Nonopioid and Opioid Analgesics
Objectives
• Differentiate between acute and chronic pain.
• Compare indications for nonopioid and opioid analgesics.
• Describe the serum therapeutic ranges of acetaminophen and aspirin.
• Contrast the side effects of aspirin and opioids.
• Explain the methadone treatment program.
• Discuss nursing interventions and patient teaching related to nonopioid and opioid analgesics.
• Apply the nursing process to the patient with patient-controlled analgesia.
Key Terms
addiction, p. 358
adjuvant analgesics, p. 363
analgesics, p. 353
cluster headaches, p. 366
endorphins, p. 353
migraine headaches, p. 365
neuropathic pain, p. 353
nociceptors, p. 353
nonopioid analgesics, p. 354
nonsteroidal antiinflammatory drugs, p. 353
opioid agonist, p. 356
opioid agonist-antagonist, p. 363
opioid antagonist, p. 365
orthostatic hypotension, p. 360
pain threshold, p. 353
pain tolerance, p. 353
patient-controlled analgesia, p. 362
withdrawal syndrome, p. 360
http://evolve.elsevier.com/KeeHayes/pharmacology/
Pain is an unpleasant sensory and emotional experience related to tissue injury. Due to the subjective nature of pain, the nurse must be knowledgeable and skillful in the assessment and measurement of pain to achieve optimal pain management.
Pain management is regarded as such a significant component of nursing care that pain has become known as the “fifth vital sign.” The Joint Commission (TJC) has incorporated the assessment, documentation, and management of pain into its 2003 standards, which reflects the importance of this vital sign. The nurse's role is to assess the patient's pain level, alleviate the patient's pain through nonpharmacologic and pharmacologic treatments, thoroughly document the patient's response to treatment, and teach patients and their significant others to manage pain control themselves when appropriate.
An individual's pain threshold reflects the level of stimulus needed to create a painful sensation. Individual genetic makeup contributes to the variations in pain threshold from person to person. The mu (µ) opioid receptor gene controls the number of µ receptors present. When an individual has a large amount of µ receptors, the pain threshold is high and pain sensitivity is reduced.
The amount of pain a person can endure without having it interfere with normal functioning is called pain tolerance. This psychological aspect of pain varies greatly in individuals, because it is very subjective. Pain tolerance is influenced by factors such as age, gender, culture, ethnicity, previous experience, anxiety level, and specific circumstances.
Analgesics, both nonopioid and opioid, are prescribed for the relief of pain. The choice of analgesic depends upon the severity of the pain. Mild to moderate pain is frequently relieved with the use of nonopioid (also known as nonnarcotic) analgesics. Moderate to severe pain usually requires an opioid (also known as narcotic) analgesic.
Drugs used for pain relief are presented in this chapter. Many of the same nonopioid analgesics that are taken for pain, such as the nonsteroidal antiinflammatory drugs (NSAIDs), are also taken for antiinflammatory purposes. This application for these drugs is covered in Chapter 25.
The most common classification of pain is by duration. Acute pain can be mild, moderate, or severe and is usually associated with a specific tissue injury. The onset of acute pain is usually sudden and of short duration. Chronic pain usually has a vague origin and onset with a prolonged duration.
Pain may also be classified by its origin. Nociceptors (sensory pain receptors) are activated by noxious stimuli (mechanical, thermal, and chemical) in peripheral tissues. When tissue damage occurs, injured cells release chemical mediators that affect the exposed nerve endings of the nociceptors. Pain that originates from tissue injury is nociceptor pain, which includes somatic (structural tissues: bones, muscles) and visceral (organ) pain. Neuropathic pain is an unusual sensory disturbance often involving neural supersensitivity. This pain is due to injury or disease of the peripheral or central nervous system (CNS). The patient with neuropathic pain usually complains of burning, tingling, or electrical shocks in the affected area, often triggered by light touch. Diabetic neuropathy associated with diabetes mellitus is an example of peripheral neuropathic pain. Severe, intractable pain from a herniated disk or spinal cord injury is evidence of neuropathic pain in the CNS.
Pathophysiology
The most common pain theory is called the gate theory, proposed by Melzack and Wall in 1965. According to this theory, tissue injury activates nociceptors and causes the release of chemical mediators such as substance P, prostaglandins, bradykinin, histamine, serotonin, acetylcholine, glutamate, adenosine triphosphate, leukotrienes, and potassium. These substances initiate an action potential along a sensory nerve fiber and sensitize pain receptors. Nociceptive action potentials are transmitted via afferent nerve fibers. One type of pain fiber that primarily transmits impulses from the periphery is the A delta (δ) fiber. Because A δ pain fibers are wrapped in a myelin sheath, they transmit impulses rapidly in acute pain. The C fiber is a type of pain fiber that is small and unmyelinated, and because C fibers are unmyelinated, they transmit impulses slowly. C fibers are more often associated with chronic, dull pain.
A pain signal begins at the nociceptors in the periphery and proceeds throughout the CNS. Knowing how and where pharmacologic agents work is essential to controlling pain. The body produces neurohormones called endorphins (peptides) that naturally suppress pain conduction, although the method is not completely understood. Opioids such as morphine activate the same receptors as endorphins to reduce pain. NSAIDs control pain at the peripheral level by blocking the action of cyclooxygenase (pain-sensitizing chemical) and interfering with the production of prostaglandins. Cortisone decreases pain by blocking the action of phospholipase, reducing the production of both prostaglandins and leukotrienes. In neuropathic pain, anticonvulsant drugs prevent the production of nerve impulses by stabilizing the neuronal membrane and inactivating peripheral sodium channels.
To ascertain severity of pain, the health care provider should ask the patient to rate the degree of pain on a scale of 1 to 10, with 10 being the worst or most severe pain. The patient's comfort level should also be determined. A patient who indicates a pain level of 9 may verbalize a decrease in pain to a level of 3 within 30 to 45 minutes after receiving pain medication. Table 26-1 lists the types of pain and the drug groups that may be effective in relieving each type of pain.
TABLE 26-1
IM, Intramuscular; IV, intravenous; NSAIDs, nonsteroidal antiinflammatory drugs; PCA, patient-controlled analgesia; PO, by mouth.
Undertreatment of Pain
Undertreatment of pain is a major issue in health care today. The National Pharmaceutical Council and TJC state that up to 75% of patients have unrelieved pain. Some reasons for undertreatment are sociocultural variables that mediate a patient's willingness to acknowledge being in pain, the patient's inability to describe pain, the nurse's inability to measure pain, lack of regular pain assessment rounds, attitudes of the health care team, an unwillingness to believe the patient's report of pain, inaccurate knowledge of the health care provider concerning addiction and tolerance, and prescription of an inadequate analgesic dose. Many scales and instruments are available to the nurse for assessment and measurement of the patient's pain level.
Unrelieved pain leads to a multitude of harmful effects involving almost all organs of the body. As a result of unrelieved pain, the patient may develop increased respiratory rate and heart rate, hypertension, increased stress response, urinary retention, fluid overload, electrolyte imbalance, glucose intolerance, hyperglycemia, pneumonia, atelectasis, anorexia, paralytic ileus, constipation, weakness, confusion, and infection.
In addition to psychological and physical suffering, inadequate pain management leads to high health care costs. It is estimated the cost of extended hospital stays, readmissions to the hospital, and outpatient visits due to inadequate pain management exceeds $100 billion per year.
Nonopioid Analgesics
Nonopioid analgesics (aspirin, acetaminophen, ibuprofen, naproxen) are less potent than opioid analgesics. They are used to treat mild to moderate pain. Nonopioids are usually purchased over-the-counter (OTC), but COX-2 inhibitors require a prescription. Nonopioids are effective for the dull, throbbing pain of headaches, dysmenorrhea (menstrual pain), inflammation, minor abrasions, muscular aches and pain, and mild to moderate arthritis. Most analgesics also have an antipyretic effect and will lower an elevated body temperature. Some, such as aspirin, have antiinflammatory and antiplatelet effects as well.
Nonsteroidal Antiinflammatory Drugs
All NSAIDs have an analgesic effect as well as an antipyretic and antiinflammatory action. NSAIDs such as aspirin (ASA), ibuprofen (Motrin, Advil), and naproxen (Aleve) can be purchased as OTC drugs. Aspirin, a salicylate NSAID, is the oldest nonopioid analgesic drug still in use. Adolf Bayer marketed the original formulation in 1899, and currently aspirin can be purchased under many names and with added ingredients. Examples are Bufferin, Ecotrin (enteric-coated tablet), Anacin (containing caffeine), and Alka-Seltzer.
Aspirin should not be used in children younger than 12 years of age, and it is contraindicated for any elevated temperature, regardless of the cause, because of the danger of Reye's syndrome (neurologic problems associated with viral infection treated with salicylates). In these circumstances, acetaminophen (Tylenol) is recommended instead of aspirin.
In addition to its analgesic, antipyretic, and antiinflammatory properties, aspirin decreases platelet aggregation (clotting). Some health care providers may therefore prescribe one 81-mg, 162-mg, or 325-mg aspirin tablet every day or one 325-mg tablet every other day as a preventive measure against transient ischemic attacks (TIAs, or “small strokes”), heart attacks, or any thromboembolic episode. Aspirin is discussed in depth in Chapter 25 along with other NSAIDs.
Aspirin and other NSAIDs relieve pain by inhibiting biosynthesis of prostaglandin by different forms of the enzyme cyclooxygenase (COX). Inhibition of COX-2 decreases inflammation and pain, but inhibition of COX-1 decreases protection of the stomach lining. As a result of an NSAID's inhibition of COX-1, stomach ulcers and bleeding may occur. Aspirin is the drug of choice for alleviating pain and inflammation in arthritic conditions, but when given in high doses, severe GI problems develop in approximately 20% of patients. Some pharmaceutical companies have developed antiinflammatory and analgesic drugs that inhibit only COX-2. The COX-2 inhibitors were developed to eliminate the GI side effects associated with aspirin and other NSAIDs. COX-2 inhibitors are discussed in depth in Chapter 25.
Side Effects and Adverse Reactions
A common side effect of NSAIDs is gastric irritation. These drugs should be taken with food, at mealtime, or with a full glass of fluid to help reduce this problem.
If an NSAID is taken for dysmenorrhea during the first 2 days of menstruation, excess bleeding might occur (more so with aspirin than with ibuprofen).
Some patients are hypersensitive to aspirin. Tinnitus, vertigo, bronchospasm, and urticaria are some of the symptoms that indicate hypersensitivity or overdose of the salicylate product. Certain foods also contain salicylates: prunes, raisins, paprika, and licorice. Those with a hypersensitivity to aspirin and salicylate products may be sensitive to other NSAIDs. This hypersensitivity may be related to inhibition of the enzyme cyclooxygenase by the salicylate product.
Acetaminophen
The analgesic acetaminophen (paraaminophenol derivative) is a popular nonprescription drug for the relief of pain, discomfort, and fever in infants, children, adults, and older adults. Acetaminophen is a nonopioid drug, but it is not an NSAID. Acetaminophen does not have the antiinflammatory properties of aspirin, so it is not the drug of choice for any inflammatory process. It constitutes 25% of all OTC drugs sold. Examples of OTC products that contain acetaminophen include Anacin; Excedrin; Midol: Maximum Strength Menstrual Formula; and Vicks: Cold & Flu Relief. Examples of prescription products on the market that contain acetaminophen include Lortab, Percocet, and Vicodin. Acetaminophen (Tylenol), first marketed in the mid-1950s, is an analgesic and antipyretic drug used for muscular aches and pains and for fever caused by viral infections. It is a safe, effective drug when used at therapeutic doses. It causes little to no gastric distress and does not interfere with platelet aggregation. An IV formulation was FDA approved in 2010 for treating pain and fever. There is no link between acetaminophen and Reye's syndrome, and it does not increase the potential for excessive bleeding if taken for dysmenorrhea, as do aspirin and NSAIDs (Prototype Drug Chart 26-1).
Prototype Drug Chart 26-1
Acetaminophen
: 2-4 h
A, Adult; C, child; d, day; h, hour; min, minute; PB, protein-binding; PO, by mouth; q.i.d., four times a day; 
, half-life; UK, unknown; y, year; <, less than; >, greater than.
Pharmacokinetics
Acetaminophen is well absorbed from the gastrointestinal (GI) tract. Rectal absorption may be erratic because of the presence of fecal material or a decrease in blood flow to the colon. Because of acetaminophen's short half-life, it can be administered every 4 hours as needed with a maximum dose of 4 g/day. However, it is suggested that a patient who frequently takes acetaminophen limit the dose to 2000 mg/day (2 g/day) to avoid the possibility of hepatic or renal dysfunction. More than 85% of acetaminophen is metabolized to drug metabolites by the liver.
Large doses or overdoses can be toxic to the hepatic cells, so when large doses are administered over a long period, the serum level of acetaminophen should be monitored. The therapeutic serum range is 10 to 25 mcg/mL. Liver enzyme levels (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP]) and serum bilirubin should also be monitored. Large doses of acetaminophen with regular alcohol intake may lead to liver injury. When acetaminophen toxicity occurs, acetylcysteine (Mucomyst) is the antidote, which reduces liver injury by converting toxic metabolites to a nontoxic form.
Pharmacodynamics
Acetaminophen weakly inhibits prostaglandin synthesis, which decreases pain sensation. It is effective in eliminating mild to moderate pain and headaches and is useful for its antipyretic effect. Acetaminophen does not possess antiinflammatory action. Its onset of action is rapid, and the duration of action is 5 hours or less. Severe adverse reactions may occur with an overdose, so acetaminophen in liquid or chewable form should be kept out of children's reach.
Side Effects and Adverse Reactions
An overdose of acetaminophen can be extremely toxic to liver cells, causing hepatotoxicity. Death could occur in 1 to 4 days from hepatic necrosis. If a child or adult ingests excessive amounts of acetaminophen tablets or liquid, a poison control center should be contacted immediately and the child or adult should be taken to the emergency department. Early symptoms of hepatic damage include nausea, vomiting, diarrhea, and abdominal pain.
Table 26-2 lists the commonly used nonopioid analgesics and their dosages, uses, and considerations.
Nursing Process
Patient-Centered Collaborative Care
Analgesic: Acetaminophen
Assessment
Nursing Diagnoses
Planning
Nursing Interventions
Check liver enzyme tests such as alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, 5′ nucleotidase, and bilirubin for elevations in patients taking high doses or overdoses of acetaminophen.
Patient Teaching
General
Teach patient to keep acetaminophen out of children's reach. Acetaminophen for children is available in flavored tablets and liquid. High doses can cause hepatotoxicity.
Advise patient not to self-medicate with acetaminophen longer than 10 days. Teach adult caregiver not to medicate child longer than 5 days without health care provider's approval.
Direct parent to call poison control center immediately if a child has taken a large or unknown amount of acetaminophen.
Teach patient to check acetaminophen dosage on package label of OTC drugs. Do not exceed the recommended dosage. Suggested safe adult acetaminophen dose is 2000 mg/d (2 g/day), not to exceed 4 g/day to avoid liver damage (see Prototype Drug Chart 26-1).
Side Effects
Encourage patient to report side effects. Overdosing can cause severe liver damage and death.
Inform patient that liver damage may occur with excess use of acetaminophen.
Check serum acetaminophen level if toxicity is suspected. Normal serum level is 5 to 20 mcg/mL; toxic level is >50 mcg/mL. Levels of >200 mcg/mL could indicate hepatotoxicity. The antidote for acetaminophen is acetylcysteine (Mucomyst). Dosage is based on serum acetaminophen level.
Cultural Considerations
Involving the extended family may be important for teaching health strategies and providing support.
Evaluation
Herbal Alert 26-1
Capsaicin
Capsaicin, which is found naturally in cayenne pepper, is selective for C fiber nociceptors and relieves some arthritis pain in topical cream or gel form.
TABLE 26-2
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Paraaminophenol | ||
| acetaminophen | See Prototype Drug Chart 26-1. | |
| NSAIDs | ||
| aspirin (Bayer, Ecotrin) | Analgesic: A: PO/PR: 325 to 650 mg, q4h; max: 4 g/d C: PO/PR: 10-15 mg/kg/d q4-6h; max: 4 g/d |
Effective in relieving headaches, muscle pain, inflammation and pain from arthritis; mild anticoagulant. Can displace other highly protein-bound drugs. If taken with acetaminophen, GI bleeding could result. Side effects: gastric discomfort, tinnitus, vertigo, deafness (reversible), increased bleeding. Should be taken with foods or at mealtime. Should not be taken with alcohol. Pregnancy category: D; PB: 80%-90%;  : 15-20 min |
| diflunisal (Dolobid) | A: PO: Initially 1000 mg; maint: 500 mg q12h; max: 1500 mg/d Older adults: PO: Initially 500 mg; maint: 250 q8-12h; max: 1500 mg/d |
Used for mild to moderate pain. Considered to be less toxic than aspirin. Pregnancy category: C; PB: 99%,  : 8-12 h |
| Propionic Acid | ||
| ibuprofen (Motrin, Advil) ibuprofen: IV injection (Caldolor) |
Pain: A: PO: 400 mg q4-6h; max: 3200 mg/d A: IV: 400-800 mg over 30 min q6h Fever: A: IV: 400 mg over 30 min q4-6h PRN |
For mild to moderate muscle aches and pains. Causes some gastric distress but less than aspirin. Should be taken with food, at mealtime, or with plenty of fluids. Pregnancy category: C (D, third trimester); PB: 90%-99%;  : 2-4 h |
| naproxen (Naprosyn) | Mild to moderate pain: A: PO: initially 500 mg, then 250 mg q6-8h; max: 1250 mg/d |
Treatment of inflammation and pain from osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, and dysmenorrhea. Pregnancy category: C; PB: 99%;  : 12-17 h |
| ketorolac (Toradol) | A: PO: 10 mg q6h PRN; max: 40 mg/d Older adults: PO: 10 mg q4-6h PRN; max: 40 mg/d A: IM/IV: 30-60 mg q6h PRN; max: 120 mg/d Older adults: IM/IV: 15 mg q6h PRN; max: 60 mg/d |
For short-term pain management (5 days or less). Pregnancy category: C; PB: 99%;  : 2.5-9 h |
| Oxicams | ||
| meloxicam (Mobic) | A: PO: Initially 7.5-15 mg/d; max: 15 mg/d | Treatment of pain from osteoarthritis. Pregnancy category: C (first and second trimester), D (third trimester); PB: 99%;  : 15-20 h |
| Naphthylalkanones | ||
| nabumetone (Relafen) | A: PO: 1000 mg/d or 500 mg b.i.d.; max: 2000 mg/d | Treatment of pain from osteoarthritis, rheumatoid arthritis. Pregnancy category: C (D, third trimester); PB: 99%;  : 24 h |
| COX-2 Inhibitors | ||
| celecoxib (Celebrex) | A: PO: 100-400 mg b.i.d.; max: 800 mg/d Older adults: 100-200 mg b.i.d.; max: 400 mg/d |
Treatment of osteoarthritis and rheumatoid arthritis. Not indicated for patients <18 y. Use caution for patients with severe renal or liver disorders and for those allergic to sulfonamides. Pregnancy category: C (D, third trimester); PB: 97%;  : 11.2 h |
| Miscellaneous | ||
| tramadol (Ultram) tramadol ER (Ultram ER, Ryzolt) |
A: PO: Initially: 25 mg/d, maint: 50-100 mg q4-6h PRN; max: 400 mg/d A >75 y: max: 300 mg/d A: PO: ER: 100 mg/d; max: 300 mg/d |
Used for moderate to severe pain. Contraindicated in severe alcoholism or with use of opioids. Nausea, vomiting, dizziness, constipation, headache, anxiety, and seizures may occur. Pregnancy category: C; PB: 20%;  : 6.3 h for immediate release, 7.9 h for ER |
A, Adult; b.i.d., twice a day; C, child; d, day; ER, extended-release; GI, gastrointestinal; h, hour; IM, intramuscular; IV, intravenous; maint, maintenance; max, maximum; min, minute; NSAIDs, nonsteroidal antiinflammatory drugs; PB, protein-binding; PO, by mouth; PRN, as needed; 
, half-life; UK, unknown; y, year; >, greater than; <, less than.
Opioid Analgesics
Opioid analgesics, called opioid agonists,are prescribed for moderate and severe pain. In the United States, the Harrison Opioid Act of 1914 required that all forms of opium be sold with a prescription and that it no longer be used as a nonprescription drug. The Controlled Substances Act of 1970 classified addicting drugs, opioids among them, in five schedule categories according to their potential for drug abuse (see Chapter 9). Addiction is defined as a psychological and physical dependence upon a substance beyond normal voluntary control, usually after prolonged use of a substance.
Herbal Alert 26-2
Opioids
Opioids taken with kava kava, valerian, and St. John's wort may increase sedation.
Morphine, a prototype opioid, is obtained from the sap of seed pods of the opium poppy plant. Codeine is another drug obtained from opium. In the past decades, many synthetic and semisynthetic opioids have been developed.
While nonopioid analgesics act on the peripheral nervous system at the pain receptor sites, opioid analgesics act mostly on the CNS. Opioids act primarily by activating the µ receptors, while also exerting a weak activation of the kappa (κ) receptors. Analgesia, respiratory depression, euphoria, and sedation are effects of µ activation. Activation of κ receptors leads to analgesia and sedation, having no effect on respiratory depression and euphoria.
Opioids not only suppress pain impulses but also respiration and coughing by acting on the respiratory and cough centers in the medulla of the brainstem. One example of such an opioid is morphine, a potent analgesic that can readily depress respirations. Codeine is not as potent as morphine (1/15 to 1/20 as potent), but it also relieves mild to moderate pain and suppresses cough, which allows it also to be classified as an antitussive. Most opioids, with the exception of meperidine (Demerol), have an antitussive (cough suppression) effect. The opioids have two isomers, levo and dextro. The levo-isomers of opioids produce an analgesic effect only; however, both levo- and dextro-isomers possess an antitussive response. The dextro-isomers do not cause physical dependence, but the levo-isomers do. Synthetic cough suppressants are discussed in Chapter 40.
In addition to pain relief and antitussive effects, many opioids possess antidiarrheal effects. Common side effects with high doses of most opioids include nausea and vomiting (particularly in ambulatory patients), constipation, a moderate decrease in blood pressure, and orthostatic hypotension. High doses of opioids may also cause respiratory depression, urinary retention (usually in older adults), and antitussive effects.
Morphine
Morphine, an extraction from opium, is a potent opioid analgesic (Prototype Drug Chart 26-2). Morphine is effective against acute pain resulting from acute myocardial infarction (AMI), cancer, and dyspnea resulting from pulmonary edema. It may be used as a preoperative medication. Although it is effective in relieving severe pain, it can cause respiratory depression, orthostatic hypotension, miosis, urinary retention, constipation resulting from reduced bowel motility, and cough suppression. An antidote for morphine excess or overdose is the opioid antagonist naloxone (Narcan)
.
Prototype Drug Chart 26-2
Morphine Sulfate
: 1.5-2 h
A, Adult; ALT, alanine aminotransferase; AST, aspartate aminotransferase; C, child; CNS, central nervous system; CSS, Controlled Substances Schedule; h, hour; IM, intramuscular; IV, intravenous; min, minute; PB, protein binding; PO, by mouth; PRN, as necessary; subQ, subcutaneous; SR, sustained-release; 
, half-life; UK, unknown; <, less than.
Pharmacokinetics
Morphine may be taken orally, although GI absorption can be somewhat erratic. For severe pain, such as with AMI, it is given intravenously (IV). Morphine is 30% protein-bound and may also be administered rectally and epidurally. Oral morphine undergoes first hepatic pass, meaning the liver metabolizes the drug before bioavailability to the rest of the body occurs. Only a small amount of morphine crosses the blood-brain barrier to produce an analgesic effect. It has a short half-life, and 90% is excreted in the urine. Morphine crosses the placenta and is excreted in breast milk.
Pharmacodynamics
Morphine binds with the opiate receptor in the CNS. Parenterally the onset of action is rapid, especially IV. Onset of action is slower for subcutaneous (subQ) and intramuscular (IM) injections. Duration of action with most types of drug administration is 3 to 5 hours; with controlled-release morphine sulfate tablets (MS Contin), duration is 8 to 12 hours.
Nursing Process
Patient-Centered Collaborative Care
Opioid Analgesic: Morphine Sulfate
Assessment
Obtain a medical history. Contraindications for morphine include severe respiratory disorders, increased intracranial pressure, and severe renal disease. Morphine may cause seizures.
Determine a drug history. Report if a drug-drug interaction is probable. Morphine increases the effects of alcohol, sedatives or hypnotics, antipsychotic drugs, and muscle relaxants and might cause respiratory depression.
Assess vital signs, noting rate and depth of respirations for future comparisons; opioids commonly decrease respirations and systolic blood pressure.
Monitor urinary output; morphine can cause urinary retention.
Assess type of pain, location, and duration before giving opioids.
Nursing Diagnoses
Planning
Nursing Interventions
Administer morphine before pain reaches its peak to maximize effectiveness of the drug.
Monitor vital signs at frequent intervals to detect respiratory changes. Respirations of <10/min can indicate respiratory distress.
Record patient's urine output because urinary retention is a side effect of morphine. Urine output should be at least 600 mL/day.
Check bowel sounds for decreased peristalsis; constipation is a side effect of morphine. Dietary change or mild laxative might be needed.
Check for pupil changes and reaction. Pinpoint pupils can indicate morphine overdose.
Have naloxone (Narcan) available as an antidote to reverse respiratory depression if morphine overdose occurs.
Validate dose of morphine before its administration. Check older adults for alertness and orientation because confusion is a side effect of morphine. Use side rails, and take other safety precautions as necessary.
Patient Teaching
General
Side Effects
Alert patient that with continuous use, opioids such as morphine can become addicting. If addiction occurs, inform patient about methadone treatment programs and other resources in the area.
Encourage patient to report dizziness while taking morphine. Dizziness could be due to orthostatic hypotension. Advise patient to ambulate with caution or only with assistance.
Teach patient to report difficulty in breathing, blurred vision, and headaches.
Cultural Considerations
Evaluation
Meperidine
One of the first synthetic opioids, meperidine (Demerol) became available in the mid-1950s. It is classified as a schedule II drug according to the Controlled Substances Act. Meperidine has a shorter duration of action than morphine, and its potency varies according to the dosage. Meperidine, which can be given orally, IM, and IV, is primarily effective in GI procedures. It does not have the antitussive property of opium preparations.
During pregnancy, meperidine is preferred to morphine because it does not diminish uterine contractions and causes less neonatal respiratory depression. Meperidine causes less constipation and urinary retention than morphine. Meperidine is not indicated for patients with chronic pain, severe liver dysfunction, sickle cell disease, a history of seizures, severe coronary artery disease (CAD), or cardiac dysrhythmias. When older adults and patients with advanced cancer receive large doses of meperidine, neurotoxicity (e.g., nervousness, tremors, agitation, irritability, seizures) have been reported. Meperidine should not be prescribed for long-term use; the dose is frequently limited to 600 mg in a 24-hour period for no longer than 48 to 72 hours.
Meperidine is metabolized in the liver to an active metabolite; therefore the dose should be decreased for patients with hepatic or renal insufficiency. It is excreted in the urine in a metabolite form called normeperidine. Meperidine should not be taken with alcohol or sedative-hypnotics, because the combination of these drugs causes an additive CNS depression. A major side effect of meperidine is a decrease in blood pressure, which should be monitored, especially if the patient is an older adult.
Table 26-3 lists opioids and their dosages, uses, and considerations.
SafetyTABLE 26-3
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| codeine sulfate, codeine phosphate) CSS II | A: PO/subQ/IM: 15-60 mg q4-6h PRN; max: 360 mg/d C: PO/subQ/IM: 0.5-1 mg/kg q4-6h, max: 60 mg/dose | Effective for mild to moderate pain and as an antitussive. Can be used with nonopioids (acetaminophen) for pain relief. Can cause decreased respirations, constipation, and physical dependence. Pregnancy category: C/D; PB: 7%,  : 2.5-4 h |
| hydrocodone bitartrate (Hycodan) CSS II combination with acetaminophen (Lortab, Vicodin), aspirin (Lortab ASA), ibuprofen (Vicoprofin), and chlorpheniramine (Tussionex) | Analgesic: A: PO: 5 mg q4-6h PRN; max: 30 mg/d C >6 y: PO: 2.5 mg q4-6h PRN; max: 15 mg/d | For moderate to moderately severe pain. Used for antitussive purposes. Pregnancy category: C/D; PB: UK;  : 4 h |
| hydromorphone HCl (Dilaudid) CSS II | A: PO: 2.5-10 mg q4-6h PRN A: IV: 0.2-1 mg q2-3h PRN Rectal: 3 mg q6-8h | For moderate to severe pain. Can be prescribed for analgesic and antitussive purposes. Pregnancy category: C; PB: 8%-19%;  : 2-3 h |
| levorphanol tartrate (Levo-Dromoran) CSS II | A: PO/IV: 1 mg q3-6h A: IM/subQ: 1-2 mg q6-8h PRN | For moderate to severe pain. Has side effects similar to morphine. Pregnancy category: B; PB: 40%;  : 11-16 h |
| meperidine (Demerol) CSS II | A: PO/subQ/IM/IV: 50-150 mg q3-4h PRN C: PO/subQ/IM/IV: 1-1.5 mg/kg q3-4h PRN; max: 150 mg q4h | For moderate to severe pain, GI procedures, and preoperative sedation. Pregnancy category: C/D; PB: 60%-80%;  : 3-5 h |
| morphine sulfate CSS II | See Prototype Drug Chart 26-2. | |
| oxycodone HCl (OxyContin) CSS II |
A: PO: 5-10 mg q6h PRN C >12 y: PO: 2.5 mg q6h PRN C 6-12 y: PO: 1.25 mg q6h PRN |
For moderate to moderately severe pain, including postoperative and postpartum pain. Avoid taking drug over an extended period of time. As potent as morphine. Take with food to avoid GI distress. Pregnancy category: B (D in third trimester); PB: 40%;  : 3-5 h |
| oxycodone HCl with acetaminophen (Percocet) and oxycodone terephthalate with aspirin (Percodan) CSS II |
A: PO: 2.5-10 mg q4-6h PRN or 5-10 mg q6h PRN | For moderate to severe pain. Percocet contains acetaminophen. Percodan contains aspirin and can cause gastric irritation, so it should be taken with food or plenty of liquid. Pregnancy category: C; PB: UK;  : 4 h |
| alfentanil (Alfenta) CSS II |
A: IV: 3-8 mcg/kg for surgery Continuous infusion: 0.25-1 mcg/kg/min Total dose: 3-40 mcg/kg |
Opioid analgesic with rapid onset of action. May be used to induce anesthesia. Pregnancy category: C; PB: 92%;  : 90-111 min |
| fentanyl (Duragesic, Sublimaze) CSS II |
A: IM: 50-100 mcg q1-2h PRN A: Sublimaze IM: 50-100 mcg q1-2h PRN A: Duragesic transdermal patch: Initially 25 mcg/h patch q3d |
Short-acting potent opioid analgesic. May be used with short-term surgery. Drug available as a lozenge and transdermal patch for controlling chronic pain. Pregnancy category: C; PB: 80%-89%;  : 7 h IV; 17 h transdermal |
| sufentanil citrate (Sufenta) CSS II |
Primary anesthetic: A: IV: 8-30 mcg/kg with 100% oxygen and muscle relaxant Adjunct to anesthesia: IV: 1-8 mcg/kg |
Potent synthetic opioid; used as part of the balanced anesthesia group. May be used as a primary anesthetic. Pregnancy category: C; PB: 93%;  : 1-3 h |
| remifentanil (Ultiva) CSS II |
A: IV: Postop: 0.025-0.2 mcg/min | Newest opioid analgesic. Rapid onset of action, short-acting duration (5-10 min). Can cause respiratory depression, hypotension, and bradycardia. Pregnancy category: C; PB: 70%;  : 3-10 min |
| methadone (Dolophine) CSS II |
Pain: A: PO/subQ/IM: 2.5-10 mg q8-12h PRN |
For moderate to severe acute pain. Similar to morphine but longer duration of action. Used in drug abuse programs. Helps alleviate craving for opioids. Peak action 30-60 min. Pregnancy category: C; PB: 85%-90%;  : 2-3 h |
A, Adult; C, child; CSS, Controlled Substances Schedule; GI, Gastrointestinal; h, hour; IM, intramuscular; IV, intravenous; maint; maintenance; max, maximum; min, minute; PB, protein-binding; PO, by mouth; PRN, as necessary; subQ, subcutaneous; 
, half-life; UK, unknown; y, year.
Hydromorphone
Hydromorphone (Dilaudid) is a semisynthetic opioid similar to morphine. The analgesic effect is approximately six times more potent than morphine with fewer hypnotic effects and less GI distress. This opioid has a faster onset and shorter duration of action than morphine. Hydromorphone is classified as a schedule II drug according to the Controlled Substances Act. Tolerance to hydromorphone increases gradually.
This drug is given orally, rectally, subQ, IM, and IV for the relief of moderate to severe pain. When given IV, dilution of each dose with 5 mL of sterile water or normal saline is preferred. Direct IV administration of 2 mg or less should be given over 2 to 5 minutes. Hydromorphone is readily absorbed in the body and excreted in the urine. Respirations should be monitored closely, and adequate hydration should be provided.
Side Effects and Adverse Reactions
Many side effects are known to accompany the use of opioids. Of particular importance are signs of respiratory depression (respiration <10/min). Other side effects include orthostatic hypotension (decrease in blood pressure when rising from a sitting or lying position), tachycardia, drowsiness and mental clouding, constipation, and urinary retention. In addition, pupillary constriction (a sign of toxicity), tolerance, and psychological and physical dependence may occur with prolonged use.
Increased metabolism of opioids contributes to tolerance, which causes an increased need for higher doses of the opioid. If chronic use of the opioid is discontinued, withdrawal (cessation of drug administration) symptoms usually occur within 24 to 48 hours after the last opioid dose. Withdrawal syndrome is caused by physical dependence. Symptoms of withdrawal syndrome include irritability, diaphoresis (sweating), restlessness, muscle twitching, and an increase in pulse rate and blood pressure. Withdrawal symptoms from opioids are unpleasant but not as severe or life-threatening as those that accompany withdrawal from sedative-hypnotics—a process that may lead to convulsions.
Contraindications
Use of opioid analgesics is contraindicated for patients with head injuries. Opioids decrease respiration, thus causing an accumulation of carbon dioxide (CO2). With an increase in carbon dioxide retention, blood vessels dilate (vasodilation), especially cerebral vessels, which causes increased intracranial pressure.
Opioid analgesics given to a patient with a respiratory disorder only intensify the respiratory distress. In the patient with asthma, opiates decrease respiratory drive while simultaneously increasing airway resistance.
Opioids may cause hypotension and are not indicated for patients in shock or for those who have very low blood pressure. If an opioid is necessary, the dosage needs to be adjusted accordingly; otherwise, the hypotensive state may worsen. For an older adult or a person who is debilitated, the opioid dose usually needs to be decreased.
Morphine is the opioid analgesic prototype, and all other opioids are measured in comparison to morphine.
Combination Drugs
To treat moderate to severe pain, combination drugs of an NSAID and an opioid analgesic may be used. Examples are hydrocodone and ibuprofen (Vicoprofen), which is a combination of an NSAID and an opioid. Another combination for the treatment of mild to moderate pain is acetaminophen and codeine. Using a combination of drugs for pain helps to decrease drug dependency that may result from possible long-term use of an opioid agent.
Patient-Controlled Analgesia
Patient-controlled analgesia (PCA) is an alternative route for opioid administration for self-administered pain relief as needed. Usually a loading dose (e.g., 2 to 10 mg of morphine) is given initially to achieve pain relief. Then within predetermined safety limits, the patient controls administration of the opioid analgesic, depending on the amount of pain. To receive the opioid, the patient pushes a button on the PCA device, releasing a specific dose of analgesic (e.g., 1 mg morphine) into the IV line. The nurse titrates the opioid analgesic dose by regulating the time intervals (every several minutes) at which the drug can be received. A lockout mechanism on the electronically controlled infusion pump prevents the patient from constantly pushing the button and causing a drug overdose. The PCA device maintains a near-constant analgesic level, avoiding episodes of severe pain and oversedation. Morphine is used most often for PCA, but fentanyl (Sublimaze) and hydromorphone (Dilaudid) may also be given.
Transdermal Opioid Analgesics
Transdermal opioid analgesics provide a continuous “around-the-clock” pain control that is helpful to patients who suffer from chronic pain. The transdermal method is not useful for acute or postoperative pain. An example of a transdermal opioid analgesic is fentanyl (Duragesic), which is administered via a transdermal patch. This patch comes in various strengths—12.5, 25, 50, 75, and 100 mcg/h. Maximum serum fentanyl levels occur within 24 hours of when the patch is first applied. Fentanyl is also available for IM and IV use. Fentanyl is more potent than morphine. For older adults, the use of a lower fentanyl transdermal dose is usually suggested. The health care provider must exercise caution when prescribing fentanyl for patients who weigh less than 110 pounds.
Analgesic Titration
Analgesics may be titrated to increase or decrease the dosage. Usually postoperative pain will decrease over time, and analgesics will be titrated downward. However, the patient with cancer-related pain usually has a continual increase in pain and will require an upward titration. Titration can be accomplished by changing the dose, the interval between doses, the route of administration, or the drug. When titrating analgesics, the dosage is decided after assessing the patient's respiratory rate and pain level.
Opioid Use in Special Populations
Children
Pain management in children is complex, because it is more difficult to assess their pain. Some children will not verbalize discomfort when they are in severe pain, and some are fearful of treatments like injections that relieve pain. Nurses should use age-appropriate communication skills to ascertain a child's need for pain relief. The “ouch scale” illustrated in Figure 26-1 can be helpful in determining a child's level of pain. Also, the parent may help identify the presence and degree of the child's pain. Crying and whining may be indicators of a need for pain relief or may represent other needs.
A child, like an adult, should be given medication before the pain becomes severe. The use of oral liquid medication for pain relief, if appropriate, is generally more acceptable to the child. The nurse may alleviate the child's fear and help with drug compliance by using drawings and pictures related to areas of pain in the body and pain relief with smiling faces.
Older Adults
Usually, adults who are 65 years of age or older require adjustment to drug doses to avoid severe side effects. Merely decreasing the usual adult dosage of opioid analgesic is not always the answer for older adults. Many take an array of medications for their health problems, increasing the possibility of drug interactions and drug side effects. In older adults, side effects from the use of opioids become more pronounced. The nurse needs to closely monitor for adverse reactions in older adults who take opioid analgesics. As a person ages, liver and renal functions decrease, causing the rate of metabolism and excretion of the drug to decrease. As a result, drug accumulation may occur.
Older adults tend to have different beliefs and fears than younger generations regarding opioids. They may believe that pain is inevitable due to aging or fear addiction. Older adults may not want to report pain, because they do not want to be a burden. The nurse must perform pain assessment with a supportive approach in an unhurried manner and teach the patient accurate drug information.
Pain assessment may be more difficult with older adults due to the decrease in cognitive and sensory-perceptual abilities. Dementia or hearing and visual deficits may interfere with communication. The nurse may need to rely on a more thorough physical assessment to discover the presence of pain, because self-reporting may not be reliable.
In the presence of decreased renal and hepatic function, drugs that tend to be more toxic in older adults include meperidine (Demerol), pentazocine (Talwin), and propoxyphene (Darvon). Analgesics are usually metabolized in the liver and excreted in the urine. Usual doses of analgesics in older adults may result in excessive sedation and prolonged duration of action. Chronologic age is one of several factors that influence medication use and dosage. Comorbidity must also be considered.
Cognitively Impaired Individuals
Any cognitively impaired individual may be unable to report pain adequately. The nurse should use a measurement scale that is appropriate for the patient. Some physical signs of pain include moans, grimacing, clenched teeth, noisy respirations, and restlessness.
Oncology Patients
Cancer pain is managed according to three levels of analgesia based on the World Health Organization (WHO) Ladder as follows:
Step 1—Mild Pain: Nonopioids with or without an adjuvant medication
Step 2—Moderate Pain: Nonopioids and mild opioid with or without an adjuvant medication
Step 3—Severe Pain: Stronger opioid at higher dosage levels with or without an adjuvant medication
Opioids are titrated for oncology patients until pain relief is achieved or the side effects become intolerable. For effective pain management in patients with cancer, extremely high doses may be required. There are no set dosage limits for oncology patients.
Individuals with a History of Substance Abuse
Often patients with a history of substance abuse require pain medication. A thorough pain assessment is necessary to find out the cause of pain. The nurse needs to know that opioids are effective and safe in this population, even though larger doses in greater frequency may be required. Studies have shown that withholding opioids in this population has not increased recovery from addiction. However, opioid agonist-antagonists such as pentazocine (Talwin) should be avoided in chemically dependent patients, because these drugs may precipitate withdrawal syndrome.
Adjuvant Therapy
Medications used as adjuvant analgesics have been developed for other purposes and later found to be effective for pain relief in neuropathy. Adjuvant therapy is usually used along with a nonopioid and opioid. Examples of adjuvant analgesics include anticonvulsants, antidepressants, corticosteroids, antidysrhythmics, and local anesthetics.
Anticonvulsant medications (gabapentin [Neurontin]) act on the peripheral nerves and CNS by inhibiting spontaneous neuronal firing. They are used for neuropathic pain and the prevention of migraine headaches. Tricyclic antidepressants (amitriptyline [Elavil]) prevent the reuptake of serotonin and norepinephrine in the cells. Lower doses of tricyclic antidepressants than those usually prescribed for depression are effective in treating peripheral neuropathy. Corticosteroids serve as effective analgesics by reducing nociceptive stimuli. Antidysrhythmics (mexiletine [Mexitil]) block sodium channels to reduce pain. Local anesthetics (lidocaine patch) can be effective analgesics by interrupting the transmission of pain signals to the brain.
Adjuvant medications potentiate opioid analgesia for severe persistent pain in diabetic neuropathy, cancer, migraine headaches, and rheumatoid arthritis. When any of the adjuvant medications are used in conjunction with an NSAID and opioid, dosages may be kept lower to reduce adverse effects.
Treatment for Opioid-Addicted Individuals
Refer to Chapter 5 for a discussion of therapies for addiction.
Opioid Agonist-Antagonists
Opioid agonist-antagonists, medications in which an opioid antagonist (e.g., naloxone [Narcan]) is added to an opioid agonist, were developed in hopes of decreasing opioid abuse. Pentazocine (Talwin), the first opioid analgesic, can be given orally (tablet) and by injection (subQ, IM, and IV). Pentazocine is classified as a schedule IV drug. Butorphanol tartrate (Stadol), buprenorphine (Buprenex), and nalbuphine hydrochloride (Nubain) are examples of other opioid agonist-antagonist analgesics. Reports say that pentazocine and butorphanol can cause dependence. Opioid agonist-antagonist drugs are not given for cancer pain, because of the risk of potential CNS toxicity from the high doses required. These analgesics are considered safe for use during labor, but their safety during early pregnancy has not been established.
Prototype Drug Chart 26-3 details the pharmacologic behavior of nalbuphine, and Table 26-4 lists the various opioid agonist-antagonists.
Prototype Drug Chart 26-3
Nalbuphine
| Drug Class | Dosage |
| Opioid: agonist-antagonist Trade Name: Nubain Pregnancy Category: B/D | A: IV/IM/subQ: 10-20 mg q3-6h; max: 160 mg/d |
| Contraindications | Drug-Lab-Food Interactions |
| Hypersensitivity Caution: History of drug abuse or emotional instability, impaired respirations, head injury, increased intracranial pressure, MI, biliary tract surgery, renal or hepatic dysfunction | Drug: CNS depression is potentiated with alcohol or other CNS depressants |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: readily occurs parenterally Distribution: PB: <30%; crosses placenta, excreted in breast milk Metabolism:  : 3-6 hExcretion: In urine, bile, feces | Onset: 2-3 min IV; 15 minutes IM Peak: 30 min IV; 30 min IM Duration: 3-4 h IV; 3-6 h IM |
| Therapeutic Effects/Uses | |
| To relieve moderate to severe pain | |
| Mode of Action: Inhibition of pain impulses transmitted in the CNS by binding with opiate receptor and increasing pain threshold | |
| Side Effects | Adverse Reactions |
| Dizziness, confusion, hallucinations, blurred vision, headache, flushing, sedation, nervousness, restlessness, euphoria, depression, crying, dysphoria, unusual dreams, dry mouth, bitter taste, nausea, vomiting, abdominal cramps, clammy skin, urinary urgency | Bradycardia, tachycardia, hypotension, hypertension, dyspnea Life-threatening: Respiratory depression |
CNS, Central nervous system; d, day; h, hour; IM, intramuscular; IV, intravenous; max, maximum; MI, myocardial infarction; min, minute; PB, protein-binding; subQ, subcutaneous; 
, half- life.
TABLE 26-4
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| buprenorphine HCl (Buprenex) CSS V | Pain: A: IM/IV: Initially: 0.3 mg q4h PRN | For moderate to severe pain associated with surgery, cancer, urinary calculi, myocardial infarction, and trauma. Avoid alcohol and CNS depressants. Pregnancy category: C; PB: 96%;  : 2-37 h |
| butorphanol tartrate (Stadol) CSS IV | A: IM: 1-4 mg q3-4h PRN A: IV: 0.5-2 mg q3-4h PRN Nasal spray: 1 mg (1 spray) q3-4h | Management of moderate to severe pain associated with cancer, urinary calculi, labor, musculoskeletal, and burns. Pregnancy category: C; PB: 80%;  : 5 h |
| nalbuphine HCl (Nubain) CSS IV | See Prototype Drug Chart 26-3. | |
| pentazocine lactate (Talwin) CSS IV |
A: PO: 50-100 mg q3-4h PRN; max: 600 mg/d A: subQ/IM/IV: 30 mg q3-4 h PRN; max: 360 mg/d |
To control moderate to severe pain. Pregnancy category: C; PB: 60%;  : 1.5-10 h |
A, Adult; CNS, central nervous system; CSS, Controlled Substances Schedule; d, day; h, hour; IM, intramuscular; IV, intravenous; max, maximum; PB, protein-binding; PO, by mouth; PRN, as needed; subQ, subcutaneous; 
, half-life; UK, unknown; >, greater than.
Pharmacokinetics
Nalbuphine can be administered orally, IM, subQ, or IV. It is rapidly absorbed parenterally. Nalbuphine has a short half-life. It is metabolized in the liver and excreted in the urine.
Pharmacodynamics
Nalbuphine is effective in alleviating moderate to severe pain. Onset of action is rapid, and peak time occurs within 30 minutes with IV administration. Duration of action is the same for all routes of administration: approximately 5 hours.
Nursing Process
Patient-Centered Collaborative Care
Opioid Agonist-Antagonist Analgesic: Nalbuphine (Nubain)
Assessment
Nursing Diagnosis
Planning
Nursing Interventions
Monitor vital signs. Note any changes in respirations.
Check bowel sounds and date of last bowel movement to identify constipation. Decreased peristalsis may result in constipation. A mild laxative may be necessary.
Determine urine output. Report if urine output is <30 mL/h or <600 mL/day.
Administer IV nalbuphine undiluted. Do not mix with barbiturates.
Patient Teaching
General
Warn patient not to use alcohol or CNS depressants while taking nalbuphine. Respiratory depression can occur.
Suggest nonpharmacologic methods for lessening pain like changing position or ambulation.
Side Effects
Cultural Considerations
Evaluation
Opioid Antagonists
Opioid antagonists are antidotes for overdoses of natural and synthetic opioid analgesics. The opioid antagonists have a higher affinity to the opiate receptor site than the opioid being taken. An opioid antagonist blocks the receptor and displaces any opioid that would normally be at the receptor, inhibiting the opioid action. Indications for opioid antagonists include reversal of postoperative opioid depression and opioid overdose.
Naloxone (Narcan), administered IM or IV; naltrexone hydrochloride (ReVia), administered orally by tablet or liquid; and nalmefene are opioid antagonists. These drugs are perfect examples of pharmacologic antagonists because they reverse the respiratory and CNS depression (sedation and hypotension) caused by opioids. Table 26-5 lists the opioid antagonists.
TABLE 26-5
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| naloxone HCl (Narcan) | Opiate overdose or opioid-induced respiratory distress: A: IV: 0.4-2 mg; may repeat q2-3 min; max: 10 mg C: IV: 0.01-0.1 mg/kg; may repeat q2-3 min; max: 10 mg |
To treat opioid overdose. Approved for use in neonates to reverse respiratory depression induced by maternal opioid use. Pregnancy category: B; PB: UK;  : 0.5-1.5 h |
| naltrexone HCl (Vivitrol, ReVia) | A: PO: 25 mg/d; repeat 25 mg in 1 h if no withdrawal response; max: 150 mg/d A: IM: 380 mg/dose q4wk; max: 380 mg/dose |
To treat opioid and alcohol abuse. Three to five times more potent than naloxone. Decreases but does not prevent craving for opioids. Use after patient is off opioids for 7 days or more. Do not give if patient is in opiate withdrawal; can precipitate a withdrawal reaction. High doses can cause hepatotoxicity. Pregnancy category: C; PB: 21%-28%;  : 5-10 h |
A, Adult; C, child; h, hour; IM, intramuscular; IV, intravenous; max, maximum; min, minute; PB, protein-binding; PO, by mouth; PRN, as needed; 
, half-life; UK, unknown.
When receiving opioid antagonists, the patient should be monitored continuously. The opioid action may exceed that of opioid antagonists, and further analgesia may be needed. For example, fentanyl and a combination of drugs given during surgery may lead to excessive respiratory depression. Naloxone may be given as an opioid antidote. The patient's respiratory and CNS status should be monitored closely for indications of analgesic reversal (tachycardia, nausea, vomiting, and sweating) and possible need of further analgesia. The patient receiving naloxone should also be observed for bleeding, because this drug may cause an elevated partial thromboplastin time.
Headaches: Migraine and Cluster
Migraine headaches are characterized by a unilateral throbbing head pain accompanied by nausea, vomiting, and photophobia. These symptoms frequently persist for 4 to 24 hours and for several days in some cases. Two thirds of migraine headaches are experienced by women in their twenties and thirties. Symptoms usually decrease or are absent during pregnancy and menopause. The intensity of migraine pain can disrupt daily activities.
Pathophysiology
Migraine headaches are caused by inflammation and dilation of the blood vessels in the cranium. The etiology is unknown, but some theories suggest an imbalance in the neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) that causes vasoconstriction and suppresses migraine headaches. The tendency of calcitonin gene-related peptide (CGRP) is to promote a migraine attack. Serum CGRP levels are elevated during a migraine attack. Foods such as cheese, chocolate, and red wine can trigger an attack.
The two types of migraine are (1) classic migraines, which are associated with an aura that occurs minutes to 1 hour before onset, and (2) common migraines, which are not associated with an aura.
Cluster headaches are characterized by a severe unilateral nonthrobbing pain usually located around the eye. They occur in a series of cluster attacks—one or more attacks every day for several weeks. They are not associated with an aura and do not cause nausea and vomiting. Men are more commonly affected by cluster headaches than women.
Treatment of Migraine Headaches
Preventive treatment for migraines includes (1) beta-adrenergic blockers such as propranolol (Inderal) and atenolol (Tenormin); (2) anticonvulsants such as valproic acid (Depakote) and gabapentin (Neurontin); and (3) tricyclic antidepressants such as amitriptyline (Elavil) and imipramine (Tofranil).
Treatment or cessation of a migraine attack depends on the intensity of pain. Drugs used to treat migraines include analgesics, opioid analgesics, ergot alkaloids, and selective serotonin1 (5-HT) receptor agonists, also known as triptans. For mild migraine attacks, aspirin, acetaminophen, or NSAIDs, such as ibuprofen or naproxen (Aleve), may be prescribed. Aspirin may be used in combination with caffeine. Meperidine (Demerol) and butorphanol nasal spray (Stadol NS) are opioid analgesics that are occasionally used.
Antimigraine medication should be taken early during a migraine attack. Nausea and vomiting might occur; antiemetics decrease these symptoms. Dihydroergotamine, an ergot alkaloid, can be administered subcutaneously, intramuscularly, intravenously, and by means of a nasal spray.
The triptans (5-HT1 receptor agonists) are the most recently developed group of drugs for the treatment of migraine headaches. Sumatriptan (Imitrex), a selective serotonin receptor agonist with a short duration of action, was the first triptan drug. It is considered more effective than ergot alkaloids in treating acute migraine attacks. Table 26-6 lists the ergot alkaloids and the selective serotonin1 (5-HT) receptor agonists and their dosages, uses, and considerations. Do not confuse sumatriptan with zolmitriptan. Both drugs are triptans but have different dosages. Also, do not confuse Amerge (triptan used for migraines) with Amaryl (sulfonylurea used for diabetes mellitus) or Altace (angiotensin-converting enzyme inhibitor) used for hypertension and heart failure. Prototype Drug Chart 26-4 provides further pharmacology of sumatriptan.
TABLE 26-6
DRUGS USED TO TREAT SEVERE MIGRAINE HEADACHES
| DRUG | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Ergot Alkaloids | ||
| dihydroergotamine mesylate (Migranal) | A: Intranasal: 1 spray in each nostril; may repeat in 15 min; max: 4 sprays (2 mg)/attack, 8 sprays/d, 24 sprays/wk A: IM/IV: 1 mg; may repeat in 1 h; max: 6 mg/wk |
To prevent or abort migraine attack. Pregnancy category: X; PB: 90%-93%;  : 21-32 h |
| Selective Serotinin1 Receptor Agonists (Triptans) | ||
| sumatriptan (Imitrex) | See Prototype Drug Chart 26-4. | |
| naratriptan (Amerge) | A: PO: 1-2.5 mg; may repeat in 4 h; max: 5 mg/d | For acute migraines. Has a longer half-life, thus duration of action is longer. Causes vasoconstriction of cranial arteries. Avoid if patient has uncontrolled hypertension, IHD, prior MI. Pregnancy category: C; PB: 28%-31%;  : 6 h |
| rizatriptan benzoate (Maxalt) | A: PO: 5-10 mg; may repeat in 2 h; max: 30 mg/d | For acute migraines. Two types of tablets: regular and melt-in-mouth. Avoid if patient has uncontrolled hypertension, IHD, prior MI. Pregnancy category: C; PB: 14%;  : 2-3 h |
| zolmitriptan (Zomig) | A: PO: 2.5-5 mg; may repeat in 2 h; max: 10 mg/d | For acute migraines. 65% of patients respond in 2 h. Avoid if patient has uncontrolled hypertension, IHD, prior MI. Pregnancy category: C; PB: 25%;  : 3 h |
| almotriptan (Axert) | A: PO: 6.25-12.5 mg; may repeat in 2 h; max: 25 mg/d | For acute migraines. Pregnancy category: C; PB: 35%;  : 3-4 h |
| frovatriptan (Frova) | A: PO: 2.5 mg; may repeat in 2 h; max: 7.5 mg/d | For acute migraines. Pregnancy category: C; PB: 15%;  : 26 h |
| eletriptan (Relpax) | A: PO: 20-40 mg; may repeat in 2 h; max: 80 mg/d | For acute migraines. Pregnancy category: C; PB: 85%;  : 4-5 h |
A, Adult; h, hour; IHD, ischemic heart disease; IM, intramuscular; IV, intravenous; max, maximum; MI, myocardial infarction; min, minute; PB, protein-binding; PO, by mouth; SL, sublingual; subQ, subcutaneous; 
, half-life; UK, unknown, wk, week.
Prototype Drug Chart 26-4
Sumatriptan
: 2 h
A, Adult; h, hour; MAOI, monoamine oxidase inhibitor; max, maximum; min, minute; PB, protein-binding; PO, by mouth; subQ, subcutaneous; 
, half-life; UK, unknown.
Key Websites
Information on Duragesic (fentanyl transdermal patch): www.rxlist.com/cgi/generic/fentanyl.htm
Information on acetaminophen: www.nlm.nih.gov/medlineplus/druginfo/meds/a681004.html
Information on zolmitriptan (Zomig): www.zomig.com/index.aspx?ce5set
Critical Thinking Case Study
RJ, a 79-year-old man, underwent abdominal surgery for resection of his colon. His physician prescribed morphine 10 mg every 3 to 4 hours PRN after the surgery. RJ did not ask for “pain medication,” because he worried he might become addicted. A day after the surgery, his nurse noted that he was restless and grimaced whenever he moved in bed. He refused to breathe deeply or cough when instructed to do so. The nurse compared RJ's vital signs to his baseline findings and noted an increased pulse rate and a drop in systolic blood pressure of 6 mm Hg.
1. Should the nurse give morphine? Explain your answer.
2. What would your reaction be to RJ in regard to his restlessness, grimacing, and refusal to deep breathe and cough?
3. What is the significance of the change in vital signs?
4. What classic side effects of opioid analgesics should the nurse assess?
5. What are some possible nonpharmacologic measures that might be helpful in alleviating RJ's pain?
The second postoperative day, RJ began asking for morphine every 3 hours. On the fifth day, the physician discontinued RJ's morphine and prescribed acetaminophen with codeine.
6. Why was the opioid analgesic order changed?
7. RJ does not want to ambulate. What is an appropriate nursing response?