MS11.pdf

10/24/23, 3:24 PM Realizeit for Student Pharmacologic Management The triptans, which are serotonin receptor agonists, are the most specific antimigraine agents available. These agents cause vasoconstriction, reduce inflammation, and may reduce pain transmission. The triptans in routine clinical us...

10/24/23, 3:24 PM Realizeit for Student Pharmacologic Management The triptans, which are serotonin receptor agonists, are the most specific antimigraine agents available. These agents cause vasoconstriction, reduce inflammation, and may reduce pain transmission. The triptans in routine clinical use include sumatriptan, naratriptan, rizatriptan, zolmitriptan, almotriptan, eletriptan, and frovatriptan (Comerford & Durkin, 2020). Many of the triptan medications are available in a variety of formulations, such as nasal sprays, inhalers, conventional tablet, disintegrating tablet, suppositories, or injections. The nasal sprays may be useful for patients experiencing nausea and vomiting (Tepper, 2019). The triptans are considered first-line treatment of the management of moderate to severe migraine pain. Best results are achieved with early use of triptans; oral dosing takes effect within 20 to 60 minutes of taking the drug and if needed may be repeated in 2 to 4 hours. Triptans are contraindicated in patients with ischemic heart disease. Careful administration and dosing instructions to patients are important to prevent adverse reactions such as increased blood pressure, drowsiness, muscle pain, sweating, and anxiety. Interactions are possible if the medication is taken in conjunction with St. John’s wort (Comerford & Durkin, 2020). Ergotamine preparations (taken orally, sublingually, subcutaneously, intramuscularly, by rectum, or by inhalation) may be effective in aborting the headache if taken early in the migraine process. They are low in cost. Ergotamine tartrate acts on smooth muscle, causing prolonged constriction of the cranial blood vessels. Each patient’s dosage is based on individual needs. Side effects include aching muscles, paresthesias (numbness and tingling), nausea, and vomiting. Pretreatment with antiemetic agents may be required. None of the triptan medications should be taken concurrently with medications containing ergotamine because of the potential for a prolonged vasoactive reaction (Comerford & Durkin, 2020). Other nonspecific medications are also used in the treatment of migraine and include NSAIDs, antispasmodic agents, and neuroleptics. Neuroleptic agents can be used alone or in conjunction with triptans and/or NSAIDs (Tepper, 2019). Prophylactic treatment of migraine includes the use of beta-blockers, antiepileptics, antidepressants, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers. Calcitonin gene– related peptides (CGRPs) have been found in increased levels in patients with migraine, and three CGRP monoclonal antibodies have been approved by the U.S. Food and Drug Administration (FDA) for migraine prevention: erenumab, fremanezumab, and galcanezumab (Hickey & Strayer, 2020). The medical management of an acute attack of cluster headaches may include 100% oxygen by facemask for 15 minutes, subcutaneous sumatriptan, or intranasal zolmitriptan (Hickey & Strayer, 2020). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 1/27 10/24/23, 3:24 PM Realizeit for Student The medical management of cranial arteritis consists of early administration of a corticosteroid to prevent the possibility of loss of vision due to vascular occlusion or rupture of the involved artery (Starling, 2018). The patient is instructed not to stop the medication abruptly, because this can lead to relapse. Analgesic agents are prescribed for comfort. Drug Therapy Cluster Headaches Treatment of a cluster headache involves subcutaneous sumatriptan and high-flow (100%) oxygen. Because the adverse effects of oxygen use are less than those of sumatriptan, high-flow oxygen may be administered for 15 minutes to determine effectiveness. Although oxygen may be effective in some patients, resuming the use of high-flow oxygen within a short period of time following relief of the headache should be avoided, because evidence shows that the frequency of cluster headaches may increase in some patients with overuse of high-flow oxygen. Ergot derivatives, lidocaine, and octreotide are also effective in the treatment of acute cluster headaches. Cluster headaches often are not treated as effectively as migraines. New guidelines have suggested that sumatriptan, administered subcutaneously, and zolmitriptan nasal spray, augmented by high-flow oxygen, may be effective. Steroid injections as well as calcium channel blockers may offer an option. Nonpharmacologic options include occipital and vagal nerve stimulation. Migraine Headaches Drug therapy to manage a migraine is guided mainly by several factors: (1) the severity of the attacks; (2) the presence of associated symptoms, such as nausea and vomiting; (3) the type of treatment setting (outpatient or inpatient); and (4) patient-specific factors, such as the patient’s medication preference and the presence of vascular risk factors. There are two specific courses of treatment for migraine headaches: abortive and preventive therapy. Abortive therapy is the administration of medications to treat the symptoms of migraine headache. Preventive therapy is the administration of medications to prevent the development of a migraine headache. Medications used in the treatment of migraine headaches are listed in Table 52.1. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 2/27 10/24/23, 3:24 PM Realizeit for Student The abortive agents administered for the treatment of migraine headaches include nonsteroidal antiinflammatory agents, acetaminophen–aspirin with caffeine medication, the ergot alkaloids, and the triptans (serotonin receptor [5-HT1B and 5-HT1D] agonists). Although it can produce nervousness and dizziness, caffeine was found to be an effective analgesic adjuvant in the acute treatment of migraine headache. The pharmacologic and nonpharmacologic treatment of long-term migraine is to reduce the frequency, severity, and disability. The initial pharmacotherapy for acute treatment of migraine is the administration of triptans subcutaneously. In addition, intravenous metoclopramide and prochlorperazine are also used in eligible adults who present to an emergency department with acute migraine. Metoclopramide has been shown to be highly effective in relieving migraine-associated symptoms. In children, ketorolac, administered intramuscularly or intravenously, is highly effective. Initial abortive therapy for women who experience acute menstrual migraines is the same as that for migraine occurring at any other time. People who suffer from migraines take preventive medications, which are discussed later in this module. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 3/27 10/24/23, 3:24 PM Realizeit for Student Tension-Type Headaches Acute therapy for tension-type headaches entails the use of nonpharmacologic methods such as rest, relaxation techniques, or stress reduction strategies as well as medication. Pharmacologic treatment of tension-type headaches includes acetaminophen, aspirin, and nonsteroidal anti-inflammatory agents (see Chap. 16). Studies have shown that tricyclic drugs can reverse the central sensitization and chronicity of these headaches. In addition, a meta-analysis of eight placebo-controlled clinical trials found that botulinum toxin type A led to a small decrease in number of headaches per month, although the result was not statistically significant. Nonsteroidal Anti-Inflammatory Agents Ibuprofen is the traditional prototype of the nonsteroidal anti-inflammatory agents (see Chap. 16). However, naproxen sodium is more commonly prescribed for the treatment of migraine headaches because it is more rapidly absorbed and produces more rapid analgesia. Thus, naproxen (Naprosyn) or naproxen sodium (Aleve) serves as the prototype described in detail in this module. Pharmacokinetics There are two types of naproxen: naproxen and naproxen sodium. Naproxen has an onset of action of 1 hour, a peak of action of 2 to 4 hours, and duration of action of 7 hours or less. Naproxen sodium has an onset of action of 1 hour, a peak of action of 1 to 2 hours, and the same duration of action as naproxen. Metabolism of both agents occurs in the liver, and they have a half-life of 12 to 15 hours. Excretion is in the urine. Naproxen and naproxen sodium cross the placental barrier and enter the breast milk. Action Naproxen is a nonselective inhibitor of cyclooxygenase resulting in the inhibition of prostaglandin synthesis of COX-1 and COX-2. Naproxen sodium improves the solubility of naproxen through faster absorption and rapid onset of action. Use Prescribers order naproxen sodium to reduce the pain resulting from an acute migraine headache. Table 52.2 presents dosage information for naproxen and related drugs. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 4/27 10/24/23, 3:24 PM Realizeit for Student Use in Older Adults Older people should not take more than 200 mg of naproxen sodium every 12 hours. Use in Patients With Renal Impairment Caution is necessary with the administration of naproxen sodium in patients with renal disease because the renal system excretes the drug. It should be avoided in patients with advanced renal disease. Use in Patients With Hepatic Impairment Caution is warranted with the administration of naproxen sodium in patients with hepatic impairment because the site of metabolism is the liver. Adverse Effects The most severe adverse effects of naproxen sodium include bronchospasm and anaphylaxis. Gastrointestinal (GI) adverse effects include GI bleeding, nausea, dyspepsia, and GI pain. The U.S. Food and Drug Administration (FDA) has issued a BLACK BOX WARNING ♦ stating that naproxen sodium https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 5/27 10/24/23, 3:24 PM Realizeit for Student may put patients at increased risk for cardiovascular events and GI bleeding. Contraindications Contraindications to naproxen or naproxen sodium include a known allergy to aspirin or other nonsteroidal anti-inflammatory drugs as well as pregnancy and lactation. It is important to administer the medication cautiously to patients with asthma, cardiovascular dysfunction, hypertension, GI bleeding, and peptic ulcer. Nursing Implications Preventing Interactions The administration of naproxen sodium with lithium results in increased lithium levels and the risk of lithium toxicity. Assessing for Therapeutic Effects Following the administration of naproxen or naproxen sodium, the patient should exhibit diminished pain. The nurse assesses the patient's pain level using a pain scale. Assessing for Adverse Effects The nurse assesses the patient for GI upset, dyspepsia, or bleeding. He or she also assesses pulmonary function and lung sounds for bronchospasm or anaphylactic reaction. Patient Teaching Box 52.1 identifies patient teaching guidelines for naproxen sodium. BOX 52.1 Patient Teaching Guidelines for Naproxen Sodium Take the medication with meals to prevent gastrointestinal upset. Take medication as prescribed. Do not cut, crush, or chew tablets. Do not operate machinery if dizziness or drowsiness occurs. Report sore throat, fever, rash, itching, edema, visual changes, and black, tarry stools to your health care provider. Other Drugs in the Class Migraine sufferers often seek treatment in the emergency department when the more commonly used abortive therapies are ineffective. In the emergency setting, ketorolac tromethamine is the most frequently administered intravenous drug. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 6/27 10/24/23, 3:24 PM Realizeit for Student Acetaminophen, Aspirin, and Caffeine The combination of acetaminophen, aspirin, and caffeine may be effective for the treatment of headaches. In the United States, brand names include Anacin Advanced Headache Formula, Excedrin Extra Strength, Excedrin Migraine, and Goody’s Extra Strength. Pharmacokinetics To understand the pharmacokinetics of acetaminophen, aspirin, and caffeine, it is important to review each medication individually. Acetaminophen reaches a peak of action in 0.5 to 2 hours and possesses a 1- to 3-hour half-life. It crosses the placental barrier and enters the breast milk. The drug is metabolized in the liver and excreted in the urine. Aspirin has an onset of action of 5 to 30 minutes, reaches a peak of action in 15 to 120 minutes, and has a duration of action of 3 to 6 hours. The half-life of aspirin is 15 minutes to 12 hours. The drug is absorbed in the stomach and metabolized in the liver. Caffeine has an onset of action of 15 minutes and reaches a peak of action in 15 to 45 minutes. It readily crosses the placental barrier and enters breast milk. Like acetaminophen and aspirin, caffeine is metabolized in the liver. It is eliminated by the kidneys. Action Acetaminophen may act as an analgesic, and its mechanism of action is unknown. Aspirin has the ability to inhibit the synthesis of prostaglandins, which are a mediator of inflammation. Caffeine increases calcium permeability in the sarcoplasmic reticulum to promote the accumulation of cyclic adenosine monophosphate (cAMP) and block the adenosine receptors, stimulating the CNS, cardiac activity, gastric acid secretion, and diuresis. It causes constriction of the blood vessels, which is known as vascular constriction . Migraine headaches result from the vasodilation of blood vessels. In addition, caffeine increases the effectiveness of acetaminophen and aspirin by approximately 40%.. Use Acetaminophen–aspirin–caffeine products are administered to reduce pain related to migraine or tension headache. Table 52.3 presents oral dosage of information for these combination products. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 7/27 10/24/23, 3:24 PM Realizeit for Student Use in Children Children older than 12 years of age may receive the adult dose of the combination agent. Use in Patients With Hepatic Impairment People with hepatic impairment should not receive this combination agent on an ongoing basis. They may not metabolize acetaminophen in this combined medication effectively, leading to hepatotoxicity. Adverse Effects Each component of the combination medication has adverse effects, which will be addressed individually. Acetaminophen may result in headache, chest pain, dyspnea, myocardial damage with doses of 5 to 8 g/d, and hepatic impairment. Aspirin may lead to GI effects such as dyspepsia, heartburn, and epigastric discomfort, as well as hematologic effects such as occult blood loss and hemostatic defects. Aspirin toxicity involves respiratory alkalosis, tachypnea, hemorrhage, excitement, confusion, seizures, tetany, cardiovascular collapse, and metabolic acidosis. Caffeine may result in excitement, insomnia, restlessness, tremors, headaches, and lightheadedness, as well as cardiovascular effects such as tachycardia, hypertension, extrasystole, and palpitations. Contraindications https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 8/27 10/24/23, 3:24 PM Realizeit for Student Contraindications to acetaminophen include a known allergy to the drug. Caution is necessary in impaired hepatic function, chronic alcoholism, pregnancy, and lactation. Contraindications to aspirin include a known hypersensitivity to the drug or other anti-inflammatory agents. Vigilance is warranted with renal impairment. Contraindications to caffeine include duodenal ulcers, diabetes, and lactation. Caution is essential in pregnancy, renal and hepatic impairment, and cardiovascular disease. Nursing Implications People most commonly take the acetaminophen–aspirin–caffeine in the home setting. It is important to be familiar with all aspects of each medication to maintain medication safety. Preventing Interactions Several drug–drug interactions may occur with acetaminophen–aspirin–caffeine combinations. Box 52.2 names the specific medications that increase or decrease the effects of each of the medications in the combined drug. Other drug–drug interactions include the following: Oral anticoagulants combined with acetaminophen increase hypothrombinemic effects. Aspirin combined with sulfonylureas and insulin results in greater glucose-lowering effects. Valproic acid combined with aspirin puts patients at risk for seizure activity secondary to protein receptor site displacement. Spironolactone or furosemide combined with aspirin leads to decreased diuretic effects. Theophylline or clozapine combined with caffeine increases the serum levels of theophylline or clozapine. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 9/27 10/24/23, 3:24 PM Realizeit for Student BOX 52.2 Drug Interactions: Acetaminophen, Aspirin, and Caffeine Drugs That Increase the Effects of Acetaminophen Alcohol, barbiturates, carbamazepine, hydantoins, rifampin, sulfinpyrazone Increase the risk of hepatotoxicity Drugs That Increase the Effects of Aspirin Alcohol, anticoagulants, nonsteroidal anti-inflammatory agents Increase the bleeding risk Carbonic anhydrase inhibitors Increase the risk of salicylate toxicity Drugs That Increase the Effects of Caffeine Cimetidine, hormonal contraceptive, disulfiram, ciprofloxacin, mexiletine Increase the central nervous system effects Drugs That Decrease the Effects of Aspirin Acetazolamide, methazolamide, antacids, alkalinizers Decrease the salicylate levels Drugs That Decrease the Effects of Caffeine Nicotine Produces vasoconstriction Oral anticoagulants combined with acetaminophen increase hypothrombinemic effects. Aspirin combined with sulfonylureas and insulin results in greater glucose-lowering effects. Valproic acid combined with aspirin puts patients at risk for seizure activity secondary to protein receptor site displacement. Spironolactone or furosemide combined with aspirin leads to decreased diuretic effects. Theophylline or clozapine combined with caffeine increases the serum levels of theophylline or clozapine. The concomitant administration of caffeine and guarana, ma huang, and ephedra is not recommended. Assessing for Therapeutic Effects Following the administration of the acetaminophen–aspirin–caffeine combination, the patient should exhibit diminished pain. The nurse assesses for pain using a pain scale. Assessing for Adverse Effects The nurse assesses for hepatotoxicity, allergic reaction, fluid and electrolyte imbalance, hypoglycemia, agitation, and cardiovascular effects. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 10/27 10/24/23, 3:24 PM Realizeit for Student Patient Teaching Box 52.3 identifies patient teaching guidelines for acetaminophen–aspirin–caffeine combinations. BOX 52.3 Patient Teaching Guidelines for Acetaminophen–Aspirin–Caffeine Combinations Never exceed the recommended dosage of acetaminophen–aspirin–caffeine combinations. Avoid the use of over-the-counter and prescription forms of medications that contain acetaminophen. Keep the medication out of the reach of children. Take the drug with food or after meals if possible. Do not stop caffeine abruptly. Do not consume foods high in caffeine. Report the following conditions to your health care provider: Any signs and symptoms of bleeding Ringing in the ears, dizziness, confusion, abdominal pain, dyspnea, nausea, and vomiting Abnormal heart rate and palpitations Ergot Alkaloids The ergotamine preparations are administered for abortive therapy for migraine headaches, although they have been largely replaced by the triptans (see later discussion). Clinical studies have shown that oral ergotamine plus caffeine is less effective than triptans for acute migraine. The prototype medication is ergotamine tartrate (Ergomar), an alpha-adrenergic antagonist. Pharmacokinetics Ergotamine has a variable rate of absorption and onset of action. The peak of action is 0.5 to 3 hours. The half-life of ergotamine is 2 hours, but the effects of the medication can continue for 24 hours. The medication is metabolized by the cytochrome P450 enzyme CYP3A4 in the liver and excreted in the bile. Ergotamine is excreted in the breast milk and may cause vomiting, diarrhea, and changes in heart rate and blood pressure in the nursing infant. It has caused fetal growth retardation in animal studies. Action Ergotamine produces stimulation of the cranial and peripheral vascular smooth muscles while depressing the effects of the central vasomotor centers. It is a partial agonist and antagonist that act against tryptaminergic, dopaminergic, and alpha-adrenergic receptors to constrict the cranial and peripheral blood vessels. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 11/27 10/24/23, 3:24 PM Realizeit for Student Use Prescribers order ergotamine individually or in combination with caffeine to prevent or stop migraine, cluster, or vascular headaches. Children, as well as people with renal or hepatic impairment, should not take ergotamine. Table 52.4 gives dosage information for the ergot alkaloids. Use in Older Adults It is necessary to administer ergotamine cautiously in older adults because of the drug's vasoconstrictive properties and cardiovascular adverse effects. Adverse Effects The cardiovascular adverse effects of ergotamine include absence of pulse, bradycardia, cardiac valvular fibrosis, cyanosis, edema, heart rhythm changes, gangrene, hypertension, ischemia, precordial distress, chest pain, tachycardia, and vasospasm. Musculoskeletal adverse effects include muscle pain, https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 12/27 10/24/23, 3:24 PM Realizeit for Student numbness, paresthesia, and weakness. Other side effects may include vertigo, nausea, vomiting, itching, pulmonary fibrosis, and genitourinary retroperitoneal fibrosis. Contraindications Contraindications of ergotamine include a known hypersensitivity reaction to the drug or its components. Additional contraindications are the existence of peripheral vascular disease, hepatic and renal disease, coronary artery disease, hypertension, and sepsis. The FDA has issued a BLACK BOX WARNING ♦ stating that ergotamine is contraindicated with potent inhibitors of CYP3A4 medications. These drugs include the protease inhibitors, azole antifungals, and some macrolide antibiotics. Concomitant use of these medications results in the risk of vasospasm, producing serious or life-threatening cerebral and limb ischemia. Pregnancy and lactation are also contraindications to the use of ergotamine. Nursing Implications Preventing Interactions Ergot derivatives may increase the hypertensive effects of alpha 1 agonists. Ergotamine is metabolized by the cytochrome P450 enzyme CYP3A4 in the liver; therefore, it is important to avoid all CPY3A4 inhibitors. In addition, many medications and foods interact with ergotamine, increasing its effects ( Boxes 52.4 and 52.5). BOX 52.4 Drug Interactions: Ergotamine Drugs That Increase the Effect of Ergotamine Alpha and beta-adrenergic blockers, sympathomimetics Have additive vasoconstrictive effects Erythromycin, troleandomycin Increase the risk of peripheral vasospasm Rizatriptan, sumatriptan, zolmitriptan Increase the risk of coronary ischemia Azole antifungals, nefazodone, fluoxetine, fluvoxamine, amprenavir, delavirdine, efavirenz, indinavir, nelfinavir, ritonavir, saquinavir Inhibit ergotamine metabolism and increase toxicity Sibutramine, dexfenfluramine, nefazodone, fluvoxamine Increase the risk of muscle rigidity, also known as serotonin rigidity Clarithromycin, boceprevir, cobicistat, crizotinib, posaconazole Increase the serum concentration of ergotamine https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 13/27 10/24/23, 3:24 PM Realizeit for Student BOX 52.5 Herb and Dietary Interactions: Ergotamine Foods That Increase the Effect of Ergotamine Cola Coffee Tea Grapefruit juice Administering the Medication Administration of ergotamine is sublingual, and the tablet should be dissolved under the tongue. It is important that tablets not be crushed, chewed, or swallowed whole. Patients should not drink, eat, or smoke while the medication is being dissolved. Assessing for Therapeutic Effects The nurse assesses for a decrease in headache pain. Assessing for Adverse Effects Following administration of ergotamine, the nurse assesses for cardiovascular adverse effects. Measurement of pulse and blood pressure is essential. The nurse also assesses for vertigo, muscle pain, numbness, paresthesia, and weakness, as well as for signs and symptoms of a hypersensitivity reaction to ergotamine. It is important to assess the patient’s fluid and electrolyte status if the patient is suffering from nausea and vomiting. In addition, the nurse assesses the patient’s urinary elimination due to the adverse effect of retroperitoneal fibrosis in which the patient develops an obstruction of the ureters. Patient Teaching Box 52.6 identifies patient teaching guidelines for ergotamine. BOX 52.6 Patient Teaching Guidelines for Ergotamine Take ergotamine or ergot alkaloids at the onset of the migraine headache. Notify the prescriber if the migraine attacks occur more frequently or are not relieved. Rest in a dark room for 2 to 3 hours after taking the medication. Provide information on adverse effects and notify the prescriber if muscle pain, weakness of extremities, changes in heart rate, nausea, or vomiting develops. Never crush, swallow, or chew tablets. Do not increase dose unless indicated by the prescriber. Other Drugs in the Class https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 14/27 10/24/23, 3:24 PM Realizeit for Student Dihydroergotamine mesylate reduces the rate of serotonin-induced platelet aggregation and has a weaker vasoconstrictive action than ergotamine. It has a greater adrenergic blocking activity to relieve migraine headaches. Triptans Triptans are serotonin 5-HT1B and 5-HT1D agonists that affect the pathophysiologic mechanism of migraine or cluster headaches, thus relieving the associated symptoms. The mechanism of action of the triptans, although similar to that of the ergot alkaloids, has a more selective serotonin agonist receptor profile, and it does not interact with adrenergic and dopaminergic receptors. In addition, the advantage of the administration of triptans over the ergot alkaloids is that these medications can be easily taken by patients during their daily lives. The prototype triptan is sumatriptan (Imitrex, Onzetra Xsail, others). Pharmacokinetics The oral preparation of sumatriptan has an onset of action of 60 to 90 minutes and a peak of action of 2 to 4 hours. The onset of action of intranasal sumatriptan is rapid, with a peak of action of 90 minutes. The onset of action of subcutaneous sumatriptan varies, with a peak of action of 5 to 20 minutes. Sumatriptan is widely distributed and is 10% to 20% protein bound. Its therapeutic half-life is 115 minutes. Metabolism occurs in the liver. Excretion is in the urine, with excretion of the oral preparation in the feces. Sumatriptan crosses the placenta and enters the breast milk. Action Sumatriptan binds to the serotonin receptors 5-HT1D, producing vascular constriction of the cranial blood vessels and relieving the pain of a migraine headache. It also relieves the nausea, vomiting, photophobia, and phonophobia that accompany the migraine headache. Use Health care providers use sumatriptan to treat acute migraine headache pain with or without an aura. They also use it to treat cluster headaches. Older adults should not take sumatriptan and other triptans. Table 52.5 gives dosage information for the triptans. Table 52-5 DRUGS AT A GLANCE: Triptans https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 15/27 10/24/23, 3:24 PM Realizeit for Student Use in Patients With Renal Impairment Caution is necessary when administering sumatriptan to patients with impaired renal function because elimination takes place in the renal system. Use in Patients With Hepatic Impairment https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 16/27 10/24/23, 3:24 PM Realizeit for Student Caution is also warranted when administering sumatriptan to patients with impaired hepatic function because metabolism takes place in the liver. Adverse Effects CNS adverse effects of all sumatriptan preparations are dizziness, vertigo, headache, anxiety, malaise, myalgia, and fatigue. Cardiovascular adverse effects include alterations in blood pressure and chest pain as well as the most severe cardiovascular adverse effect, shock. The nasal administration of sumatriptan produces nausea, nasal and throat irritation, and a bad taste in the mouth. The injectable form of the drug may cause injection site discomfort. Contraindications Contraindications include a history of hypersensitivity reactions to the drug. Other contraindications are existing cerebrovascular or peripheral vascular syndromes. Nursing Implications Preventing Interactions QSEN Alert: Safety It is important to ask the patient about the recent administration ergot alkaloids. The ergot alkaloids should not be given within 24 hours of the administration of triptans. The combination of ergotcontaining drugs and the triptans results in cardiac ischemia. Also, administration of monoamine oxidase (MAO) inhibitors leads to increased serum levels of sumatriptan and sumatriptan toxicity. Two weeks after an MAO inhibitor has been discontinued, it is permissible to give sumatriptan in combination with the MAO inhibitor. In addition, administration of the herb St. John's wort with triptans results in triptan toxicity. Administering the Medication It is important to administer sumatriptan at the onset of migraine symptoms. Although it is appropriate to administer a second dose of the oral preparation when symptoms return, this should not occur earlier than 2 hours after the first tablet is taken. Dosages should not exceed 100 mg in a single dose or 200 mg/d. It is necessary to administer the oral preparation with fluids and the intranasal preparation as a single dose of one spray in each nostril. With the subcutaneous preparation, administration just below the skin as soon as symptoms develop is best. If relief does not occur or if symptoms reappear, a second injection may follow 1 hour or longer after the first one. A person may have two injections in 24 hours. With the administration of all sumatriptan preparations, it is necessary to monitor the blood pressure for hypertension. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 17/27 10/24/23, 3:24 PM Realizeit for Student Assessing Therapeutic Effects The nurse assesses for diminished pain and ultimate relief of migraine headaches. Assessing for Adverse Effects The nurse assesses for increased blood pressure, as well as chest pain, shock, dizziness, and vertigo. With subcutaneous administration, the nurse also assesses for irritation at the injection site. Patient Teaching Box 52.7 identifies patient teaching guidelines for sumatriptan. BOX 52.7 Patient Teaching Guidelines for Sumatriptan Provide instruction about the administration of subcutaneous sumatriptan or use of the autoinjector. Do not administer more than two injections in 24 hours. Inject just below the skin as soon as symptoms are noted. Properly dispose of the autoinjector, syringes, and needles. Administer nasal spray as a single dose; repeat if necessary in 2 hours. Do not administer the medication if you are pregnant. Do not operate machinery after the administration of sumatriptan. Report symptoms of hypersensitivity such as heat, flushing, tiredness, and feeling sick to your health care provider. Other Drugs in the Class Almotriptan (Axert) is similar in action to other triptans; however, it can be administered with MAO inhibitors. After oral administration, it has a variable onset of action and a peak of action of 1 to 3 hours. Prior to administering almotriptan, it is necessary to determine whether the patient has received any ergot alkaloids in the past 24 hours. Eletriptan (Relpax) has a rapid onset of action, with a 1.5- to 2-hour peak of action. It is administered orally in 20- or 40-mg doses. It is important to ensure the patient has not taken an ergot-containing compound within 24 hours and to control the environment for light and sound. The drug is usually well tolerated and causes no major harm; however, any elevation in blood pressure or chest pain requires discontinuation of the medication. Frovatriptan (Frova) has a variable onset of action and reaches the peak of action in 2 to 4 hours. It interacts unfavorably with selective serotonin reuptake inhibitors such as fluoxetine, fluvoxamine, paroxetine, and sertraline, producing weakness, hyperreflexia, and diminished CNS effects such as alertness. Frovatriptan may lead to serotonin syndrome, and a potentially life-threatening reaction may https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 18/27 10/24/23, 3:24 PM Realizeit for Student occur when two drugs that affect serotonin levels in the body are taken concurrently. Other symptoms of serotonin syndrome include restlessness, hallucinations, fever, loss of consciousness, tachycardia, and a rapid change in blood pressure. Naratriptan (Amerge) has a slow onset of action. Contraindications include a creatinine clearance less than 15 mL/min or severe hepatic impairment. Women of childbearing age should use barrier contraceptives due to the risk of serious birth defects. Rizatriptan (Maxalt) is an oral preparation that can be swallowed or administered in a “melt-away” (orally disintegrating) formulation. It is effective in the treatment of acute migraine. The most common adverse effects are dizziness, fatigue, nausea, and somnolence. Patients with risk factors for coronary artery disease should receive the initial dose in a health care setting where their response can be evaluated. Zolmitriptan (Zomig) is a triptan that may be administered orally or intranasally. The onset of action of the oral drug is variable, whereas that of the intranasal preparation is 15 minutes. Two large studies have found that zolmitriptan is effective for acute migraine therapy, with an optimal starting dose of 2.5 mg. The most commonly reported adverse effects were dizziness, nausea, somnolence, paresthesia, fatigue, and tightness of the throat or chest. Sumatriptan–naproxen sodium (Treximet) is a combination drug that is administered orally. Patients should not divide, chew, or crush the tablets. This combination is effective in treating acute migraine and decreasing photophobia. The FDA has issued two BLACK BOX WARNINGS : (1) cardiovascular risk from sumatriptan, with an increased risk of adverse thrombotic events, including myocardial infarction and stroke, and (2) GI risk due to naproxen sodium, with an increased risk of GI irritation, inflammation, ulceration, bleeding, and perforation. Estrogen Estrogen in the form of estradiol is a treatment for menstrual migraines, which are most likely 2 days prior to menses through the 3rd day of bleeding. Perimenstrual estrogen supplementation is based on evidence that the natural decline in estrogen in the late luteal phase of the menstrual cycle, prior to menstruation, is associated with the increased risk of migraine. Pharmacokinetics https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 19/27 10/24/23, 3:24 PM Realizeit for Student Metabolism of estradiol occurs in the liver. Excretion takes place in the urine. The drug crosses the placenta and enters the breast milk. Action Estradiol binds to intracellular receptors to form a complex that stimulates synthesis of proteins responsible for estrogenic effects. Prophylactic administration minimizes the premenstrual decline in estrogen that precipitates the development of the migraine headache. Use Transcutaneous administration of estradiol increases the estrogen levels in the late luteal phase of the menstrual cycle that contribute to the development of menstrual migraine headaches. Table 52.6 gives dosage information for estradiol. Adverse Effects The major adverse effect associated with the administration of estrogen preparations is thromboembolic disorders. Menstrual irregularity can occur because of the suppression of endogenous estrogen during treatment. Contraindications Contraindications include incomplete bone growth, which occurs in adolescents. Other contraindications are the presence of neoplasms, breast cancer, thromboembolic disorders, fibroids, endometriosis, thyroid disease, and pregnancy. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 20/27 10/24/23, 3:24 PM Realizeit for Student Nursing Implications Preventing Interactions Some drugs interact with estradiol, increasing or decreasing its effects (Box 52.8). In addition, the combination of estradiol and bromocriptine interferes with the effects of bromocriptine. BOX 52.8 Drug Interactions: Estradiol Drugs That Increase the Effects of Estradiol Cyclosporine, theophylline, tricyclic antidepressants Increase serum levels Drugs That Decrease the Effects of Estradiol Phenytoin and rifampin Decrease serum levels Nicotine Reduces or cancels efficacy Administering the Medication Prior to applying the transcutaneous preparation, it is necessary to clean and dry the skin area. It is important to apply the preparation to the trunk. Assessing for Therapeutic Effects The nurse assesses for the development of migraine headache in the later luteal phase of the menstrual cycle. If a headache does not develop, the dose is adequate. Assessing for Adverse Effects The nurse assesses for the development of leg pain or chest pain indicative of the development of thromboembolism. He or she also assesses for breakthrough bleeding. Patient Teaching Box 52.9 identifies patient teaching guidelines for estradiol. BOX 52.9 Patient Teaching Guidelines for Estradiol Take estradiol transdermal as ordered by the prescriber. Notify your health care provider of intermittent breakthrough bleeding, spotting, or unexplained pain, especially calf or chest pain. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 21/27 10/24/23, 3:24 PM Realizeit for Student Preventive Therapy for Migraine Headaches Many medications are administered for the prevention of migraine headaches. These medications are primarily administered for the treatment of other conditions and are thoroughly covered in other modules. Their use in the prevention of migraines medications is discussed briefly. For complete information about these drugs, one may review the information in the modules indicated. Carboxylic Acid Derivative Valproic acid is a carboxylic acid derivative that is most commonly administered to control seizures. However, it has proved effective in the prevention of migraine headaches. Valproic acid is available in two forms. The dosage for valproic acid tablets is 250 mg orally two times per day, with a maximum dosage of 1000 mg. The dosage of the extended-release preparation is 500 mg orally once per day. Limited data suggest that valproic acid is safe for children as young as 7 years of age, and extended-release valproic acid is well tolerated by adolescents with migraine headaches. The risk of hepatotoxicity with valproic acid in children younger than 2 years has been reported. Gamma-Aminobutyric Acid Gabapentin (Neurontin) is a gamma-aminobutyric acid medication commonly administered to control neuropathic pain and as an adjunctive agent for control of seizures. Studies have shown that gabapentin is effective in reducing the frequency of migraines. At the end of 12 weeks, 46% of patients who received 2400 mg/day had a 50% reduction in the 4-week rate of migraine. The most commonly reported adverse effects were dizziness and somnolence. Sulfamate-Substituted Monosaccharide Topiramate (Topamax) is a sulfamate-substituted monosaccharide agent used most commonly as an antiepileptic agent (see Chap. 53). In clinical trials, the mean monthly migraine frequency decreased significantly with either 100 or 200 mg/day compared with placebo. However, with 50 mg/day, there was no statistically significant reduction in migraine frequency. The most commonly reported adverse effects include paresthesia, fatigue, anorexia, diarrhea, weight loss, altered memory, difficulty concentrating, and nausea. Limited data from comparative trials suggest that topiramate is as effective as the betaadrenergic blocking agent propranolol; however, topiramate is much more expensive than propranolol. Beta-Adrenergic Blocking Agents The most common beta-adrenergic blocking agent administered prophylactically for migraine headaches is propranolol (Inderal). The recommended dosage is two divided doses, starting at 40 mg daily. The maintenance dosage may be increased to 160 to 240 mg/day. Studies have shown that propranolol is effective in reducing migraine frequency. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 22/27 10/24/23, 3:24 PM Realizeit for Student In addition, two other beta-adrenergic blockers, metoprolol (50 mg daily in two divided doses, ranging to 200 mg daily) and timolol (5 mg once daily, ranging from 10 to 30 mg daily in two divided doses), are effective for migraine prophylaxis. It takes several weeks for these drugs to become effective, and it is necessary to titrate the dose for at least 3 months to ascertain effectiveness. A concern related to the use of beta-adrenergic blockers is the increased risk of stroke and other cardiovascular events, which limits their use in patients older than 60 and in those who smoke. Calcium Channel Blockers Verapamil is the calcium channel blocker of choice for migraine prophylaxis. It takes several weeks for benefits of the medication to be noted. It seems to be the most effective calcium channel blocker for migraine prevention. It is necessary to take 120 mg in three divided doses. Studies have also noted that tolerance may develop with calcium channel blockers. Tolerance to the medication can be overcome by increasing the dosage or switching to a different calcium channel blocker. Calcium channel blocking agents such as nifedipine (Procardia) have been used for prevention of migraine headache. However, data supporting the efficacy of calcium channel blockers are weak and conflicting. Angiotensin-Converting Enzyme Inhibitors Enalapril maleate is the prototype angiotensin-converting enzyme (ACE) inhibitor, but clinical trials have shown that lisinopril seems to be more effective in the prevention of migraine headaches. A study has shown that a dose of 10 mg/day for 1 week and then 20 mg/day reduced the number of hours and days with headache and headache severity compared to a placebo. However, the small sample size and design of this clinical trial and another performed by the same investigators limits any definitive conclusions regarding the use of ACE inhibitors in migraine prevention. These drugs are not widely used in migraine management. An adverse effect with ACE inhibitors is the development of a cough, which is the result of an interference with bradykinin, substance P, or tachykinin metabolism. Angiotensin II Receptor Blockers Angiotensin II receptor blockers (see Chap. 26) can be effective in the prevention of migraine headache but are not commonly used. Studies on the effectiveness of candesartan have revealed that it produces favorable results in the prevention of migraine headaches. It is necessary to inform women of childbearing age that barrier contraceptives are required with this medication. The FDA has issued a BLACK BOX WARNING stating that fetal injury and death have been reported with candesartan. Olmesartan is effective and well tolerated as a migraine prophylactic agent for patients with comorbid hypertension and prehypertension. Researchers have studied patients with hypertension and prehypertension to determine the effectiveness of this medication. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 23/27 10/24/23, 3:24 PM Realizeit for Student Tricyclic Antidepressants Imipramine (Tofranil) and other tricyclic antidepressants are effective in the prevention of migraine and tension headaches. Amitriptyline 10 to 50 mg at bedtime is also effective for migraine prophylaxis. Tricyclic antidepressants have a sedative effect, and to minimize this, it helps to administer the drugs at bedtime. Other side effects of tricyclic antidepressants include dry mouth, constipation, tachycardia, palpitations, orthostatic hypotension, weight gain, and urinary retention. Herbal and Vitamin Supplements People with migraines may use herbal supplements to treat these headaches. Several herbs, including feverfew and butterbur, and vitamins, such as magnesium and riboflavin, have shown modest efficacy for migraine prevention. In general, it is necessary to encourage patients to try standard methods of preventing and treating migraine before taking products with uncertain benefits and risks. Feverfew, an herbal medicine, is most widely studied for migraine prevention, but evidence of its benefit is conflicting. The main active ingredient of feverfew is thought to be parthenolide, which functions by inhibiting platelet aggregation, prostaglandin synthesis, and the release of inflammatory mediators such as histamine. Its exact mechanism in migraine prophylaxis is unknown. Study results have not established that feverfew is more effective than placebo for the prevention of migraine. Contraindications include pregnancy and lactation. The safety of the herb is unknown. Butterbur is an extract of a perennial shrub. Two small clinical trials have shown limited efficacy in migraine prophylaxis. Concerns that the pyrrolizidine alkaloids in feverfew are hepatotoxic and potentially carcinogenic have raised concerns about their long-term safety. The most common adverse effect in the trials was burping. Magnesium may be successful in treating and preventing migraine headaches in pregnant women. Adverse effects include diarrhea and GI discomfort. Riboflavin, vitamin B2, has demonstrated statistically significant benefit in the reduction in the frequency of headaches, the number of headache days per month, and mean headache severity. Its use is well tolerated. Riboflavin is inexpensive and produces minimal side effects. However, the benefits of the vitamin are not realized for up to 3 months of therapy. Without additional studies, it is uncertain who would most likely benefit from the administration of riboflavin and what dose produces optimal benefits. Adjuvant Medications for Migraine Headaches Adjuvant medications administered for severe migraine headaches include antiemetics and opioids. Antiemetic agents are adjuvant medications administered to control the symptoms of nausea and vomiting related to migraine, tension, and cluster headaches. Table 52.7 gives dosage information for the https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 24/27 10/24/23, 3:24 PM Realizeit for Student antiemetics. Opioid use is controversial because these agents can contribute to the development of chronic daily headache and interference with preventive therapy. Opioids are not discussed in this section. Antiemetic agents may be useful for treatment of symptoms related to migraine headache. Chlorpromazine hydrochloride (see Chap. 56) is a phenothiazine that has been shown to be effective in treating both the headache itself and the associated nausea and vomiting. Investigators have also shown that antiemetic drugs decrease the photophobia and phonophobia that may accompany the migraine headache. The mechanism of action involved in the decrease of nausea and vomiting is related to the suppression of the chemoreceptor zone. Besides chlorpromazine, related antiemetics include https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 25/27 10/24/23, 3:24 PM Realizeit for Student metoclopramide and prochlorperazine. Parenteral preparations of these drugs appear more effective than oral preparations. When administering the antiemetic agents, it is necessary to assess the patient for relief of headache, nausea, and vomiting. Chlorpromazine also depresses the CNS, so it is important to assess the patient’s level of consciousness. Metoclopramide is a GI stimulant that is effective in reducing headache, nausea, and vomiting. It is less effective than chlorpromazine in reducing symptoms. Metoclopramide is a potent central dopamine receptor antagonist that increases esophageal sphincter tone and elevates the chemoreceptor zone threshold. Although the drug can be administered by numerous routes, the American Headache Society guidelines prefer the intravenous route for migraine relief (see Table 52.7 ). Prochlorperazine has the same antiemetic action as chlorpromazine and metoclopramide. When taking prochlorperazine orally, it is important to swallow it whole and not chew or crush the tablets. When administering the medication parenterally, it is necessary to give it intramuscularly (deep) and never subcutaneously. When administering metoclopramide and prochlorperazine, it is necessary to assess the patient for signs and symptoms of dystonia, which is indicative of a hypersensitivity reaction. If the patient develops dystonia, it is necessary to administer diphenhydramine to counteract this reaction. With all of these medications, the patient should be assessed for urinary retention due to the anticholinergic effects. The Nursing Process A concept map outlines the nursing process related to drug therapy considerations in this module. Additional nursing implications related to the disease process should also be considered in care decisions. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 26/27 10/24/23, 3:24 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 27/27