Pharmacologic Therapy PDF

10/24/23, 3:56 PM Realizeit for Student Pharmacologic Therapy Many medications are available to control seizures, although the exact mechanisms of action are unknown. The objective is to achieve seizure control with minimal side effects. Medication therapy controls—rather than cures—seizures. Medi...

10/24/23, 3:56 PM Realizeit for Student Pharmacologic Therapy Many medications are available to control seizures, although the exact mechanisms of action are unknown. The objective is to achieve seizure control with minimal side effects. Medication therapy controls—rather than cures—seizures. Medications are selected on the basis of the type of seizure being treated and the effectiveness and safety of the medications. If properly prescribed and taken, medications control seizures in 70% to 80% of patients with seizures. However, 20% of patients with generalized seizures and 30% of those with focal seizures do not demonstrate improvement with any prescribed medication or may be unable to tolerate the side effects of medications (AANN, 2016a). Table 61-5 lists select anticonvulsant medications. Treatment usually starts with a single medication. The starting dose and the rate at which the dosage is increased depend on the occurrence of side effects. The medication levels in the blood are monitored, because the rate of drug absorption varies among patients. Changing to another medication may be necessary if seizure control is not achieved or if toxicity makes it impossible to increase the dosage. The medication may need to be adjusted because of concurrent illness, weight changes, or increases in stress. Side effects of anticonvulsant medications may be divided into three groups: idiosyncratic or allergic disorders, which manifest primarily as skin reactions; acute toxicity, which may occur when the medication is initially prescribed; and chronic toxicity, which occurs late in the course of therapy. The manifestations of drug toxicity are variable, and any organ system may be involved. For example, gingival hyperplasia (swollen and tender gums) can be associated with long-term use of phenytoin (Comerford & Durkin, 2020). Periodic physical and dental examinations and laboratory tests are performed for patients receiving medications that are known to have hematopoietic, genitourinary, or hepatic effects. Medical Management The management of epilepsy is individualized to meet the needs of each patient and not just to manage and prevent seizures. Management differs from patient to patient, because some forms of epilepsy arise from brain damage and others result from altered brain chemistry. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 1/17 10/24/23, 3:56 PM Realizeit for Student Drugs Used to Treat Seizure Disorders Barbiturates Phenobarbital is the prototype AED of the barbiturate class. Since its development in 1912, it has been used as an antiepileptic or sedative. Pharmacokinetics Phenobarbital, like all barbiturates, is absorbed rapidly through the gastrointestinal (GI) tract, usually within 1 hour. The oral drug has an onset of action of greater than 60 minutes and a duration of 10 to 12 hours. The intravenous (IV) form begins to act in 5 minutes and lasts approximately 6 hours. Phenobarbital has a half-life of 53 to 118 hours. In children, the half-life is 60 to 180 hours. The drug takes approximately 2 to 3 weeks to reach therapeutic serum levels and 3 weeks to reach a steady-state concentration. It is also lipid bound, which means that it crosses the placenta and is present in breast milk. Phenobarbital is metabolized in the liver and excreted by the renal system. Action Phenobarbital depresses the CNS by inhibiting the conduction of impulses in the ascending reticular activating system, thus depressing the cerebral cortex and cerebellar function. Use Prescribers order oral phenobarbital as a sedative and antiepileptic agent in the treatment of generalized tonic–clonic and partial seizures. Clinicians use the parenteral form to control acute seizures. Older adults may experience greater sedation due to decreased absorption and altered renal excretion of phenobarbital, placing them at risk for injury. These patients may also be at risk for adverse drug reactions related to altered metabolism and excretion. Use in Patients With Renal or Hepatic Impairment Patients who have decreased creatinine clearance (CrCl) may not be able to excrete phenobarbital adequately. Patients with hepatic impairment require a lower dose to prevent adverse effects associated with the drug. Use in Patients With Critical Illness When administering phenobarbital parenterally, it is best to do so in a critical care unit. This allows for constant monitoring of drug effects and early resuscitation in the event of respiratory arrest. Adverse Effects https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 2/17 10/24/23, 3:56 PM Realizeit for Student As with all AEDs, CNS depression, possibly cognitive impairment with sedation, is the most common adverse effect. Other reported conditions include somnolence, agitation, confusion, vertigo, and nightmares. The most severe adverse effect is Stevens-Johnson syndrome, a hypersensitivity reaction. Respiratory problems may occur, particularly with parenteral phenobarbital. Sudden withdrawal of the medication places the patient at risk for status epilepticus. The FDA has issued a BLACK BOX WARNING ♦ for phenobarbital. Patients who take phenobarbital are at risk for suicidal ideation. It is important to monitor the patient for statements that indicate depression and suicide. Contraindications Contraindications to phenobarbital include a known hypersensitivity to barbiturates. Other contraindications include liver failure, nephritis, porphyria, respiratory depression, pregnancy, or addiction to barbiturates. Caution is necessary in acute or chronic pain, lactation, fever, hyperthyroidism, diabetes, decreased liver renal function, and pulmonary and cardiac disease. Nursing Implications Preventing Interactions Several drugs interact with phenobarbital, increasing its effects ( Box 53.1 ). Opioid analgesics combined with phenobarbital result in enhanced CNS depression. When administered with phenobarbital, corticosteroids, doxycycline, estrogens, hormonal contraceptives, oral anticoagulants, and tricyclic antidepressants have an increased metabolism and a decreased effect. Oil of primrose increases the effects of phenobarbital. Combined with vitamin D, phenobarbital increases the hepatic metabolism of the vitamin. In addition, it reduces calcium absorption. Because of this, it may be necessary to take supplemental vitamin D and calcium. BOX 53.1 Drug Interactions: Phenobarbital Drugs That Increase the Effects of Phenobarbital Alcohol, chloramphenicol, diazepam, and monoamine oxidase inhibitors May increase central nervous system and respiratory depression Gabapentin and valproate Increase serum level Mephobarbital and primidone May increase serum level Administering the Medication Oral administration of phenobarbital may occur without regard to food. Parenteral administration may involve combining the medication with dextrose, lactated Ringer’s, or normal saline. However, if a precipitate forms, administration should not take place. Also, the drug is incompatible with acidic solutions, amphotericin B, chlorpromazine, diphenhydramine, insulin, and vancomycin. The nurse always https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 3/17 10/24/23, 3:56 PM Realizeit for Student injects IV phenobarbital into large veins at an infusion rate no faster than 60 mg/minute. Inadvertent intraarterial injection can cause spasm of the artery and gangrene. When administering the intramuscular (IM) drug, the nurse uses a large needle and injects into deep muscle. Assessing for Therapeutic Effects The ultimate goal of therapy with phenobarbital is to decrease seizure effects. The patient's EEG reveals decreased brain waves consistent with seizure activity. Assessing for Adverse Effects The nurse assesses for increases in CNS activity consistent with paradoxical excitation, as noted most often in the elderly. It is essential to assess respiratory problems such as hypoventilation, apnea, respiratory depression, laryngospasm, bronchospasm, and circulatory collapse, particularly in patients receiving parenteral phenobarbital. In addition, it is necessary to: Assess for bradycardia, hypotension, and syncope Assess the serum drug level for signs of toxicity or inadequate seizure treatment Assess for changes in the integumentary system indicative of the onset of Stevens-Johnson syndrome Assess complete blood count (CBC) and differential Assess blood urea nitrogen (BUN) and creatinine Patient Teaching Box 53.2 identifies patient teaching guidelines for phenobarbital. BOX 53.2 Patient Teaching Guidelines for Phenobarbital Understand that this drug is administered long term for the treatment of seizure activity. Take the medication as prescribed, and do not stop the medication abruptly. Have regular tests to determine serum levels of the drug. Change positions slowly. This drug may cause drowsiness or syncope. Do not drive or operate machinery with central nervous system depression. If you are of childbearing age, use two forms of contraception. Notify your prescriber about the development of rashes or skin eruptions. Wear a medical alert bracelet or necklace stating that you have a seizure disorder and naming the medications you take. Benzodiazepines Drugs belonging to this class have a broad range of uses; they may act as antidepressants, antiepileptics, or skeletal muscle relaxants. The benzodiazepines potentiate the effects of GABA by increasing the attraction to the receptor sites. The prototype of this class is diazepam (Valium, Diastat). Pharmacokinetics https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 4/17 10/24/23, 3:56 PM Realizeit for Student This varies with the preparation of diazepam. For the IV drug, the onset of action is 1 to 5 minutes, with a peak of 30 minutes and a duration of 15 to 60 minutes. For the oral drug, the onset of action is 30 to 60 minutes, with a peak of 1 to 2 hours and a duration of 3 hours. For the IM drug, the onset of action is generally within 15 to 30 minutes, with a peak of 30 to 45 minutes and a duration of 3 hours. For the rectal drug, the onset is rapid, with a peak of 1.5 hours and a duration of 3 hours. Its half-life, which is longer in newborns and the elderly, is 20 to 80 hours. Diazepam crosses the placenta and enters the breast milk. It is metabolized by the liver and excreted by the kidneys. Action The exact mechanism of action of diazepam is unknown. However, authorities believe that the drug acts primarily on the limbic system and reticular formation to produce skeletal muscle relaxation. It potentiates the effect of GABA by increasing the attraction of the medication to the receptor sites. Use IV diazepam is an adjunctive skeletal muscle relaxant administered for the treatment of severe recurrent convulsive seizures and status epilepticus. Oral diazepam is an adjunctive agent used for seizure disorders. Clinicians also order benzodiazepines such as diazepam for treatment of Lennox-Gastaut syndrome, a mixed seizure disorder that presents at approximately 2 years of age. Use in Older Adults It is necessary to reduce the dosage of diazepam administered to older adults because the drug has an extended half-life in this population. Use in Patients With Renal or Hepatic Impairment Diazepam is excreted by the kidneys after being metabolized in the liver. Thus, patients with renal or hepatic impairment should take reduced dosages of diazepam. Use in Patients With Critical Illness Patients with critical illness or those in debilitated states should take reduce dosages of diazepam. During IV administration, patients should receive oxygen. Adverse Effects CNS adverse effects of diazepam include depression, disorientation, restlessness, and confusion. In the first 2 weeks of treatment, paradoxical excitatory reactions may occur. The most serious cardiovascular adverse effect is cardiovascular collapse with bradycardia and hypotension. Also, potentially lifethreatening tachycardia may occur. In addition, in August of 2016, the FDA issued a BLACK BOX WARNING ♦. The combination of a benzodiazepine, such as diazepam, and an opioid medication depresses the CNS, resulting in serious adverse effects, including respiratory depression or death. Other reported problems include constipation, diarrhea, incontinence, urinary retention, and changes in libido. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 5/17 10/24/23, 3:56 PM Realizeit for Student Contraindications Patients with known hypersensitivity to benzodiazepines should not receive diazepam. Contraindications also include acute narrow-angle glaucoma, shock, coma, acute alcohol intoxication, and pregnancy. Nursing Implications Preventing Interactions Many medications and herbs interact with diazepam, decreasing or increasing its effects. QSEN Alert: Safety A review by the FDA has shown that the combination of (1) an opioid medication and (2) a benzodiazepine or any drug that suppresses the CNS results in serious adverse effects. Administering the Medication When preparing diazepam, the nurse does not mix the drug in plastic bags or tubing or combine it with other solutions. During administration, it is important to monitor pulse, blood pressure, and respiration. During parenteral administration, it is necessary to administer oxygen as well as to put the patient on bed rest for 3 hours. The nurse injects the IV form of the drug slowly into a large vein at 1 mL/minute—over at least 3 minutes in children—never intra-arterially or into small veins. Intra-arterial administration results in arterial spasm. Assessing for Therapeutic Effects When administering diazepam for a seizure disorder, the goal of therapy is to control seizure activity. When administering drug for status epilepticus, the goal is to eliminate the seizure activity. Assessing for Adverse Effects The nurse assesses for changes in cardiovascular status that could indicate hypotension, bradycardia, or tachycardia. He or she closely monitors the CNS response. In addition, the nurse assesses for alterations in elimination patterns. Patient Teaching Box 53.5 identifies patient teaching guidelines for diazepam. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 6/17 10/24/23, 3:56 PM Realizeit for Student BOX 53.5 Patient Teaching Guidelines for Diazepam Take the medication as prescribed and do not skip doses or stop therapy. Do not use alcohol or smoke. Alcohol is more potent when combined with diazepam. Smoking may constrict blood vessels, resulting in reduced elimination of the drug. Obtain instructions about the administration of rectal diazepam. Use two types of contraceptives if you are a woman of childbearing age and are sexually active. Ask your prescriber about safety and central nervous system (CNS) depression. Protect yourself from falls. Do not drive or operate machinery if you have CNS depression. Wear a medical alert bracelet or necklace stating that you have a seizure disorder and naming the medications you take. Gamma-Aminobutyric Acid Structural Analogs In 1993, the FDA approved gabapentin (Neurontin) for treatment of partial seizures. In May of 2002, the FDA approved it for treatment of postherpetic neuralgia pain. Pharmacokinetics and Action Gabapentin reaches its peak in 1 hour. It binds to sites in the brain that have a high affinity for gabapentin. The drug crosses the placenta and may enter the breast milk. Metabolism occurs in the liver and elimination takes place in the urine. Structurally, gabapentin is related to GABA. Its antiepileptic action is related to its ability to inhibit postsynaptic responses and block posttetanic potentiation. Use Prescribers order gabapentin as an adjunctive treatment for partial seizures and postherpetic neuralgia. There are many off-label uses, some of which include alcohol withdrawal, fibromyalgia, and neuropathic pain. Use in Patients With Renal Impairment Patients with impaired renal function require the following dosage adjustment depending on their CrCl. CrCl ≥ 60 mL/min: 30 to 1200 mg three times per day CrCl > 30 to 59 mL/min: 200 to 700 mg twice daily CrCl > 15 to 29 mL/min: 200 to 700 mg once daily CrCl 15 mL/min: 100 to 300 mg once daily CrCl < 15 mL/min: reduced daily dose in proportion to CrCl based on dose for CrCl of 15 mL/min (reduce dose by half [range: 50 to 150 mg/d]) Use in Patients With Hepatic Impairment https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 7/17 10/24/23, 3:56 PM Realizeit for Student Patients with impaired liver function require monitoring for elevated liver enzymes but do not require a dosage adjustment. Adverse Effects The most common adverse effects of gabapentin are associated with CNS depression and include dizziness, somnolence, insomnia, and ataxia. Other reported adverse effects are pruritus, dry mouth, dyspepsia, nausea, vomiting, and suicidal ideation. Contraindications Contraindications to gabapentin include a known hypersensitivity to the medication. Nursing Implications Preventing Interactions Antacids do not affect the serum level, but they decrease absorption of gabapentin when administered at the same time. The herb Ginkgo biloba decreases the effect of the drug. Administering the Medication The nurse ensures that gabapentin is taken orally. People may take the drug with food to prevent GI upset. Extended-release tablets should be swallowed whole and not crushed or chewed. Assessing for Therapeutic and Adverse Effects The nurses assess for the absence of partial seizures, the most important therapeutic effect. It is also necessary to assess changes in mood and personality in patients receiving gabapentin, as with all antiepileptic medications, because suicidal ideation is the result of CNS depression. The nurse assesses for CNS depression that could affect patient safety. Hydantoins The prototype antiepileptic of the hydantoin class is phenytoin (Dilantin). The oldest and most widely used AED, it is often the initial drug of choice, especially in adults. In addition to using it to treat seizure disorders, prescribers sometimes order it for cardiac dysrhythmias. Pharmacokinetics Phenytoin is highly bound (90%) to plasma proteins, and only the free drug (the fraction not bound to plasma albumin) is therapeutically active. The oral preparation, absorbed by the GI tract, has a slow onset of action, with a peak of 2 to 12 hours and a duration of 6 to 12 hours. The IV preparation has an onset of action of 1 to 2 hours with a rapid peak and a duration of 12 to 24 hours. The drug is metabolized by the liver and excreted in the urine. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 8/17 10/24/23, 3:56 PM Realizeit for Student Action Phenytoin stabilizes the neuronal membrane by delaying the influx of sodium ions into the neurons and preventing the excitability caused by excessive stimulation. Use Clinicians use phenytoin to control tonic–clonic seizures, psychomotor seizures, and nonepileptic seizures. They also use it to prevent seizure activity in patients during and following neurosurgery and brain injury. Use in Older Adults It is necessary to administer phenytoin cautiously to older adults. Elderly patients may have altered albumin levels, decreasing the affinity of phenytoin for albumin and causing displacement of the drug. Use in Patients With Renal Impairment Renal impairment or failure also causes displacement of the drug, placing the patient at risk for toxicity. Use in Patients With Hepatic Impairment Hepatic impairment results in altered albumin levels, decreasing the affinity of phenytoin for albumin and causing displacement of the drug. Use in Patients With Critical Illness The IV administration of phenytoin can result in cardiovascular collapse. It is important to assess blood pressure, pulse, and respirations. Monitoring the patient's cardiovascular status is necessary with the use of telemetry. Adverse Effects The most common adverse effects of phenytoin affect the CNS (e.g., ataxia, drowsiness, lethargy) and GI tract (e.g., nausea, vomiting). Gingival hyperplasia, an overgrowth of gum tissue, is also common, especially in children. Long-term use may lead to an increased risk of osteoporosis because of its effect on vitamin D metabolism. Serious reactions are uncommon but may include allergic reactions, hepatitis, nephritis, bone marrow depression, and mental confusion. Contraindications Contraindications to phenytoin include a known hypersensitivity to the hydantoins. Other conditions that require caution are seizures related to hypoglycemia, sinus bradycardia, heart block, and Stokes-Adams syndrome. In patients exhibiting seizures related to hypoglycemia, the primary treatment involves interventions to increase blood glucose (not the use of AEDs). Given the sedative effects associated with https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMqg… 9/17 10/24/23, 3:56 PM Realizeit for Student phenytoin, the patient is at risk for decreased heart rate; thus, frequent assessment of cardiac output is required if phenytoin is administered to these patients. Caution is also required when administering phenytoin to pregnant women. The risk of birth defects is a significant adverse effect. Nursing Implications Preventing Interactions Several medications interact with phenytoin, increasing or decreasing its effects. The effectiveness of corticosteroids, oral contraceptives, and nisoldipine is reduced when combined with phenytoin. Absorption of folic acid, calcium, and vitamin D is decreased with the administration of phenytoin. The herb Ginkgo biloba decreases the effect of the drug. Administering the Medication The injectable solution is highly irritating to tissues. Therefore, when giving the drug intravenously, it is necessary to use special techniques. Assessing for Therapeutic and Adverse Effects The nurse assesses for the absence of tonic–clonic and psychomotor seizures. The nurse assesses for the presence of a rash or skin eruption indicative of a hypersensitivity reaction; the presence of a skin eruption could be indicative of Stevens-Johnson syndrome. In addition, the nurse assesses for cardiovascular collapse with IV administration. Patient Teaching Box 53.8 identifies patient teaching guidelines for phenytoin. BOX 53.8 Patient Teaching Guidelines for Phenytoin Take the drug as prescribed and do not stop taking it abruptly. Take the medication with food to prevent gastric upset. Have serum drug levels checked as ordered by your prescriber. Maintain good oral hygiene (regular brushing and flossing) to prevent gum disease. Have regular dental checkups. Use contraception if you are of childbearing age and are sexually active. Wear a medical alert bracelet or necklace stating that you have a seizure disorder and naming the medications you take. Iminostilbenes The AEDs classified as the iminostilbenes include the prototype carbamazepine (Tegretol). Pharmacokinetics https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 10/17 10/24/23, 3:56 PM Realizeit for Student Carbamazepine is administered orally and absorbed by the GI tract. The onset of action is slow in both the oral and oral extended-release preparations. The regular oral preparation peaks in 4 to 5 hours, whereas the oral suspension peaks in 1.5 hours. The extended-release preparation peaks in 3 to 12 hours. The half-life of the drug is 12 to 17 hours. Carbamazepine induces the liver enzymes to increase metabolism and shorten the half-life over time. The variability of the half-life is related to autoinduction, which is usually complete in 3 to 5 weeks. The drug is metabolized by the liver and excreted in the feces and urine. It crosses the placenta and enters breast milk. Action The mechanism of action of carbamazepine is not understood, but its antiepileptic activity may be related to inhibition of polysynaptic responses that block posttetanic potentiation. Like the tricyclic antidepressants, the drug affects sodium channels within the cortical neurons. It has the ability to decrease action potential of the cell by inhibiting the influx of sodium into the cell. Use Clinicians use carbamazepine to prevent partial seizures with complex symptoms, as in patients with psychomotor and temporal lobe epilepsy. Prescribers order the drug for generalized tonic–clonic and mixed seizures, either partial or generalized. Patients who have uncontrolled seizures or CNS depression on other AEDs use it commonly. Use in Older Adults Carbamazepine may result in increased sedation and confusion. It is necessary to assess patient safety when using this medication in older adults. Use in Patients With Renal or Hepatic Impairment Caution is necessary with carbamazepine in patients with renal or hepatic impairment. The drug may cause hepatic cellular necrosis. Adverse Effects Carbamazepine may have serious adverse effects. The FDA has issued a BLACK BOX WARNING ♦ for carbamazepine concerning aplastic anemia and agranulocytosis. Other adverse effects include heart block, Stevens-Johnson syndrome, respiratory depression, hepatitis, massive hepatic cellular necrosis with total loss of intact liver tissue, and suicidal ideation. Contraindications Contraindications include a hypersensitivity reaction to carbamazepine or tricyclic antidepressants as well as administration of monoamine oxidase inhibitors. Caution is warranted in patients with a history of increased intraocular pressure; adverse hematologic reaction to other medications; cardiac, hepatic, or renal damage; and latent psychosis. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 11/17 10/24/23, 3:56 PM Realizeit for Student Nursing Implications Preventing Interactions Some medications interact with carbamazepine, increasing or decreasing its effects. Warfarin combined with carbamazepine produces greater anticoagulant effects. The herb Ginkgo biloba decreases the effect of the drug. Administering the Medication It is essential that carbamazepine not be administered within 14 days of use of a monoamine oxidase inhibitor. The nurse should tell patients never to crush or chew extended-release tablets. When the nurse administers carbamazepine suspension, he or she never mixes the preparation with other liquid medications because a precipitate may develop. The nurse ensures that the medication is taken with food to prevent GI upset. Assessing for Therapeutic Effects The nurse assesses the patient for absence of partial, tonic–clonic, and mixed seizures. Assessing for Adverse Effects There is a risk of aplastic anemia with the administration of carbamazepine, and hematologic assessments are most important. The nurse also assesses the integumentary system for StevensJohnson syndrome. It is also important that he or she assess hepatic function to check for hepatic adverse effects, including hepatic failure. In addition, to prevent toxicity, the nurse assesses serum levels as ordered. Patient Teaching Box 53.10 identifies patient teaching guidelines for carbamazepine. BOX 53.10 Patient Teaching Guidelines for Carbamazepine Take the medication with food. Do not chew or crush extended-release tablets. Do not stop taking the medication abruptly. Avoid alcohol, sleep agents, or over-the-counter medications. Have hematologic testing as ordered by your prescriber. Use contraceptives if you are of childbearing age and are sexually active. Wear medical alert bracelet or necklace stating that you have a seizure disorder and naming the medications you take. Report symptoms of bruising or bleeding immediately to your prescriber. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 12/17 10/24/23, 3:56 PM Realizeit for Student Histone Deacetylase Inhibitor Valproate (Depakote, Depakote ER), a histone deacetylase inhibitor, has been in use for approximately 40 years. A researcher identified its antiseizure ability while studying laboratory rats. The drug is synthesized from valeric acid, which is found in the herb valerian. Pharmacokinetics The onset of action for oral and parenteral valproate varies, and it reaches its peak in serum in 15 minutes to 4 hours. Parenteral valproate reaches a peak of action in 1 hour. The drug is metabolized by the liver and excreted by the kidneys. It crosses the placenta and enters breast milk. Action The action of valproate is not understood, but it is thought to produce antiepileptic activity by increasing GABA effects, thus decreasing electrical activity. Use Clinicians use valproate alone or in combination with other AEDs for the treatment of simple and complex absence seizures, and prescribers also order the drug for the treatment of seizures related to LennoxGastaut syndrome. Use in Older Adults When administering valproate to the elderly, it is necessary to adjust the dosage slowly. Use in Patients With Renal or Hepatic Impairment Caution is necessary in renal or hepatic impairment. Adverse Effects The most life-threatening adverse effects associated with valproate are pancreatitis and hepatic failure. Other significant adverse effects include altered bleeding time, thrombocytopenia, bruising, and hemorrhage. The most common GI adverse effects are nausea, vomiting, indigestion, diarrhea, and abdominal cramps. CNS adverse effects include sedation, tremor, emotional upset, weakness, and suicidal ideation, as well as brain atrophy. The FDA has issued several BLACK BOX WARNINGS ♦ for valproate. The first instructs patients to discontinue valproate at any sign of pancreatitis. The development of this condition is life threatening. The second points out that valproate is a teratogenic medication. Women of childbearing age should not take the drug without using two forms of birth control. The third instructs the patient to check for signs of bleeding or bruising. Altered bleeding times may occur. The nurse should tell the patient to have platelet counts, bleeding time determination, and clotting times according to the prescriber's orders. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 13/17 10/24/23, 3:56 PM Realizeit for Student Contraindications Contraindications to valproate include significant hepatic impairment as well as a hypersensitivity reaction to the drug. Nursing Implications Preventing Interactions Certain medications interact with valproate, decreasing or increasing its effects. Serum levels of phenobarbital, primidone, ethosuximide, diazepam, lamotrigine, and zidovudine may increase when these drugs are combined with valproate. The herb Ginkgo biloba decreases the effect of the drug. Administering the Medication The nurse dilutes the vial in 5% dextrose, 0.9% sodium chloride, or lactated Ringer's solution for IV administration. The reconstituted medication is stable for 24 hours and does not need to be refrigerated. Infusion should occur over 1 hour, no faster than 20 mg/min. IV administration is permissible only for 14 days, and a switch to an oral preparation is necessary. When administering Depakote to children, the nurse may open the tablets and sprinkle the contents on applesauce or pudding. It is important to note that Depakote ER should be swallowed whole and never crushed or chewed. Assessing for Therapeutic Effects The absence of simple and complex absent seizures is indicative that the therapeutic effects of the valproate have been attained. Assessing for Adverse Effects The nurse assesses the patient for signs and symptoms of pancreatitis, which include severe abdominal pain and back pain ( Hinkle & Cheever, 2018 ). He or she should also assess for bleeding and bruising. In addition, the nurse needs to assess the patient’s liver function tests routinely. Finally, it is necessary to assess the patient’s motor and cognitive function because of brain atrophy. Pyrrolidine Derivatives Levetiracetam (Keppra) is an AED that is effective in the treatment of a wide variety of seizure disorders. The use of levetiracetam has increased in treating seizure disorders in adults and children. It is approved for use in patients with myoclonic, tonic–clonic, and partial seizures. In the United States, an unlabeled use of levetiracetam is status epilepticus. A Swiss study showed that the drug was not as effective in treating status epilepticus as other approved agents. Pharmacokinetics Levetiracetam is administered orally or intravenously and is rapidly absorbed, reaching its peak in 1 hour. It is 10% protein bound with minimal hepatic metabolism. It is excreted in the urine and has a 7.1-hour half-life. The half-life in older adults is 9.6 hours. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 14/17 10/24/23, 3:56 PM Realizeit for Student Action Levetiracetam is chemically unrelated to other AEDs, and its mechanism of action is unknown. It inhibits abnormal neuronal firing but does not affect normal neuronal excitability or function. Use Clinicians use levetiracetam as adjunctive therapy for partial-onset and generalized tonic–clonic seizures. Use in Patients With Renal Impairment It is essential to reduce the dose in patients with impaired renal function, because the kidneys eliminate the majority of a dose (66%). A study conducted by Lima-Rogel et al. (2018) found that a neonate’s CrCl and weight affects the pharmacokinetic properties of levetiracetam. Adverse Effects and Contraindications Common adverse effects of levetiracetam include drowsiness, dizziness, and fatigue. Others include decreases in red and white blood cell counts, double vision, amnesia, anxiety, ataxia, emotional lability, hostility, nervousness, paresthesia, pharyngitis, and rhinitis. Postmarketing research noted that there is a risk of hepatic failure, acute renal failure, and multiorgan failure. There is also a risk for the development of Stevens-Johnson syndrome. Contraindications include a known hypersensitivity to the medication, pregnancy, lactation, and suicidal ideation. Nursing Implications Preventing Interactions CNS depressants combined with levetiracetam may increase symptoms of sedation. Administering the Medication It is essential that the IV preparation of levetiracetam be administered only on a short-term basis. The nurse tells patients not to crush extended-release forms of the drug. To prevent GI upset, the nurse administers the oral preparation with food. Although food may delay absorption, it does not affect the degree of absorption. The nurse monitors patients for psychosis and depression. Assessing for Therapeutic and Adverse Effects The nurse assesses the patient for symptoms of partial-onset and generalized tonic–clonic seizures, which should be absent. The nurse assesses the patient for ocular changes, CNS depression, and hematologic changes. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 15/17 10/24/23, 3:56 PM Realizeit for Student Sulfamate-Substituted Monosaccharides Topiramate (Topamax) is a sulfamate-substituted monosaccharide that was identified during a research project to develop a new antidiabetic agent. The drug has many unlabeled uses, including migraine prophylaxis, alcohol dependence, and weight loss. Pharmacokinetics Topiramate is absorbed in the GI tract and produces peak plasma levels about 2 hours after oral administration. The average half-life is about 21 hours, and steady-state concentrations are reached in about 4 days with normal renal function. The drug is 20% bound to plasma proteins. Topiramate is not extensively metabolized and is primarily eliminated via the kidneys. Action The mechanism of action of topiramate is not understood, but the antiepileptic action may be related to the blockage of sodium channels in neurons with sustained depolarization. This action increases GABA activity at the receptors, potentiating the inhibition of the neurotransmitters blocking excitatory neurotransmitters at the neuron receptor sites. Use Clinicians use topiramate as monotherapy in partial-onset or primary generalized tonic–clonic seizures as well as in adjunctive therapy for partial-onset or primary generalized seizures. Lennox-Gastaut syndrome is also an indication. In addition, prescribers order the medication as a preventive for migraine headaches. Use in Patients With Renal Impairment Patients with a CrCl less than 70 mL/min should receive one-half of the usual dose. Use in Patients With Hepatic Impairment Patients with elevated liver enzymes should receive reduced doses of topiramate, with the dosage increased slowly over time. It is necessary to monitor patients closely for increased hepatic effects. Adverse Effects and Contraindications Adverse effects of topiramate include CNS effects such as ataxia, somnolence, dizziness, and nystagmus, as well as GI adverse effects such as nausea and dyspepsia. The metabolic adverse effects of topiramate are a decreased serum bicarbonate and weight loss. Renal stones may develop. Other adverse effects are increased intraocular pressure and fatigue. A rare adverse effect is oligohydrosis, which is decreased sweating and hyperthermia. These adverse effects are more common in children and exposure to high environmental temperatures. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 16/17 10/24/23, 3:56 PM Realizeit for Student Contraindications include hypersensitivity to the drug and metabolic acidosis. Anticholinergic medications will increase the patient's risk of developing oligohydrosis and hyperthermia. Nursing Implications Preventing Interactions Several medications interact with topiramate, increasing or decreasing its effects. The drug decreases the effectiveness of oral contraceptives. The herb Ginkgo biloba decreases the effect of topiramate. Administering the Medication Topiramate has a very bitter taste. To prevent patients from tasting the bitterness, the nurse instructs them never to chew the medication. In addition, the nurse notes that it is necessary to store topiramate in a tightly closed container at 59°F to 86°F. Assessing for Therapeutic and Adverse Effects Patients are without symptoms of partial or generalized seizures. Those with Lennox-Gastaut syndrome have no seizure activity. The nurse assesses the patient for pain or discomfort related to kidney stones. The patient should have an annual eye examination to determine the onset of increased intraocular pressure. Monitor the patient's temperature and diminished sweating when exposed to high environmental temperatures. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUAYD8aTcEKqA9iFsBPwk2RFvtNozNlLKTVk0W5HMq… 17/17