molecular "pony express" Both may get sexual dysfunction neurobiological factors that contribute to psychosis and schizophrnia - Answer--genetics -neuroanatomy -neural networks -neural signaling neuroanatomy: symptoms associated with mesocortical and ventromedial prefrontal cortex - Answer-negative and affective symptoms neuroanatomy: symptoms associated with dorsolateral - Answer-cognitive symptoms neuroanatomy: symptoms associated with orbitofrontal and connections to amygdala - Answer-aggressive, impulsive symptoms Worst toxin for someone who has at risk genes for schizophrenia - Answer- marijuana Medications to treat psychosis are classified as either: - Answer-first generation antipsychotics (FGAs) or second- generation antipsychotics (SGAs) Antipsychotics are prescribed based on their: - Answer--pharmacological properties -side effect profiles -adverse effects according to the unique symptoms and needs of individuals across the lifespan First-generation antipsychotics (FGAs) - Answer-typical antipsychotics, non- selectively blocks dopamine D2 receptors, specifically in mesolimbic pathway -for the acute and chronic management of schizophrenia and psychosis -Desired effect: improve (+) symptoms -risk for developing hyperprolactinemia & extrapyramidal symptoms Extrapyramidal symptoms (EPSs) - Answer-group of symptoms related to motor control and coordination, caused by dopamine blockade or depletion in the basal ganglia -dystonia -akathisia -parkinsonism -bradykinesia -tremors -tardive dyskinesia dystonia - Answer-Involuntary contractions of muscles; can cause pain akathisia - Answer-Inner restlessness leading to repetitive motion (rocking, tapping fingers). parkinsonism - Answer-Combination of abnormal movements like those seen in Parkinson's Disease, including tremor, slow movement, impaired speech, or muscle stiffness -akinesia, rigidity, tremor bradykinesia - Answer-Slowness of movement tardive dyskinesia - Answer-hyperkinetic movement disorder characterized by abnormal facial and tongue movements and quick, jerky limb movements -Can occur from long-term blockade of D2 receptors in the nigrostriatal DA pathway -25% of clients will develop symptoms within 5 years of medication start -Failure to discontinue typical antipsychotics prior to symptom onset can result in this permanent condition Hyperprolactinemia - Answer-when the serum prolactin level rises due to the blockade of dopamine in the hypothalamus -may be asymptomatic -irregular menses -male gynecomastia -nipple discharge -osteoporosis -sexual dysfunction and infertility (both genders) Neurolepsis - Answer-antipsychotic medication effects on psychotic clients, with respect to cognition and behavior. -Neurolepsis syndrome has three major features (PEA acronym) Psychomotor slowing-extreme form of slowness or absence of motor movement (nigrostriatal pathway) Emotional quieting-worsening of (-) & cognitive symptoms (mesocortical pathways) Affective indifference-worsening of affective symptoms (mesocortical pathway) Additional adverse effects of excessive D2 receptor blockade (D2 antagonist actions) include: - Answer--cardiac concerns: QT prolongation, torsades de pointes, and sudden cardiac death -blood dyscrasias (neutropenia, leukopenia, and agranulocytosis) -esophageal dysmotility, aspiration -increased fall risk imbalance of dopamine (DA) and acetylcholine (ACh) can result in anticholinergic effects such as: - Answer--dry mouth -blurred vision -racing heart -constipation -drowsiness *due to muscarinic blockade The PMHNP must monitor for adverse effects in clients who are prescribed SGAs. Which of the following physical exams and labs should be ordered or requested from another provider? - Answer-BMI -monthly x3 months then quarterly Fasting lipids -within first three months then check annually Electrocardiogram -baseline electrocardiogram should be obtained to evaluate for prolonged QT syndrome BP Fasting plasma glucose -within first three months then check annually Carbamazepine - Answer-glutamate, voltage-gated sodium and calcium channel blocker -Primary target symptoms: Seizures, unstable mood, mania, pain. -Side Effects: SEDATION, dizziness, confusion, unsteadiness, headache, nausea, vomiting, diarrhea, blurred vision, rash, benign leukopenia (up to 10%) -Before starting: blood count, liver, kidney, and thyroid function tests ✽SUBSTRATE for CYP450 3A4 and an inducer of CYP450 3A4 thus, carbamazepine induces its own metabolism, often requiring an upward dosage adjustment Carbamazepine drug interactions - Answer--Enzyme-inducing antiepileptic drugs (carbamazepine itself as well as phenobarbital, phenytoin, and primidone) may increase the clearance of carbamazepine and LOWER its plasma levels -CYP450 3A4 inhibitors, such as nefazodone, fluvoxamine, and fluoxetine, can INCREASE plasma levels of carbamazepine Olanzapine (zyprexa) - Answer-SGA - Atypical serotonin-dopamine antagonist Indication: schizophrenia age 13 and older, acute agitation, acute mania/mixed mania, bipolar maintenance, bipolar depression, borderline personality disorder, PTSD -Starting dose: Initial 5-10 mg once daily orally Risk: High metabolic risk Highest risk for weight gain, sedation, blood dyscrasias, QT prolongation, cardiovascular disease, cerebrovascular effects, hyperglycemia, and hyperprolactinemia quetiapine (seroquel) - Answer-SGA - Atypical serotonin-dopamine antagonist Indication: schizophrenia ages 13 and older, mania, bipolar maintenance, depression, severe treatment-resistant anxiety, PTSD, behavioral disturbances in dementias, Parkinson's disease, children, and adolescents. -Starting dosing: initial 25 mg/day twice a day; increase by 25-50 mg twice a day each day until desired efficacy is reached; maximum approved dose 800 mg/day Risk: Sedation Moderate metabolic risk Low EPS risk Risk of orthostatic hypotension, blood dyscrasias (neutropenia, leukopenia, and agranulocytosis), QT prolongation, weight gain, and renal and hepatic impairment asenapine (Saphris) - Answer-SGA - Atypical dopamine, serotonin, norepinephrine receptor antagonist Indication: schizophrenia ages 10 and older, mania, bipolar, depression, impulse control, PTSD, behavior disturbances in dementia and in children and adolescents -Starting dosing: usual dosage range Schizophrenia and bipolar mania (sublingual): 10- 20 mg/day in 2 divided doses, Schizophrenia (transdermal): 3.8 mg/24 hours Risk: Low metabolic risk Tardive dyskinesia (reduced risk compared to conventional antipsychotics) clozapine (Clozaril) - Answer-SGA - Atypical serotonin-dopamine antagonist Indication: treatment-resistant schizophrenia, chronic SUICIDAL behavior in schizophrenia or schizoaffective disorder, treatment-resistant bipolar disorder, violent aggressive patients with psychosis and other brain disorders not responsive to other treatments. -Starting dosing: Initial 25 mg at night, increase 25-50 mg/day every 48-72 hours as tolerated Not indicated in acute presentation of schizophrenia Special Comments: The Absolute Neutrophil Count (ANC) must be >1500/mm3 when used and requires initial and weekly monitoring of WBC, granulocyte, and neutrophil counts. Risk: High metabolic risk Highest risk for weight gain. Sedation Low EPS risk. BLACK BOX WARNING: may cause severe neutropenia Contraindicated in liver disease and hepatic failure brexpiprazole (Rexulti) - Answer-SGA - Atypical Dopamine partial agonist Indication: schizophrenia, treatment-resistant depression, mania, bipolar maintenance/depression, impulse control, PTSD, behavioral disturbances in dementias and in children and adolescents -Dosing: schizophrenia 2-4 mg once daily, Depression: 2 mg once daily. Special Comments: Considered procognitive Risk: Low metabolic risk Akathisia TD (reduced) cariprazine (Vraylar) - Answer-SGA - Atypical dopamine-serotonin partial agonist Indication: schizophrenia, mania, bipolar maintenance/depression, depression, impulse control, PTSD, behavioral disturbances in dementias and in children and adolescents -Dosing: •Schizophrenia: 1.5-6 mg once daily •Bipolar mania: 3-6 mg once daily •Bipolar depression: 1.5-3 mg once daily Risk: Low metabolic risk Sedation Akathisia, parkinsonism, TD (reduced) Haloperidol - Answer-Typical FGA (conventional) dopamine receptor antagonist High potency Indication: Psychotic disorders, tourette's syndrome, schizophrenia, bipolar disorder, behavior disturbances in dementia -Dosing: 1-40 mg/day orally, IR injection 2-5 mg each dose Risks: Neuroleptic-induced deficit syndrome Akathisia Parkinsonism Tardive dyskinesia Galactorrhea, amenorrhea Weight gain and sedation Thioridazine - Answer-Typical FGA (conventional) dopamine and serotonin receptor antagonist Low potency Indication: Schizophrenic patients who fail to respond to treatment with other antipsychotic drugs. -Dosing: 200-800 mg/day in divided doses Risks: Neuroleptic-induced deficit syndrome Akathisia Priapism Parkinsonims Tardive dyskinesia Galactorrhea, amenorrhea Sedation & weight gain QTc prolongation Sexual dysfuction Pigmentary retinopathy Pearls: -Generally, the benefits of thioridazine do not outweigh its risks for most patients -Because of its effects on the QTc interval, thioridazine is not intended for use unless other options (at least 2 antipsychotics) have failed -Phenotypic testing may be necessary to detect 7% of Caucasian population whom thioridazine is contraindicated due to a genetic variant leading to reduced activity of CYP450 2D6 Thiothixene - Answer-Typical FGA (conventional) -dopamine 2 antagonist -High potency Indication: Schizophrenia, bipolar disorder, other psychotic disorders. -Dosing: 15-30 mg/day, initial 5-10 (max 60mg/day) Risk: Neuroleptic-induced deficit syndrome Akathisia Parkinsonism Tardive dyskinesia Sedation Dry mouth, constipation, vision disturbance hypotension Fluphenazine - Answer-Typical FGA (conventional) Blocks dopamine 2 receptors -High potency -Indication: Psychotic disorders, bipolar disorder -Dosing: 1-20 mg/day oral, IM generally 1/3 to 1/2 the oral dose Risks: Neuroleptic-induced deficit syndrome -Establish efficacy and an effective med dose before switching to a long- acting injectable (LAI). dose of LAI will be same as the effective oral dose. -Most antipsychotic side effects and adverse effects are dose-related. When prescribing, document the at every visit. - Answer- targeted symptoms, response, and any adverse effects Many persons with schizophrenia are treated successfully in an , though some clients may require for initial treatment and subsequent treatment of psychotic episodes - Answer-outpatient setting, inpatient hospitalizations Why begin with monotherapy? (antipsychotics) - Answer-The use of multiple antipsychotics can increase the risk of QT prolongation. -Combinations considered only after single med have provided inadequate response. If antipsychotics switched too quickly - Answer-can develop agitation, activation, insomnia, and experience withdrawal -due to the binding differences in each medication subcategory *Cross titration over several days to weeks is required to prevent side effects Clients are more likely to experience side effects when changing from a medication in subcategory (ex: pine to done) special considerations: Pregnancy (antipsychotics) - Answer--Risk of withdrawal symptoms in the newborn: extrapyramidal symptoms may be present at delivery. -atypical antipsychotics appear more harmful than typical antipsychotics due to increased risk of gestational metabolic complications, increased gestational age weight, and increased birth weight. -Avoid Clozapine, Ziprasidone, olanzapine, risperidone, and quetiapine, especially in the third trimester special considerations: breast feeding (antipsychotics) - Answer-All antipsychotics are assumed to be secreted in breast milk. -recommended drug is discontinued or the infant bottle feeds. special considerations: Older Adult (antipsychotics) - Answer-2019 American Geriatric Society (AGS) Beers Criteria recommendations: Avoid the use of haloperidol, ziprasidone, and olanzapine due to an increased risk of cerebrovascular accident (CVA), cognitive decline, and death in persons with dementia and with dementia-related psychosis. special consideration: children (antipsychotics) - Answer-Black box warnings: -Aripiprazole: Increased risk of suicide in children. one to a medication in another - Answer- -Quetiapine: Increased risk of suicidal ideation and suicidal behavior in adolescents/young adults during the initial 1-2 months of treatment special considerations: caution (antipsychotics) - Answer--Olanzapine - exercise caution in suspected alcohol withdrawal, stimulant intoxication, or anticholinergic intoxication -High and repeated doses of amphetamines or cocaine can mimic positive symptoms of paranoid schizophrenia legal issues/considerations when prescribing antipsychotics - Answer- informed consent -required due to serious side effects challenges -psychosis can be an obstacle -provide education before obtaining a signature in outpatient setting contingency planning -establish a plan with client and family for emergencies -designate a mental healthcare proxy if possible Prescribing Pearls - Answer--Use the lowest effective dose and slow dosage titration. -Avoid agents with anticholinergic properties. -Avoid combining benzodiazepines with intramuscular olanzapine due to an increased risk of sudden death. -Avoid the combination of intramuscular benzodiazepines with clozapine due to a risk of respiratory failure. Terence is a 23-year-old male who presented to the emergency department (ED) with hallucinations. He is highly agitated, and nonpharmacological treatment methods have not been able to calm his behaviors. His agitation continues to escalate which is interfering with their ability to gain an accurate history and assessment. Limited information is available regarding his past medical and psychiatric history. The attending providers are unclear whether his presentation is due to a mental health disorder with a need to intervene or an underlying non- psychiatric medical condition. The PMHNP is called to assist in calming the client. Which of the following statements is inaccurate regarding the management of Terence's agitation? - Answer-Aggressive pharmacological intervention should be done early to fully sedate this client so that a full evaluation can occur. Rationale: Aggressive pharmacological intervention (such as full sedation) interferes with the ability to perform a full evaluation, including history and physical examination. Terence requires medication that will support the completion of an evaluation and differential diagnosis without putting the patient or staff at risk. Early aggressive pharmacological treatment can result in masking underlying conditions. anhedonia - Answer-a diminished ability to experience pleasure avolition - Answer--lack of motivation -reduced ability to complete everyday tasks match each symptom to hypothetically malfunctioning brain circuits: positive symptoms - Answer-mesolimbic match each symptom to hypothetically malfunctioning brain circuits: negative symptoms - Answer-mesocortical/prefrontal cortex nucleus accumbens reward circuit match each symptom to hypothetically malfunctioning brain circuits: cognitive symptoms - Answer-dorsolateral prefrontal cortex match each symptom to hypothetically malfunctioning brain circuits: aggressive symptoms - Answer-orbitofrontal cortex amygdala match each symptom to hypothetically malfunctioning brain circuits: affective symptoms - Answer-ventromedial prefrontal cortex polygenic risk score - Answer-add up all the abnormal genes an individual has amongst the known few hundred risk genes, suggesting how much risk there might be for developing schizophrenia. Barnes Akathisia Rating Scale (BARS) - Answer-rating scale to assess the severity of drug-induced akathisia. -includes objective and subjective items such as the level of the patient's restlessness Abnormal Involuntary Movement Scale (AIMS) - Answer-tool used to monitor involuntary movements and tardive dyskinesia in clients who take antipsychotic medication -best practice/recommendation to document the AIMS at minimum every 6 months for patients taking an antipsychotic agent/dopamine blocker Low-potency medications - Answer--require higher doses to achieve efficacy -have more anticholinergic, antihistaminic, and α1- properties, can result in more sedation Targeting mesolimbic/mesostriatal dopamine D2 receptors causes: - Answer- antipsychotic actions Targeting dopamine D2 receptors in Mesolimbic/mesostriatal and mesocortical pathways causes: - Answer-secondary negative symptoms Targeting tuberoinfudibular dopamine D2 receptors causes: - Answer- elevation of prolactin -associated with gynecomastia, galactorrhea, amenorrhea Targeting nigrostriatal dopamine D2 receptors causes: - Answer-motor side effects -can cause drug induced parkinsonism overactivity of the mesolimbic dopamine system - Answer-may mediate the positive symptoms of psychosis any abnormal motor symptoms caused by D2 receptor blockers are lumped together and called collectively: - Answer-extrapyramidal symptsom (EPS) -motor side effects of D2 antagonists caused by chronic blockade of D2 receptors in the nigrostriatal dopamine pathway - Answer-tardive dyskinesia (TD) -tx: interventions that lower dopamine neurotransmission, inhibiting the vesicular monoamine transporter type 2 (VMAT2) lowers the "go" signals - deuterated tetrabenazine (deutetrabenazine), Valbenazine (most selective and potent) , the most common side effect of drugs that target D2 receptors for psychosis - Answer- Drug induced parkinsonism (DIP) -akinesia, bradykinesia, rigidity, and tremor *anticholinergics-drugs that block muscarinic cholinergic receptors adding 5HT2A antagonism: - Answer-improve side effects of D2 blockade and enhance the antipsychotic efficacy of D2 blockade Sedative-hypnotic agents - Answer-benzodiazepine & barbiturates, clinical indications for use: -sedation & anxiolysis -treatment of insomnia -general anesthesia -seizures -alcohol withdrawal states -as adjunctive management with neuromuscular blockage/muscle relaxation -to induce or maintain sleep sedative-hypnotic medications: use - Answer--1 in 8 adults -Higher incidence in older adults -Often co-prescribed with opioids sedative-hypnotic medications: misuse - Answer--Taken outside of prescriptive guidelines -Taken without prescription -polysubstance Abuse -Are common as second drugs of abuse, often taken with opioids and/or alcohol -Increased respiratory and CNS depression -Increased risk of emergency department visits sedative-hypnotic medications: Withdrawal - Answer--May be severe -Signs and symptoms include psychosis, hallucinations, delirium, seizures -Mild signs and symptoms: irritability, tremor, anxiety, palpitations, insomnia, nausea, vomiting, diaphoresis, headache Benzodiazepine intoxication - Answer-Can resemble alcohol intoxication: unsteady gait, cognitive impairment, discoordination, slurred speech -Overdose may lead to respiratory depression and stupor/coma Anxiety - Answer-response to situations that are perceived as stressful or dangerous -increases alertness, heart rate, and respirations, preparing the body to respond to perceived threatening environmental stimuli *when symptoms of anxiety persist and become intense or excessive, a diagnosis of an anxiety disorder may be warranted, and treatment is required anxiety disorder - Answer--affects more women than men -one of the most common mental health concerns in the United States -about 25% of people develop pathological anxiety during their lifetime -can be debilitating and negatively impact the quality of life Types of anxiety disorders - Answer--separation anxiety disorder -selective mutism -specific phobias (animal, natural environment, blood-injection-injury, situational, other) -social anxiety disorder -panic disorder -agoraphobia -generalized anxiety disorder -substance/medication-induced anxiety disorder -anxiety disorder due to another medical condition Other closely related disorders include: -obsessive-compulsive disorder -acute stress disorder -posttraumatic stress disorder. Neurobiological factors that contribute to anxiety - Answer-Genetics -(GAD) has genetic heritability of approximately 30% SNRI's - Answer-Serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat all anxiety disorders except OCD. -preventing the reuptake of 5-HT and norepinephrine (NE) by synapses in the brain. Compared with venlafaxine and desvenlafaxine, which have serotonin reuptake inhibition (SRI) activity and dose-related affinity for norepinephrine reuptake inhibition (NRI) primarily, duloxetine has more balanced SRI and NRI activities. Levomilnacipran has higher activity at NRI than SRI. -desvenlafaxine (Pristiq) -duloxetine (Cymbalta) -venlafaxine (Effexor, Effexor XR) -levomilnacipran (Fetzima) SNRIs: adverse effects and monitoring - Answer--elevated blood pressure -sweating -anxiety -dizziness -insomnia -constipation -serotonin syndrome Monitoring: increased anxiety and suicidal ideations SNRIs: contraindication - Answer-liver problems hypertension SNRIs: clinical pearls - Answer--Due to the presence of norepinephrine, SNRIs can exacerbate anxiety. -Dosage should be started at half the recommended dose for depression to minimize side effects. Buspirone - Answer-Azapirones are Federal Drug Administration (FDA) approved for short-term anxiety treatment and are used alone or as an adjunct to antidepressants. -bind to serotonin and dopamine receptors in the brain and increase norepinephrine metabolism in the brain. -Buspirone (Buspar) Buspirone: adverse effects - Answer--dizziness -headache -sedation -nervousness -nausea Buspirone: contraindications - Answer--severe renal impairment -severe hepatic impairment -concurrent use of monoamine oxidase inhibitors (MAOIs) Buspirone: clinical pearls - Answer--Buspirone is not habit-forming, does not have abuse potential, causes withdrawal reactions, or potentiates alcohol and sedative- hypnotic effects. -It is prescribed for two or three times a day due to the short half-life; it is not prescribed as needed (PRN). -It has a gradual onset of action of 2 weeks, but over time provides the same efficacy as a benzodiazepine. -BuSpar may decrease sexual side effects when used in combination with an SSRI. Alpha 2 Delta Ligands - Answer-used off-label for general anxiety disorder (GAD). -bind with glutamate calcium channel blockers (Glu-CB) to inhibit the release of several neurotransmitters. --Pregabalin has anxiolytic properties with selective binding to the α- 2-delta subunit of voltage-gated calcium channels. -pregabalin (Lyrica) -gabapentin (Neurontin) Alpha 2 Delta Ligands: adverse effects - Answer--sedation -dizziness -impaired attention -confusion -dry mouth -constipation -blurred vision -possible weight gain Alpha 2 Delta Ligands: Precautions & Contraindications - Answer-Precautions: -suicidal ideation -substance abuse -heart failure -renal impairment Contraindications: -myopathy -avoid prescribing concurrently with benzodiazepines (BZOs) Alpha 2 Delta Ligands: clinical pearls - Answer--works quickly to reduce anxiety symptoms -pregabalin reduces anxiety with a similar onset to alprazolam. Beta blockers - Answer-can be used to treat somatic anxiety effects such as tachycardia and physical tension symptoms. -block the effects of norepinephrine and epinephrine. -propranolol (Inderal) -atenolol (Tenormin) Beta Blockers: adverse effects - Answer--dizziness, vertigo -fatigue -hypotension -decreased libido and sexual dysfunction Beta Blockers: Precautions & Contraindications - Answer-Precautions: -Use with caution in clients with asthma or heart failure; beta-adrenergic blockade can reduce heart rate and cause bronchoconstriction. -can blunt signs of hypoglycemia in diabetics -can mask clinical signs of hyperthyroidism Contraindications: -first-degree heart block -bradycardia Beta blockers: clinical pearls - Answer--not FDA-approved for the treatment of anxiety but are commonly used. -often used for test anxiety, performance anxiety, and social anxiety because these drugs are nonsedating. -may be prescribed after a traumatic event to help prevent a permanent fear response. Histamine Receptor Antagonists - Answer-used for the treatment of anxiety and skeletal muscle tension associated with psychoneurosis, for anxiety symptoms associated with alcohol withdrawal, and for anxiety related to cardiac impairment. -act by blocking histamine 1 receptors. -hydroxyzine (Atarax) Histamine Receptor Antagonists: adverse effects - Answer--sedation -dry mouth -tremor Histamine Receptor Antagonists: monitoring & contraindications - Answer- Monitoring -hepatic status -potassium level -QT interval Contraindications: -severe hepatic impairment -QT prolongation Histamine Receptor Antagonists: clinical pearls - Answer--It is unclear if efficacy is due to an anxiolytic effect or a sedative effect. -Caution clients about potential sedation when prescribing. -When used concurrently with another central nervous system (CNS) depressant, the depressant dose should be reduced to half. -Elderly clients are more sensitive to the sedative and anticholinergic side effects of hydroxyzine. enhance gamma-aminobutyric acid's (GABA's) inhibitory effects in the brain by acting on GABA receptors outside of the receiving neuron to open a channel that allows negatively charged chloride ions to pass into the neuron -negative ions "supercharge" the neuron making it less responsive to neurotransmitters that would normally excite it. -also react at specific benzodiazepine receptors on the GABA neuron. Benzodiazepine receptor subtypes have slightly different actions: *Alpha one is responsible for sedative effects. *Alpha two is responsible for anti-anxiety effects. *Alpha one, alpha two, and alpha five are responsible for anticonvulsant effects. Benzodiazepines use - Answer-short-term relief of acute anxiety -do not treat underlying cause not intended for long- term -risk of tolerance, dependence, uncomfortable withdrawal Benzodiazepines (BZO): adverse effects - Answer-oversedation -drowsiness, poor concentration, incoordination, muscle weakness, dizziness and mental confusion -increased risk of accidents, falls, and injury. memory impairment -cause "blackouts" -lack of concentration and attention, impair learning depression -inability to feel pleasure or pain. -increase suicide risk tolerance and dependence -can occur in as little as 2 weeks -psychologically and physically addictive Paradoxical Effects -increased anxiety, irritability, hyperactivity, aggression, insomnia, nightmares, hallucinations at the onset of sleep, cases of assault and homicide have been reported Benzodiazepines (BZO): Patient education - Answer--rationale for benzodiazepine prescription -expected length of treatment (short term only) -avoiding alcohol -adverse effects -risks of tolerance and dependence -avoiding driving while taking this medication Benzodiazepines Safety and Prescribing Guidelines - Answer-Set ground rules: Excitatory neurotransmitters, including , , , , -Client uses only one pharmacy. -BZO should be prescribed by only one provider. -Check the state prescription monitoring program (PMP) controlled substance database. -No early refills. Do not prescribe if the client is concurrently taking: -opioids -other benzodiazepines -z-drugs (medications for sleep) -muscle relaxants -marijuana Schedule regular follow-up: -frequency based on client risk, older and younger clients clients with history of substance use disorder -Required components during follow-up: *symptom assessment *PMP prescription monitoring review *urine drug screening *care plan with informed consent *appropriate documentation Prescribe for short course only -2-4 weeks -Longer treatment requires a clear, written plan with a rationale abrupt cessation of benzodiazepines - Answer-can lead to severe withdrawal symptoms -seizures and death necessary for alertness, memory, muscle tone, coordination, emotional responses, endocrine gland secretions, heart rate, and blood pressure control. - Answer- norepinephrine, serotonin, acetylcholine, and dopamine will induce calm but will also affect higher-level thinking - Answer- Benzodiazepines (BZOs) increase GABA's inhibitory activity, leading to the decreased output of excitatory neurotransmitters resulting in the adverse effects related to their use - Answer-Benzodiazepines (BZOs) alprazolam IR (Xanax) - Answer-Short- acting Use: GAD, panic disorder Half-life: 12-15 hours Equivalence: 0.5 mg Dosage: -anxiety: 0.75-1.5mg/day in divided doses; max dose 4 mg/day -panic: 1.5mg/day in divided doses; dosing may exceed 4 mg, increase slowly -rapid onset, less sedating -can cause sedation, fatigue, forgetfulness, hypersalivation -useful adjunct to SSRI/SNRI -recommended use: lowest effective dose for shortest period of time -risk for respiratory depression, especially when taken with CNS depressants -contraindicated in angle-closure glaucoma -tapered dosing when discontinuing, risk of seizures with withdrawal lorazepam (Ativan) - Answer-Short- acting Use: agitation, anxiety Half-life: 10-20 hours Equivalence: 1 mg Dosage: 2-6 mg/day; BID-TID dosing; max 10 mg/day elderly: 1-2 mg/day in divided doses -rapid onset -can cause sedation and fatigue (anterograde anesthesia) -safe with liver disease; use lower dosage with liver and renal impairment -increased risk of drug hangover due to longer half-life -increased depressive effects with opioids- do not prescribe together -caution with sleep apnea -contraindicated in angle-closure glaucoma, breastfeeding, and pregnancy -tapered dosing when discontinuing clonazepam (Klonopin) - Answer-Long- acting Use: panic disorder Half-life: 30-40 hours Equivalence: 0.5 mg Dosage: 0.5-2 mg/day in divided doses or at bedtime starts at 0.25 mg and increases slowly -rapid onset and less sedating, but does cause some sedation and fatigue -longer duration of action -only Category C benzodiazepine; not recommended with breastfeeding -increases salivation -contraindicated with liver disease -easier to taper dosing than other BZOs due to the long half-life Rationale: The PMHNP should increase the sertraline dose to the maximum dose of 200 mg because the client has slightly improved symptoms. It may take several months for the client to see full relief, so it is best to wait before adding additional drugs or switching drugs. At Sofia's 12-week follow-up visit, the client is taking the maximum dose of sertraline and is experiencing improvement in symptoms, but not full relief from symptoms. Which is the best action by the PMHNP? - Answer-augment with buspirone Rationale: The client has improvement in symptoms, but not full relief, so the best action is to augment the current therapy. Buspirone offers anxiety relief but does not have the effects of a CNS depressant or cause dependence like benzodiazepines. Buspirone does take approximately 4 weeks to reach full therapeutic effects. If the client did not experience an improvement in symptoms, switching to another SSRI would be the best action. Jill, a 23-year-old graduate student, presents with reports of panic attacks and worry "my whole life." She reports that she can bring on panic attacks herself when she worries. This happens almost every day and some days it is so bad she cannot go to work or school. She was offered a few Xanax by a friend, and she wants a prescription because "they really help." The PMHNP diagnoses Jill with Generalized Anxiety Disorder (GAD). Which is the best medication for the PMHNP to prescribe? - Answer- escitalopram Rationale: Escitalopram is the only listed SSRI that is the appropriate drug class for GAD. Bupropion is an SNRI. Medications that contain norepinephrine can increase anxiety. Jill has chronic anxiety, not acute anxiety. Benzodiazepines should be prescribed only for short-term use, less than 4 weeks as an adjunct until the SSRI achieves efficacy. Buspirone seems like a good choice because this medication targets 5HT1A; however, this medication is used as an adjunct therapy, not monotherapy. Mary Ann is a 55-year-old woman who scheduled an appointment with the PMHNP a month before a planned vacation to Hawaii. Mary Ann states, "I have been on a plane once before, and I had a major panic attack. It was terrible." She is concerned about having another panic attack on the long transpacific flight. She is in good health and is not taking any medications. Which is the best choice for the PMHNP to prescribe? - Answer-alprazolam #4 tabs PRN Rationale: Alprazolam #4 tabs PRN is the best choice for anxiety in a specific high- anxiety situation such as flying. Benzodiazepines can be prescribed for PRN use. Limiting the number of pills is appropriate to help prevent misuse and diversion of the medication. In this case, medication was provided for departure and return. Using daily medication is not necessary since Mary Ann does not have chronic anxiety. Providing an SSRI PRN is not appropriate as it may take up to 6 weeks for efficacy. Andrea is a 65-year-old woman who presents for care because "her nerves are a mess." Her husband was diagnosed this week with Stage IV pancreatic cancer and has less than a month to live. Andrea can not eat or sleep. She cries constantly and "her -norepinephrine -glutamate -voltage-gated ion channels Excessive amygdala activity is theoretically reduced by: - Answer- benzodiazepines -enhance phasic inhibition of GABA (γ-aminobutyric acid) by positive allosteric modulation of postsynaptic GABA receptors -blunt fear-associated outputs modulate excessive output from worry loops - Answer-benzodiazepines -enhancing the actions of inhibitory interneurons in CSTC circuits -reduce symptoms of worry also known as α2δ ligands since they bind to the α2δ subunit of presynaptic N and P/Q VSCCs, block the release of excitatory neurotransmitters such as glutamate that occurs when neurotransmission is excessive, as postulated in the amygdala to cause fear (Figure 8-17A) and in CSTC circuits to cause worry - Answer-Gabapentin and pregabalin key neurotransmitter that innervates the amygdala as well as all the elements of CSTC circuits - Answer-Serotonin -regulate both the symptoms of fear and worry Noradrenergic hyperactivity in anxiety - Answer-Norepinephrine is another neurotransmitter with important regulatory input to the amygdala, and to the prefrontal cortex and thalamus in CSTC circuits % of the population will develop an anxiety disorder - Answer-30% Treatment for anxiety disorder subtypes: Generalized Anxiety Disorder - Answer-SSRIs, SNRIs, benzodiazepines, buspirone, and α2δ ligands such as pregabalin and gabapentin Other "off-label" treatments for anxiety can include mirtazapine, trazodone, vilazodone, tricyclic antidepressants, or even sedating antihistamines such as hydroxyzine. Treatment for anxiety disorder subtypes: PTSD - Answer- psychopharmacological treatments -not as effective as these same treatments are in anxiety disorders -more effectively aimed at comorbidities: depression, insomnia, substance abuse, and pain Benzodiazepines are to be used with caution -limited evidence from clinical trials for efficacy in PTSD -many PTSD patients abuse alcohol and other substances , , , are all key modulators of the unique treatment for PTSD is the administration of α1 antagonists at night to prevent nightmares The amygdala hypothetically plays a central role in the . Cortico- striato-thalamo-cortical (CSTC) circuits are thought to play a key role in mediating the symptom of . - Answer-fear response, worry fear and worry circuits - Answer-Serotonin, norepinephrine, alpha-2 delta ligands and GABA Amygdala-centered circuit - Answer-Fear -panic -phobia cortico-striato-thalamo-corical (CSTC) circuit - Answer-worry -anxious misery -apprehensive expectation -obsession Gabapentin - Answer-Anxiolytic glutamate voltage-gated calcium channel blocker, Anticonvulsant; alpha 2 delta ligand at voltage-sensitive calcium channels -Indication: Partial seizures with or without secondary generalization, postherpetic neuralgia, restless leg syndrome, neuropathic pain/chronic pain, anxiety, bipolar disorder. -Dosing: 900-1800 mg/day in 3 divided doses Risks: CNS side effects: Sedation Ataxia fatigue nystagm us tremor Pearls: -Most use if off-label -Off-label use for first-line treatment of neuropathic pain may be justified Pregabalin - Answer-Anxiolytic glutamate voltage-gated calcium channel blocker, Anticonvulsant; alpha 2 delta ligand at voltage-sensitive calcium channels -Indication: Diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, neuropathic pain associated with spinal cord injury, partial onset seizures, peripheral neuropathic pain, GAD, panic disorder, social anxiety disorder. -Dosing: IR: 150-600 mg/day in 2-3 doses, CR: 330 mg once per day Risks: CNS side effects: Sedation Pearls: -First treatment approved for fibromyalgia -Off-label use for GAD, panic disorder, and social anxiety disorder may be justified in the USA Buspirone - Answer-Anxiolytic serotonin receptor partial agonist -Indication: Anxiety, depression, treatment-resistant depression -Dosing: usual 20-30 mg/day. Initial 15 mg twice a day; increase in 5 mg/day increments every 2-3 days until desired efficacy reached (max 60 mg/day) Risks: Dizziness Headache Nervousness Sedation Pearls: -Do not use if patient taking an MAOI -generally reserved as an augmenting agent to treat anxiety Hydroxyzine - Answer- Anxiolytic histamine receptor antagonist -Indication: Anxiety and tension associated with psychoneurosis, pruritus, sedation, hysteria, withdrawal symptoms, delirium tremens, nausea and vomiting, insomnia. -Dosing: •Anxiety: 50-100 mg 4 times a day •Sedative: 50-100 mg oral, 25-100 mg intramuscular injection •Pruritus: 75 mg/day divided into 3-4 doses Risks: Blocking histamine 1 receptors can cause sedation Pearls: -preferred anxiolytic for patients with dermatitis or skin symptoms such as pruritis Alprazolam - Answer-Anxiolytic BENZODIAZEPINE GABA positive allosteric modulator -Indication: Generalized anxiety disorder, other anxiety disorders, panic disorder, premenstrual dysphoric disorder, irritable bowel syndrome, insomnia, acute mania, acute psychosis, catatonia. -Dosing: