NR 565 Midterm Exam Study Guide (V3)(NEW, 2024):Chamberlain College of Nursing, Study Guides, Projects, Research of Nursing

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NR565 Week 4 Midterm Exam Study Guide

Chapter 15: Drugs Affecting the Central Nervous System Anorexiants (p. 226): Short-term adjuncts to calorie limiting, cognitive- behavioral, weight-loss programs for severely obese individuals. Nonamphetamine appetite suppressants are commonly used today but are chemically and pharmacologically related to amphetamines. (Phendimetrazine, Benzphetamine, Diethylpropion HCl, Phentermine, Lorcaserin) Precautions and Contraindications: High risk of tolerance and dependence. Should be used in caution with patients who have a history of alcohol or drug dependence. Use should be limited to 6 months and discontinued at any sign of tolerance. Substance Abuse: Patients who abuse substances such as cocaine, phencyclidine, and methamphetamine should not be prescribed anorexiants because of the potential for excessive adrenergic stimulation. Alcoholics: Actively drinking alcoholics taking anorexiants have experienced depression, paranoia, and psychosis. Diabetes: Patients with diabetes may experiences altered insulin or oral hypoglycemic dosage requirements. Lorcaserin: Serotonergic drug. Patients may develop serotonin syndrome or Neuroleptic Malignant Syndrome like reactions if coadministered with serotonergic drugs. Pregnancy Category X and is not approved in children under 18. Anticonvulsants (p. 227): Hydantoins: First line treatment of choice for tonic-clonic and partial complex seizures and the lease sedating drugs used to treat seizure disorders of any type. (phenytoin-Dilantin, ethotoin-Peganone, fosphenytoin-

Cerebyx). Pharmacodynamics: 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. Metabolism and Excretion: Metabolism takes place in the liver and excretion via the kidneys. Plasma half-lives range from 6- 24 hours. Precautions and Contraindications: 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 50mg/minute in adults and 1-3 mg/kg/minute in pediatric patients owing to risk of cardiovascular reactions associated with a too rapid rate of administration. Contraindicated in sinus bradycardia, sinoatrial block, second-and third-degree AV block, and Stokes-Adams syndrome. Should be used cautiously in patients with hepatic or renal disease. Ethotoin: Contraindicated in the presence of hepatic or hematological disorders. Fetal Defects: Pregnancy Category D. About 10% of babies have defects in Mother’s who take phenytoin during pregnancy. Newborns exposed to phenytoin is utero may experience decreased levels of Vitamin K-dependent clotting factors and the mother should receive Vitamin K before delivery and the newborn at birth. Adverse Drug Reactions: CNS effects (agitation, ataxia, confusion, dizziness, drowsiness, headache, and nystagmus), Cardiovascular

effects (hypotension, tachycardia, atrial and ventricular conduction depression, and ventricular fibrillation), GI effects (nausea, vomiting, anorexia, altered taste, constipation, dry mouth, and gingival hyperplasia), GU effects (urinary retention and reddish-brown discoloration of urine), Dermatologic reactions (Stevens-Johnson Syndrome and toxic epidermal necrolysis). Drug Interactions: Interactions that increase hydantoins effect because of increased metabolism, competition for binding sites or for unknown reasons occur with benzodiazepines, cimetidine, disulfiram, TCAs, salicylates, and valproic acid. Interactions that decrease hydantoin’s effect include barbiturates, rifampin, theophylline, influenza vaccine, pyridoxine, and antacids. Oral contraceptives effect is decreased with use of hydantoins. Acute alcohol intake may increase phenytoin serum levels, whereas chronic alcohol use may decrease levels. IV phenytoin should only be mixed with normal saline. Monitoring: Patients should be assessed for phenytoin hypersensitivity syndrome (fever, skin rash, lymphadenopathy), which usually occurs at 3-8 weeks. Baseline CBC, urinalysis, and LFTs 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. Patient Education: 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. Maintain good oral hygiene to prevent tenderness, bleeding, and gingival hyperplasia. Phenytoin may color the urine red, pink, or reddish brown but the color change is not a cause for alarm. Advise diabetic patients to monitor blood glucose levels and report significant changes to the clinician. Iminostilbenes (p. 235): (Carbamazepine-Tegretol and oxcarbazepine-

Trileptal). Structurally related to TCAs. Used to treat epilepsy, bipolar affective disorder, aggressive and assaultive behavior, and some neuralgias. Pharmacodynamics: Thought to affect the sodium channels, slowing influx of sodium in the cortical neurons and slowing the spread of abnormal activity. Carbamazepine exerts its effect by depressing transmission in the nucleus ventralis anterior of the thalamus. This area is associated with the spread of seizure discharge. Metabolism and Excretion: Carbamazepine is metabolized in the liver and has the unique ability to induce its own metabolism (autoinduction). Due to autoinduction, initial concentrations within a therapeutic range may later fall despite good compliance. It also induces the metabolism of many CYP450 enzymes and other substrates. Excretion is through urine and feces. Oxcarbazepine is metabolized into an active metabolite 10-monohydroxy metabolite, which is responsible for the pharmacologic effect of the drug. The metabolites of oxcarbazepine are excreted 95% in urine, 4% in feces, and 1% unmetabolized oxcarbazepine. Precautions and Contraindications: Carbamazepine: Contraindications include hypersensitivity to carbamazepine or TCAs, history of bone marrow suppression, and current administration with MAOIs. Carbamazepine is Pregnancy Category D; tetratogenic defects have occurred including spina bifida. Black-Box Warning regarding serious dermatological reactions, particularly among patients of Asian ethnicity (Stevens-Johnson Syndrome, toxic epidermal necrolysis and risk of developing aplastic anemia and agranulocytosis). Patients of Asian ethnicity should be screened for presence of the HLA-B1502* genetic variant prior to starting carbamazepine. Caution is advised in patients with a history of previous adverse hematological reactions to any drugs and in those with cardiac, renal, or hepatic impairment.

Oxcarbazepine: Pregnancy Category C; it crosses the placenta and adverse effects have been noted in animal studies. Contraindicated with hypersensitivity to oxcarbazepine. Adverse Drug Reactions: Carbamazepine has a Black Box Warning regarding the development of Stevens-Johnson Syndrome and toxic epidermal necrolysis in patients of Asian ethnicity. Carbamazepine has a Black Box Warning due to its potential to cause blood dyscrasias, some potentially lethal. Carbamazepine can depress the bone marrow and lead to leukopenia, thrombocytopenia, agranulocytosis, and aplastic anemia. For that reason, a baseline CBC, chemistry, LFTs, and TSH should be obtained, followed by periodic monitoring. Follow up studies should be more frequent initially, decreasing to every 3-4 months if the results remain normal. Other adverse reactions to carbamazepine include hepatic damage and impaired thyroid function. Less serious adverse events include drowsiness, dizziness, blurred vision, ataxia, nausea, vomiting, dry mouth, diplopia, and headache. The most common adverse effects observed in patients taking oxcarbazepine were dizziness, diplopia, somnolence, fatigue, N/V, ataxia, abdominal pain, tremor, and dyspepsia. Hyponatremia may occur, particularly in the first 3 months of therapy. Drug Interactions: Carbamazepine: 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 Abx (erythromycin, clarithromycin), isoniazid, and verapamil. 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. May decrease effectiveness of contraceptives containing ethinylestradiol and levonorgestrel. Monitoring: Patients should be monitored for seizure activity, severity, and duration. Adverse effects should be monitored, including CNS depression and suicidality or behavioral changes. Plasma carbamazepine levels should be monitored on a regular basis. Therapeutic range is 4-12 mcg/mL. Children and elderly patients may develop toxicity (HTN, tachycardia, ECG changes, stupor, agitation, nystagmus, urinary retention, respiratory depression, seizures, and coma) 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 any symptoms such as skin lesions, bruising, fever, or sore throat. 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 Stevens-Johnson Syndrome. Patients should report any mood changes or suicidal thoughts. Succinimides: Used to treat absence seizures (ethosuximide-Zarontin and methsuximide-Celontin). Pharmacodynamics: Decrease nerve impulses and transmission in the motor cortex. This produces a variety of effects, including an increase in the seizure threshold and reducing the EEG spike and wave pattern of absence seizures. Metabolism and Excretion: Metabolized in the liver and excreted

through the urinary tract, although a small amount of phensuximide is excreted in bile. Precautions and Contraindications: With careful monitoring of plasma levels, appear to be safe for use during pregnancy and are Pregnancy Category C. Contraindicated during lactation. Can cause 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. LFTs should also be obtained prior to instituting treatment. Adverse Drug Reactions: Most common are GI distress, which can be relieved by taking the medication with food or milk, and CNS depression (sedation, ataxia, and lethargy). Other adverse reactions include headache, rash, pruritus, suicidal thoughts, and mood changes. Cases of systemic lupus erythematosus have also been reported. Drug Interactions: The most significant drug interactions are those that increase CNS depression, such as alcohol, opioid agonists, benzodiazepines, and CNS depressants. May be given 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 effectives of oral contraceptives. Monitoring: Plasma levels should be monitored. Normal therapeutic range of ethosuximide is 40-100 mcg/mL; levels over 150 are considered toxic. The therapeutic range for methsuximide is 10- mcg/mL, with levels over 40 considered toxic. Should also monitor 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. 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 (p. 238) : The anti-epileptic drugs that affect GABA include benzodiazepines, gabapentin, topiramate, and tiagabine. The AEDs that affect the inhibitory neurotransmitter GABA are also used for pain, including neuropathic pain (gabapentin) and migraine (topiramate). Pharmacodynamics: Gabapentin is thought to be a GABA analogue that binds to unknown receptors in the brain; it does not bind to GABA receptors, nor does it mimic GABA. Topiramate may block sodium channels or potentiate GABA. Tiagabine may potentiate the action of GABA by blocking GABA reuptake into presynaptic neurons, allowing for more GABA to be available to bind to postsynaptic neuronal receptors. Precautions and Contraindications: Gabapentin: Should not be abruptly discontinued because it may precipitate status epilepticus; the dose should be decreased over at least a week. Increase the risk of suicidal behavior and ideation; patients should be monitored for emergence or worsening of depression, suicidal thoughts, or changes in behavior. Pregnancy Category C. Excreted in breast milk. Should be used in nursing women only if the benefits outweigh the risks. Topiramate: May have decreased concentrations of serum bicarbonate due to inhibition of carbonic anhydrase and increased renal bicarbonate loss, leading to a hyperchloremic metabolic acidosis. Serum bicarbonate should be monitored at baseline and periodically throughout therapy. An ocular syndrome consisting of acute myopia and angle closure glaucoma has been reported in adults and children taking topiramate. Patients who have eye pain or blurred vision should contact their provider immediately. A rare adverse effect of topiramate is oligohidrosis and hyperthermia. Patients, especially children should be monitored for decreased sweating and

hyperthermia. Use caution when prescribing drugs that predispose patients to heat-related disorders (anticholinergic drugs and carbonic anhydrase inhibitors). Must be gradually discontinued to avoid status epilepticus. Pregnancy Category D and has been found to be teratogenic in animal studies. Excreted in breast milk. Tiagabine: Patients without epilepsy who are prescribed tiagabine may have seizure or status epilepticus. Seizures have been reported in doses as low as 4mg/day. Most of these patients were taking other medications concomitantly such as antidepressants, antipsychotics, stimulants, or narcotics. Should not be abruptly discontinued because it may lead to increased seizure activity. Increased risk of suicidal ideation. Pregnancy Category C. Tetratogenic in fetal rats. Excreted in breast milk and not recommended in lactating women unless there are no other options for maternal treatment. Adverse Drug Reactions: Gabapentin: Most common CNS adverse effects of gabapentin include somnolence and dizziness. Less common CNS effects include ataxia and abnormal thinking. Peripheral edema may occur as well. Topiramate: Ataxia, parathesia, dizziness, somnolence, and difficulty concentrating. Anorexia, difficulty with memory, weight loss confusion, depression, mood problems, and psychomotor slowing. Increase in incident of kidney stones. Hyperammonemia with or without encephalopathy has been observed in clinical trials in patients taking topiramate both with and without concomitant valproic acid use. Metabolic acidosis. Tiagabine: Difficulty concentration, dizziness, light-headedness, somnolence, confusion, asthenia or lack of energy, and nervousness or irritability. Suicidal thoughts. Drug Interactions: Gabapentin does not interfere with the metabolism of commonly coadministered AEDs. Coadministration of naproxen increases absorption of gabapentin 12% to 15%. Gabapentin may increase the effects of alcohol and other CNS depressant drugs. Gabapentin may cause a false-

positive urinary protein level with the N-Multistik SG test. Monitoring: Seizure frequency, duration, and severity are monitored with all AEDs, as should mood changes, signs of depression, anxiety, and suicidal thoughts. Patients taking gabapentin, topiramate, and tiagabine do not require routine serum drug levels. Patients taking topiramate should have serum electrolyte, including sodium bicarbonate, monitored at baseline and periodically. Weight is monitored in all patients on topiramate as are body temperature and the ability to sweat. Serum ammonia levels should be drawn in any patient taking topiramate who exhibits any change in level of consciousness, unexplained lethargy, or vomiting. Patient Education: Missing doses may cause an increase in seizures. Patients should be warned about the possibility of suicidal thoughts, behavioral changes, somnolence, dizziness, or balance issues. Any signs of confusion, unexplained vomiting, or mental status change in patients taking topiramate require investigation for elevated ammonia levels or metabolic acidosis. Levetiracetam (p. 241): Antiepileptic indicated as an adjunct drug in the treatment of partial onset seizures in children and adults. Own unique drug class because it is chemically unrelated to other AEDs. Pharmacodynamics: It does not appear to inhibit or affect GABA, nor does it affect calcium or sodium currents or channels. Clinical trials have shown that levetiracetam inhibits burst firing without affecting normal neuronal excitability, suggesting that levetiracetam may prevent epileptiform burst firing and spread of seizure activity. Precautions and Contraindications: Increased risk of suicidal thoughts, depression, and changes in mood and behavior. Can also cause somnolence, fatigue, dizziness, and muscle coordination difficulties. Potential for withdrawal seizures if levetiracetam is abruptly stopped. May cause transient decrease in WBC count. Pregnancy Category C. Altered pharmacokinetics during pregnancy may affect Keppra serum concentrations; with decreased serum concentration reported during pregnancy. Approved for use in children age 1 month or older as adjunct therapy in partial seizures and as

adjunctive therapy in children 6 years and older with primary generalized tonic-clonic seizures. Adverse Drug Reactions: Somnolence, dizziness, behavioral changes (nervousness, anxiety, hostility, and emotional lability), alopecia, suicidal thoughts. Drug Interactions: Mostly unbound and does not use CYP450 enzymes for metabolism, thereby decreasing the likelihood of drug interactions. Does not interact with phenytoin, valproate, carbamazepine, gabapentin, lamotrigene, or phenobarbital. Does not interact with oral contraceptives or warfarin. Monitoring: Routine lab monitoring of patients on Keppra is not necessary. Efficacy is determined by decrease in the mean weekly frequency of partial onset seizures. Patient Education: Withdrawal seizures may occur if med is abruptly discontinued. Patient should be warned about potential for suicidal thoughts and actions, behavioral changes, somnolence, dizziness, or balance issues. Lamotrigine (p. 243): Used as adjunctive therapy in adults and children 2 or older in the treatment of partial seizures, primary generalized tonic-clonic seizures, and generalized seizures associated with Lennox-Gastaut syndrome. Approved for maintenance treatment of bipolar I disorder to delay occurrence of mood episodes in adults age 18 or older. Pharmacodynamics: It is thought that lamotrigine affects voltage-sensitive sodium channels and inhibits presynaptic release of glutamate and aspartate in the neuron. Precautions and Contraindications: Life threatening hypersensitivity reactions have occurred; these include multiorgan failure or dysfunction, hepatic abnormalities, and disseminated intravascular coagulation. Early symptoms of hypersensitivity, such as fever or lymphadenopathy, require evaluation and discontinuation if the reason for symptoms cannot be established. Blood dyscrasias, including neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported in patients taking lamotrigine. Black-Box Warning regarding Stevens-Johnson

Syndrome, toxic epidermal necrolysis, and rash-related death. Coadministration with valproate may increase the risk of rash. Increased risk of suicidal thoughts, depression, and mood changes. Lamotrigine should be withdrawn slowly over at least 2 weeks to prevent seizures. Pregnancy Category C, excreted in breast milk. Has low protein binding and maternal plasma levels may rise postpartum leading to elevated milk levels. Adverse Drug Reactions: Black Box Warning for life-threatening rashes such as Stevens-Johnson Syndrome. Multiorgan failure has been reported. Blood dyscrasias may occur. Increased suicidal thoughts or behavior. Abruptly stopping the med can cause withdrawal seizures. Drug Interactions: The enzyme inducers carbamazepine, phenytoin, phenobarbital, and primidone decrease lamotrigine concentrations by approximately 40%. Oral estrogen-containing contraceptives decrease lamotrigine levels by about 50%. If the patient is already taking lamotrigine and an oral contraceptive is started, the lamotrigine dose may need to be twice the normal dose. Rifampin decreases lamotrigine concentrations by 40% when taken concurrently. The most concerning interaction with lamotrigine is with valproate. When valproate is administered concurrently with lamotrigine there is an increased risk of SJS. Valproate also increases lamotrigine levels by more than 2-fold. Monitoring: Patients should be monitored closely for any newly occurring rash and for hypersensitivity reactions. CBC and differential should be monitored as well as renal and hepatic function. Watch for s/s of suicidal thoughts or mood changes. Patient Education: Tablets should not be crushed or chewed. Any rash needs to be reported to the provider immediately. Should be warned about possibility of suicidal thoughts and action and behavioral changes. TCAs (p.245): (amitriptyline, nortiptyline, imipramine, doxepin, trimipramine maleate, amoxapine, desipramine, protriptyline HCL, and clomipramine). TCAs cost less than other antidepressants, but have much more troublesome side effects. TCAs are less safe in treating depression in those who are at high risk for suicide, because overdose can be fata, whereas

the newer antidepressants are much less likely to be fatal. Pharmacodynamics: Act on neurotransmitters serotonin and norepinephrine by inhibiting their reuptake at the presynaptic neuron. However, they also act on histamine (contributing to drowsiness and weight gain) and acetylcholine. Loxapine, an active metabolite of amoxapine, acts as an antipsychotic by blocking the dopamine receptor. Precautions and Contraindications: Due to their direct alpha-adrenergic blocking effect and quinidine-like effect on the myocardium, TCAs are contraindicated with cardiovascular disorders.  Due to their acetylcholine blocking effect they should be used with caution in those who have glaucoma, prostatic hypertrophy, or urinary incontinence.  They should not be prescribed with MAOIs or to individuals who have demonstrated hypersensitivity in this class.  Pregnancy Category C.  Tardive dyskinesia and neuroleptic malignant syndrome have been reported and are more likely with amoxapine use due to its dopaminergic effect.  TCAs should be titrated gradually.  Nausea, headache, vertigo, malaise, and nightmares may occur after abrupt discontinuation of the drug.  Most significant risks related to TCA use are cardiac conduction disorder. Children and elderly at highest risk; therefore, baseline ECG and periodic monitoring should be performed.  Most common cardiovascular effect is sinus tachycardia due to the inhibition of norepinephrine reuptake and anticholinergic action.  TCAs contribute to slowing of depolarization of the cardiac muscle, contributing to prolongation of the QRS complex and the PR/QT intervals.  The index between therapeutic and toxic levels is narrow. Great care needs to be taken when prescribing for a person who is depressed and has suicidal ideas. Such patients need to be

monitored on a weekly basis.  Should be used with extreme caution if at all with the elderly. Due to their anticholinergic and norepinephrine effects, they can contribute to confusion, orthostatic hypotension, and falls. Adverse Drug Reactions: Anticholinergic adverse effects are common and can include dry mouth, constipation, urinary hesitancy or retention, blurred vision, sedation, orthostatic hypotension, weight gain, nausea and vomiting, gynecomastia, and changes in libido. Patients newly prescribed a TCA should be cautioned about safety in a situation in which mental alertness is required. Drug Interactions: The most significant drug interactions are those that increase the plasma level of the TCA and thereby increase the risk of cardiotoxicity, such as concurrent use of SRIs, cannabis, and sympathomimetics. Hyperprexia can occur with MAOIs and TCAs. Clinical Use: Efficacy in depression, panic disorder, enuresis, and chronic neuropathic pain. Due to their serotonergic and noradrenergic effects, they are especially helpful with anxiety disorders such as OCD (clomipramine) and panic disorder (imipramine). TCAs used to treat insomnia include doxepin, amitriptyline, and trazodone. Amitriptyline and imipramine are useful for neuropathic pain. MAOIs (p. 248): Infrequently used because safer drugs are available. Primarily reserved for the treatment of refractory unipolar depression. (phenelzine-Nardil, isocarboxazid-Marplan, tranylcypromine-Parnate, and selegiline-Emsam). Pharmacodynamics: Irreversibly inactive the enzymes that metabolize norepinephrine, serotonin, and dopamine, thereby increasing the bioavailability of these neurotransmitters. Prevent the breakdown of tyramine, found in many foods that are aged or fermented. Because tyramine is toxic to humans, contributing to rapid extreme HTN, these drugs require careful dietary restrictions. Selegiline transdermal (Emsam) requires dietary restriction only for doses above 9mg in 24 hours. Precautions and Contraindications: Contraindications include liver or

kidney disease, hypersensitivity, congestive heart failure or arteriosclerotic disease, and age over 60 years. They should not be used in patients who are impulsive, cognitively impaired, or cannot follow the necessary dietary restrictions. Pregnancy Category C. Excreted in breast milk. Not approved for use with children. Postural hypotension and suppression of myocardial pain may occur. Adverse Drug Reactions: Initial adverse effects may include insomnia, anxiety, and agitation as a result of the delayed metabolism of dopamine. In addition, dry mouth, blurred vision, urinary retention, and constipation occur because of anticholinergic activity. Most common side effects include dizziness, headache, insomnia, restlessness, and hypotension. Clinical Use: Because safer and more convenient drugs are available, the MAOIs are reserved for drug-resistant, refractory depressions. Drug and Food Interactions: Because MAOIs inhibit the metabolism of norepinephrine, HTN crisis can occur if they are administered concurrently with other drugs or foods that raise BP, including anticholinergics, sympathomimetics, stimulants, and foods containing tyramine. Tyramine is a precursor to dopamine, norepinephrine, and epinephrine. Foods that have been aged or fermented are rich in tyramine; therefore, dietary restriction apply during use or within 14 days following discontinuance of the MAOI.  Symptoms of HTN crisis include headache, heart palpitations, stiff or sore neck, chest tightness, tachycardia, sweating, and dilated pupils. Patient should remain standing until crisis is managed. Usual treatment is phentolamine 5mg IV and then 0.25-0.5mg IM every 4- hours.  The prolonged metabolism of norepinephrine and the pressor effect of other drugs can lead to interactions resulting in hypotension and HF.  The 14 day restriction also applies to initiating SRI or SNRI drug treatment. The increased amount of serotonin available due to inhibition of its metabolism by the MAOI leads to a risk of serotonin syndrome. As a result of other drug interactions, particularly with meperidine, CNS depression can also occur.  Avoid foods including cheese, yogurt, sour cream, aged meat and

meat products, dried fish and herring, alcohol, fermented vegetables such as sauerkraut, soy sauce, miso soup, bean curd, fava beans, avocados, bananas, raisins, caffeine, chocolate, and ginseng. Monitoring: Periodic LFTs should be performed and the drug discontinued if any abnormalities are found. SSRIS (p. 249): (fluoxetine-Prozac, paroxetine-Paxil, sertraline-Zoloft, fluvoxamine-Luvox, citalopram-Celexa, escitalopram-Lexapro, and vortioxetine-Brintellix). Pharmacodynamics: Affect the serotonin neurotransmitter in the synaptic cleft by blocking the serotonin transporter from returning remaining serotonin to the presynaptic cell. Each drug has different effects on other neurotransmitters. For example, fluoxetine affects dopamine that contributes to the development of side effects. Citalopram and escitalopram are probably the closest to a true serotonin selective reuptake inhibitor. Through this mechanism, more serotonin is available to bind with the postsynaptic receptors. Metabolism and Excretion: The SSRIs have a significant first-pass effect in the liver and are metabolized predominantly by the CYP450 system. Consideration of the half-life requires consideration of active metabolites as well as the possibility of inhibiting the SSRI’s own metabolism. For example, sertraline has a half life of 24-26 hours but inhibits the P450 2D enzyme that is also the substrate for metabolism.Excretion of the SSRIs is primarily by the kidneys. Precautions and Contraindications: Concurrent or within14 days of administration of MAOI. They should be used cautiously in patients with severe hepatic or renal impairment and should be avoided in the first and last trimesters of pregnancy. Pregnancy: Fluvoxamine and vortioxetine are Pregnancy Category C, paroxetine is Pregnancy Category D, and the others are Category B. High doses of SSRIs have caused malformations and fetal death in animal studies. Neonates exposed to SSRIs in the late third trimester have demonstrated complications soon after birth, requiring

respiratory support and tube feedings. Children: Paroxetine is not approved for use in children after studies indicated it is not effective for them. Vortioxetine has not been studied for safety or effectiveness in children. Suicidal Thoughts: There is a greater risk of suicide within the first 3 weeks of taking SSRIs and other antidepressants. This is related to the lag time in receiving the full therapeutic effect while there is an increase in neurocognitive activation early in initiation of the drug. Adverse Drug Reactions: Most common are nausea, vomiting, headache, light-headedness, dizziness, dry mouth, increased sweating, weight gain or loss, exacerbation of anxiety, and agitation. A significant adverse effect is serotonin syndrome (nausea, diarrhea, chills, sweating, hyperthermia, HTN, myoclonic jerking, tremor, agitation, ataxia, disorientation, confusion, and delirium), which occurs in the presence of excessive serotonergic activity. Therefore, maximum recommended doses must be adhered to, adjunctive combinations of serotonergic agents must be avoided, and adequate time for titration when changing from one serotonergic to another must be provided. A safe guideline when making such a change is to allow five half lives per dose decrease, so that titrating off a 20mg dose of paroxetine would need 5 days at 10 mg before starting another serotonergic drug. Withdrawal: In shorter half life drugs such as paroxetine, sertraline, citalopram, and escitaloproam can show withdrawal symptoms with just one missed dose. These symptoms are nausea, dizziness, and paresthesias such as electric shock sensations or visual tracers with eye movements. **Fluoxetine is the only SSRI that DOES NOT require gradual and slow tapering because of its long half life and active metabolites. A single dose of fluoxetine as the last step in tapering off other SSRIs is helpful to avoid withdrawal symptoms. Drug Interactions: The most significant occur with MAOIs and other serotonergic drugs. With MAOIs there needs to be at least a 14 day washout period before initiating an SSRI and at least a 21 day washout of fluoxetine before initiating an MAOI. Drugs that inhibit the P450 2D6 will increase the

effects of SRI, and many SRIs inhibit the 2D6 and 3A3/4 and will interact with drugs that use these enzymes as substrates. CNS depression can occur with alcohol, antihistamines, and opioids. St. John’s wort and/or SAMe may contribute to serotonin syndrome. SSRIs should NOT be prescribed with TCAs and require washout between drugs. The SSRI may increase the plasma level of the TCA, which increases the risk of cardiac conduction complications. Clinical Use: Citalopram: Depression, anxiety (off-label). Escitalopram: Depression, anxiety. Fluoxetine: Depression, OCD, bulimia, panic disorder. Fluvoxamine: OCD, social anxiety disorder, depression (off-label). Paroxetine: Depression, OCD, panic disorder, social phobia, PTSD, anxiety, PMDD. Sertraline: Depression, OCD, GAD, PMDD, PTSD, social anxiety disorder. Vortioxetine: Major depression Rational Drug Selection: The SRIs, except fluvoxamine, are indicated for the treatment of depressive, anxiety, and panic disorders; OCD; and bulimia. Fluvoxamine is FDA approved for the treatment of OCD, although it is likely to be as effective as the others for listed disorders. The FDA has approved the indication for premenstrual dysphoric disorder, PTSD, generalized anxiety disorder, and social phobia. Off-label uses include the treatment of anorexia, the depressive phase of bipolar disorder, chronic headaches and other types of pain, impulse control disorders, and trichotillomania. There should be at least telephone contact on a weekly basis with an agreement to notify the prescribed immediately if suicidal thoughts occur during the first 2-3 weeks of initiation. Patient Education: Drugs may take 3-4 weeks until their full therapeutic

benefits become evident and that the initial adverse reactions, commonly including nausea, intermittent light-headedness, sedation, muscle restlessness, and sleep disruptions should be minor and transient. Do not miss a dose or let the prescription run out before seeking a refill because of the withdrawal syndrome. SNRIs (p. 253): (venlafaxine-Effexor, desvenlafaxine-Pristiq, duloxetine- Cymbalta, Milnacipran-Savella, and levomilnacipran-Fetzima). Pharmacodynamics: Venlafaxine and duloxetine both block the serotonin and norepinephrine transporters, thereby inhibiting the reuptake of the neurotransmitter and increasing the availability to bind with the postsynaptic receptors. At lower doses (75mg), venlafaxine predominantly affects serotonin reuptake, contributing to greater reduction of anxiety more so than reduction of depressive symptoms. Duloxetine, however, appears to be more potent and equal serotonin and norepinephrine reuptake inhibitor than venlafaxine. For milnacipran and levomilnacipran it is thought that they inhibit reuptake of serotonin and norepinephrine. Metabolism and Excretion: Venlafaxine is metabolized by CYP450 2D with one active metabolite and two less active metabolites. Duloxetine is metabolized by CYP450 2D6 and 1A2. Venlafaxine has a half-life of 5 hours, and the active metabolite has a half-life of 11 hours. Steady state is achieved in 3-4 days. Duloxetine has a half-life of 12 hours, reaching steady state in 3 days. Both drugs are excreted mostly in the urine. Levomilnacipran is catalyzed primarily by CYP3A4 and is excreted renally 55% of milnacipran is excreted unchanged in the urine. Milnacipran is also metabolized into inactive metabolites that are excreted in the urine. Precautions and Contraindications: Increased suicidal thinking during the first few weeks of initiation and change in dosage of the medication. The patient must be monitored at least weekly and assessed for suicide risk each time. Pregnancy: Pregnancy Category C, no well controlled studies in pregnant women taking SNRIs. There have been reports of fetal

mortality and skeletal malformations in rats and rabbits. Neonates of women who took SNRIs in the 3 rd trimester have developed complications soon after birth requiring respiratory support and tube feeding. Both venlafaxine and duloxetine have been found in breast milk. No proven adverse effects to infants, but it is recommended that infants be monitored. Levomilnacipran is not recommended for nursing women. Glaucoma: Duloxetine may exacerbate narrow-angle glaucoma and should be used cautiously with these patients. Liver: Duloxetine has also shown increased serum transaminase levels and should not be used with patients with liver disorders. Adverse Drug Reactions: Most common side effects of venlafaxine and duloxetine include headache, somnolence, dizziness, insomnia, nervousness, nausea, dry mouth, constipation, and abnormal ejaculations. Appetite and weight decreases may occur. At higher doses both drugs may contribute to elevated blood pressure. Milnacipran: The most common adverse effect of milnacipran in clinical trials was nausea, other symptoms include headache, constipation, hot flush, dizziness, hyperhidrosis, and palpitations. Male patients reported ED, decreased libido, and ejaculation failure. Levomilnaciprain: Nausea, constipation, hyperhidrosis, tachycardia, ED, and urinary hesitation. Drug Interactions: CYP2D6: Drugs that inhibit CYP450 2D6 will interact with both venlafaxine and duloxetine, including fluoxetine and quinidine. With duloxetine, drugs that inhibit 1A2 will also interact, especially fluvoxamine and some quinolone ABX. Frequent alcohol use may affect liver function and therefore duloxetine should not be used with patients who abuse or are dependent on alcohol. CYP3A4: Drugs that inhibit CYP3A4 (ketoconazole) may require

adjustment of levomilnacipran dosage. Alcohol may cause an accelerated release of levomilnacipran ER, and it is recommended that levomilnacipran not be taken with alcohol. Serotonin Syndrome: May occur if milnacipran is used with a triptan. If a triptan is indicated, patients should be monitored closely. Catecholamines: Epinephrine and norepinephrine may cause paroxysmal HTN and dysrhythmias if coadministered with milnacipran because milnacipran inhibits the reuptake of norepinephrine. Digoxin: Patients taking milnacipran and digoxin have reported postural hypotension and tachycardia. Clonidine: Clonidine’s antihypertensive effect may be inhibited by milnacipran owing to inhabitation of norepinephrine reuptake. Clinical Use: Venlafaxine: Anxiety disorders such as generalized anxiety disorder, social phobia, and PTSD. Available in extended release form and immediate release form. The immediate release form must be taken at least BID and has uncomfortable discontinuation symptoms if doses are missed, including paresthesias, dizziness, nausea, and vomiting. The initial dose of extended release is 75mg/day, which is increased to 150-300mg/day in increments of 75mg every 4 days. Severely depressed patients may require higher dosage of 375-450mg/day in divided doses. Duloxetine: Neuropathic pain and overactive bladder. Initial dose is 20mg/day, which is increased to 60mg/day in increments of 20mg every 4 days. Levomilnacipran: Major depressive disorder, with the recommended dose range of 40mg-120mg daily. Patients should be started on 20mg once daily for 2 days, then increased to 40mg daily. The dose may be adjusted in increments of 40mg every 2 days until efficacy is

determined. Max dose 120mg/day. Withdrawal symptoms may be seen if discontinued abruptly; should be tapered off. Milnacipran: Fibromyalgia with recommended dose of 100mg/day (50mg BID). Withdrawal symptoms may be seen if stopped abruptly; should be tapered off. Patients may tolerate better if dose is titrated based on the following schedule: Day 1: 12.5mg once Days 2-3: 25mg/day (12.5mg BID) Days 4-7: 50mg/day (25mg BID) After Day 7: 100mg/day (50mg BID). Rationale Drug Selection: Both venlafaxine and dulocetine are more activating than the SSRIs and therefore are first-line drugs to use with patients who have the more sluggish types of depression. Venlafaxine also seems effective with adults who have both depression and ADHD. Milnacipran is only used for fibromyalgia. Monitoring: No specific serum level monitoring is available for the SNRIs. With duloxetine, liver function should be monitored once weekly, once monthly, biannually, and finally annually. Monitor for suicidal risk. Patient Education: Patients should be given written descriptions of side effects and ways to relieve them. Women who are pregnant need to be tapered off medication, especially in the third trimester. Sudden discontinuation usually leads to uncomfortable withdrawal symptoms; and patients need to request refill prescriptions in an adequate amount of time to avoid running out. Drug interactions: MAOIS. Table 15-13 (p. 249) Drug Interacting Drug Possible Effect Implications All MAOIs Anorexiants, venlafaxine, Increased serotonergic Avoid

SSRIs, bupropion, bromocriptine, L- dopa, L- tryptophan, MAO- B inhibitor, sumatriptan effect, possible serotonin syndrome CNS depressants, meperidine, antipsychotics Increased CNS depression Use cautiously in hazardous situations Amphetamines Buspirone, L- dopa, reserpine, tetrabenazine, guanethidine, meperidine Increased BP and possible hypertensive crisis Monitor BP; avoid if possible Antihypertensives, propoxyphene, meperidine, diuretics, nitroglycerin, dextromethorphan Hypotension agitation diaphoresis, vascular collapse Monitor BP; avoid concurrent administration if possible Insulin, sulfonylureas Hypoglycemia Monitor blood glucose and for s/s of hypoglycemia Carbamazepine Increased carbamazepine level Monitor level; use alternative anticonvulsant if possible TCAs and SSRIs Seizures and delirium Avoid Typical Antipsychotics (p. 256): The phenothiazine group of typical APs includes chlorpromazine (Thorazine), thioridazine (Mellaril), fluphenazine

(Prolixin), and fluphenazine decanoate, pephenazine (Trilafon), and trifluoperazine (Stelazine). Nonphenothiazine typical APs include haloperidol (Haldol) and haloperidol decanoate, thiothixene (Narvane), loxapine (Loxitane), and molindone (Moban). Pharmacodynamics: The typical APs block D2 receptors in the basal ganglia, hypothalamus, limbic system, brainstem, and medulla and reduce the positive symptoms of schizophrenia. Less effective in treating the negative symptoms of schizophrenia, such as flat affect, decreased motivation, withdrawal from interpersonal relationships, and poor grooming and hygiene. Clinical effectiveness occurs when 60-70% of D2 receptors are blocked. Too much dopamine blockade, however, leads to symptoms resembling those of parkinsonism. As D2 occupancy nears 78%, extrapyramidal symptoms (EPSs) are more prominent. Precautions and Contraindications: High potency drugs such as haloperidol and fluphenazine carry an increased risk of causing EPSs, whereas low potency drugs such as chlorpromazine and thioridazine carry less risk of EPSs but more risk of anticholinergic adverse reactions (dry mouth, constipation, urinary retention, blurred vision) and antiadrenergic effects (orthostatic hypotension). Contraindications include narrow-angle glaucoma, bone marrow depression, and severe liver or cardiovascular disease. These agents should be used cautiously in the presence of CNS tumors, epilepsy, DM, respiratory disease, and prostatic hypertrophy. Safety is not established in pregnancy and lactation. All antipsychotic medications have a Black-Box Warning regarding increased mortality in elderly patients with dementia-related psychosis and are not approved for the treatment of such patients. ADRs: A life threatening ADR is neuroleptic malignant syndrome (NMS), characterized by fever up to 107 degrees F, elevated pulse, diaphoresis, rigidity, stupor or coma, and acute renal failure. EPSs are among the most troublesome side effects and include pseudo parkinsonism (shuffling, pill rolling, cog wheeling, tremors, drooling, rigidity), akathisia (restlessness), dystonia (involuntary, painful movements), and tardive dyskinesia (involuntary buccolingual movements and difficulty speaking and swallowing). Antiparkinson, antihistamine, and anticholinergic drugs are

given to counter EPSs. Other side effects include sedation, weight gain, anticholinergic effects, photosensitivity, reduction of seizure threshold, orthostatic hypotension, sexual dysfunction, galactorrhea (milky nipple discharge), and amenorrhea. Clinical Use: Typical APs are more effective in reducing the positive than they are the negative symptoms of schizophrenia. May be more effective than atypical APs in treating very severe psychosis. Patients who need rapid control of agitation and dangerous psychosis can be treated with IV haloperidol. IM chlorpromazine also provides rapid sedation. Rational Drug Selection: The choice of a specific agent can be guided by past response to the medication, initial response, family history, and side effect profile of the medication. Usually EPSs can be decreased by the addition of drugs such as benztropine (Cogentin), diphenhydramine (Benadryl), trihexyphenidyl (Artane), and atenolol (Tenormin), or amantadine (Symmetrel). A decrease in the dose or a change to a different type of antipsychotic may also counter these effects. Some anticholinergic effects such as constipation can be addressed by nonpharmacological measures such as increased fluid intake and dietary bulk. The depot (injection, slow release, slow acting) or decanoate form of medication may be used if compliance is an issue. It is usually administered every 2-4 weeks. Monitoring: The motor function of individuals taking typical antipsychotics should be routinely assessed with the Abnormal Involuntary Movement Scale (AIMS), which rates various movements such as joint rigidity and balance numerically, thereby enabling the clinician, over time, to detect changes that represent early EPSs. May elevate prolactin levels because dopamine, which inhibits prolactin, is blocked. Patients should be monitored for the consequences of chronic prolactin elevation such as galactorrhea, gynecomastia, amenorrhea, and sexual dysfunction. Atypical Antipsychotics (p. 259): arpiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon). Address both the positive and negative symptoms of schizophrenia. Some of the superioirity in