NR565 Week 4 Study Guide Week 4 is the midterm (no quiz) and includes all material from Weeks 1-4; Be sure to also review the Weeks 1, 2 & 3 study guides to prepare for the exam

NR565 Week 4 Study Guide Week 4 is the midterm (no quiz) and includes all material from Weeks 1-4; Be sure to also review the Weeks 1, 2 & 3 study guides to prepare for the exam Many questions will are written to assess your clinical application of the material from the textbook, in real-world scenarios Chapter 15: Drugs Affecting the Central Nervous System Anorexiants: Precautions and contraindications Examples; phentermine, benzphetamine, diethylproprion, phendiametrazine and lorcaserin. Anorexiants are sympathomimetic amines and are thought to exert their action by stimulation of satiety centers in the hypothalamus and limbic region. They act through noradrenergic, dopaminergic, or serotonergic pathways. Lorcaserin promotes satiety by selectively activating 5-HT2C receptors in the hypothalamus. Thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite ADRs- CNS overstimulation, agitation, confusion, insomnia, dizziness, HTN, headache, palpiatiations, arrhythmias, dry mouth, n/v. Sudden withdrawal in patients who have a long history of use may cause withdrawal symptoms. Increases glucose uptake from skeletal muscles and must be used cautiously in diabetics- altered insulin or oral hypoglycemic dosage requirements . Carry a high risk of tolerance and dependence. Use with caution in patients with ahistory of alcohol or drug dependence. Use for a max period of 6 months. Lorcaserin is a serotonergic drug and may develop serotonin syndrome if taken with other serotonergic drugs. Drug interactions- do not use with SSRIs, careful use with serotonergic meds due to risk for serotonin syndrome, avoid MAOIs = result in hypertensive crisis, careful use with adrenergic blockers, insulin sulfonylureas, and phenothiazines = lithium toxicity, ovoid orlistat = decrease levels of levothyroxine and increases warfarin in the body. Anticonvulsants: Hydantoins, iminostilbenes, succinimides Mode of Action: Essentially, anti-seizure drugs act by stimulating an influx of chloride ions; usually this is associated with the neurotransmitter gamma-aminobutyric acid delaying an influx of sodium and delaying an influx of calcium. • Hydantoins; phenytoin, ethotoin, fosphenytoin – first line tx for tonic-clonic and complex seizures and are least sedating drugs for seizure tx. Hydantoins inhibit and stabilize electrical discharges in the motor cortex of the brain by affecting the influx of sodium ions into the neuron during depolarization and repolarization, slowing the propagation and spread of abnormal discharges. They also affect the brainstem's contribution to grand mal seizures and have antiarrhymic properties. • Metabolism and excretion 
 Metabolism of hydantoins takes place in the liver; excretion, via the kidneys. Plasma half-lives range from 6 to 24 hours. Precautions and Contraindications Hydantoins are contraindicated under conditions of hypersensitivity. Phenytoin-induced hepatitis is a common hypersensitivity reaction. Other hypersensitivity reactions include fever, rash, arthralgias, and lymphadenopathy. Phenytoin may cause severe cardiovascular events and death has resulted from too-rapid IV administration. Phenytoin has a Black-Box Warning that IV administration should not exceed 50 mg/minute in adults and 1 to 3 mg/kg/minute in pediatric patients owing to risk of cardiovascular reactions associated with a too rapid rate of administration. Phenytoin is contraindicated in sinus bradycardia, sinoatrial block, second- and third-degree atrioventricular block, and Stokes–Adams syndrome. It should be used cautiously in patients with hepatic or renal disease. Ethotoin is contraindicated in the presence of hepatic or hematological disorders. Black box warning for IV administrations – do not give too fast or can cause cardiovascular reactions. • MOAs, indications 
 • Absolute contraindications 
- bradycardian sinoatrial block, second and third degree atrioventricular block and stokes-adams syndrome. • Precautions 
- in pregnant wormen – can cause defects and low vitamin K, in patients w low liver function (may have signs of toxicity at low levels of drug), caution in patient with myocardial insufficiency and hypotension. • Monitoring 
 Patients should be assessed for phenytoin hypersensitivity syndrome (fever, skin rash, lymphadenopathy), which usually occurs at 3 to 8 weeks. Baseline complete blood count, urinalysis, and liver function tests should be assessed prior to onset of treatment, with frequent reassessment during the first few months of treatment. Plasma levels should be monitored, especially when drugs that increase plasma hydantoin, such as ibuprofen, are used. As well, other drugs that are negatively affected by concurrent administration with hydantoins may also require monitoring of the plasma level. Phenytoin may alter thyroid hormone demand, which may require monitoring. Patients started on hydantoins or any AED should be monitored for suicidality (suicidal thoughts, depression, behavior changes). 
 • Drug interactions (including oral contraceptives) 
 Drug interactions consist of those that either increase or decrease the effect of the hydantoin and those that decrease the effect of the other drug. Interactions that increase hydantoin's effect because of increased metabolism, competition for binding sites, or for unknown reasons occur with benzodiazepines, cimetidine, disulfiram, tricyclic antidepressants, salicylates, and valproic acid. Conversely, interactions that decrease hydantoin's effect include barbiturates, rifampin, theophylline, influenza vaccine, pyridoxine, and antacids. Acute acohol intake may increase phenytoin serum levels, whereas chronic alcohol use may decrease levels. IV phenytoin should only be mixed with normal saline and should not be mixed with dextrose-containing IV solutions because a precipitate may form. Concurrent administration causes the decreased effect of carbamazepine, estrogens, corticosteroids, haloperidol, methadone, levodopa, sulfonylureas, oral contraceptives, and cardiac glycosides. • Black box warnings 
Drugs that affect GABA: 
 • ADR’s 
: Possible adverse effects are multiple and may include CNS effects such as agitation, ataxia, confusion, dizziness, drowsiness, headache, and nystagmus; cardiovascular effects such as hypotension, tachycardia, atrial and ventricular conduction depression, and ventricular fibrillation; gastrointestinal (GI) effects such as nausea, vomiting, anorexia, altered taste, constipation, dry mouth, and gingival hyperplasia; and genitourinary effects such as urinary retention and reddish-brown discoloration of the urine. Serious dermatologic reactions, including Stevens–Johnson syndrome and toxic epidermal necrolysis may occur. Other possible adverse effects include skin rashes (scarlatiniform or morbilliform), hyperglycemia, tinnitus, gynecomastia, coarsening of facial features and enlargement of the lips, hematopoietic changes, photophobia, and polyarthropathy. • Pharmacotherapeutics 
 • Precautions and contraindications 
 • Patient education 
 The patient should be instructed to take the medication exactly as directed and to avoid missing doses. Abrupt withdrawal may lead to status epilepticus. Advise the patient to wear a medical identification bracelet, to avoid hazardous situations if drowsiness occurs, and to report adverse effects to the clinician. Patients should avoid alcohol use while taking a hydantoin. Advise the patient to maintain good oral hygiene to prevent tenderness, bleeding, and gingival hyperplasia. Inform the patient that phenytoin may color the urine pink, red, or reddish brown but that this color change is not a cause for alarm. Advise diabetic patients to monitor blood glucose levels and report significant changes to the clinician. Rational Drug Selection Hydantoins are used for the treatment of grand mal and psychomotor seizures. Phenytoin, however, may worsen absence seizures. Hydantoins are not the first-line treatment of status epilepticus, but IV phenytoin can be used for the control of grand mal types of seizures. Fosphenytoin is used for short-term (less than 5 days) management of seizures when oral use is not feasible. Ethotoin is dosed in 4 to 6 doses a day with food, spaced as evenly as possible, which may be a complex regimen for some patients. IMINOSTILIBENES: carbamazepine, oxycarbazepine – tx epilepsy, bipolar disorder, aggressive and assaultive behavior, neuralgias. Thought to affect sodium channgels, slowing influx of sodium in cortical neurons and slow spread of abnormal activity. Absorption and distribution- absorbed through the stomach. Metabolism and excretion- metabolize din liver and has unique ability to induce its own metablolism. Induced metabolism of many CYP450 enzymes. Extcretion in urine and feces. Precautions and contraindications; Contraindications; history of bone marrow suppression and concurrent administration with MAOIs. Carbamazapine is contraindicated in pregnancy (spina bifida) and has black box warning regarding serious dermatological relations (esp Asians, Steven-Johnson syndrome, epidermal necrolysis), and risk of aplastic anermia and agranulocytosis. Asians need screened for HLA-B*1502 gene. Caution- patients with increase intraocular pressure due to anticholinergic effects, caution with pts history of previous adverse hematological reactions to drugs and in those with cardiac, renal, or hepatic impairment. Adverse Drug Reactions Carbamazepine has a Black Box warning regarding the development of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients of Chinese ethnicity (1 to 6 per 1000) versus patients of caucasian ethnicity (1 to 6 per 10,000). There is a strong association with the HLA-B*1502 allele variant and the development of SJS/TEN. Patients from Asian countries are more likely to have the HLA-B*1502 variant and should be screened for the presence of HLA-B*1502 prior to beginning carbamazepine. Carbamazepine has a Black-Box Warning due to its potential to cause blood dyscrasias, some potentially lethal. Although a transient decrease of the white blood cell count can occur and is manageable, carbamazepine can depress the bone marrow and lead to leukopenia, thrombocytopenia, agranulocytosis, and aplastic anemia. For that reason, a baseline blood screen that includes a complete blood count (CBC), chemistry, liver function tests, and thyroid-stimulating hormone (TSH) test should be obtained, followed by periodic monitoring. Follow-up studies should be more frequent initially, decreasing to every 3 to 4 months if the results remain normal or the CBC and differential are only minimally lowered. Other adverse reactions to carbamazepine include hepatic damage and impaired thyroid function. Less serious early adverse events may include drowsiness, dizziness, blurred vision, ataxia, nausea, vomiting, dry mouth, diplopia, and headache. The most common adverse effects (5% or greater incidence) observed in patients taking oxcarbazepine were dizziness, diplopia, somnolence, fatigue, nausea, vomiting, ataxia, abdominal pain, tremor, and dyspepsia. Hyponatremia (serum sodium less than 125 mEq/L) may occur, particularly in the first 3 months of therapy. Pediatric patients experienced effects similar to those of adults. Drug Interactions The interactions of most significance are those that increase the plasma level of carbamazepine to potentially toxic levels, such as the concurrent administration of propoxyphene, hydantoins, cimetidine, some antibiotics (erythromycin, clarithromycin), isoniazid, and verapamil. Interactions that can result in hepatic damage occur with coadministration of some anesthetics and with isoniazid. Interactions that decrease plasma levels of the other drug occur with beta blockers, succinimides, valproic acid, warfarin, haloperidol, doxycycline, and nondepolarizing muscle relaxants. Grapefruit juice increases serum levels and effects of carbamazepine. Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5, leading to increased levels of drugs metabolized by CYP2C19. Oxcarbazeine may decrease the effectiveness of hormonal contraceptives containing ethinylestradiol and levonorgestrel. Rational Drug Selection Carbamazepine is indicated in the treatment of partial complex seizures. It is also useful for generalized tonic-clonic seizures. Its relative lack of side effects compared to phenytoin and phenobarbital has resulted in increased use for a variety of seizure disorders. The drug is also used as a third-line mood stabilizer for bipolar patients who have not responded to lithium or divalproex (Depakote) and for patients unable to tolerate either of the others. Carbamazepine, in a dosage range of 100 to 300 mg at bedtime, can be used to treat restless legs syndrome. Carbamazepine is sometimes used to relieve the pain of trigeminal neuralgia. Oxcarbazepine may be used as monotherapy or adjuntive therapy in the treatment if partial seizures in adults. Oxcarbazepine is approved as monotherapy for partial seizures in children age 4 and older, and adjuntive therapy for children age 2 and older with partial seizures. Monitoring Plasma carbamazepine levels should be monitored on a regular basis. The therapeutic range is 4 to 12 mcg/mL. Higher levels can lead to toxic symptoms consisting of the initial adverse effects and also hypertension, tachycardia, electrocardiogram (ECG) changes, stupor, agitation, nystagmus, urinary retention, respiratory depression, seizures, and coma. Children and elderly patients may develop toxicity at levels below 12. Oxcarbazepine does not require serum level monitoring. Serum sodium levels should be monitored for the first 3 months of therapy, especially if the patient is taking other drugs that may cause hyponatremia. Patient Education Patients taking carbamazepine should be instructed to report to the clinician any symptoms such as skin lesions, bruising, fever, or sore throat. Carbamazepine should then be discontinued and another drug substituted. Tell the patient that administration with food may increase absorption, and because carbamazepine can be sedating, care should be exercised in situations in which mental and physical alertness is required for safety. Oxcarbazepine may cause hyponatremia; therefore, patients should be educated regarding symptoms of hyponatremia, which include nausea, fatigue, headache, confusion, and increased seizures. Patients should report swelling of face, eyes, lips, or tongue, which may be symptoms of angioedema. Rash or mouth sores may be early symptoms of Stevens–Johnson syndrome. SUCCINIMIDES The succinimides are used for the treatment of absence seizures in children and adults. The succinimides include ethosuximide (Zarontin) and methsuximide (Celontin). The succinimides exert their anticonvulsant effects by decreasing nerve impulses and transmission in the motor cortex. This produces a variety of effects, including an increase in the seizure threshold and reducing the electroencephalogram (EEG) spike-and-wave pattern of absence seizures. Absorption and Distribution Succinimides are administered orally and are thoroughly absorbed from the GI tract. Metabolism and Excretion. Succinimides are metabolized in the liver and excreted through the urinary tract, although a small amount of phensuximide is excreted in bile. Precautions and Contraindications Anticonvulsants in general are associated with fetal defects, but the succinimides, with careful monitoring of plasma levels, appear to be safe for use during pregnancy and are Pregnancy Category C. They are contraindicated, as are other anticonvulsants, during lactation. Although uncommon, succinimides have caused blood dyscrasias and use should be preceded by a CBC with differential repeated at frequent intervals initially and less often as the patient continues on the medication without adverse effects. Liver function tests should also be obtained prior to instituting treatment. Adverse Drug Reactions The most common adverse reactions to the succinimides are GI distress, which can be relieved by taking the medication with food or milk, and CNS depression, characterized by sedation, ataxia, and lethargy. Other adverse reactions may include headache, rash, pruritus, and mood changes. Symptoms of toxicity are a worsening of these adverse reactions. Cases of systemic lupus erythematosus have been reported with the use of succinimides. All AEDs increase risk of suicidal ideation. Drug Interactions The most significant drug interactions are those that increase CNS depression, such as alcohol, opioid agonists, benzodiazepines, and CNS depressants. Succinimides may be given concurrently with other anticonvulsants but may antagonize them and contribute to tonic-myoclonic breakthrough seizures, therefore requiring the need for a higher dose of the other anticonvulsant. Avoid concurrent use with TCAs and phenothiazines because an antagonistic effect on succinimides may lower the patient's seizure threshold. Haloperidol may change the pattern or frequency of seizures, necessitating an adjustment in dosage of the anticonvulsant. Succinimides may decrease the effectiveness of oral contraceptives; thus, the patient should be advised to use a backup birth control method. Rational Drug Selection Succinimides are the treatment of choice for childhood absence seizure disorders. They are sometimes used for the treatment of absence seizures in adults, but valproic acid becomes the primary treatment in adults. Methsuximide is equally effective as ethosuximide but may have more adverse reactions. Monitoring Plasma levels should be monitored. The normal therapeutic range of ethosuximide is 40 to 100 mcg/mL; levels over 150 mcg/mL are considered toxic. The therapeutic range for methsuximide is 10 to 40 mcg/mL, with levels greater than 40 mcg/mL considered toxic. In addition to monitoring seizure activity, evaluate liver, renal, and hematological studies periodically for adverse effects. Patient Education Advise the patient to avoid alcohol and, if sedation occurs, to avoid hazardous activities. To decrease stomach distress, succinimides should be taken with milk or food. Because adverse mood changes can occur while taking these medications, advise the client to report any behavioral changes to the clinician. Caution the client that withdrawal of the medication may precipitate absence seizures. Inform the client taking phensuximide that harmless changes in urine color may occur. DRUGS THAT AFFECT GABA The AEDs that affect gamma aminobutyric acid (GABA) include the benzodiazepines, gabapentin (Neurontin), topiramate (Topamax), and tiagabine (Gabitril). The AEDs that affect the inhibitory neurotransmitter GABA are also used for pain, including neuropathic pain (gabapentin) and migraine (topiramate). • Drug interactions 
Antidepressants: TCAs, SSRIs, MAOIs, SNRIs, miscellaneous Tricyclic Antidepressants (TCA): • Precautions 
 • Contraindications 
 • ADRs 
 • Clinical use 
 • Monitoring 
Monoamine Oxidase Inhibitors (MAOIs): 
 • Drug interactions Table15-13 • Food and drug interactions. SSRIs and SNRIs: • Pharmacodynamics 
 • Metabolism 
 • Adverse drug reactions 
 • Pharmacotherapeutics 
 • Drug interactions (including herbals & supplement) 
 • Rational drug selection 
 • Patient education 
Antipsychotics: Typical and Atypical 
 • Pharmacodynamics 
 • Pharmacotherapeutics 
 • Contraindications 
 • ADRs 
 • Clinical use 
 • Rational drug selection 
 • Monitoring 
 • Atypical antipsychotics used in the treatment of major depressive disorder 
Dopaminergics 
• Pharmacodynamics • Precautions
• ADRs 
Anxiolytics and Hypnotics
Benzodiazepines and serotonergic anxiolytics (buspirone): 
 • Pharmacodynamics 
 • Pharmacotherapeutics 
 • Precautions and contraindications 
 • ADRs 
 • Rational drug selection 
 • Patient education 
 • Alternatives for generalized anxiety treatment 
Barbituates: Phenobarbital Nonbenzodiazepine hypnotics 
 Mood stabilizers: Lithium Valproates: Monitoring Non-classified mood stabilizers Muscle relaxants and antispasmodics: Centrally acting, direct acting • Pharmacodynamics
• Pharmacotherapeutics • ADRs Opioid Analgesics and their antagonists Stimulants
Chapter 29: Anxiety & Depression Intro Figure 29-1: General algorithm for treatment of depression Figure 29-2: General algorithm for treatment of anxiety NNSRIs: Drugs in class, side effects
SSRIs: Drugs in class Table 29-2: Cytochrome P450 isoenzymes and potential drug interactions including grapefruit juice SNRIs: Drugs in class
NDRI: 1 drug in this class: bupropion, benefits and risks
SARIs: drugs in class, side effects
Norepinephrine and Serotonin Specific Agonists: Mirtazapine/Remeron- benefits MAOI: dietary restrictions
Benzodiazepines: appropriate use, long-term use and disadvantages • ADRs 
 • Rational drug selection 
 • Monitoring 
 • Clinical pearls Chapter 35: Headache Migraine, Tension, Chronic Migraine, Cluster: • Medication overuse 
 • Pathophysiology 
 • Goals of treatment 
 • Rational drug selection 
 • Acute vs. preventive therapies 
 • Non-pharmacologic management and alternative therapies 
 • Monitoring 
 • Outcome evaluation 
 • Patient education