N215 Unit 5 Chapter 18. Drugs for the Control of Pain Flashcards
morphine (Astramorph PF, Duramorph, others)
Therapeutic Class: Opioid analgesic
Pharmacologic Class: Opioid receptor agonist
ACTIONS AND USES
Morphine binds with both mu and kappa receptor sites to produce profound analgesia. It causes euphoria, constriction of the pupils, and stimulation of cardiac muscle. It is used for symptomatic relief of serious acute and chronic pain after nonnarcotic analgesics have failed, as preanesthetic medication, to relieve shortness of breath associated with heart failure and pulmonary edema, and for acute chest pain connected with MI.
ADMINISTRATION ALERTS
- The oral solution may be given sublingually.
- The oral solution comes in multiple strengths; carefully observe drug orders and labels before administering.
- Morphine causes peripheral vasodilation, which results in orthostatic hypotension.
- Pregnancy category B (D in long-term use or with high doses).
PHARMACOKINETICS
Onset
Peak
Duration
Less than 60 min
60 min PO; 20-60 min rectally; 50-90 min subcutaneously; 30-60 min IM; 20 min IV
Up to 7 h
ADVERSE EFFECTS
Morphine may cause dysphoria (restlessness, depression, and anxiety), hallucinations, nausea, constipation, dizziness, and an itching sensation. Overdose may result in severe respiratory depression or cardiac arrest. Tolerance develops to the sedative, nausea-producing, and euphoric effects of the drug. Cross-tolerance also develops between morphine and other opioids such as heroin, methadone, and meperidine. Physical and psychological dependence develops when high doses are taken for prolonged periods.
Black Box Warning: When morphine is administered as an epidural drug, due to the risk of adverse effects, patients must be observed in a fully equipped and staffed environment for at least 24 hours. Morphine administered as extended-release tablets has an abuse liability similar to other opioid analgesics. Morphine is a Schedule II controlled substance and should be taken properly according to dispensing instructions (i.e., tablets/capsules should be taken whole and not broken, chewed, dissolved, or crushed). Alcohol should be avoided with morphine products (e.g., Avinza). Failure to follow these warnings could result in fatal respiratory depression.
Contraindications: Morphine may intensify or mask the pain of gallbladder disease, due to biliary tract spasms. Morphine should also be avoided in cases of acute or severe asthma, GI obstruction, and severe hepatic or renal impairment.
INTERACTIONS
Drug-Drug: Morphine interacts with several drugs. For example, concurrent use of CNS depressants, such as alcohol, other opioids, general anesthetics, sedatives, and antidepressants such as monoamine oxidase (MAO) inhibitors and tricyclics, potentiate the action of opiates, increasing the risk of severe respiratory depression and death.
Lab Tests: Unknown.
Herbal/Food: Yohimbe, kava kava, valerian, and St. John’s wort may potentiate the effect of morphine.
Treatment of Overdose: IV administration of naloxone is the specific treatment. Other treatments include activated charcoal, a laxative, and a counteracting narcotic antagonist. Multiple doses may be needed.
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What drugs are used for control of pain?
OPIOID ANALGESICS page 224
Opioid Agonists page 225 morphine (Astramorph PF, Duramorph, others) page 228
Opioid Antagonists page 228 naloxone (Narcan) page 231
Opioids with Mixed Agonist-Antagonist Activity page 231
buprenorphine page 231
NONOPIOID ANALGESICS page 231
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) page 233
Aspirin and Other Salicylates page 234 aspirin (acetylsalicylic acid, ASA) page 234
Ibuprofen and Related Drugs page 232
COX-2 Inhibitors page 232
Acetaminophen page 234
Centrally Acting Drugs page 234 tramadol (Ultram) page 234
ANTIMIGRAINE DRUGS page 237
Ergot Alkaloids page 238 ergotamine (Ergostat) page 238
Triptans page 238 sumatriptan (Imitrex) page 239
naloxone (Narcan)
Therapeutic Class: Drug for treatment of acute opioid overdose and misuse
Pharmacologic Class: Opioid receptor antagonist
ACTIONS AND USES
Naloxone is a pure opioid antagonist, blocking both mu and kappa receptors. It is used for complete or partial reversal of opioid effects in emergency situations when acute opioid overdose is suspected. Given intravenously, it begins to reverse opioid-initiated CNS and respiratory depression within minutes. It will immediately cause opioid withdrawal symptoms in patients physically dependent on opioids. It is also used to treat postoperative opioid depression. It is occasionally given as adjunctive therapy to reverse hypotension caused by septic shock.
ADMINISTRATION ALERTS
- Administer for a respiratory rate of fewer than 10 breaths/minute. Keep resuscitative equipment accessible.
- Pregnancy category B.
PHARMACOKINETICS
Onset
Peak
Duration
1-2 min IV; 2-5 min IM; 2-5 min subcutaneously
5-15 min
45 min
ADVERSE EFFECTS
Naloxone itself has minimal toxicity. However, reversal of the effects of opioids may result in rapid loss of analgesia, increased blood pressure, tremors, hyperventilation, nausea and vomiting, and drowsiness.
Black Box Warning: None; however, naltrexone, a similar opioid receptor antagonist, has the capacity to produce hepatic injury when taken in excessive doses or if taken by patients with hepatic injury or acute liver disease.
Contraindications: Naloxone should not be used for respiratory depression caused by nonopioid medications.
INTERACTIONS
Drug-Drug: Drug interactions include a reversal of the analgesic effects of opioid agonists and mixed agonist drugs.
Lab Tests: Unknown.
Herbal/Food: Echinacea may increase the risk of hepatotoxicity.
Treatment of Overdose: Naloxone overdose requires the use of oxygen, IV fluids, vasopressors, and other supportive measures as indicated. These treatments may be useful in combination drug overdose (for example, pentazocine with naloxone [Talwin NX]).
buprenorphine
Although effective at relieving pain, the opioids have a greater risk for dependence than almost any other class of medications. Tolerance develops relatively quickly to the euphoric effects of opioids, causing abusers to escalate their doses and take the drugs more frequently. The higher and more frequent doses rapidly cause physical dependence in opioid abusers.
When physically dependent patients attempt to discontinue drug use, they experience extremely uncomfortable symptoms that convince many to continue their drug-taking behavior to avoid the suffering. As long as the drug is continued, they feel “normal,” and many can continue work or social activities. In cases when the drug is abruptly discontinued, the patient experiences about 7 days of withdrawal symptoms before overcoming the physical dependence.
The intense craving characteristic of psychological dependence may occur for many months, and even years, following discontinuation of opioids. This often results in a return to drug-seeking behavior unless significant support groups are established.
One method of treating opioid dependence has been to switch the patient from IV and inhalation forms of illegal drugs to methadone (Dolophine). Although oral methadone is an opioid, it does not cause the euphoria of the injectable opioids. Methadone also does not cure the dependence, and the patient must continue taking the drug to avoid withdrawal symptoms. This therapy, called methadone maintenance, may continue for many months or years, until the patient decides to enter a total withdrawal treatment program. Methadone maintenance allows patients to return to productive work and social relationships without the physical, emotional, and criminal risks of illegal drug use.
A newer treatment option is to administer buprenorphine (Buprenex, Butrans, Suboxone), a mixed opioid agonist-antagonist, by the sublingual or transdermal route. Buprenorphine is used early in opioid abuse therapy to prevent opioid withdrawal symptoms. Suboxone, contains both buprenorphine and naloxone and is used later in the maintenance of opioid addiction.
Health care providers should always be aware that when administering opioids with mixed agonist-antagonist activity, their pain-blocking properties are reduced when administered in combination with opioid agonists. Thus, there may be a tendency to overprescribe mixed opioids, promoting drug misuse. This is true even though in most cases the potential for causing opioid addiction is lower with mixed agonist-antagonists compared with pure opioid agonists.
aspirin (Acetylsalicylic Acid, ASA)
Therapeutic Class: Nonopioid analgesic; nonsteroidal anti-inflammatory drug (NSAID); antipyretic
Pharmacologic Class: Salicylate; cyclooxygenase (COX) inhibitor
ACTIONS AND USES
Aspirin inhibits prostaglandin synthesis involved in the processes of pain and inflammation and produces mild to moderate relief of fever. It has limited effects on peripheral blood vessels, causing vasodilation and sweating. Aspirin has significant anticoagulant activity, and this property is responsible for its ability to reduce the risk of mortality following MI, and to reduce the incidence of strokes. Aspirin has also been found to reduce the risk of colorectal cancer, although the mechanism by which it affords this protective effect is unknown.
ADMINISTRATION ALERTS
- Platelet aggregation inhibition caused by aspirin is irreversible. Aspirin should be discontinued 1 week prior to elective surgery.
- Aspirin is excreted in the urine and affects urine testing for glucose and other metabolites, such as vanillylmandelic acid (VMA).
- Pregnancy category D.
PHARMACOKINETICS
Onset
Peak
Duration
1 h
2-4 h
24 h
ADVERSE EFFECTS
At high doses, such as those used to treat severe inflammatory disorders, aspirin may cause gastric discomfort and bleeding because of its antiplatelet effects. Enteric-coated tablets and buffered preparations are available for patients who experience GI side effects.
Contraindications: Because aspirin increases bleeding time, it should not be given to patients receiving anticoagulant therapy such as warfarin, heparin, and plicamycin.
INTERACTIONS
Drug-Drug: Concurrent use of phenobarbital, antacids, and glucocorticoids may decrease aspirin’s effects. Aspirin may potentiate the action of oral hypoglycemic drugs. Effects of NSAIDs, uricosuric drugs such as probenecid, beta blockers, spironolactone, and sulfa drugs may be decreased when combined with aspirin. Insulin, methotrexate, phenytoin, sulfonamides, and penicillin may increase effects. When aspirin is taken with alcohol, pyrazolone derivatives, steroids, or other NSAIDs, there is an increased risk for gastric ulcers.
Lab Tests: Aspirin may cause prolonged prothrombin time by decreasing prothrombin production. Aspirin may also interfere with pregnancy tests and decrease serum levels of cholesterol, potassium, PBI, T3, and T4. High salicylate levels may cause abnormalities in liver function tests.
Herbal/Food: Feverfew, garlic, ginger, and ginkgo may increase the risk of bleeding.
Treatment of Overdose: Treatment may include any of the following: activated charcoal, gastric lavage, laxative, or drug therapy for overdose symptoms such as dizziness, drowsiness, abdominal pain, or seizures.
Ibuprofen (Advil, Motrin, others)
Pharmacologic Class: NSAID
ACTIONS AND USES
Ibuprofen is an older drug that is prescribed for the treatment of mild to moderate pain, fever, and inflammation. Its effectiveness is equivalent to that of aspirin and other NSAIDs. Its actions are primarily due to inhibition of prostaglandin synthesis. Common indications include pain associated with chronic musculoskeletal disorders such as RA and osteoarthritis, headache, dental pain, and dysmenorrhea. Chewable tablets, drops, and solutions are available in low doses for administration to children.
ADMINISTRATION ALERTS
- Give the drug on an empty stomach as tolerated. If nausea, vomiting, or abdominal pain occurs, give with food.
- Be aware that patients with asthma or who have allergies to aspirin are more likely to exhibit a hypersensitivity reaction to ibuprofen.
- Pregnancy category B.
PHARMACOKINETICS
Onset
Peak
Duration
30-60 min
1-2 h
6-8 h
ADVERSE EFFECTS
Adverse effects of ibuprofen are generally mild and include nausea, heartburn, epigastric pain, and dizziness. GI ulceration with occult or gross bleeding may occur, especially in patients who are taking high doses for prolonged periods. Chronic use of ibuprofen may lead to renal impairment.
Black Box Warning: NSAIDs may cause an increased risk of serious thrombotic events, MI, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. NSAIDs are contraindicated for the treatment of perioperative pain in those undergoing coronary artery bypass graft surgery. NSAIDs increase the risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events occur more frequently in older adults and can occur at any time during use or without warning symptoms.
Contraindications: Patients with active peptic ulcers should not take ibuprofen. This drug is also contraindicated in patients with significant renal or hepatic impairment and in those who have a syndrome of nasal polyps, angioedema, or bronchospasm due to aspirin or other NSAID use. It should be used cautiously in patients who have HF, serious HTN, or a history of stroke or MI.
INTERACTIONS
Drug-Drug: Because ibuprofen can affect platelet function, its use should be avoided when taking anticoagulants and other coagulation modifiers. Aspirin use can decrease the anti-inflammatory action of ibuprofen. The antihypertensive action of diuretics, beta blockers, and ACE inhibitors may be reduced if taken with ibuprofen. The actions of certain diuretics may be diminished when taken concurrently with ibuprofen. Use with other NSAIDs, alcohol, or corticosteroids may cause serious adverse GI events.
Lab Tests: Ibuprofen may increase bleeding time, aspartate transaminase (AST), and alanine transaminase (ALT) levels. It may decrease hemoglobin and hematocrit.
Herbal/Food: Feverfew, garlic, ginger, or ginkgo may increase the risk of bleeding.
Treatment of Overdose: There is no specific treatment for overdose. Administration of an alkaline drug may increase the urinary excretion of ibuprofen.
Acetaminophen (Tylenol, others)
Therapeutic Class: Antipyretic and analgesic
Pharmacologic Class: Centrally acting COX inhibitor
ACTIONS AND USES
Acetaminophen reduces fever by direct action at the level of the hypothalamus and dilation of peripheral blood vessels, which enables sweating and dissipation of heat. Acetaminophen, ibuprofen, and aspirin have equal efficacy in relieving pain and reducing fever.
Acetaminophen has no anti-inflammatory properties; therefore, it is not effective in treating arthritis or pain caused by tissue swelling following injury. The primary therapeutic usefulness of acetaminophen is for the treatment of fever in children and for relief of mild to moderate pain when aspirin is contraindicated. In the treatment of severe pain, acetaminophen may be combined with opioids. This allows the dose of opioid to be reduced, thus decreasing the risk of dependence and serious opioid toxicity. It is available as tablets, caplets, solutions, and suppositories.
Acetaminophen has no effect on platelet aggregation and does not exhibit cardiotoxicity. Most importantly, it does not cause GI bleeding or ulcers, as do the NSAIDs.
ADMINISTRATION ALERT
- Liquid forms are available in varying concentrations. Use the appropriate strength product in children to avoid toxicity.
- Never administer to patients who consume alcohol regularly due to the potential for hepatotoxicity.
- Advise patients that acetaminophen is found in many OTC products and that extreme care must be taken to not duplicate doses by taking several of these products concurrently.
- Pregnancy category B.
PHARMACOKINETICS
Onset
Peak
Duration
30-60 min
0.5-2 h
1-4 h
ADVERSE EFFECTS
Acetaminophen is generally safe, and adverse effects are uncommon at therapeutic doses. Acetaminophen causes less gastric irritation than aspirin and does not affect blood coagulation. It is not recommended in patients who are malnourished. In such cases, acute toxicity may result, leading to renal failure, which can be fatal. Other signs of acute toxicity include nausea, vomiting, chills, abdominal discomfort, and fatal hepatic necrosis.
A major concern with the use of high doses of acetaminophen is the risk for liver damage, which is especially important for patients who consume alcohol.
Black Box Warning: Acetaminophen has the potential to cause severe and even fatal liver injury and may cause serious allergic reactions with symptoms of angioedema, difficulty breathing, itching, or rash. In 2011, the Food and Drug Administration (FDA) asked drug manufacturers to limit the strength of acetaminophen in prescription combination products to 325 mg per tablet, capsule, or dosing unit to lower the potential for acetaminophen-induced hepatotoxicity.
Contraindications: Contraindications include hypersensitivity to acetaminophen or phenacetin and chronic alcoholism.
INTERACTIONS
Drug-Drug: Acetaminophen inhibits warfarin metabolism, causing the anticoagulant to accumulate to toxic levels. High-dose or long-term acetaminophen use may result in elevated warfarin levels and bleeding. Ingestion of this drug with alcohol or other hepatotoxic drugs, such as phenytoin or barbiturates, is not recommended because of the possibility of liver failure from hepatic necrosis.
Lab Tests: Acetaminophen may increase hepatic function test values such as serum bilirubin, AST, and ALT. It may increase urinary 5-hydroxyindole acetic acid (5-HIAA) and serum uric acid.
Herbal/Food: The patient should avoid taking herbs that have the potential for liver toxicity, including comfrey, coltsfoot, and chaparral.
Treatment of Overdose: The specific treatment for overdose is the oral or IV administration of N-acetylcysteine (Acetadote) as soon as possible after the overdose. This drug protects the liver from toxic metabolites of acetaminophen.
tramadol (Ultram)
Tramadol (Ultram) and ziconotide (Prialt) are centrally acting analgesics. Of the two drugs, tramadol is the most widely prescribed. Tramadol has weak opioid activity, although it is not thought to relieve pain by this mechanism. Its main action is to inhibit reuptake of norepinephrine and serotonin in spinal neurons. Tramadol is well tolerated, but common adverse effects are vertigo, dizziness, headache, nausea, vomiting, constipation, and lethargy.
Sumatriptan (Imitrex)
Therapeutic Class: Antimigraine drug
Pharmacologic Class: Triptan; 5-HT (serotonin) receptor drug; vasoconstrictor of intracranial arteries
ACTIONS AND USES
Sumatriptan belongs to a relatively newer group of antimigraine drugs known as the triptans. The triptans act by causing vasoconstriction of cranial arteries; this vasoconstriction is moderately selective and does not usually affect overall blood pressure. This medication is available in oral, intranasal, and subcutaneous forms. Subcutaneous administration terminates migraine attacks in 10 to 20 minutes; the dose may be repeated 60 minutes after the first injection to a maximum of two doses per day. If taken orally, sumatriptan should be administered as soon as possible after the migraine is suspected or has begun.
ADMINISTRATION ALERTS
- Sumatriptan may produce cardiac ischemia in susceptible persons with no previous cardiac events. Health care providers may opt to administer the initial dose of sumatriptan in the health care setting.
- Sumatriptan’s systemic vasoconstrictor activity may cause hypertension and may result in dysrhythmias or myocardial infarction. Keep resuscitative equipment accessible.
- Sumatriptan selectively reduces carotid arterial blood flow. Monitor changes in level of consciousness and observe for seizures.
- Pregnancy category C.
PHARMACOKINETICS
Onset
Peak
Duration
15 min nasal; 30 min PO; 10 min subcutaneous
2 h PO; 12 min subcutaneous, 60-90 min nasal
24-48 h
ADVERSE EFFECTS
Some dizziness, drowsiness, or a warming sensation may be experienced after taking sumatriptan; however, these effects are not normally severe enough to warrant discontinuation of therapy.
Contraindications: Because of its vasoconstricting action, the drug should be used cautiously, if at all, in patients with recent myocardial infarction, or with a history of angina pectoris, hypertension, or diabetes.
INTERACTIONS
Drug-Drug: Sumatriptan interacts with several drugs. For example, an increased effect may occur when taken with monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). Further vasoconstriction can occur when taken with ergot alkaloids and other triptans.
Lab Tests: Unknown.
Herbal/Food: Ginkgo, ginseng, echinacea, and St. John’s wort may increase triptan toxicity.
Treatment of Overdose: Treatment may include drug therapy for the following symptoms: weakness, lack of coordination, watery eyes and mouth, tremors, seizures, or breathing problems.
What are the primary factors that facilitate the inflammation response?
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What other chemicals influence the inflammatory reponse?
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What are COx1 and COx2? Describe location, function and inhibition by medications.
COx1 Location: present in all tissues Function: -protects gastric mucosa -supports kidney function -promotes platlet aggregation Inhibition by medications: undesirable (increases risk of gastric bleeding and kidney failure) e.g.
COx2 Location: present at sites of tissue injury Function: -mediates inflammation -sensitizes pain receptors -mediates fever in the pain Inhibition by medications: desirable (results in suppression of inflammation) e.g. fever, pain
What is the impact of NSAIDs on COx1 and COx2?
Introduction
NSAIDs inhibit cyclooxygenase, an enzyme responsible for the formation of prostaglandins. When cyclooxygenase is inhibited, inflammation and pain are reduced. NSAIDs are drugs of choice for mild to moderate pain, especially for pain associated with inflammation. These drugs have many advantages over the opioids in that the NSAIDs have antipyretic and anti-inflammatory activity as well as analgesic properties.
Aspirin, Ibuprofen, and COX-2 Inhibitors
Aspirin and ibuprofen are available OTC and are inexpensive. Ibuprofen and related medications are available in many different formulations, including those designed for children. They are safe and well tolerated by most patients when used at low to moderate doses.
After tissue damage, prostaglandins are formed with the help of two enzymes called cyclooxygenase type 1 (COX-1) and cyclooxygenase type 2 (COX-2). Aspirin and ibuprofen-related drugs inhibit both COX-1 and COX-2. Thus, COX inhibition is the basis of NSAID therapy. Because the COX-2 enzyme is more specific for the synthesis of inflammatory prostaglandins, the selective COX-2 inhibitors provide more specific and peripheral pain relief. Celecoxib (Celebrex) is the representative COX-2 inhibitor. Other COX-2 inhibitors are available outside of the United States. Figure 18.3 illustrates the mechanism of pain transmission at the nociceptor level.
Compare a COx vs histamine reaction.
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